WO1997002357A1 - Integrated nucleic acid diagnostic device - Google Patents
Integrated nucleic acid diagnostic device Download PDFInfo
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- WO1997002357A1 WO1997002357A1 PCT/US1996/011147 US9611147W WO9702357A1 WO 1997002357 A1 WO1997002357 A1 WO 1997002357A1 US 9611147 W US9611147 W US 9611147W WO 9702357 A1 WO9702357 A1 WO 9702357A1
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Definitions
- polynucleotide sequences can also be specifically involved in, for example, the control and regulation of gene expression.
- disorders which are caused by mutations, deletions or repeats in specific portions of the genome may be readily diagnosed and/or treated using genetic techniques.
- disorders caused by external agents may be diagnosed by detecting the presence of genetic material which is unique to the external agent, e.g., bacterial or viral DNA.
- the present invention generally provides miniature integrated fluidic systems for carrying out a variety of preparative and analytical operations, as well a ⁇ method ⁇ of operating the ⁇ e ⁇ y ⁇ tem ⁇ and method ⁇ of u ⁇ ing the ⁇ e ⁇ y ⁇ tems.
- the present invention provides a miniature fluidic system which comprises a body having at least first and second chambers dispo ⁇ ed therein. Each of these first and second chambers ha ⁇ a fluid inlet and i ⁇ in fluid connection.
- At lea ⁇ t one of the ⁇ e fir ⁇ t and ⁇ econd chambers is a hybridization chamber for analyzing a component of a fluid sample.
- the hybridization chamber include ⁇ a polymer array which ha ⁇ a plurality of different polymer ⁇ equence ⁇ coupled to a surface of a ⁇ ingle ⁇ ub ⁇ trate, each of the plurality of different polymer sequences being coupled to the surface in a different, known location.
- the sy ⁇ tem further includes a sample inlet, fluidly connected to at least one of the fir ⁇ t and second chamber ⁇ , for introducing a fluid ⁇ ample into the system, and a fluid transport system for moving a fluid sample from the first chamber to the second chamber.
- the fluid direction system comprises a pneumatic manifold for applying a differential pressure between the first chamber and the ⁇ econd chamber, to move said fluid ⁇ ample from the fir ⁇ t chamber to the ⁇ econd chamber.
- the p ** -j ⁇ ent invention provides a miniature fluidic system, which is substantially the same a ⁇ that de ⁇ cribed above, except that in place or in addition to a hybridization chamber, the ⁇ y ⁇ tem compri ⁇ e ⁇ a ⁇ eparation channel for separating a component of ⁇ aid fluid ⁇ ample.
- the separation channel is fluidly connected to at least one of the chambers and includes at least first and second electrodes in electrical contact with opposite ends of the separation channel for applying a voltage acros ⁇ said separation channel.
- the present invention provides a substantially similar fluidic system as described, except where at least one of the chambers comprise ⁇ an in vitro transcription reaction chamber, the in vitro transcription reaction chamber having an effective amount of an RNA polymerase and four different nucleoside triphosphate ⁇ , di ⁇ posed therein.
- the sy ⁇ tem may compri ⁇ e a body wherein at lea ⁇ t one of the chamber ⁇ is a cell lysis chamber which includes a cell lysi ⁇ system, for lysing cells in said fluid sample.
- At least one of the chambers may be a nucleic acid purification chamber, for separating nucleic acids in said fluid sample from other contaminants in ⁇ aid fluid ⁇ ample.
- the pre ⁇ ent invention al ⁇ o provide ⁇ a miniature fluidic system which comporise ⁇ a differential pre ⁇ ure delivery system for transporting fluids through the ⁇ y ⁇ tem.
- the pre ⁇ ent invention provide ⁇ a miniature fluidic ⁇ y ⁇ tem, which include ⁇ a body having at least a first reaction chamber fluidly connected to a second reaction chamber by a fluid pas ⁇ age.
- the ⁇ y ⁇ tem al ⁇ o includes a sample inlet, fluidly connected to the first chamber, for introducing a fluid sample into the sy ⁇ tem.
- the ⁇ y ⁇ tem further include ⁇ a differential pressure delivery ⁇ ystem for maintaining the fir ⁇ t chamber at a fir ⁇ t pressure and the second chamber at a second pressure, wherein the fir ⁇ t pre ⁇ sure is greater than ambient pres ⁇ ure and the ⁇ econd pressure is greater than said first pres ⁇ ure.
- the first pre ⁇ ure forces a liquid sample in the first chamber into the ⁇ econd chamber.
- the fluidic ⁇ ystem employ ⁇ a differential pre ⁇ ure delivery ⁇ ource for maintaining the fir ⁇ t chamber at a fir ⁇ t pre ⁇ ure and the ⁇ econd chamber at a second pre ⁇ ure, where the ⁇ econd pre ⁇ ure i ⁇ le ⁇ s than ambient pres ⁇ ure and the first pres ⁇ ure i ⁇ less than the second pres ⁇ ure.
- the second pressure draws a liquid sample in the first chamber into the second chamber.
- the present invention also provides methods of directing, controlling and manipulating fluids in miniature or micro-fluidic systems.
- the present invention provides a method for directing a fluid sample in a miniature fluidic system which comprise ⁇ providing a microfabricated device having at lea ⁇ t fir ⁇ t and ⁇ econd chamber ⁇ di ⁇ posed therein, wherein each of ⁇ aid at lea ⁇ t fir ⁇ t and ⁇ econd chamber ⁇ i ⁇ in fluid connection with a common chamber or channel, ha ⁇ at lea ⁇ t first and second controllable valve ⁇ disposed acros ⁇ ⁇ aid fluid connection, re ⁇ pectively, and include ⁇ at lea ⁇ t one vent.
- the method compri ⁇ e ⁇ applying a positive pre ⁇ ure to the common chamber or channel.
- the at lea ⁇ t first controllable valve is selectively opened, whereby the positive pres ⁇ ure force ⁇ the fluid ⁇ ample from the common chamber or channel into the fir ⁇ t chamber.
- the method may further comprise applying a positive pressure to the first chamber and selectively opening the least first controllable valve, whereby the positive pre ⁇ ure force ⁇ said fluid sample from the lea ⁇ t first chamber into the common chamber or channel.
- the present invention also provides methods of mixing at least two discrete fluid component ⁇ in a microfabricated fluidic system.
- the method comprises providing a microfabricated channel having a vent disposed at an intermediate location in said channel.
- the vent includes a gas permeable, fluid barrier disposed across the vent.
- At least two di ⁇ crete fluid component ⁇ are then introduced into the channel ⁇ eparated by a gas bubble. Upon flowing the at least two fluid components past the vent, the bubble will exit the vent, allowing the at least two fluid components to mix.
- the present invention al ⁇ o provide ⁇ method ⁇ of repeatedly mea ⁇ uring a known volume of a fluid in a miniature fluidic system.
- the method comprise ⁇ providing a microfabricated device having at lea ⁇ t fir ⁇ t and ⁇ econd chambers disposed therein, wherein the at least first and second chambers are in fluid connection, and wherein at least one of the chambers i ⁇ a volumetric chamber having a known volume.
- the volumetric chamber i ⁇ filled with the fluid to create a fir ⁇ t aliquot of the fluid. This aliquot is then transported to the at least second chamber and the filling and transporting steps are repeated.
- Figure 1 shows a schematic representation of a nucleic acid diagnostic system for analysis of nucleic acids from sample ⁇ .
- Figure ⁇ 2A and 2b show schematic representation ⁇ of two alternate reaction chamber de ⁇ ign ⁇ from a cut-away view.
- Figure 3 shows a schematic representation of a miniature integrated diagnostic device having a number of reaction chambers arranged in a serial geometry.
- Figures 4A-C show a representation of a microcapillary electrophoresi ⁇ device.
- Figure ⁇ 4A and 4B show the microcapillary configured for carrying out alternate loading strategies for the microcapillary whereas Figure 4C illustrates the microcapillary in running mode.
- Figure 5A illustrate ⁇ a top view of a miniature integrated device which employ ⁇ a centralized geometry.
- Figure 5B ⁇ how ⁇ a ⁇ ide view of the ⁇ ame device wherein the central chamber i ⁇ a pumping chamber, and employing diaphragm valve structures for sealing reaction chambers.
- Figure 6 ⁇ how ⁇ ⁇ chematic illustrations of pneumatic control manifolds for transporting fluid within a miniature integrated device.
- Figure 6A show ⁇ a manifold configuration suitable for application of negative pre ⁇ ure, or vacuum
- Figure 6B show ⁇ a manifold configuration for application of po ⁇ itive pressures.
- Figure 6C illustrate ⁇ a pressure profile for moving fluids among several reaction chambers.
- Figure 7A shows a schematic illustration of a reaction chamber incorporating a PZT element for u ⁇ e in mixing the content ⁇ of the reaction chamber.
- Figure 7B ⁇ hows mixing within a reaction chamber applying the PZT mixing element as shown in Figure 7A.
- Figure 7C is a bar graph ⁇ howing a comparison of hybridization intensities using mechanical mixing, acou ⁇ tic mixing, ⁇ tagnant hybridization and optimized acoustic mixing.
- Figure 8 i ⁇ a ⁇ chematic illu ⁇ tration of a side and top view of a base-unit for u ⁇ e with a miniature integrated device.
- Figure 9 i ⁇ a time temperature profile of thermal cycling in a miniature reaction chamber and a di ⁇ play of the programmed cycling parameter ⁇ .
- Figure IOA i ⁇ a gel ⁇ howing a time course of an RNA fragmentation reaction.
- Figure 10B is a gel showing a comparison of the product of an in vitro transcription reaction in a microchamber vs. a control (te ⁇ t tube) .
- Figure IOC is a compari ⁇ on of the PCR product produced in a PCR thermal cycler and that produced by a microreactor.
- Figure 11 how ⁇ an embodiment of a reaction chamber employing an electronic pH control ⁇ ystem.
- Figure 12A-C show a schematic representation of a miniature integrated device employing a pneumatic fluid direction ⁇ y ⁇ tem utilizing a ga ⁇ permeable fluid barrier bound vents, e.g., a poorly wetting or hydrophobic membrane,and pneumatically controlled valves.
- Figure 12A show ⁇ an embodiment of a single chamber employing this system.
- Figure 12B is a schematic illustration of a debubbling chamber for linking discrete fluid plugs that are ⁇ epareted by a ga ⁇ bubble.
- Figure 12C schematically illustrate ⁇ thi ⁇ system in an integrated device having numerous chambers, including degassing chamber, dosing or volumetric chamber, storage and reaction chambers.
- Figure 12D is an illustration of an injection molded substrate which embodies the sy ⁇ tem schematically illustrated in Figure 12C.
- Figure 13 is a ⁇ chematic representation of a device configuration for carrying generic sample preparation reactions.
- Figure 14 is a schematic representation of a device configuration for carrying multiple parallel reactions.
- Figure 15 show ⁇ a demon ⁇ tration of integrated reaction ⁇ in a microfabricated polycarbonate device.
- Figure 15A shows the layout of the device including the thermal configuration of the device.
- Figure 15B show ⁇ the re ⁇ ult ⁇ of PCR amplification and ⁇ ub ⁇ equent in vitro transcription within the chambers of the device.
- the device of the invention is generally capable of performing one or more sample acquisition and preparation operations, in combination with one or more sample analysis operations.
- the device can integrate several or all of the operations involved in sample acqui ⁇ ition and ⁇ torage, ⁇ ample preparation and ⁇ ample analy ⁇ i ⁇ , within a ⁇ ingle, miniaturized, integrated unit.
- the device i ⁇ u ⁇ eful in a variety of application ⁇ and most notably, nucleic acid based diagnostic applications and de novo seguencing applications.
- the device of the invention will typically be one component of a larger diagnostic ⁇ y ⁇ tem which further includes a reader device for scanning and obtaining the data from the device, and a computer based interface for controlling the device and/or interpretation of the data derived from the device.
- one embodiment of the device of the invention will typically incorporate a plurality of distinct reaction chamber ⁇ for carrying out the sample acqui ⁇ ition, preparation and analy ⁇ is operation ⁇ .
- a sample to be analyzed is introduced into the device whereupon it will be delivered to one of these di ⁇ tinct reaction chamber ⁇ which are de ⁇ igned for carrying out a variety of reaction ⁇ a ⁇ a prelude to analy ⁇ is of the ⁇ ample.
- These preparative reactions generally include, e.g., sample extraction, PCR amplification, nucleic acid fragmentation and labeling, extension reactions, transcription reactions and the like. Following sample preparation, the sample can be subjected to one or more different analysi ⁇ operation ⁇ .
- analy ⁇ i ⁇ operations may generally be performed, including size based analysi ⁇ u ⁇ ing, e.g., microcapillary electrophore ⁇ is, and/or ⁇ equence ba ⁇ ed analy ⁇ is using, e.g., hybridization to an oligonucleotide array.
- the device will generally comprise a series of fluid channels which allow for the transportation of the sample or a portion thereof, among the various reaction chambers. Further chambers and components may also be included to provide reagents, buffer ⁇ , sample manipulation, e.g., mixing, pumping, fluid direction (i.e., valve ⁇ ) heating and the like.
- the sample collection portion of the device of the present invention generally provides for the identification of the sample, while preventing contamination of the sample by external elements, or contamination of the environment by the sample. Generally, this is carried out by introducing a sample for analysi ⁇ , e.g., preamplified ⁇ ample, ti ⁇ ue, blood, saliva, etc., directly into a sample collection chamber within the device. Typically, the prevention of cros ⁇ -contamination of the sample may be accompli ⁇ hed by directly injecting the sample into the sample collection chamber through a sealable opening, e.g., an injection valve, or a septum. Generally, sealable valves are preferred to reduce any potential threat of leakage during or after sample injection. Alternatively, the device may be provided with a hypodermic needle integrated within the device and connected to the sample collection chamber, for direct acquisition of the sample into the sample chamber. This can substantially reduce the opportunity for contamination of the sample.
- a sample for analysi ⁇ e.g., preamplified ⁇ ample, ti
- the ⁇ ample collection portion of the device may al ⁇ o include reagent ⁇ and/or treatment ⁇ for neutralization of infectiou ⁇ agent ⁇ , stabilization of the specimen or sample, pH adjustments, and the like.
- Stabilization and pH adjustment treatments may include, e.g., introduction of heparin to prevent clotting of blood samples, addition of buffering agents, addition of protease or nuclease inhibitors, preservative ⁇ and the like.
- Such reagents may generally be stored within the sample collection chamber of the device or may be stored within a separately accessible chamber, wherein the reagent ⁇ may be added to or mixed with the ⁇ ample upon introduction of the ⁇ ample into the device.
- These reagents may be incorporated within the device in either liquid or lyophilized form, depending upon the nature and stability of the particular reagent used.
- the ⁇ e sample preparation operations will include such manipulations as extraction of intracellular material, e.g., nucleic acids from whole cell samples, viruse ⁇ and the like, amplification of nucleic acids, fragmentation, transcription, labeling and/or extension reactions.
- extraction of intracellular material e.g., nucleic acids from whole cell samples, viruse ⁇ and the like
- amplification of nucleic acids e.g., fragmentation, transcription, labeling and/or extension reactions.
- One or more of these various operations may be readily incorporated into the device of the present invention.
- nucleic acids may be liberated from the collected cells, viral coat, etc., into a crude extract, followed by additional treatments to prepare the sample for subsequent operations, e.g., denaturation of contaminating (DNA binding) protein ⁇ , purification, filtration, de ⁇ alting, and the like.
- Liberation of nucleic acid ⁇ from the sample cells or viru ⁇ es, and denaturation of DNA binding proteins may generally be performed by physical or chemical methods.
- chemical method ⁇ generally employ lysing agents to disrupt the cells and extract the nucleic acids from the cells, followed by treatment of the extract with chaotropic salts such as guanidinium isothiocyanate or urea to denature any contaminating and potentially interfering proteins.
- chaotropic salts such as guanidinium isothiocyanate or urea
- the appropriate reagents may be incorporated within the extraction chamber, a separate accessible chamber or externally introduced.
- cell extraction and denaturing of contaminating proteins may be carried out by applying an alternating electrical current to the sample. More specifically, the sample of cells is flowed through a microtubular array while an alternating electric current is applied across the fluid flow.
- alternating electrical current may be applied across the fluid flow.
- other method ⁇ may be utilized within the device of the pre ⁇ ent invention to effect cell lysis/extraction, including, e.g., subjecting cells to ultrasonic agitation, or forcing cells through microgeometry apertures, thereby subjecting the cell ⁇ to high shear ⁇ tre ⁇ s resulting in rupture.
- nucleic acids e.g., denatured proteins, cell membrane particles, salts, and the like. Removal of particulate matter is generally accomplished by filtration, flocculation or the like. A variety of filter types may be readily incorporated into the device. Further, where chemical denaturing method ⁇ are used, it may be desirable to desalt the sample prior to proceeding to the next step.
- Desalting of the sample, and isolation of the nucleic acid may generally be carried out in a single step, e.g., by binding the nucleic acids to a solid phase and washing away the contaminating ⁇ alt ⁇ or performing gel filtration chromatography on the sample, pas ⁇ ing ⁇ alt ⁇ through dialysis membranes, and the like.
- Suitable solid supports for nucleic acid binding include, e.g. , diatomaceous earth, silica (i.e., glass wool), or the like.
- Suitable gel exclusion media also well known in the art, may also be readily incorporated into the devices of the present invention, and i ⁇ commercially available from, e.g., Pharmacia and Sigma Chemical.
- the isolation and/or gel filtration/desalting may be carried out in an additional chamber, or alternatively, the particular chromatographic media may be incorporated in a channel or fluid pas ⁇ age leading to a ⁇ ub ⁇ equent reaction chamber.
- the interior ⁇ urface ⁇ of one or more fluid pa ⁇ sages or chambers may themselves be derivatized to provide functional groups appropriate for the desired purification, e.g., charged group ⁇ , affinity binding group ⁇ and the like, i.e., poly-T oligonucleotide ⁇ for mRNA purification.
- de ⁇ alting methods may generally take advantage of the high electrophoretic mobility and negative of DNA compared to other elements.
- Electrophoretic methods may al ⁇ o be utilized in the purification of nucleic acid ⁇ from other cell contaminant ⁇ and debri ⁇ .
- a ⁇ eparation channel or chamber of the device i ⁇ fluidly connected to two separate "field" channels or chambers having electrodes, e.g., platinum electrodes, dispo ⁇ ed therein.
- the two field channels are separated from the separation channel using an appropriate barrier or "capture membrane" which allows for pas ⁇ age of current without allowing pa ⁇ sage of nucleic acids or other large molecules.
- the barrier generally serves two basic functions: first, the barrier acts to retain the nucleic acids which migrate toward the po ⁇ itive electrode within the ⁇ eparation chamber; and ⁇ econd, the barrier ⁇ prevent the adver ⁇ e effect ⁇ a ⁇ sociated with electroly ⁇ is at the electrode from entering into the reaction chamber (e.g., acting a ⁇ a salt junction).
- Such barriers may include, e.g., dialysi ⁇ membranes, dense gels, PEI filters, or other suitable materials.
- the nucleic acids present in the sample will migrate toward the positive electrode and become trapped on the capture membrane. Sample impurities remaining free of the membrane are then washed from the chamber by applying an appropriate fluid flow.
- the nucleic acid ⁇ are relea ⁇ ed from the membrane in a ⁇ ubstantially purer form.
- the field channel ⁇ may be di ⁇ posed on the same or opposite sides or ends of a separation chamber or channel, and may be used in conjucton with mixing elements described herein, to ensure maximal efficiency of operation.
- coarse filters may also be overlaid on the barriers to avoid any fouling of the barriers by particulate matter, proteins or nucleic acid ⁇ , thereby permitting repeated u ⁇ e.
- the high electrophoretic mobility of nucleic acids with their negative charges may be utilized to ⁇ eparate nucleic acid ⁇ from contaminant ⁇ by utilizing a short column of a gel or other appropriate matrix or gel which will slow or retard the flow of other contaminants while allowing the faster nucleic acids to pas ⁇ .
- it may be de ⁇ irable to extract and ⁇ eparate messenger RNA from cells, cellular debris, and other contaminants.
- the device of the pre ⁇ ent invention may, in ⁇ ome ca ⁇ es, include an mRNA purification chamber or channel. In general, such purification take ⁇ advantage of the poly-A tail ⁇ on mRNA.
- poly-T oligonucleotides may be immobilized within a chamber or channel of the device to serve as affinity ligands for mRNA.
- Poly-T oligonucleotides may be immobilized upon a solid support incorporated within the chamber or channel, or alternatively, may be immobilized upon the surface(s) of the chamber or channel itself. Immobilization of oligonucleotides on the surface of the chambers or channels may be carried out by methods described herein including, e.g., oxidation and silanation of the surface followed by standard DMT synthesis of the oligonucleotides.
- the ly ⁇ ed ⁇ ample is introduced into thi ⁇ chamber or channel in a high ⁇ alt ⁇ olution to increa ⁇ e the ionic ⁇ trength for hybridization, whereupon the mRNA will hybridize to the immobilized poly-T. Hybridization may also be enhanced through incorporation of mixing elements, also as described herein. After enough time has elapsed for hybridization, the chamber or channel is washed with clean salt solution. The mRNA bound to the immobilized poly-T oligonucleotides is then washed free in a low ionic strength buffer.
- the surface area upon which the poly-T oligonucleotides are immobilized may ⁇ a increased through the use of etched structures within the chamber or channel, e.g., ridges, grooves or the like. Such structures also aid in the agitation of the contents of the chamber or channel, as described herein.
- the poy-T oligonucleotides may be immobiliized upon poroussurfaces, e.g. , porous silicon, zeolites silica xerogels, scintered particle ⁇ , or other ⁇ olid supports.
- nucleic acid portion of the sample is typically subjected to one or more preparative reactions. These preparative reactions include in vitro transcription, labeling, fragmentation, amplification and other reactions. Nucleic acid amplification increases the number of copies of the target nucleic acid sequence of interest.
- a variety of amplification methods are suitable for u ⁇ e in the method ⁇ and device of the pre ⁇ ent invention, including for example, the polymera ⁇ e chain reaction method or (PCR) , the liga ⁇ e chain reaction (LCR) , ⁇ elf ⁇ u ⁇ tained ⁇ equence replication (3SR) , and nucleic acid ba ⁇ ed ⁇ equence amplification (NASBA) .
- the latter two amplification method ⁇ involve isothermal reactions based on isothermal tran ⁇ cription, which produce both ⁇ ingle stranded RNA ( ⁇ sRNA) and double stranded DNA (dsDNA) a ⁇ the amplification product ⁇ in a ratio of approximately 30 or 100 to 1, re ⁇ pectively.
- ⁇ sRNA ⁇ ingle stranded RNA
- dsDNA double stranded DNA
- amplification product ⁇ in a ratio of approximately 30 or 100 to 1, re ⁇ pectively.
- a ⁇ a re ⁇ ult where these latter methods are employed, ⁇ eguence analysis may be carried out using either type of ⁇ ubstrate, i.e., complementary to either DNA or RNA.
- the amplification step is carried out using PCR techniques that are well known in the art. See PCR Protocol ⁇ : A Guide to Methods and Applications (Innis, M.
- PCR amplification generally involves the use of one strand of the target nucleic acid sequence as a template for producing a large number of complement ⁇ to that sequence.
- two primer sequence ⁇ complementary to different end ⁇ of a segment of the complementary strands of the target sequence hybridize with their respective strands of the target sequence, and in the presence of polymerase enzymes and nucleoside triphosphates, the primers are extended along the target sequence.
- PCR amplification typically involve ⁇ repeated cycles of denaturation, hybridization and extension reactions to produce sufficient amounts of the target nucleic acid.
- the first step of each cycle of the PCR involves the separation of the nucleic acid duplex formed by the primer extension. Once the strand ⁇ are separated, the next step in PCR involve ⁇ hybridizing the separated strands with primers that flank the target sequence. The primers are then extended to form complementary copies of the target strand ⁇ .
- the primer ⁇ are de ⁇ igned ⁇ o that the po ⁇ ition at which each primer hybridizes along a duplex sequence is such that an extension product synthe ⁇ ized from one primer, when separated from the template (complement) , serves as a template for the extension of the other primer.
- strand separation i ⁇ normally achieved by heating the reaction to a ⁇ ufficiently high temperature for a ⁇ ufficient time to cau ⁇ e the denaturation of the duplex but not to cause an irreversible denaturation of the polymerase enzyme (see U.S. Patent No. 4,965,188, incorporated herein by reference) .
- Typical heat denaturation involves temperatures ranging from about 80°C to 105°C for times ranging from second ⁇ to minute ⁇ .
- Strand ⁇ eparation can be accompli ⁇ hed by any ⁇ uitable denaturing method including phy ⁇ ical, chemical, or enzymatic mean ⁇ .
- Strand separation may be induced by a helicase, for example, or an enzyme capable of exhibiting helicase activity.
- the enzyme RecA has helicase activity in the presence of ATP.
- the reaction conditions suitable for strand separation by helicases are known in the art (see Kuhn Hoffman-Berling, 1978, CSH-Quantitative Biology, 43:63-67; and Radding, 1982, Ann . Rev. Genetics 16:405-436, each of which is incorporated herein by reference) .
- Other embodiments may achieve strand separation by application of electric fields acros ⁇ the sample.
- Published PCT Application Nos. WO 92/04470 and WO 95/25177 describe electrochemical methods of denaturing double stranded DNA by application of an electric field to a sample containing the DNA.
- Structures for carrying out this electrochemical denaturation include a working electrode, counter electrode and reference electrode arranged in a potentiostat arrangement across a reaction chamber (See, Published PCT Application No ⁇ . WO 92/04470 and WO 95/25177, each of which i ⁇ incorporated herein by reference for all purposes) .
- Such devices may be readily miniaturized for incorporation into the devices of the present invention utilizing the microfabrication techniques described herein.
- Template-dependent extension of primers in PCR is catalyzed by a polymerizing agent in the presence of adequate amounts of at least 4 deoxyribonucleotide triphosphate ⁇ (typically ⁇ elected from dATP, dGTP, dCTP, dUTP and dTTP) in a reaction medium which compri ⁇ e ⁇ the appropriate ⁇ alt ⁇ , metal cation ⁇ , and pH buffering ⁇ y ⁇ tem.
- Reaction component ⁇ and conditions are well known in the art (See PCR Protocols : A Guide to Methods and Applications (Innis, M. , Gelfand, D., Sninsky, J. and White, T. , eds.) Academic Pres ⁇ (1990), previously incorporated by reference) .
- Suitable polymerizing agents are enzymes known to catalyze template-dependent DNA synthesis.
- the amplification reaction chamber of the device may comprise a sealable opening for the addition of the various amplification reagents.
- the amplification chamber will have an effective amount of the various amplification reagents described above, predisposed within the amplification chamber, or within an as ⁇ ociated reagent chamber whereby the reagent ⁇ can be readily transported to the amplification chamber upon initiation of the amplification operation.
- an effective amount is meant a quantity and/or concentration of reagents required to carry out amplification of a targeted nucleic acid sequence. These amounts are readily determined from known PCR protocols. See, e.g., Sambrook, et al. Molecular Cloning: A Laboratory Manual , (2nd ed.) Vols. 1-3, Cold Spring Harbor Laboratory, (1989) and PCR Protocols : A Guide to Methods and Applications (Innis, M. , Gelfand, D. , Sninsky, J. and White, T. , eds.) Academic Pres ⁇ (1990) , both of which are incorporated herein by reference for all purpo ⁇ e ⁇ in their entirety.
- the variou ⁇ reagent ⁇ are predi ⁇ po ⁇ ed within the amplification or adjacent chamber, it will often be de ⁇ irable for the ⁇ e reagents to be in lyophilized form ⁇ , to provide maximum ⁇ helf life of the overall device.
- Introduction of the liguid ⁇ ample to the chamber then reconstitutes the reagents in active form, and the particular reactions may be carried out.
- the polymerase enzyme may be present within the amplification chamber, coupled to a suitable solid support, or to the walls and surface ⁇ of the amplification chamber.
- Suitable solid supports include those that are well known in the art, e.g., agarose, cellulose, silica, divinylbenzene, polystyrene, etc. Coupling of enzymes to solid supports has been reported to impart stability to the enzyme in question, which allow ⁇ for ⁇ torage of day ⁇ , week ⁇ or even month ⁇ without a ⁇ ub ⁇ tantial lo ⁇ in enzyme activity, and without the nece ⁇ ity of lyophilizing the enzyme.
- the 94 kd, single subunit DNA polymerase from Thermus aquaticus is particularly ⁇ uited for the PCR ba ⁇ ed amplification methods used in the present invention, and i ⁇ generally commercially available from, e.g., Promega, Inc., Madison, WI.
- monoclonal antibodies are available which bind the enzyme without affecting its polymerase activity.
- covalent attachment of the active polymera ⁇ e enzyme to a solid support, or the walls of the amplification chamber can be carried out by using the antibody as a linker between the enzyme and the ⁇ upport.
- the methods and devices of the pre ⁇ ent invention are al ⁇ o applicable to a number of other reaction type ⁇ , e.g., rever ⁇ e tran ⁇ cription, nick translation, and the like.
- the nucleic acids in a sample will generally be labeled to facilitate detection in sub ⁇ equent steps. Labeling may be carried out during the amplification, in vitro transcription or nick translation processes. In particular, amplification, in vitro transcription or nick translation may incorporate a label into the amplified or transcribed sequence, either through the use of labeled primers or the incorporation of labeled dNTPs into the amplified sequence. Alternatively, the nucleic acids in the sample may be labeled following amplification. Post amplification labeling typically involve ⁇ the covalent attachment of a particular detectable group upon the amplified ⁇ equence ⁇ . Suitable label ⁇ or detectable group ⁇ include a variety of fluorescent or radioactive labeling groups well known in the art.
- amplified sequence ⁇ may be ⁇ ubjected to other post amplification treatments.
- additional treatment ⁇ may be performed within the amplification chamber, or alternatively, may be carried out in a ⁇ eparate chamber.
- physical fragmentation methods may involve moving the sample containing the nucleic acid over pits or spikes in the surface of a reaction chamber or fluid channel. The motion of the fluid sample, in combination with the surface irregularities produces a high shear rate, resulting in fragmentation of the nucleic acids.
- this may be accompli ⁇ hed in a miniature device by placing a piezoelectric element, e.g., a PZT ceramic element adjacent to a ⁇ ubstrate layer that covers a reaction chamber or flow channel, either directly, or through a liquid layer, as de ⁇ cribed herein.
- the ⁇ ub ⁇ trate layer ha ⁇ pit ⁇ , spikes or apertures manufactured in the surface which are within the chamber or flow channel.
- a standing wave is set up within the chamber. Cavitation and/or streaming within the chamber result ⁇ in ⁇ ub ⁇ tantial ⁇ hear.
- Similar shear rates may be achieved by forcing the nucleic acid containing fluid sample through restricted ⁇ ize flow passages, e.g., apertures having a cros ⁇ - ⁇ ectional dimen ⁇ ion in the micron or submicron scale, thereby producing a high shear rate and fragmenting the nucleic acid.
- a number of sample preparation operation ⁇ may be carried out by adju ⁇ ting the pH of the sample, such as cell lysis, nucleic acid fragmentation, enzyme denaturation and the like.
- pH control may also play a role in a wide variety of other reactions to be carried out in the device, i.e., for optimizing reaction conditions, neutralizing acid or base additions, denaturing exogenously introduced enzymes, quenching reactions, and the like.
- pH monitoring and control may be readily accomplished u ⁇ ing well known method ⁇ .
- pH may be monitored by incorporation of a pH sensor or indicator within a particular chamber. Control may then be carried out by titration of the chamber contents with an appropriate acid or base.
- the device may include an electronically controlled pH system.
- an electrode i ⁇ placed adjacent, e.g., in fluid contact, to a reaction chamber wehile a counter electrode i ⁇ po ⁇ itioned within a second chamber or channel fluidly connected to the first.
- a pH sensor may also be included within the reaction chamber to provide for monitoring and/or feedback control of the precise pH within the chamber.
- reaction chamber employing an electronic pH control sy ⁇ tem is shown in Figure 11.
- the reference chamber 1106 typically includes a reference electrode 1118.
- the reference electrode may be fabricated, e.g., from a platinum, gold or nickel screen pressed with a mixture of teflon and platinum black (producing a hydrogen electrode) .
- the reaction chamber 1108 typically includes an electrolysis electrode 1120, e.g., a platinum, gold or nickel screen coated with an appropriate barrier, e.g., polyacrylamide gel layer, and a hydrogen electrode 1122, also protected with an appropriate barrier.
- the reference electrode 1118 and hydrogen electrode 1122 are connected to an electrometer 1126 for monitoring the pH within the reaction chamber.
- the counter-electrode chamber 1110 typically includes the counter-electrode 1123, e.g., a single platinum, gold or nickel screen electrode. Tlu electrolysis electrode and counter-electrode are connected to an appropriate current cource 1124.
- a current is applied by the current source.
- Electrolysi ⁇ at the electroly ⁇ i ⁇ electrode alters the pH within the reaction chamber 1108.
- the electrometer compare ⁇ the pH ⁇ ensed by the voltage between the reference and hydrogen electrodes. This signal may be compared to a set-point by appropriate mean ⁇ , e.g., an appropriately programmed computer or other microproce ⁇ sor 1128, and used to control the application of current.
- the resulting sy ⁇ tem allow ⁇ the automated control of pH within the reaction chamber by varying the ⁇ et-point signal.
- the sample will generally be ⁇ ubjected to one or more analy ⁇ i ⁇ operation ⁇ .
- Particularly preferred analy ⁇ i ⁇ operations include, e.g. , seguence based analy ⁇ e ⁇ u ⁇ ing an oligonucleotide array and/or ⁇ ize ba ⁇ ed analy ⁇ e ⁇ u ⁇ ing, e.g., microcapillary array electrophore ⁇ i ⁇ .
- the nucleic acid sample is probed using an array of oligonucleotide probes.
- Oligonucleotide arrays generally include a substrate having a large number of positionally di ⁇ tinct oligonucleotide probe ⁇ attached to the ⁇ ubstrate. These oligonucleotide arrays, also described as "GenechipTM arrays,” have been generally described in the art, for example, U.S. Patent No. 5,143,854 and PCT patent publication Nos. WO 90/15070 and 92/10092.
- the ⁇ e reference ⁇ disclose methods of forming vast arrays of peptides, oligonucleotides and other polymer sequence ⁇ u ⁇ ing, for example, light-directed ⁇ ynthe ⁇ is techniques. Techniques for the synthesis of these arrays u ⁇ ing mechanical ⁇ ynthe ⁇ i ⁇ strategies are described in, e.g., PCT Publication No. 93/09668 and U.S. Patent No. 5,384,261, each of which is incorporated herein by reference in its entirety for all purpo ⁇ es. Incorporation of these arrays in injection molded polymeric casing ⁇ has been described in Published PCT Application No. 95/33846.
- the basic strategy for light directed synthesis of oligonucleotide arrays is as follows.
- the ⁇ urface of a solid support, modified with photosensitive protecting groups is illuminated through a photolithographic mask, yielding reactive hydroxyl groups in the illuminated regions.
- a selected nucleotide typically in the form of a 3 '-O- phosphoramidite-activated deoxynucleoside (protected at the 5' hydroxyl with a photosen ⁇ itive protecting group) , i ⁇ then pre ⁇ ented to the ⁇ urface and coupling occur ⁇ at the ⁇ ite ⁇ that were expo ⁇ ed to light.
- the substrate is rinsed and the surface is illuminated through a second mask, to expose additional hydroxyl groups for coupling.
- a second selected nucleotide e.g., 5 '-protected, 3 '-O-phosphoramidite-activated deoxynucleoside
- the selective deprotection and coupling cycles are repeated until the desired set of products is obtained. Since photolithography is used, the proces ⁇ can be readily miniaturized to generate high den ⁇ ity arrays of oligonucleotide probes. Furthermore, the seguence of the oligonucleotides at each site i ⁇ known. See, Pease, et al.
- the array ⁇ u ⁇ ed in the pre ⁇ ent invention will have a ⁇ ite density of greater than 100 different probes per cm 2 .
- the arrays will have a site den ⁇ ity of greater than 500/cm 2 , more preferably greater than about 1000/cm 2 , and most preferably, greater than about 10,000/cm 2 .
- the arrays will have more than 100 different probes on a single substrate, more preferably greater than about 1000 different probes still more preferably, greater than about 10,000 different probes and most preferably, greater than 100,000 different probes on a single substrate.
- oligonucleotide array ⁇ may be prepared having all po ⁇ ible probes of a given length. Such arrays may be used in such areas a ⁇ ⁇ equencing or ⁇ equence checking application ⁇ , which offer ⁇ ub ⁇ tantial benefit ⁇ over traditional method ⁇ .
- the u ⁇ e of oligonucleotide arrays in such applications is described in, e.g., U.S. Patent application Serial No. 08/515,919, filed July 24, 1995, and U.S. Patent Application Serial No. 08/284,064, filed August 2, 1994, each of which is incorporated herein by reference in its entirety for all purpose ⁇ .
- the ⁇ e methods typically use a set of short oligonucleotide probes of defined sequence to search for complementary sequences on a longer target strand of DNA.
- the hybridization pattern of the target sequence on the array is used to reconstruct the target DNA sequence.
- Hybridization analysis of large numbers of probes can be used to sequence long stretches of DNA.
- a 12-mer target DNA sequence is probed on an array having a complete set of octanucleotide probe ⁇ .
- Five of the 65,536 octamer probe ⁇ will perfectly hybridize to the target ⁇ equence.
- the identity of the probe ⁇ at each ⁇ ite i ⁇ known. Thu ⁇ by determining the location ⁇ at which the target hybridizes on the array, or the hybridization pattern, one can determine the sequence of the target seguence. While these strategies have been proposed and utilized in some applications, there has been difficulty in demonstrating seguencing of larger nucleic acids using these same strategies.
- oligonucleotide probes may be prepared having every possible sequence of length n, it will often be de ⁇ irable in practicing the pre ⁇ ent invention to provide an oligonucleotide array which i ⁇ ⁇ pecific and complementary to a particular nucleic acid sequence.
- the oligonucleotide array will contain oligonucleotide probe ⁇ which are complementary to specific target sequences, and individual or multiple mutations of these.
- the target sequence may be that of a particular exogenous disease causing agent, e.g., human immunodeficiency virus (see, U.S. Application Serial No. 08/284,064, previously incorporated herein by reference) , or alternatively, the target sequence may be that portion of the human genome which is known to be mutated in instances of a particular disorder, i.e., sickle cell anemia (see, e.g., U.S. Application Serial No.08/082,937, previously incorporated herein by reference) or cystic fibrosis.
- a particular exogenous disease causing agent e.g., human immunodeficiency virus
- the target sequence may be that portion of the human genome which is known to be mutated in instances of a particular disorder, i.e., sickle cell anemia (see, e.g., U.S. Application Serial No.08/082,937, previously incorporated herein by reference) or cystic fibrosis.
- the array generally comprises at lea ⁇ t four ⁇ et ⁇ of oligonucleotide probes, usually from about 9 to about 21 nucleotides in length.
- a first probe set has a probe corresponding to each nucleotide in the target sequence.
- a probe i ⁇ related to it ⁇ corresponding nucleotide by being exactly complementary to a subsequence of the target sequence that includes the corresponding nucleotide.
- each probe has a position, designated an interrogation position, that i ⁇ occupied by a complementary nucleotide to the corresponding nucleotide in the target sequence.
- the three additional probe set ⁇ each have a corresponding probe for each probe in the first probe set, but substituting the interrogation position with the three other nucleotides.
- the three corre ⁇ ponding probes in the three additional probe set ⁇ are identical to the corre ⁇ ponding probe from the first probe or a sub ⁇ equence thereof that includes the interrogation position, except that the interrogation position is occupied by a different nucleotide in each of the four corre ⁇ ponding probe ⁇ .
- Some array ⁇ have fifth, ⁇ ixth, seventh and eighth probe sets.
- the probes in each set are selected by analogou ⁇ principle ⁇ to tho ⁇ e for the probe ⁇ in the fir ⁇ t four probe set ⁇ , except that the probes in the fifth, sixth, seventh and eighth sets exhibit complementarity to a second reference sequence.
- the fir ⁇ t ⁇ et of probes is complementary to the coding strand of the target sequence while the second ⁇ et i ⁇ complementary to the noncoding ⁇ trand.
- the second reference sequence can be a subsequence of the first reference ⁇ equence having a substitution of at least one nucleotide.
- the target sequence has a sub ⁇ tituted nucleotide relative to the probe ⁇ equence in at least one undetermined position, and the relative specific binding of the probe ⁇ indicate ⁇ the location of the po ⁇ ition and the nucleotide occupying the po ⁇ ition in the target sequence.
- the nucleic acid sample is incubated with the oligonucleotide array in the hybridization chamber. Hybridization between the ⁇ ample nucleic acid and the oligonucleotide probes upon the array is then detected, u ⁇ ing, e.g., epifluore ⁇ cence confocal microscopy. Typically, sample is mixed during hybridization to enhance hybridization of nucleic acids in the sample to nucleoc acid probes on the array.
- mixing may be carried out by the methods described herein, e.g., through the use of piezoelectric elements, electrophoretic methods, or physical mixing by pumping fluids into and out of the hybridization chamber, i.e., into an adjoining chamber.
- the detection operation will be performed using a reader device external to the diagnostic device. However, it may be desirable in some ca ⁇ es, to incorporate the data gathering operation into the diagnostic device itself.
- the hybridization data is next analyzed to determine the presence or absence of a particular seguence within the sample, or by analyzing multiple hybridizations to determine the sequence of the target nucleic acid using the SBH techniques already described.
- hybridized oligonucleotide ⁇ may be labeled following hybridization.
- wghere biotin labeled dNTP ⁇ are used in, e.g. , amplification or transcription, streptavidin linked reporter groups may be used to label hybridized complexes.
- streptavidin linked reporter groups may be used to label hybridized complexes.
- Such operations are readily integratable into the sy ⁇ tem ⁇ of the pre ⁇ ent invention.
- Capillary Electrophore ⁇ i ⁇ In ⁇ ome embodiment ⁇ , it may be de ⁇ irable to provide an additional, or alternative mean ⁇ for analyzing the nucleic acid ⁇ from the sample.
- the device of the invention will optionally or additionally comprise a micro capillary array for analysis of the nucleic acids obtained from the ⁇ ample.
- Microcapillary array electrophore ⁇ is generally involves the use of a thin capillary or channel which may or may not be filled with a particular separation medium. Electrophoresi ⁇ of a sample through the capillary provides a size based separation profile for the sample.
- the use of microcapillary electrophoresis in size ⁇ eparation of nucleic acid ⁇ ha ⁇ been reported in, e.g., Woolley and Mathie ⁇ , Proc . Nat ' l Acad . Sci . USA (1994) 91:11348-11352.
- Microcapillary array electrophore ⁇ is generally provides a rapid method for size based sequencing, PCR product analysi ⁇ and re ⁇ triction fragment sizing.
- the high surface to volume ratio of the ⁇ e capillarie ⁇ allows for the application of higher electric fields across the capillary without substantial thermal variation acros ⁇ the capillary, consequently allowing for more rapid separations. Furthermore, when combined with confocal imaging methods, these methods provide sensitivity in the range of attomole ⁇ , which i ⁇ comparable to the ⁇ en ⁇ itivity of radioactive ⁇ equencing method ⁇ .
- Microfabrication of microfluidic devices including microcapillary electrophoretic devices has been discu ⁇ ed in detail in, e.g., Jacob ⁇ en, et al., Anal . Chem . (1994) 66:1114- 1118, Effenhau ⁇ er, et al., Anal. Chem . (1994) 66:2949-2953, Harrison, et al.. Science (1993) 261:895-897, Effenhauser, et al. Anal. Chem . (1993) 65:2637-2642, and Manz, et al., J. Chromatog. (1992) 593:253-258.
- the ⁇ e method ⁇ comprise photolithographic etching of micron scale channel ⁇ on a silica, silicon or other rigid sub ⁇ trate or chip, and can be readily adapted for u ⁇ e in the miniaturized device ⁇ of the present invention.
- the capillary array ⁇ may be fabricated from the ⁇ ame polymeric material ⁇ de ⁇ cribed for the fabrication of the body of the device, u ⁇ ing the injection molding techniques described herein.
- the capillary and other fluid channels may be molded into a first planar element.
- a second thin polymeric member having ports corresponding to the termini of the capillary channels disposed therethrough, is laminated or sonically welded onto the first to provide the top surface of these channels.
- Electrodes for electrophoretic control are dispo ⁇ ed within the ⁇ e port ⁇ /wells for application of the electrical current to the capillary channels.
- the capillary channel ⁇ may be coated with more thermally conductive material, e.g., gla ⁇ s or ceramic, to enhance heat dis ⁇ ipation.
- the capillaries e.g., fu ⁇ ed ⁇ ilica capillarie ⁇ or channel ⁇ etched, machined or molded into planar ⁇ ub ⁇ trate ⁇ , are filled with an appropriate ⁇ eparation/ ⁇ ieving matrix.
- ⁇ ieving matrice ⁇ are known in the art may be used in the microcapillary arrays.
- matrices include, e.g., hydroxyethyl cellulose, polyacrylamide, agarose and the like.
- Gel matrices may be introduced and polymerized within the capillary channel.
- thi ⁇ may result in entrapment of bubbles within the channels which can interfere with sample separation ⁇ . Accordingly, it i ⁇ often desirable to place a preformed separation matrix within the capillary channel(s), prior to mating the planar elements of the capillary portion. Fixing the two parts, e.g., through sonic welding, permanently fixes the matrix within the channel.
- the specific gel matrix, running buffers and running conditions are selected to maximize the separation characteristic ⁇ of the particular application, e.g., the ⁇ ize of the nucleic acid fragments, the required resolution, and the presence of native or undenatured nucleic acid molecule ⁇ .
- running buffer ⁇ may include denaturant ⁇ , chaotropic agent ⁇ such as urea or the like, to denature nucleic acd ⁇ in the ⁇ ample.
- capillary arrays may also be used in sequencing applications.
- gel based sequencing techniques may be readily adapted for capillary array electrophoresi ⁇ .
- capillary electrophore ⁇ i ⁇ may be combined with the Sanger dideoxy chain termination ⁇ equencing methods as discu ⁇ sed in Sambrook, et al. (See al ⁇ o Brenner, et al., Proc . Nat ' l Acad . Sci . (1989) 86:8902-8906).
- the sample nucleic acid is amplified in the presence of fluorescent dideoxynucleoside tripho ⁇ phate ⁇ in an exten ⁇ ion reaction.
- the random incorporation of the dideoxynucleotide ⁇ terminate ⁇ tran ⁇ cription of the nucleic acid.
- Gathering data from the variou ⁇ analy ⁇ is operations will typically be carried out using methods known in the art.
- the arrays may be scanned using lasers to excite fluorescently labeled targets that have hybridized to regions of probe arrays, which can then be imaged using charged coupled device ⁇ ("CCDs") for a wide field scanning of the array.
- CCDs charged coupled device ⁇
- another particularly useful method for gathering data from the array ⁇ i ⁇ through the u ⁇ e of laser confocal microscopy which combines the ease and speed of a readily automated proces ⁇ with high resolution detection.
- Particularly preferred scanning devices are generally described in, e.g., U.S. Patent Nos.
- the data will typically be reported to a data analysis operation.
- the data obtained by the reader from the device will typically be analyzed using a digital computer.
- the computer will be appropriately programmed for receipt and storage of the data from the device, a ⁇ well a ⁇ for analy ⁇ i ⁇ and reporting of the data gathered, i.e., interpreting fluore ⁇ cence data to determine the ⁇ equence of hybridizing probe ⁇ , normalization of background and single base mismatch hybridizations, ordering of sequence data in SBH application ⁇ , and the like, a ⁇ de ⁇ cribed in, e.g., U.S. Patent Application Serial No. 08/327,525, filed October 21, 1994, and incorporated herein by reference.
- FIG. 1 A schematic of a representative analytical system based upon the device of the invention is shown in Figure 1.
- the system includes the diagnostic device 2 which performs one or more of the operation ⁇ of ⁇ ample ' ollection, preparation and/or analy ⁇ i ⁇ u ⁇ ing, e.g., hybridization and/or ⁇ ize based separation.
- the diagnostic device i ⁇ then placed in a reader device 4 to detect the hybridization and or ⁇ eparation information pre ⁇ ent on the device.
- the hybridization and/or separation data is then reported from the reader device to a computer 6 which is programmed with appropriate software for interpreting the data obtained by the reader device from the diagnostic device.
- Interpretation of the data from the diagnostic device may be u ⁇ ed in a variety of ways, including nucleic acid ⁇ equencing which i ⁇ directed toward a particular di ⁇ ea ⁇ e causing agent, such as viral or bacterial infection ⁇ , e.g., AIDS, malaria, etc., or genetic di ⁇ orders, e.g., sickle cell anemia, cy ⁇ tic fibrosis. Fragile X syndrome, Duchenne muscular dystrophy, and the like. Alternatively, the device can be employed in de novo sequencing applications to identify the nucleic acid sequence of a previously unknown sequence.
- the Diagnostic Device 1. Generally, the device can be employed in de novo sequencing applications to identify the nucleic acid sequence of a previously unknown sequence.
- the device of the pre ⁇ ent invention i ⁇ generally capable of carrying out a number of preparative and analytical reaction ⁇ on a ⁇ ample.
- the device generally compri ⁇ e ⁇ a number of di ⁇ crete reaction, ⁇ torage and/or analytical chamber ⁇ di ⁇ po ⁇ ed within a ⁇ ingle unit or body. While referred to herein as a "diagnostic device,” those of skill in the art will appreciate that the device of the invention will have a variety of applications out ⁇ ide the ⁇ cope of diagno ⁇ tics, alone.
- Such applications include sequencing application ⁇ , ⁇ ample identification and characterization applications (for, e.g., taxonomic studies, forensic applications, i.e., criminal investigation ⁇ , and the like) .
- the body of the device defines the various reaction chambers and fluid passages in which the above described operations are carried out. Fabrication of the body, and thus the various chamber ⁇ and channel ⁇ di ⁇ po ⁇ ed within the body may generally be carried out u ⁇ ing one or a combination of a variety of well knc * n manufacturing technique ⁇ and material ⁇ .
- the material from which the body i ⁇ fabricated will be ⁇ elected ⁇ o a ⁇ to provide maximum resistance to the full range of conditions to which the device will be exposed, e.g., extremes of temperature, salt, pH, application of electric fields and the like, and will also be selected for compatibility with other materials used in the device. Additional components may be later introduced, as neces ⁇ ary, into the body.
- the device may be formed from a plurality of di ⁇ tinct part ⁇ that are later a ⁇ embled or mated. For example, ⁇ eparate and individual chamber ⁇ and fluid passage ⁇ may be a ⁇ embled to provide the variou ⁇ chamber ⁇ of the device.
- the body of the device will typically be approximately 1 to 20 cm in length by about 1 to 10 cm in width by about 0.1 to about 2 cm thick.
- the devices of the invention may be embodied in any number of shape ⁇ depending upon the particular need.
- the ⁇ e dimen ⁇ ion ⁇ will typically vary depending upon the number of operation ⁇ to be performed by the device, the complexity of these operations and the like.
- the ⁇ e dimen ⁇ ion ⁇ are provided a ⁇ a general indication of the size of the device.
- the number and size of the reaction chambers included within the device will also vary depending upon the specific application for which the device is to be used.
- the device will include at least two distinct reaction chambers, and preferably, at lea ⁇ t three, four or five di ⁇ tinct reaction chamber ⁇ , all integrated within a single body.
- Individual reaction chambers will also vary in size and shape according to the specific function of the reaction chamber.
- circular reaction chamber ⁇ may be employed.
- elongate reaction chamber ⁇ may be u ⁇ ed.
- the reaction chamber ⁇ will be from about 0.05 to about 20 mm in width or diameter, preferably from about 0.1 or 0.5 to about 20 mm in width or diameter and about 0.05 to about 5 mm deep, and preferably 0.05 to about 1 mm deep.
- length will also typically vary along these same ranges.
- Fluid channel ⁇ are typically distinguished from chambers in having smaller dimen ⁇ ion ⁇ relative to the chamber ⁇ , and will typically range from about 10 to about 1000 ⁇ m wide, preferably, 100 to 500 ⁇ m wide and about 1 to 500 ⁇ m deep. Although de ⁇ cribed in term ⁇ of reaction chambers, it will be appreciated that these chambers may perform a number of varied functions, e.g., as storage chamber ⁇ , incubation chamber ⁇ , mixing chamber ⁇ and the like.
- volumetric chambers In ⁇ ome cases, a separate chamber or chambers may be used as volumetric chambers, e.g., to precisely measure fluid volume ⁇ for introduction into a ⁇ ubsequent reaction chamber. In such cases, the volume of the chamber will be dictated by volumetric needs of a given reaction. Further, the device may be fabricated to include a range of volumetric chamber ⁇ having varied, but known volumes or volume ratios (e.g., in comparison to a reaction chgamber or other volumetric chambers) .
- the body of the device is generally fabricated using one or more of a variety of methods and materials ⁇ uitable for microfabrication technique ⁇ .
- the body of the device may comprise a number of planar members that may individually be injection molded parts fabricated from a variety of polymeric materials, or may be silicon, gla ⁇ , or the like.
- methods for etching, milling, drilling, etc. may be used to produce wells and depre ⁇ ion ⁇ which make up the variou ⁇ reaction chamber ⁇ and fluid channels within the device.
- Microfabrication techniques such as those regularly used in the semiconductor and microelectronics indu ⁇ tries are particularly suited to these materials and method ⁇ .
- the ⁇ e techniques include, e.g., electrodeposition, low-pressure vapor deposition, photolithography, wet chemical etching, reactive ion etching (RIE) , laser drilling, and the like. Where these methods are used, it will generally be desirable to fabricate the planar members of the device from materials similar to tho ⁇ e u ⁇ ed in the semiconductor industry, i.e., silica, silicon, gallium arsenide, polyimide substrates.
- RIE reactive ion etching
- photoresists include those used extensively in the semiconductor industry. Such materials include polymethyl methacrylate (PMMA) and its derivatives, and electron beam resists such as poly(olefin sulfones) and the like (more fully discussed in, e.g., Ghandi, "VLSI Fabrication Principle ⁇ , " Wiley (1983) Chapter 10, incorporated herein by reference in its entirety for all purpose ⁇ ) .
- PMMA polymethyl methacrylate
- electron beam resists such as poly(olefin sulfones) and the like (more fully discussed in, e.g., Ghandi, "VLSI Fabrication Principle ⁇ , " Wiley (1983) Chapter 10, incorporated herein by reference in its entirety for all purpose ⁇ ) .
- the wells manufactured into the surface of one planar member make up the various reaction chambers of the device.
- Channels manufactured into the surface of this or another planar member make up fluid channels which are used to fluidly connect the various reaction chambers.
- Another planar member is then placed over and bonded to the first, whereby the wells in the first planar member define cavities within the body of the device which cavities are the various reaction chamber ⁇ of the device.
- fluid channel ⁇ manufactured in the surface of one planar member, when covered with a second planar member define fluid passages through the body of the device.
- These planar members are bonded together or laminated to produce a fluid tight body of the device. Bonding of the planar members of the device may generally be carried out using a variety of methods known in the art and which may vary depending upon the material ⁇ u ⁇ ed. For example, adhe ⁇ ives may generally be used to bond the planar members together. Where the planar members are, e.g., glass, silicon or combination ⁇ thereof, thermal bonding, anodic/electro ⁇ tatic or silicon fusion bonding methods may be applied.
- this adhesive tapes may be employed as one portion of the device forming a thin wall of the reaction chamber/channel structures.
- the body may comprise a combination of materials and manufacturing techniques described above.
- the body may include ⁇ ome parts of injection molded plastic ⁇ , and the like, while other portion ⁇ of the body may compri ⁇ e etched silica or silicon planar member ⁇ , and the like.
- injection molding technique ⁇ may be u ⁇ ed to form a number of di ⁇ crete cavitie ⁇ in a planar ⁇ urface which define the various reaction chambers, whereas additional components, e.g., fluid channels, arrays, etc, may be fabricated on a planar glas ⁇ , silica or silicon chip or substrate. Lamination of one set of parts to the other will then result in the formation of the variou ⁇ reaction chamber ⁇ , interconnected by the appropriate fluid channels.
- the body of the device i ⁇ made from at lea ⁇ t one injection molded, pre ⁇ molded or machined polymeric part that ha ⁇ one or more well ⁇ or depression ⁇ manufactured into its surface to define several of the walls of the reaction chamber or chamber ⁇ .
- Mold ⁇ or mold face ⁇ for producing these injection molded parts may generally be fabricated using the methods described herein for, e.g., ⁇ ilicon mold ⁇ .
- suitable polymers for injection molding or machining include, e.g., polycarbonate, polystyrene, polypropylene, polyethylene, acrylic, and commercial polymers such as Kapton, Valox, Teflon, ABS, Delrin and the like.
- a second part that is similarly planar in shape is mated to the surface of the polymeric part to define the remaining wall of the reaction chamber(s) .
- Published PCT Application No. 95/33846 incorporated herein by reference, describes a device that is used to package individual oligonucleotide arrays.
- the device includes a hybridization chamber disposed within a planar body.
- the chamber is fluidly connected to an inlet port and an outlet port via flow channels in the body of the device.
- the body includes a plurality of injection molded planar parts that are mated to form the body of the device, and which define the flow channels and hybridization chamber.
- the surfaces of the fluid channels and reaction chambers which contact the samples and reagents may al ⁇ o be modified to better accomodate a de ⁇ ired reaction.
- Surfaces may be made more hydrophobic or more hydrophilic depending upon the particular application.
- surface ⁇ may be coated with any number of material ⁇ in order to make the overall system more compatible to the reactions being carried out.
- it may be desireable to coat the surface ⁇ with, e.g., a teflon or other non-stick coating, to prevent adhesion of nucleic acid ⁇ to the surface.
- insulator coatings may also be desirable in those instances where electrical leads are placed in contact with fluids, to prevent shorting out, or excess gas formation from electroly ⁇ i ⁇ .
- in ⁇ ulator ⁇ may include those well known in the art, e.g., silicon oxide, ceramics or the like. Additional surface treatments are de ⁇ cribed in greater detail below.
- FIG. 2A and 2B show a ⁇ chematic representation of one embodiment of a reaction chamber for inclusion in the device of the invention.
- the reaction chamber includes a machined or injection molded polymeric part 102 which has a well 104 manufactured, i.e., machined or molded, into its . surface.
- This well may be closed at the end opposite the well opening as shown in Figure 2A, or optionally, may be supplied with an additional opening 118 for inclusion of an optional vent, as shown in Figure 2B.
- the reaction chamber is also provided with additional elements for transporting a fluid sample to and from the reaction chamber.
- These elements include one or more fluid channel ⁇ (122 and 110 in Figure ⁇ 2A and 2B, respectively) which connect the reaction chamber to an inlet/outlet port for the overall device, additional reaction chambers, storage chambers or one or more analytical chambers.
- a second part 124 typically planar in structure, is mated to the polymeric part to define a closure for the reaction chamber. This second part may incorporate the fluid channels, as ⁇ hown in Figure ⁇ 2A and 2B, or may merely define a further wall of the fluid channel ⁇ provided in the ⁇ urface of the fir ⁇ t polymeric part (not ⁇ hown) .
- this second part will comprise a multitude ⁇ of fluid channels manufactured into one of its surfaces, for fluidly connecting the reaction chamber to an inlet port in the overall device or to another reaction or analytical chamber.
- this second part may be a second polymeric part made by injection molding or machining techniques.
- this second part may be manufactured from a variety of other materials, including glass, silica, silicon or other crystalline sub ⁇ trates. Microfabrication technigue ⁇ suited for these sub ⁇ trates are generally well known in the art and are described above.
- the reaction chamber is provided without an inlet/outlet valve structure, as shown in Figure 2A.
- the fluid channels 122 may be provided in the ⁇ urface of the second part that is mated with the surface of the polymeric part such that upon mating the ⁇ econd part to the fir ⁇ t polymeric part, the fluid channel 122 i ⁇ fluidly connected to the reaction chamber 104.
- the reaction chamber may be provided with an inlet/outlet valve structure for sealing the reaction chamber to retain a fluid sample therein.
- the second part 124 mated to the polymeric part may compri ⁇ e a plurality of mated planar members, wherein a first planar member 106 is mated with the first polymeric part 102 to define a wall of the reaction chamber.
- the first planar member 106 has an opening 108 disposed therethrough, defining an inlet to the reaction chamber.
- This first planar member also includes a fluid channel 110 etched in the surface oppo ⁇ ite the ⁇ urface that i ⁇ mated with the fir ⁇ t polymeric part 102. The fluid channel terminates adjacent to, but not within the reaction chamber inlet 108.
- the first planar member will generally be manufactured from any of the above de ⁇ cribed materials, using the above-de ⁇ cribed method ⁇ .
- Deflection of the diaphragm valve may be carried out by a variety of methods including, e.g., application of a vacuum, electromagnetic and/or piezoelectric actuators coupled to the diaphragm valve, and the like.
- the second planar member will typically be fabricated, at least in part, from a flexible material, e.g., silicon, silicone, latex, mylar, polyimide, Teflon or other flexible polymers.
- a flexible material e.g., silicon, silicone, latex, mylar, polyimide, Teflon or other flexible polymers.
- these diaphragm ⁇ will al ⁇ o be of miniature ⁇ cale.
- valve and pump diaphragms used in the device will typically range in size depending upon the size of the chamber or fluid passage to which they are fluidly connected. In general, however, these diaphragms will be in the range of from about 0.5 to about 5 mm for valve diaphragm ⁇ , and from about 1 to about 20 mm in diameter for pumping diaphragms.
- second part 124 includes an additional planar member 116 having an opening 126 for application of pressure or vacuum for deflection of valve 114.
- reagent ⁇ involved in a particular analy ⁇ i ⁇ are incompatible with the material ⁇ used to manufacture the device, e.g., silicon, glas ⁇ or polymeric parts
- a variety of coatings may be applied to the surface ⁇ of the ⁇ e part ⁇ that contact the ⁇ e reagents.
- components that have silicon elements may be coated with a silicon nitride layer or a metallic layer of, e.g., gold or nickel, may be ⁇ puttered or electroplated on the surface to avoid adverse reactions with these reagents.
- inert polymer coating ⁇ e.g., Teflon and the like, pyraline coating ⁇ , or ⁇ urface silanation modifications may also be applied to internal surfaces of the chambers and/or channels.
- the reaction/ ⁇ torage chamber 104 ⁇ hown in Figure 2B i ⁇ al ⁇ o shown with an optional vent 118, for release of displaced gas present in the chamber when the fluid is introduced.
- this vent may be fitted with a gas permeable fluid barrier 120, which permits the pa ⁇ sage of ga ⁇ without allowing for the pa ⁇ sage of fluid, e.g., a poorly wetting filter plug.
- a variety of materials are suitable for use as poorly wetting filter plugs including, e.g., porous hydrophobic polymer materials, such a ⁇ ⁇ pun fibers of acrylic, polycarbonate, teflon, pressed polypropylene fiber ⁇ , or any number commercially available filter plug ⁇ (American Filtrona Corp., Richmond, VA, Gelman Science ⁇ , and the like) .
- a hydrophobic membrane can be bonded over a thru-hole to ⁇ upply a ⁇ imilar structure.
- Modified acrylic copolymer membranes are commercially available from, e.g., Gelman Sciences (Ann Arbor, MI) and particle-track etched polycarbonate membranes are available from Poretics, Inc. (Livermore, CA) .
- Venting of heated chambers may incorporate barriers to evaporation of the sample, e.g., a reflux chamber or a mineral oil layer dispo ⁇ ed within the chamber, and over the top ⁇ urface of the ⁇ ample, to permit the evolution of ga ⁇ while preventing exce ⁇ ive evaporation of fluid from the ⁇ ample.
- barriers to evaporation of the sample e.g., a reflux chamber or a mineral oil layer dispo ⁇ ed within the chamber, and over the top ⁇ urface of the ⁇ ample, to permit the evolution of ga ⁇ while preventing exce ⁇ ive evaporation of fluid from the ⁇ ample.
- the overall geometry of the device of the invention may take a number of form ⁇ .
- the device may incorporate a plurality of reaction chamber ⁇ , storage chambers and analytical chambers, arranged in series, whereby a fluid sample is moved serially through the chambers, and the re ⁇ pective operation ⁇ performed in the ⁇ e chambers.
- the device may incorporate a central fluid distribution channel or chamber having the various reaction/storage/analytical chambers arranged around and fluidly connected to the central channel or chamber, which central channel or chamber act ⁇ as a conduit or hub for ⁇ ample redi ⁇ tribution to the variou ⁇ chamber ⁇ .
- the illustrated device includes a plurality of reaction/storage/analytical chambers for performing a number of the operations described above, fluidly connected in memori ⁇ . The ⁇ chematic repre ⁇ entation of the device in
- Figure 3 shows a device that comprise ⁇ ⁇ everal reaction chamber ⁇ arranged in a ⁇ erial geometry.
- the body of the device 200 incorporate ⁇ reaction chamber ⁇ 202, 206, 210, 214 and 218.
- the ⁇ e chamber ⁇ are fluidly connected in series by fluid channels 208, 212 and 216, re ⁇ pectively.
- reaction chamber 202 may be a sample collection chamber which i ⁇ adapted for receiving a fluid sample, i.e., a cell containing sample.
- this chamber may include an opening to the outside of the device adapted for receipt of the sample.
- the opening will typically incorporate a sealable closure to prevent leakage of the sample, e.g., a valve, check-valve, or septum, through which the sample i ⁇ introduced or ir ected.
- the apparatus may include ⁇ e a hypodermic needle or other sample conduit, integrated into the body of the device and in fluid connection with the sample collection chamber, for direct transfer of the sample from the host, patient, sample vial or tube, or other origin of the sample to the sample collection chamber.
- the sample collection chamber may have disposed therein, a reagent or reagents for the stabilization of the sample for prolonged storage, a ⁇ de ⁇ cribed above.
- the ⁇ e reagent ⁇ may be di ⁇ po ⁇ ed within a reagent storage chamber adjacent to and fluidly connected with the sample collection chamber.
- the sample collection chamber is connected via a first fluid channel 204 to second reaction chamber 210 in which the extraction of nucleic acids from the cell ⁇ within the sample may be performed.
- This is particularly suited to analytical operations to be performed where the sample ⁇ include whole cell ⁇ .
- the extraction chamber will typically be connected to ⁇ ample collection chamber, however, in ⁇ ome cases, the extraction chamber may be integrated within and exist as a portion of the sample collection chamber. As previou ⁇ ly de ⁇ cribed, the extraction chamber may include phy ⁇ ical and or chemical mean ⁇ for extracting nucleic acids from cells.
- the extraction chamber is fluidly connected via a second fluid channel 208, to third reaction chamber 210 in which amplification of the nucleic acids extracted from the sample is carried out.
- the amplification proce ⁇ begins when the sample is introduced into the amplification chamber.
- amplification reagents may be exogenously introduced, or will preferably be predispo ⁇ ed within the reaction chamber. However, in alternate embodiment ⁇ , these reagents will be introduced to the amplification chamber from an optional adjacent reagent chamber or from an external source through a sealable opening in the amplification chamber.
- denaturation and hybridization cycling will preferably be carried out by repeated heating and cooling of the sample.
- PCR based amplification chambers will typically include a a temperature controller for heating the reaction to carry out the thermal cycling.
- a heating element or temperature control block may be dispo ⁇ ed adjacent the external surface of the amplification chamber thereby transferring heat to the amplification chamber.
- preferred devices will include a thin external wall for chambers in which thermal control is desired. This thin wall may be a thin cover element, e.g., polycarbonate sheet, or high temperature tape, i.e. silicone adhesive on Kapton tape (commercially available from, e.g., 3M Corp.). Micro-scale PCR devices have been previou ⁇ ly reported. For example, published PCT Application No.
- WO 94/054144 to Northrup and White reports a miniaturized reaction chamber for use as a PCR chamber, incorporating microheaters, e.g., resi ⁇ tive heater ⁇ .
- microheaters e.g., resi ⁇ tive heater ⁇ .
- the high surface area to volume ratio of the chamber allows for very rapid heating and cooling of the reagent ⁇ di ⁇ posed therein.
- U.S. Patent No. 5,304,487 to Wilding et al. previously incorporated by reference, also discu ⁇ e ⁇ the use of a microfabricated PCR device.
- the amplification chamber will incorporate a controllable heater disposed within or adjacent to the amplification chamber, for thermal cycling of the sample.
- Thermal cycling is carried out by varying the current supplied to the heater to achieve the desired temperature for the particular stage of the reaction.
- thermal cycling for the PCR reaction may be achieved by transferring the fluid ⁇ ample among a number of different reaction chamber ⁇ or regions of the same reaction chamber, having different, although constant temperatures, or by flowing the sample through a serpentine channel which travels through a number of varied temperature 'zones'.
- Heating may alternatively be supplied by exposing the amplification chamber to a la ⁇ er or other light or electromagnetic radiation ⁇ ource.
- a fluid channel e.g., fluid channel 212
- additional reaction chamber 214 which can carry out additional preparative operations, such as labeling or fragmentation.
- a fourth fluid channel 216 connects the labeling or fragmentation chamber to an analytical chamber 218.
- the analytical chamber includes an oligonucleotide array 220 a ⁇ the bottom surface of the chamber.
- Analytical chamber 218 may optionally, or additionally comprise a microcapillary electrophoresis device 226 and additional preparative reaction chambers, e.g., 224 for performing, e.g., extension reactions, fluidly connected to, e.g., chamber 210.
- the analytical chamber will typically have as at lea ⁇ t one ⁇ urface, a transparent window for observation or scanning of the particular analysis being performed.
- Figure ⁇ 4A-C illu ⁇ trate an embodiment of a microcapillary electrophore ⁇ i ⁇ device.
- the sample to be analyzed is introduced into sample reservoir 402.
- Thi ⁇ sample reservoir may be a separate chamber, or may be merely a portion of the fluid channel leading from a previous reaction chamber.
- Reservoir ⁇ 404, 406 and 414 are filled with sample/running buffer.
- Figure 4A illustrate ⁇ the loading of the sample by plug loading, where the sample i ⁇ drawn acro ⁇ s the intersection of loading channel 416 and capillary channel 412, by application of an electrical current across buffer reservoir 406 and sample reservoir 402.
- Fabrication of the microcapillary electrophore ⁇ i ⁇ device may generally be carried u ⁇ ing the method ⁇ de ⁇ cribed herein and as described in e.g., Woolley and Mathies, Proc. Nat'l Acad. Sci. USA 91:11348-11352 (1994) , incorporated herein by reference in its entirety for all purpose ⁇ .
- each capillary will be fluidly connected to a separate extension reaction chamber for incorporation of a different dideoxynucleotide.
- An alternate layout of the reaction chambers within the device of the invention includes a centralized geometry having a central chamber for gathering and distribution of a fluid sample to a number of separate reaction/storage/analytical chamber ⁇ arranged around, and fluidly connected to the central chamber.
- An example of thi ⁇ centralized geometry i ⁇ ⁇ hown in Figure 5.
- a fluid sample is introduced into the device through sample inlet 502, which is typically fluidly connected to a sample collection chamber 504. The fluid sample is then tran ⁇ ported to a central chamber 508 via fluid channel 506.
- reaction/ ⁇ torage/analytical chamber ⁇ 510, 512, 514 which are arranged around and fluidly connected to the central chamber.
- reaction chamber ⁇ 510, 512 and 514 include ⁇ a diaphragm 516, 518 and 520, re ⁇ pectively, a ⁇ ⁇ hown in Figure 2B, for opening and closing the fluid connection between the central chamber 508 and the reaction chamber.
- Additional reaction chambers may be added fluidly connected to the central chamber, or alternatively, may be connected to any of the above described reaction chambers.
- the central chamber may have a dual function as both a hub and a pumping chamber.
- this central pumping chamber can be fluidly connected to one or more additional reaction and/or storage chambers and one or more analytical chambers.
- the central pumping chamber again function ⁇ a ⁇ a hub for the variou ⁇ operation ⁇ to be carried out by the device a ⁇ a whole a ⁇ described above.
- Thi ⁇ embodiment provide ⁇ the advantage of a single pumping chamber to deliver a sample to numerous operations, as well as the ability to readily incorporate additional ⁇ ample preparation operation ⁇ within the device by opening another valve on the central pumping chamber.
- the central chamber 508 may incorporate a diaphragm pump a ⁇ one ⁇ urface of the chamber, and in preferred a ⁇ pect ⁇ , will have a zero di ⁇ placement when the diaphragm i ⁇ not deflected.
- the diaphragm pump will generally be ⁇ imilar to the valve ⁇ tructure de ⁇ cribed above for the reaction chamber.
- the diaphragm pump will generally be fabricated from any one of a variety of flexible material ⁇ , e.g., silicon, latex, teflon, mylar and the like. In particularly preferred embodiments, the diaphragm pump is silicon.
- central chamber 508 is fluidly connected to sample collection chamber 504, via fluid channel 506.
- the sample collection chamber end of fluid channel 506 includes a diaphragm valve 524 for arresting fluid flow.
- a fluid sample is typically introduced into sample collection chamber through a ⁇ ealable opening 502 in the body of the device, e.g., a valve or ⁇ eptum.
- sample chamber 504 may incorporate a vent to allow displacement of gas or fluid during ⁇ ample introduction.
- the ⁇ ample i ⁇ introduced into the ⁇ ample collection chamber may be drawn into the central pumping chamber 508 by the operation of pump diaphragm 526.
- opening of ⁇ ample chamber valve 524 open ⁇ fluid channel 506.
- Sub ⁇ eguent pulling or deflection of pump diaphragm 526 create ⁇ negative pre ⁇ ure within pumping chamber 508, thereby drawing the ⁇ ample through fluid channel 506 into the central chamber.
- Sub ⁇ equent clo ⁇ ing of the ⁇ ample chamber valve 524 and relaxation of pump diaphragm 526 create ⁇ a positive pres ⁇ ure within pumping chamber 508, which may be used to deliver the sample to additional chambers in the device.
- these reagents may be stored in liquid or solid form within an adjacent storage chamber 510. Opening valve 516 open ⁇ fluid channel 528, allowing delivery of the sample into storage chamber 510 upon relaxation of the diaphragm pump.
- the operation of pumping chamber may further be employed to mix reagents, by repeatedly pulling and pushing the sample/reagent mixture to and from the storage chamber. This has the additional advantage of eliminating the neces ⁇ ity of including additional mixing component ⁇ within the device.
- Additional chamber/valve/fluid channel ⁇ tructures may be provided fluidly connected to pumping chamber 508 as needed to provide reagent storage chambers, additional reaction chamber ⁇ or additional analytical chamber ⁇ .
- Figure 5A illu ⁇ trate ⁇ an additional reaction/ ⁇ torage chamber 514 and valve 520, fluidly connected to pumping chamber 508 via fluid channel 530.
- Thi ⁇ will typically vary depending upon the nature of the ⁇ ample to be analyzed, the analy ⁇ i ⁇ to be performed, and the de ⁇ ired sample preparation operation.
- reaction chamber 514 which may include an analytical device such as an oligonucleotide array for determining the hybridization of nucleic acids in the sample to the array, or a microcapillary electrophoresi ⁇ device for performing a ⁇ ize ba ⁇ ed analy ⁇ i ⁇ of the sample.
- an analytical device such as an oligonucleotide array for determining the hybridization of nucleic acids in the sample to the array, or a microcapillary electrophoresi ⁇ device for performing a ⁇ ize ba ⁇ ed analy ⁇ i ⁇ of the sample.
- fluid tran ⁇ portation of fluid within the device of the invention may be carried out by a number of varied method ⁇ .
- fluid tran ⁇ port may be affected by the application of pre ⁇ sure differential ⁇ provided by either external or internal sources.
- internal pump elements which are incorporated into the device may be used to transport fluid samples through the device.
- fluid samples are moved from one reaction/storage/analytical chamber to another chamber via fluid channel ⁇ by applying a po ⁇ itive pressure differential from the originating chamber, the chamber from which the sample is to be transported, to the receiving chamber, the chamber to which the fluid ⁇ ample is to be transported.
- the various reaction chamber ⁇ of the device will typically incorporate pressure inlets connecting the reaction chamber to the pres ⁇ ure ⁇ ource (positive or negative) .
- a negative pressure i.e., to the receiving chamber
- po ⁇ itive pressure i.e., to the originating chamber
- application of the pressure differential to a particular reaction chamber may generally be carried out by selectively lowering the pre ⁇ sure in the receiving chamber.
- the pres ⁇ ure inlet for the reaction chambers may be equipped with a controllable valve structure which may be selectively operated to be opened to the pressure source.
- Application of the pres ⁇ ure source to the ⁇ ample chamber then force ⁇ the sample into the next reaction chamber which is at a lower pressure.
- the device will include a pres ⁇ ure/vacuum manifold for directing an external vacuum source to the various reaction/storage/analytical chamber ⁇ .
- a pres ⁇ ure/vacuum manifold for directing an external vacuum source to the various reaction/storage/analytical chamber ⁇ .
- the vacuum/pres ⁇ ure manifold produce ⁇ a ⁇ tepped pre ⁇ sure differential between each pair of connected reaction chambers.
- ambient pres ⁇ ure i ⁇ defined a ⁇ having a value of 1
- a vacuum i ⁇ applied to a fir ⁇ t reaction chamber which may be written l-3x, where x i ⁇ an incremental pre ⁇ ure differential.
- a vacuum of l-2x i ⁇ applied to a ⁇ econd reaction chamber in the ⁇ eries, and a vacuum of 1-x is applied to a third reaction chamber. Thu ⁇ , the first reaction chamber is at the lowest pre ⁇ ure and the third is at the highest, with the second being at an intermediate level. All chamber ⁇ , however, are below ambient pressure, e.g., atmospheric.
- the sample is drawn into the first reaction chamber by the pressure differential between ambient pressure (1) and the vacuum applied to the reaction chamber (l-3x) , which differential is -3x.
- the sample doe ⁇ not move to the second reaction chamber due to the pressure differential between the first and second reaction chambers (l-3x vs. l-2x, respectively) .
- the vacuum is removed from the first chamber, allowing the first chamber to come to ambient pressure, e.g., 1.
- the sample is then drawn from the first chamber into the second by the pressure difference between the ambient pressure of the first reaction chamber and the vacuum of the second chamber, e.g., 1 vs. 1- 2x.
- the vacuum to thi ⁇ chamber is removed and the sample moves to the third reaction chamber.
- FIG. 6A A schematic representation of a pneumatic manifold configuration for carrying out this pres ⁇ ure differential fluid tran ⁇ port system is shown in Figure 6A.
- the pneumatic manifold includes a vacuum source 602 which is coupled to a main vacuum channel 604.
- the main vacuum channel is connected to branch channels 606, 608 and 610, which are in turn connected to reaction chambers 612, 614 and 616, re ⁇ pectively, which reaction chamber ⁇ are fluidly connected, in series.
- the first reaction chamber in the series 616 typically includes a sample inlet 640 which will typically include a sealable closure for retaining he fluid sample and the pres ⁇ ure within the reaction chamber.
- Each branch channel is provided with one or more fluidic resistor ⁇ 618 and 620 incorporated within the branch channel.
- Fluidic resi ⁇ tor ⁇ result in a transformation of the pres ⁇ ure from the pressure/vacuum source, i.e., a step down of the gas pre ⁇ ure or vacuum being applied acro ⁇ the re ⁇ i ⁇ tance.
- Fluidic resi ⁇ tor ⁇ may employ a variety of different ⁇ tructure ⁇ . For example, a narrowing of the diameter or cro ⁇ s-sectional area of a channel will typically result in a fluidic re ⁇ istance through the channel.
- a plug within the channel which has one or more holes disposed therethrough, which effectively narrow the channel through which the pres ⁇ ure i ⁇ applied, will re ⁇ ult in a fluidic re ⁇ i ⁇ tance, which re ⁇ i ⁇ tance can be varied depending upon the number and/or ⁇ ize of the hole ⁇ in the plug.
- the plug may be fabricated from a porou ⁇ material which provide ⁇ a fluidic re ⁇ i ⁇ tance through the plug, which resistance may be varied depending upon the porosity of the material and/or the number of plugs used. Variations in channel length can also be used to vary fluidic resi ⁇ tance.
- Each branch channel will typically be connected at a pre ⁇ sure node 622 to the reaction chamber via pres ⁇ ure inlet ⁇ 624.
- Pre ⁇ ure inlet ⁇ 624 will typically be fitted with poorly wetting filter plugs 626, to prevent drawing of the sample into the pneumatic manifold in the ca ⁇ e of vacuum ba ⁇ ed method ⁇ . Poorly wetting filter plug ⁇ may generally be prepared from a variety of material ⁇ known in the art and as described above.
- Each branch channel is connected to a vent channel 628 which is opened to ambient pres ⁇ ure via vent 630.
- fluidic re ⁇ i ⁇ tance ⁇ upplied by fluidic re ⁇ istor 632 will be less than fluidic resi ⁇ tance ⁇ upplied by fluidic resistor 634 which will be le ⁇ than fluidic resistance supplied by fluidic resi ⁇ tor 636.
- thi ⁇ differential fluidic re ⁇ istance may be accompli ⁇ hed by varying the diameter of the vent channel, varying the number of channel ⁇ included in a ⁇ ingle vent channel, varying channel length, or providing a plug in the vent channel having a varied number of hole ⁇ disposed therethrough.
- reaction chamber 616 may have a pres ⁇ ure of l-3x
- reaction chamber 614 may have a pressure of l-2x
- reaction chamber 612 may have a pressure of 1-x.
- the pres ⁇ ure of a c ven reaction chamber may be raised to ambient pre ⁇ ure, thu ⁇ allowing the drawing of the sample into the ⁇ ub ⁇ equent chamber, by opening the chamber to ambient pressure. This is typically accomplished by providing a sealable opening 638 to ambient pre ⁇ ure in the branch channel.
- This sealable opening may be a controllable valve structure, or alternatively, a rupture membrane which may be pierced at a desired time to allow the particular reaction chamber to achieve ambient pres ⁇ ure, thereby allowing the sample to be drawn into the subseguent chamber. Piercing of the rupture membrane may be carried out by the inclusion of solenoid operated pins incorporated within the device, or the device's base unit (discu ⁇ ed in greater detail below). In some cases, it may be desirable to prevent back flow from a previou ⁇ or ⁇ ub ⁇ equent reaction chamber which i ⁇ at a higher pressure. This may be accomplished by equipping the fluid channels between the reaction chambers 644 with one-way check valves. Examples of one-way valve structure ⁇ include ball and seat structure ⁇ , flap valve ⁇ , duck billed check valve ⁇ , sliding valve structures, and the like.
- FIG. 6C A graphical illustration of the pres ⁇ ure profile ⁇ between three reaction chambers employing a vacuum based pneumatic manifold is shown in Figure 6C.
- the solid line indicates the ⁇ tarting pressure of each reaction chamber/pressure node.
- the dotted line indicates the pres ⁇ ure profile during operation. The piercing of a rupture membrane results in an increase in the pressure of the reaction chamber to ambient pres ⁇ ure, re ⁇ ulting in a pre ⁇ ure drop being created between the particular chamber and the subsequent chamber. This pressure drop draws the ⁇ ample from the fir ⁇ t reaction chamber to the subsequent reaction chamber.
- a positive pressure source may be applied to the originating chamber to push the sample into subsequent chambers.
- a pneumatic pres ⁇ ure manifold u ⁇ eful in thi ⁇ regard is shown in Figure 6B.
- a pres ⁇ ure source 646 provides a positive pres ⁇ ure to the main channel 604.
- controllable valve 648 is opened to vent the pres ⁇ ure from the pre ⁇ ure ⁇ ource and allow the fir ⁇ t reaction chamber in the series 650 to remain at ambient pres ⁇ ure for the introduction of the ⁇ ample.
- the fir ⁇ t chamber in the series typically includes a sample inlet 640 having a sealable clo ⁇ ure 642.
- controllable valve 648 is clo ⁇ ed, bringing the system up to pres ⁇ ure.
- Suitable controllable valves include any number of a variety of commercially available solenoid valves and the like.
- each subsequent chamber is kept at an incrementally higher pressure by the presence of the appropriate fluidic resi ⁇ tor ⁇ and vents, as described above.
- sealable opening 656 is opened to ambient pres ⁇ ure.
- the fir ⁇ t reaction chamber 650 i ⁇ maintained at a pre ⁇ ure of 1+x, by application of thi ⁇ pre ⁇ sure at originating pre ⁇ ure node 652.
- the ⁇ econd reaction chamber 654 i ⁇ maintained at pre ⁇ ure l+2x and the third reaction chamber 658 i ⁇ maintained at a pre ⁇ sure of 1 +3x. Opening ⁇ ealable valve 656 results in a drop in the pres ⁇ ure of the ⁇ econd reaction chamber 654 to 1 (or ambient pre ⁇ ure) .
- Fluidic resistor 660 i ⁇ provided between pre ⁇ ure node 662 and sealable valve 656 to prevent the escape of exces ⁇ pre ⁇ ure when sealable valve 656 is opened. This allows the sy ⁇ tem to maintain a po ⁇ itive pre ⁇ ure behind the ⁇ ample to pu ⁇ h it into subsequent chambers.
- a controllable pre ⁇ sure ⁇ ource may be applied to the originating reaction ve ⁇ el to pu ⁇ h a sample through the device.
- the pre ⁇ ure ⁇ ource i ⁇ applied intermittently, a ⁇ needed to move the sample from chamber to chamber.
- a variety of devices may be employed in applying an intermittent pres ⁇ ure to the originating reaction chamber, e.g., a syringe or other positive displacement pump, or the like.
- a thermopneumatic pump may be readily employed.
- An example of such a pump typically includes a heating element, e.g., a small scale resistive heater dispo ⁇ ed in a pre ⁇ ure chamber.
- a controlled vapor pre ⁇ ure fluid ⁇ uch a ⁇ a fluorinated hydrocarbon liquid, e.g., fluorinert liquid ⁇ available from 3M Corp.
- a controlled vapor pre ⁇ ure fluid ⁇ uch a ⁇ a fluorinated hydrocarbon liquid, e.g., fluorinert liquid ⁇ available from 3M Corp.
- These liquids are commercially available having a wide range of available vapor pressures.
- An increase in the controllable temperature of the heater increase ⁇ pre ⁇ ure in the pre ⁇ ure chamber, which i ⁇ fluidly connected to the originating reaction chamber.
- Thi ⁇ increa ⁇ e in pre ⁇ ure re ⁇ ult ⁇ in a movement of the ⁇ ample from one reaction chamber to the next.
- the temperature in the pressure chamber is reduced.
- gas permeable fluid barriers e.g., poorly wetting filter plugs or hydrophobic membranes
- gas permeable fluid barriers e.g., poorly wetting filter plugs or hydrophobic membranes
- a fluid inlet will allow air or other ga ⁇ present in the reaction chamber to be expelled during introduction of the fluid component into the chamber.
- the fluid sample Upon filling of the chamber, the fluid sample will contact the hydrophobic plug thus stopping net fluid flow.
- Fluidic resistances may al ⁇ o be employed a ⁇ gas permeable fluid barriers, to accomplish this same re ⁇ ult, e.g., using fluid pas ⁇ age ⁇ that are ⁇ ufficiently narrow a ⁇ to provide an exce ⁇ ive fluid re ⁇ i ⁇ tance, thereby effectively stopping or retarding fluid flow while permitting air or gas flow.
- Expelling the fluid from the chamber then involves applying a positive pressure at the plugged vent. This permits chambers which may be filled with no valve at the inlet, i.e., to control fluid flow into the chamber.
- a single valve will be employed at the chamber inlet in order to ensure retention of the fluid sample within the chamber, or to provide a mechanism for directing a fluid sample to one chamber of a number of chambers connected to a common channel.
- the reaction chamber 1202 includes a fluid inlet 1204 which is sealed from a fluid pas ⁇ age 1206 by a valve 1208.
- this valve can employ a variety of structure ⁇ , as described herein, but is preferably a flexible diaphragm type valve which may be displaced pneumatically, magnetically or electrically.
- the valves are controlled pneumatically, e.g., by applying a vacuum to the valve to deflect the diaphragm away from the valve seat, thereby creating an opening into adjoining pas ⁇ age ⁇ .
- hydrophobic membrane 1212 At the end opposite from the inlet, i ⁇ an outlet vent 1210, and disposed across this outlet vent is a hydrophobic membrane 1212.
- a number of different commercially available hydrophobic membranes may be used as described herein, including, e.g., Versapore 200 R membranes available from Gelman Science ⁇ . Fluid introduced into the reaction chamber fills the chamber until it contacts the membrane 1212. Clo ⁇ ure of the valve then allow ⁇ performance of reaction ⁇ within the reaction chamber without influencing or influence from element ⁇ out ⁇ ide of the chamber.
- the ⁇ e plug ⁇ or membrane ⁇ may be used for degas ⁇ ing or debubbling fluid ⁇ within the device.
- a chamber may be provided with one or more vents or with one wall completely or substantially bounded by a hydrophobic membrane to allow the passage of dis ⁇ olved or trapped gases. Additionally, vacuum may be applied on the external surface of the membrane to draw gases from the sample fluid ⁇ . Due to the ⁇ mall cross sectional dimensions of reaction chambers and fluid pas ⁇ age ⁇ , elimination of such gases takes on greater importance, as bubbles may interfere with fluid flow, and/or result in production of irregular data.
- such membranes may be used for removing bubbles purposely introduced into the device, i.e., for the purpose of mixing two fluids which were previously desired to be separated.
- discrete fluids e.g. , reagents
- reagents may be introduced into a single channel or debubbling chamber, separated by a gas bubble which is sufficient to separete the fluid plugs but not to inhibit fluid flow.
- These fluid plugs may then be flowed along a channel having a vent dispo ⁇ ed therein, which vent include ⁇ a hydrophobic membrane.
- a schematic illustration of such a debubbling chamber is shown in Figure 12B.
- FIG. 12C shows a schematic illustration of a device employing a fluid flow sy ⁇ tem which utilize ⁇ hydrophobic membrane bound vent ⁇ for control of fluid flow.
- the device 1250 includes a main channel 1252.
- the main channel is fluidly connected to a multitude ⁇ of ⁇ eparate chamber ⁇ 1254-1260.
- Each of the ⁇ e fluid connection ⁇ with the main channel 1252 i ⁇ mediated (opened or clo ⁇ ed) by the inclu ⁇ ion of a separate valve 1262-1268, respectively, at the intersection of these fluid connections with the main channel.
- each of the various chambers will typically include a vent port 1270-1276 to the outside environment, which vent ports will typically be bounded by a hydrophobic or poorly wetting membrane.
- the basic design of thi ⁇ ⁇ ystem i ⁇ reflected in the device schematic shown in Figure 5, as well, in that it employs a central distribution chamber or channel.
- sample ⁇ or other fluid ⁇ may be introduced into the main channel 1252 via a valved or otherwise sealable liguid inlet 1278 or 1280.
- Application of a positive pressure to the fluid inlet, combined with the selective opening of the elastomeric valve at the fluid connection of a selected chamber with the main channel will force the fluid into that chamber, expelling air or other gase ⁇ through the vent port at the terminu ⁇ of the ⁇ elected chamber, until that vent i ⁇ contacted with the fluid, whereupon fluid flow i ⁇ ⁇ topped.
- the valve to the ⁇ elected chamber may then be returned to the clo ⁇ ed po ⁇ ition to ⁇ eal the fluid within the chamber.
- the requisite pres ⁇ ure differential needed for fluid flow may alternatively or additionally involve the application of a negative pre ⁇ sure at the vent port to which fluid direction is sought.
- a sample introduced into the main channel 1252 is first forced into the degassing chamber 1254 by opening valve 1262 and applying a positive pres ⁇ ure at inlet port 1278.
- valve 1262 may then be clo ⁇ ed.
- Degassing of the fluid may then be carried out by drawing a vacuum on the sample through the hydrophobic membrane disposed across the vent port 1270.
- Degassed sample may then be moved from the degassing chamber 1254 to, e.g., reaction chamber 1256, by opening valves 1262 and 1264, and applying a positive pressure to the degas ⁇ ing chamber vent port 1270.
- the device includes a volumetric or measuring chamber 1258 as well a ⁇ a storage chamber 1260, including similar valve:vent port arrangements 1266:1274 and 1268:1276, respectively.
- the fluid may then be selectively directed to other chambers a ⁇ de ⁇ cribed.
- Figure 12D shows a top view of a portion of an injection molded substrate for carrying out the operations schematically illu ⁇ trated in Figure 12C.
- this device include ⁇ liguid loading chamber ⁇ 1278a and 1280a which are in fluid communication with the fluid inlet ⁇ 1278 and 1280 (not shown) .
- the ⁇ e fluid inlet ⁇ may typically be fabricated into the injection molded portion, e.g., drilled into the loading chamber, or fabricated into an overlaying planar member (not shown).
- reaction chambers 1254, degassing chambers 1256 and 1256a, mea ⁇ uring chamber ⁇ 1258, and storage chambers 1260 are also included. Each of these chambers i ⁇ fluidly connected to main channel 1252.
- a number of the operation ⁇ performed by the variou ⁇ reaction chamber ⁇ of the device require a controllable temperature.
- PCR amplification, a ⁇ de ⁇ cribed above require ⁇ cycling of the sample among a strand separation temperature, an annealing reaction temperature and an extension reaction temperature.
- a number of other reactions, including extension, transcription and hybridization reactions are also generally carried out at optimized, controlled temperatures.
- Temperature control within the device of the invention is generally supplied by thin film resistive heaters which are prepared using methods that are well known in the art. For example, these heaters may be fabricated from thin metal films applied within or adjacent to a reaction chamber u ⁇ ing well known method ⁇ ⁇ uch a ⁇ sputtering, controlled vapor deposition and the like.
- the thin film heater will typically be electrically connected to a power source which delivers a current across the heater.
- the electrical connections will also be fabricated using methods similar to those described for the heaters.
- these heaters will be capable of producing temperatures in excess of 100 degrees without suffering adverse effects as a result of the heating.
- resistor heaters include, e.g., the heater discu ⁇ sed in Published PCT Application No. WO 94 ⁇ 05414, laminated thin film NiCr/polyimide/copper heaters, as well as graphite heaters. These heaters may be provided as a layer on one surface of a reaction chamber, or may be provided as molded or machined in ⁇ ert ⁇ for incorporation into the reaction chambers.
- Figure 2B illustrate ⁇ an example of a reaction chamber 104 having a heater insert 128, dispo ⁇ ed therein.
- the re ⁇ i ⁇ tive heater i ⁇ typically electrically connected to a controlled power source for applying a current across the heater. Control of the power source is typically carried out by an appropriately programmed computer.
- the above-described heaters may be incorporated within the individual reaction chambers by depositing a resi ⁇ tive metal film or insert within the reaction chamber, or alternatively, may be applied to the exterior of the device, adjacent to the particular reaction chamber, whereby the heat from the heater i ⁇ conducted into the reaction chamber.
- Temperature controlled reaction chamber ⁇ will also typically include a miniature temperature sen ⁇ or for monitoring the temperature of the chamber, and thereby controlling the application of current acro ⁇ the heater.
- a miniature temperature sen ⁇ or for monitoring the temperature of the chamber, and thereby controlling the application of current acro ⁇ the heater.
- micro ⁇ en ⁇ or ⁇ are available for determining temperatures, including, e.g., thermocouples having a bimetallic junction which produces a temperature dependent electromotive force (EMF) , resistance thermometer ⁇ which include material having an electrical resi ⁇ tance proportional to the temperature of the material, thermi ⁇ tor ⁇ , IC temperature sensors, quartz thermometers and the like. See, Horowitz and Hill, The Art of Electronics, Cambridge
- Control of reaction parameters within the reaction chamber may be carried out manually, but is preferably controlled via an appropriately programmed computer.
- the temperature measured by the temperature sensor and the input for the power source will typically be interfaced with a computer which is programmed to receive and record this data, i.e., via an analog- digital/digital-analog (AD/DA) converter.
- AD/DA analog- digital/digital-analog
- the same computer will typically include programming for instructing the delivery of appropriate current for rai ⁇ ing and lowering the temperature of the reaction chamber.
- the computer may be programmed to take the reaction chamber through any number of predetermined time/temperature profile ⁇ , e.g., thermal cycling for PCR, and the like.
- time/temperature profile ⁇ e.g., thermal cycling for PCR, and the like.
- cooling of the reaction chambers will typically occur through exposure to ambient temperature, however additional cooling element ⁇ may be included if desired, e.g., coolant sy ⁇ tems, peltier coolers, water bath ⁇ , etc.
- one or more of the reaction chamber ⁇ of the device may al ⁇ o incorporate a mixing function.
- mixing may be applied merely by pumping the sample back and forth into and out of a particular reaction chamber.
- ca ⁇ e ⁇ con ⁇ tant mixing within a single reaction/analytical chamber is desired, e.g., PCR amplification reactions and hybridization reactions.
- acou ⁇ tic mixing is used to mix the sample within a given reaction chamber.
- a PZT element (element composed of lead, zirconium and titanium containing ceramic) is contacted with the exterior surface of the device, adjacent to the reaction chamber, as shown in Figure 7A.
- PZT element 702 is contacting the external surface 704 of hybridization chamber 706.
- the hybridization chamber includes a ⁇ one internal ⁇ urface, an oligonucleotide array 708.
- Application of a current to this element generates ⁇ onic vibration ⁇ which are translated to the reaction chamber whereupon mixing of the sample di ⁇ po ⁇ ed therein occur ⁇ .
- the vibration ⁇ of thi ⁇ element re ⁇ ult in substantial convection being generated within the reaction chamber.
- a symmetric mixing pattern generated within a micro reaction chamber incorporating this mixing system is shown Figure 7B.
- Incomplete contact (i.e., bonding) of the element to the device may re ⁇ ult in an incomplete mixing of a fluid sample.
- the element will typically have a fluid or gel layer (not shown) dispo ⁇ ed between the element 702 and the external surface of the device ir ⁇ , e.g., water.
- This fluid layer will generally be incorporated within a membrane, e.g., a latex balloon, having one surface in contact with the external surface of the reaction chamber and another surface in contact with the PZT element.
- An appropriately programmed computer 714 may be used to control the application of a voltage to the PZT element, via a function generator 712 and RF amplifier 710 to control the rate and/or timing of mixing.
- mixing may be supplied by the incorporation of ferromagnetic elements within the device which may be vibrated by ⁇ upplying an alternating current to a coil adjacent the device.
- the o ⁇ cillating current creates an oscillating magnetic field through the center of the coil which results in vibratory motion and rotation of the magnetic particles in the device, resulting in mixing, either by direct convection or accoustic streaming.
- the devices of the present invention may include additional component ⁇ for optimizing ⁇ ample preparation or analy ⁇ i ⁇ .
- electrophoretic force may be u ⁇ ed to draw target molecule ⁇ into the surface of the array.
- electrodes may be disposed or patterned on the surface of the array or on the surface opposite the array. Application of an appropriate electric field will either push or pull the target ⁇ in solution onto the array.
- a variety of similar enhancements can be included without departing from the ⁇ cope of the invention.
- control elements for the device e.g., temperature control, mixing and fluid transport element ⁇ may be supplied within a reu ⁇ able ba ⁇ e-unit.
- the reaction chamber portion of the • ' rvice can be mated with a reusable base unit that i ⁇ adapted for receiving the device.
- the base unit may include one or more heaters for controlling the temperature within selected reaction chambers within the device.
- the base unit may incorporate mixing elements such as tho ⁇ e described herein, as well as vacuum or pressure sources for providing sample mixing and transportation within the device.
- the ba ⁇ e unit may include a fir ⁇ t surface having disposed thereon, one or more resi ⁇ tive heater ⁇ of the type de ⁇ cribed above.
- the heater ⁇ are positioned on the surface of the base unit such that when the reaction chamber device is mated to that surface, the heater ⁇ will be adjacent to and preferably contacting the exterior ⁇ urface of the device adjacent to one or more reaction chambers in which temperature control is desired.
- one or more mixing element ⁇ may al ⁇ o be disposed upon this surface of the base unit, whereby when mated with the reaction chamber device, the mixing element ⁇ contact the outer ⁇ urface of the reaction/storage/analytical chambers in which such mixing i ⁇ de ⁇ ired.
- interspersed heaters and mixers may be provided on the surface of the ba ⁇ e unit.
- the base unit may include a second surface which contacts the opposite surface of the device from the first surface, to apply heating on one exterior surface of the reaction chamber and mixing at the other.
- the base unit also typically includes appropriate electrical connections for linking the heating and mixing element ⁇ to an appropriate power source.
- the base unit may also be used to connect the reaction chamber device itself to external power source ⁇ , pre ⁇ ure/vacuum ⁇ ource ⁇ and the like.
- the ba ⁇ e unit can provide manifold ⁇ , port ⁇ and electrical connection ⁇ which plug into receiving connectors or ports on the device to provide power, vacuum or pres ⁇ ure for the various control elements that are internal to the device.
- mating of the device to the base unit may provide a connection from a vacuum source in the base unit to a main vacuum manifold manufactured into the device, as described above.
- the ba ⁇ e unit may provide electrical connectors which couple to complementary connectors on the device to provide electrical current to any number of operations within the device via electrical circuitry fabricated into the device.
- appropriate connections are al ⁇ o provided for monitoring variou ⁇ operation ⁇ of the device, e.g., temperature, pre ⁇ ure and the like.
- the ba ⁇ e unit will al ⁇ o typically include one or more solenoid mounted rupture pins.
- the solenoid mounted rupture pin ⁇ are disposed within receptacle ⁇ which are manufactured into the ⁇ urface of the ba ⁇ e unit, which receptacle ⁇ correspond to position ⁇ of the rupture membranes upon the device.
- the pin ⁇ are retained below the ⁇ urface of the base unit when not in operation. Activation of the solenoid extends the pin above the surface of the base unit, into and through the rupture membrane.
- FIG. 8 A schematic representation of one embodiment of a base unit is shown in Figure 8.
- the base unit 800 includes a body structure 802 having a mating surface 804.
- the body structure house ⁇ the variou ⁇ element ⁇ that are to be incorporated into the ba ⁇ e unit.
- the ba ⁇ e unit may also include one or more thermoelectric heating/cooling elements 806 dispo ⁇ ed within the ba ⁇ e unit ⁇ uch that when the reaction chamber contianing portion of the apparatu ⁇ i ⁇ mated to the mating surface of the base unit, the reaction chamber ⁇ will be in contact or immediatly adjacent to the heating elements.
- the base unit may typically include a pressure source opening to the mating surface via the pres ⁇ ure source port 810.
- the base unit will also typically include other elements of the ⁇ e ⁇ y ⁇ tem ⁇ , ⁇ uch a ⁇ ⁇ olenoid 812 driven pins 814 for piercing rupture membranes. These pin ⁇ are typically within rece ⁇ sed ports 816 in the mating surface 804.
- the base unit will also typically include mounting structures on the mating surface to ensure proper mating of the reaction chamber containing portion of the device to the base unit.
- Such mounting structures generally include mounting pins or holes (not shown) disposed on the mating surface which correspond to complementary structures on the reaction chamber containing portion of the device.
- Mounting pins may be differentially sized, and/or tapered, to ensure mating of the reaction chamber and base unit in an appropriate orientation.
- the base unit may be fabricated to include a well in which the reaction chamber portion mounts, which well has a nonsymetrical shape, matching a nonsymetrical ⁇ hape of the reaction chamber portion.
- Such a design is similar to that used in the manufacture of audio tape cas ⁇ ette ⁇ and players.
- the device of the present invention may include a number of other components to further facilitate analyses.
- a number of the operations of sample transport, manipulation and monitoring may be performed by elements external to the device, per se. These elements may be incorporated within the above-de ⁇ cribed base unit, or may be included as further attachments to the device and/or base unit.
- external pumps or fluid flow devices may be used to move the sample through the various operations of the device and/or for mixing
- temperature controls may be applied externally to the device to maximize individual operations
- valve controls may be operated externally to direct and regulate the flow of the sample. In preferred embodiments, however, these various operations will be integrated within the device.
- the integrated device of the invention will typically incorporate a number of additional components for sample transporting, direction, manipulation, and the like. Generally, this will include a plurality of micropumps, valves, mixers and heating elements.
- Pumping devices that are particularly useful include a variety of micromachined pumps that have been reported in the art.
- suitable pumps include pumps which having a bulging diaphragm, powered by a piezoelectric stack and two check valve ⁇ , such as those described in U.S. Patent Nos. 5,277,556, 5,271,724 and 5,171,132, or powered by a thermopneumatic element, a ⁇ de ⁇ cribed in U.S. Patent No.
- Ferrofluidic fluid transport and mixing ⁇ y ⁇ tem ⁇ may al ⁇ o be incorporated into the device of the pre ⁇ ent invention.
- the ⁇ e ⁇ ystems incorporate a ferrofluidic ⁇ ubstance which is placed into the apparatus.
- the ferrofluidic substance is controlled/directed externally through the use of magnets.
- the ferrofluidic sub ⁇ tance provides a barrier which can be selectively moved to force the sample fluid through the apparatus, or through an individual operation of the apparatus.
- These ferrofluidic sy ⁇ tems may be used for example, to reduce effective volumes where the sample occupies insufficient volume to fill the hybridization chamber. Insufficient sample fluid volume may result in incomplete hybridization with the array, and incomplete hybridization data.
- ferrofluidic sy ⁇ tem is u ⁇ ed to sandwich the ⁇ ample fluid in a ⁇ ufficiently ⁇ mall volume. This small volume is then drawn acros ⁇ the array in a manner which ensures the ⁇ ample contact ⁇ the entire surface of the array.
- Ferrofluids are generally commercially available from, e.g., FerroFluidic ⁇ Inc., New Hamp ⁇ hire.
- Alternative fluid tran ⁇ port mechani ⁇ m ⁇ for inclu ⁇ ion within the device of the pre ⁇ ent invention include, e.g. electrohydrodynamic pump ⁇ ( ⁇ ee, e.g., Richter, et al. 3rd IEEE Workshop on Micro Electro Mechanical System ⁇ , February 12-14, 1990, Napa Valley, USA, and Richter et al., Sensors and Actuators 29:159-165 (1991), U.S. Patent No. 5,126,022, each of which is incorporated herein by reference in it ⁇ entirety for all purposes) .
- electrohydrodynamic pump ⁇ ⁇ ee, e.g., Richter, et al. 3rd IEEE Workshop on Micro Electro Mechanical System ⁇ , February 12-14, 1990, Napa Valley, USA, and Richter et al., Sensors and Actuators 29:159-165 (1991), U.S. Patent No. 5,126,022, each of which is incorporated herein by reference in it ⁇ entirety for all purposes
- Such pumps employ a multitude ⁇ of electrodes disposed across one surface of
- Indium-tin oxide film ⁇ may be particularly suited for patterning electrodes on sub ⁇ trate surfaces, e.g., a glass or silicon sub ⁇ trate. These methods can also be used to draw nucleic acids onto an array. For example, electrodes may paterned on the surface of an array substrate and modified with suitable functional group ⁇ for coupling nucleic acid ⁇ to the ⁇ urface of the electrodes. Application of a current betwen the electrodes on the surface of an array and an oppo ⁇ ing electrode re ⁇ ult ⁇ in electrophoretic movement of the nucleic acids toward the surface of the array.
- Electrophoretic pumping by application of transient electric fields can also be employed to avoid electrolysis at the surface of the electrodes while ⁇ till cau ⁇ ing ⁇ ufficient sample movement.
- the electrophoretic mobility of a nucleic acid is not constant with the electric field applied.
- An increa ⁇ e in an electric field of from 50 to 400 v/cm result ⁇ in a 30% increa ⁇ e in mobility of a nucleic acid sample in an acrylamide gel.
- a high electric field is applied in the forward direction of sample movement and a lower field is then applied in the reverse direction.
- the above de ⁇ cribed micropump ⁇ may also be used to mix reagent ⁇ and samples within the apparatus, by directing a recirculating fluid flow through the particular chamber to be mixed. Additional mixing methods may also be employed.
- electrohydrodynamic mixers may be employed within the various reaction chambers. These mixers typically employ a traveling electric field for moving a fluid into which a charge has been introduced. See Bart, et al., Sensor ⁇ and Actuators (1990) A21-A-23:193-197.
- thermopneumatic pumping mechanism This typically involves the inclusion of small heaters, disposed behind apertures within a particular chamber. When the liquid in contact with the heater is heated, it expand ⁇ through the apertures causing a convective force to be introduced into the chamber, thereby mixing the sample.
- a pumping mechanism retained behind two one way check valves ⁇ uch a ⁇ the pump de ⁇ cribed in U.S. Patent No. 5,375,979 to Trah, incorporated herein by reference in it ⁇ entirety for all purpo ⁇ es, can be employed to circulate a fluid sample within a chamber.
- the fluid is then expelled from the pump chamber through another one way check valve during the reciprocal pump cycle, resulting in a circular fluid flow within the reaction chamber.
- the pumping mechanism may employ any number of designs, as described herein, i.e., diaphragm, thermal pressure, electrohydrodynamic, etc.
- insulating materials may be used for thi ⁇ function, including, e.g., teflon coating, Si0 2 , Si 3 N 4 , and the like.
- insulating layers will be Si0 2 , which may generally be sputtered over the surface of the component to provide an insulating layer.
- the device of the present invention will also typically incorporate a number of microvalves for the direction of fluid flow within the device.
- a variety of microvalve de ⁇ ign ⁇ are particularly well ⁇ uited for the in ⁇ tant device.
- Example ⁇ of valve ⁇ that may be u ⁇ ed in the device are described in, e.g., U.S. Patent No. 5,277,556 to van Lintel, incorporated herein by reference.
- Preferred valve structures for use in the present devices typically incorporate a membrane or diaphragm which may be deflected onto a valve seat.
- the electrostatic valves, silicon/aluminum bimetallic actuated valves or thermopneumatic actuated valves can be readily adapted for incorporation into the device of the invention.
- fluidic valve ⁇ may al ⁇ o be employed.
- Such fluidic valve ⁇ typically include a "liquid curtain" which compri ⁇ e ⁇ a fluid that i ⁇ immi ⁇ cible in the aqueou ⁇ system ⁇ used in the device, e.g., silicone oil, ferrofluidic fluids, and the like.
- a fluidic valve include ⁇ a shallow valving channel, e.g.
- the valving channel is connected to at least one oil port.
- the valving channel is first filled with oil (or other appropriate fluid element) , which is drawn into the channel by capillary action.
- oil or other appropriate fluid element
- the oil, or "fluid curtain” moves aside and allow ⁇ pa ⁇ age.
- the oil will return to seal the fluid or gas behind a vapor barrier.
- these fluidic valve ⁇ are useful in the prevention of evaporation of fluid samples or reagents within the device.
- the device may also incorporate one or more filters for removing cell debris and protein solids from the sample.
- the filters may generally be within the apparatus, e.g., within the fluid pas ⁇ age ⁇ leading from the ⁇ ample preparation/extraction chamber.
- a variety of well known filter media may be incorporated into the device, including, e.g., cellulo ⁇ e, nitrocellulo ⁇ e, poly ⁇ ulfone, nylon, vinyl/acrylic copolymer ⁇ , glass fiber, polyvinylchloride, and the like.
- the filter may be a structure fabricated into the device similar to that described in U.S. Patent No. 5,304,487 to Wilding et al. , previously incorporated herein.
- separation chamber ⁇ having a separation media e.g., ion exchange resin, affinity resin or the like, may be included within the device to eliminate contaminating proteins, etc.
- the device of the present invention may also contain one or more sensor ⁇ within the device it ⁇ elf to monitor the progre ⁇ of one or more of the operations of the device.
- sensor ⁇ within the device it ⁇ elf to monitor the progre ⁇ of one or more of the operations of the device.
- optical sensor ⁇ and pre ⁇ sure ⁇ en ⁇ ors may be incorporated into one or more reaction chamber ⁇ to monitor the progress of the various reactions, or within flow channels to monitor the progress of fluids or detect characteristic ⁇ of the fluid ⁇ , e.g., pH, temperature, fluorescence and the like.
- reagents used in each operation integrated within the device may be exogenously introduced into the device, e.g., through sealable openings in each respective chamber.
- these reagents will be predisposed within the device.
- these reagents may be di ⁇ po ⁇ ed within the reaction chamber which perform ⁇ the operation for which the reagent will be used, or within the fluid channels leading to that reaction chamber.
- the reagents may be dispo ⁇ ed within storage chambers adjacent to and fluidly connected to their respective reaction chambers, whereby the reagents can be readily transported to the appropriate chamber as needed.
- the amplification chamber will typically have the appropriate reagents for carrying out the amplification reaction, e.g., primer probe sequence ⁇ , deoxynucleo ⁇ ide triphosphates ("dNTPs") , nucleic acid polymera ⁇ e ⁇ , buffering agents and the like, predisposed within the amplification chamber.
- sample stabilization reagents will typically be predisposed within the sample collection chamber.
- four domains of the device are each addres ⁇ ed by an array of valves, e.g., a 10 valve array, with its own common channel.
- the four domains may generally be defined as: (1) reagent storage; (2) reaction; (3) sample preparation; and (4) po ⁇ t proce ⁇ sing, which are fluidically interconnected.
- the sample preparation domain i ⁇ typically used to extract and purify nucleic acids from a sample.
- included in the ⁇ ample preparation domain are 5 reagent inlet ⁇ that are fluidly connected to larger volume ⁇ torage vessel ⁇ , e.g., within the base unit.
- Examples of such reagent ⁇ for extraction reaction ⁇ may include, e.g., 4M guanidine i ⁇ othiocyanate, 1 X TBE and 50:50 EtOH:H 2 0.
- the two reaction chamber ⁇ may include, e.g., affinity media for purification of nucleic acid ⁇ such as glas ⁇ wool, or bead ⁇ coated with poly-T oligonucleotides.
- the storage domain is linked to the ⁇ ample preparation domain, and i ⁇ u ⁇ ed for ⁇ torage of reagent ⁇ and mixtures, e.g., PCR mix with FITC-dG ⁇ and dUTP but no template, UNG reaction mix and IVT reaction mix without template.
- the reaction domain is also linked to the sample preparation domain as well as the storage domain and includes a number of reaction chambers (5) , measuring chambers (2) and debubbling chambers (1) . Both sample preparation and reaction domains may be addressed by a thermal controller, e.g., heaters or thermoelectric heater/cooler.
- the post proces ⁇ ing domain i ⁇ typically linked to the reaction domain and include ⁇ a number of reagent inlet ⁇ (5) , reaction chamber ⁇ (2) , ⁇ torage chamber ⁇ (1) and ⁇ ample inlets (1) .
- the reagent inlets may be used to introduce buffers, e.g., 6 X SSPE or water into the analytical element, e.g., an oligonucleotide array.
- valves are addres ⁇ ed by 4 column ⁇ each of pneumatic port ⁇ .
- Two additional array ⁇ of 10 valve ⁇ address a sample preparation and post proces ⁇ ing domain.
- a bank of solenoid valve ⁇ may be u ⁇ ed to drive the pneumatic port ⁇ and the valve array ⁇ .
- the device and ⁇ y ⁇ tem of the pre ⁇ ent invention ha ⁇ a wide variety of u ⁇ e ⁇ in the manipulation, identification and/or seguencing of nucleic acid sample ⁇ .
- the ⁇ e ⁇ amples may be derived from plant, animal, viral or bacterial sources.
- the device and sy ⁇ tem of the invention may be used in diagnostic application ⁇ , ⁇ uch a ⁇ in diagno ⁇ ing genetic disorders, as well as diagno ⁇ ing the pre ⁇ ence of infectious agent ⁇ , e.g., bacterial or viral infection ⁇ .
- the device and system may be used in a variety of characterization applications, such as foren ⁇ ic analy ⁇ i ⁇ , ' e.g., genetic fingerprinting, bacterial, plant or viral identification or characterization, e.g., epidemiological or taxonomic analy ⁇ is, and the like.
- characterization applications such as foren ⁇ ic analy ⁇ i ⁇ , ' e.g., genetic fingerprinting, bacterial, plant or viral identification or characterization, e.g., epidemiological or taxonomic analy ⁇ is, and the like.
- the device and sy ⁇ tem of the present invention is used in the analysis of human sample ⁇ . More particularly, the device i ⁇ u ⁇ ed to determine the pre ⁇ ence or absence of a particular nucleic acid sequence within a particular human sample. This include ⁇ the identification of genetic anomalie ⁇ a ⁇ ociated with a particular disorder, as well as the identification within a sample of a particular infectious agent, e.g., virus, bacteria, yeast or fungus.
- a particular infectious agent e.g., virus, bacteria, yeast or fungus.
- the devices of the present invention may also be u ⁇ ed in de novo sequencing applications.
- the device may be used in sequencing by hybridization (SBH) technique ⁇ .
- SBH sequencing by hybridization
- the use of oligonucleotide arrays in de novo SBH applications is described, for example, in U.S. Application Serial No. 08/082,937, filed June 25, 1993.
- the lysate wa ⁇ passed through a cartridge containing glass wool (20 ⁇ l) , a cartridge with soda glas ⁇ walls ( 20 ⁇ l) , and a glas ⁇ tube. After 30 minutes at room temperature, the remaining lysate was washed away with several volumes of ethanol:water (1:1) and the captured DNA was eluted at 60°C using IX TBE.
- the yield of eluted DNA was measured using ethidum bromide staining on an agarose gel, and purity was tested by using the eluted material as a template for a PCR reaction. Elution yield ⁇ ranged from 10% to 25% and PCR yield ⁇ ranged from 90 to 100% a ⁇ compared to control ⁇ u ⁇ ing pure template.
- a model miniature reactor system was designed to investigate the efficacy of miniaturized devices in carrying out prehybridization preparative reaction ⁇ on target nucleic acids.
- a dual reaction chamber system for carrying out in vitro transcription and fragmentation was fabricated.
- the device employed a tube based structure using a polymer tubing a ⁇ an in vitro tran ⁇ cription reactor coupled to a glass capillary fragmentation reactor. Reagents not introduced with the sample were provided as dried deposits on the internal surface of the connecting tubing.
- the experiment was designed to investigate the effect ⁇ of reaction chamber materials and reaction volume in RNA preparative reaction chambers.
- the sample including the target nucleic acid, DNA amplicons containing a 1 kb portion of the HIV gene flanked with promoter regions for the T3 and T7 RNA primer ⁇ on the sense and antisense strands, re ⁇ pectively, RNA polymera ⁇ e, NTP ⁇ , fluorinated UTP and buffer, were introduced into the reactor system at one end of the tubing based system.
- In vitro transcription was carried out in a silicone tubing reactor immersed in a water bath. Following thi ⁇ initial reaction, the sample was moved through the sy ⁇ tem into a gla ⁇ capillary reactor which wa ⁇ maintained at 94°C, for carrying out the fragmentation reaction.
- the product ⁇ of a representative time-course fragmentation reaction are shown in the gel of Figure 10A.
- the tubing connecting the IVT reactor to the fragmentation reactor contained additional MgCl 2 for addition to the ⁇ ample.
- the glass capillary was first coated with BSA to avoid interactions between the sample and the glas ⁇ .
- the sample was hybridized with an appropriately tiled oligonucleotide array, a ⁇ de ⁇ cribed above.
- Preparation u ⁇ ing this system with 14 mM MgCl 2 addition resulted in a correct base calling rate of 96.5%.
- Omis ⁇ ion of the MgCl 2 gave a correct ba ⁇ e calling rate of 95.5%.
- a similar preparative transcription reaction wa ⁇ carried out in a micro-reaction chamber fabricated in polycarbonate.
- a well wa ⁇ machined in the ⁇ urface of a first polycarbonate part.
- the well was 250 ⁇ m deep and had an approximate volume of 5 ⁇ l.
- a second polycarbonate part was then acou ⁇ tically welded to the fir ⁇ t to provide a top wall for the reaction chamber.
- the ⁇ econd part had two hole ⁇ drilled through it, which hole ⁇ were po ⁇ itioned at oppo ⁇ ite end ⁇ of the reaction chamber.
- Temperature control for the tran ⁇ cription reaction wa ⁇ ⁇ upplied by applying external temperature control ⁇ to the reaction chamber, a ⁇ de ⁇ cribed for the tubing ba ⁇ ed system. 3 ⁇ l sample ⁇ were u ⁇ ed for both transcription and fragmentation experiments.
- Transcription reactions performed in the micro- reactor achieved a 70% yield as compared to conventional methods, e.g., same volume in microfuge tube and water bath or PCR thermal cycler.
- a comparison of in vitro transcription reaction products using a microchamber versu ⁇ a larger scale control are shown in Figure 10B.
- the miniature polymeric reaction chamber similar to the one described in Example 2 was u ⁇ ed for carrying out PCR amplification.
- the chamber wa ⁇ fabricated from a planar piece of poycarbonate 4 mm thick, and having a cavity measuring 500 ⁇ m deep machined into its surface.
- a second planar polycarbonate piece was welded over the cavity.
- Thermal control was supplied by applying a peltier heater against the thinner second wall of the cavity.
- Amplification of a target nucleic acid was performed with Perkin-Elmer GeneAmp® PCR kit.
- the reaction chamber wa ⁇ cycled for 20 second ⁇ at 94°C (denaturing) , 40 ⁇ econds at 65°C (annealing) and 50 ⁇ econd ⁇ at 72°C (exten ⁇ ion) .
- Figure IOC show ⁇ production of amplified product in the microchamber as compared to a control using a typical PCR thermal cycler.
- a microfabricated polycarbonate device was manufactured having the structure shown in Figure 15A.
- the device included three discrete vented chambers. Two of the chambers (top and middle) were thermally isolated from the PCR chamber (bottom) to prevent any denaturation of the RNA polymera ⁇ e used in IVT reractions at PCR temperatures. Thermal i ⁇ olation was accomplished by fabricating the chambers more than 10 mm apart in a thin polycarbonate substrate and controlling the temperatures in each region through the use of thermoelectric temperature controllers, e.g., peltier devices.
- the reactor device dimension ⁇ were as follows: channels were 250 ⁇ m wide by 125 ⁇ m deep; the three reaction chambers were 1.5 mm wide by 13 mm in length by 125 to 500 ⁇ m deep, with the reactor volumes ranging from 2.5 to 10 ⁇ l. Briefly, PCR was carried out by introducing 0.3 unit ⁇ of Taq polymerase, 0.2 mM dNTP ⁇ , 1.5 mM MgCl 2 , 0.2 ⁇ M primer sequences, approximately 2000 molecules of template sequence and IX Perkin-Elmer PCR buffer into the bottom chamber.
- the thermal cycling program included (1) an initial denaturation at 94°C for 60 seconds, (2) a denaturation step at 94°C for 20 seconds, (3) an annealing step at 65°C for 40 second ⁇ , (4) an extension step at 72°C for 50 ⁇ econd ⁇ , (5) repeated cycling through steps 2-4 35 times, and (6) a final extension step at 72°C for 60 second ⁇ .
- RNAguard Pharmacia
- Fluid transfer was carried out by applying pressure to the vents at the termini of the chambers.
- IVT wa ⁇ carried out at 37°C for 60 minute ⁇ . The results of PCR and IVT are ⁇ hown in Figure 15B, compared with control experiment ⁇ , e.g., performed in eppendorf tube ⁇ .
- Example 5- Acou ⁇ tic Mixing The efficacy of an acou ⁇ tic element for mixing the contents of a reaction chamber was tested.
- a 0.5" X 0.5" X 0.04" crystal of PZT-5H was bonded to the external ⁇ urface of a 0.030" thick region of a planar piece of delrin which had cavity machined in the ⁇ urface oppo ⁇ ite the PZT element.
- a fluore ⁇ cently labeled oligonucleotide target sequence having the seguence 5 '-GAGATGCGTCGGTGGCTG-3 ' and an array having a checkerboard pattern of 400 ⁇ m square ⁇ having complement ⁇ to thi ⁇ ⁇ equence synthesized thereon were used.
- Hybridization of a 10 nM solution of the target in 6xSSPE was carried out.
- the external surface of the array was kept in contact with a thermoelectric cooler set at 15°C.
- the resulting average intensity was identical to that achieved using mechanical mixing of the chamber (vertical rotation with an incorporated bubble) .
- Ela ⁇ tomeric valve ⁇ were opened and clo ⁇ ed by application of vacuum or pre ⁇ ure (approx. 60 p ⁇ i) to the space above the individual valves.
- debubbling chamber Functioning of the debubbling chamber was demonstrated by moving four separate plug ⁇ of colored water from the reaction chamber to the debubbling chamber. The discrete plugs, upon pas ⁇ ing into the debubbling chamber, joined together as a single fluid plug.
- the functioning of the measuring chamber was demonstrated by repetetively moving portions of a 10 ⁇ l colored water sample from the ⁇ torage chamber to the mea ⁇ uring chamber, followed by exhau ⁇ ting thi ⁇ fluid from the mea ⁇ uring chamber. Thi ⁇ fluid transfer was carried out 6 times, indicating repeated aliquoting of approximately 1.6 ⁇ l per measuring chamber volume (10 ⁇ l in 6 aliguots) .
Abstract
Description
Claims
Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
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AT96923572T ATE235559T1 (en) | 1995-06-29 | 1996-06-27 | INTEGRATED NUCLEIC ACID DIAGNOSTIC DEVICE |
DE69626988T DE69626988T2 (en) | 1995-06-29 | 1996-06-27 | INTEGRATED NUCLEIC ACID DIAGNOSTIC DEVICE |
JP9505261A JPH11509094A (en) | 1995-06-29 | 1996-06-27 | Integrated nucleic acid diagnostic device |
AU64049/96A AU6404996A (en) | 1995-06-29 | 1996-06-27 | Integrated nucleic acid diagnostic device |
EP96923572A EP0843734B1 (en) | 1995-06-29 | 1996-06-27 | Integrated nucleic acid diagnostic device |
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US70395P | 1995-06-29 | 1995-06-29 | |
US85995P | 1995-07-03 | 1995-07-03 | |
US60/000,859 | 1995-07-03 | ||
US60/000,703 | 1995-07-29 | ||
US08/589,027 US5856174A (en) | 1995-06-29 | 1996-01-19 | Integrated nucleic acid diagnostic device |
US08/589,027 | 1996-01-19 |
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EP (2) | EP1304388B1 (en) |
JP (1) | JPH11509094A (en) |
AT (2) | ATE235559T1 (en) |
AU (1) | AU6404996A (en) |
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US6670153B2 (en) | 2000-09-14 | 2003-12-30 | Caliper Technologies Corp. | Microfluidic devices and methods for performing temperature mediated reactions |
US6669831B2 (en) | 2000-05-11 | 2003-12-30 | Caliper Technologies Corp. | Microfluidic devices and methods to regulate hydrodynamic and electrical resistance utilizing bulk viscosity enhancers |
US6681788B2 (en) | 2001-01-29 | 2004-01-27 | Caliper Technologies Corp. | Non-mechanical valves for fluidic systems |
US6707561B1 (en) | 1999-07-05 | 2004-03-16 | Novartis Ag | Sensor platform, apparatus incorporating platform, and process using the platform |
US6720148B1 (en) | 2001-02-22 | 2004-04-13 | Caliper Life Sciences, Inc. | Methods and systems for identifying nucleotides by primer extension |
US6733645B1 (en) | 2000-04-18 | 2004-05-11 | Caliper Technologies Corp. | Total analyte quantitation |
US6752966B1 (en) | 1999-09-10 | 2004-06-22 | Caliper Life Sciences, Inc. | Microfabrication methods and devices |
US6756019B1 (en) | 1998-02-24 | 2004-06-29 | Caliper Technologies Corp. | Microfluidic devices and systems incorporating cover layers |
US6767510B1 (en) | 1992-05-21 | 2004-07-27 | Biosite, Inc. | Diagnostic devices and apparatus for the controlled movement of reagents without membranes |
US6771376B2 (en) | 1999-07-05 | 2004-08-03 | Novartis Ag | Sensor platform, apparatus incorporating the platform, and process using the platform |
US6777184B2 (en) | 2000-05-12 | 2004-08-17 | Caliper Life Sciences, Inc. | Detection of nucleic acid hybridization by fluorescence polarization |
AU778696B2 (en) * | 1999-12-15 | 2004-12-16 | Ge Healthcare Bio-Sciences Ab | Compositions and methods for performing biological reactions |
US6858185B1 (en) | 1999-08-25 | 2005-02-22 | Caliper Life Sciences, Inc. | Dilutions in high throughput systems with a single vacuum source |
US6857449B1 (en) | 1998-01-20 | 2005-02-22 | Caliper Life Sciences, Inc. | Multi-layer microfluidic devices |
US6864050B2 (en) | 1999-07-30 | 2005-03-08 | Affymetrix, Inc. | Single-phase amplification of nucleic acids |
US6878540B2 (en) | 1999-06-25 | 2005-04-12 | Cepheid | Device for lysing cells, spores, or microorganisms |
US6905882B2 (en) | 1992-05-21 | 2005-06-14 | Biosite, Inc. | Diagnostic devices and apparatus for the controlled movement of reagents without membranes |
US6915679B2 (en) | 2000-02-23 | 2005-07-12 | Caliper Life Sciences, Inc. | Multi-reservoir pressure control system |
US6977163B1 (en) | 2001-06-13 | 2005-12-20 | Caliper Life Sciences, Inc. | Methods and systems for performing multiple reactions by interfacial mixing |
US6990851B2 (en) | 2000-02-23 | 2006-01-31 | Caliper Life Sciences, Inc. | Microfluidic viscometer |
US7033474B1 (en) | 1997-04-25 | 2006-04-25 | Caliper Life Sciences, Inc. | Microfluidic devices incorporating improved channel geometries |
US7037416B2 (en) | 2000-01-14 | 2006-05-02 | Caliper Life Sciences, Inc. | Method for monitoring flow rate using fluorescent markers |
US7040144B2 (en) | 2000-02-23 | 2006-05-09 | Caliper Life Sciences, Inc. | Microfluidic viscometer |
US7060171B1 (en) | 2001-07-31 | 2006-06-13 | Caliper Life Sciences, Inc. | Methods and systems for reducing background signal in assays |
US7069952B1 (en) | 2001-11-14 | 2006-07-04 | Caliper Life Sciences, Inc. | Microfluidic devices and methods of their manufacture |
US7150999B1 (en) | 2001-03-09 | 2006-12-19 | Califer Life Sciences, Inc. | Process for filling microfluidic channels |
US7161356B1 (en) | 2002-06-05 | 2007-01-09 | Caliper Life Sciences, Inc. | Voltage/current testing equipment for microfluidic devices |
US7160423B2 (en) | 2002-03-05 | 2007-01-09 | Caliper Life Sciences, Inc. | Mixed mode microfluidic systems |
WO2007016367A2 (en) | 2005-07-29 | 2007-02-08 | Bayer Healthcare Llc | Neoplastic disease-related methods, kits, systems and databases |
US7247274B1 (en) | 2001-11-13 | 2007-07-24 | Caliper Technologies Corp. | Prevention of precipitate blockage in microfluidic channels |
US7259021B2 (en) | 2000-03-07 | 2007-08-21 | Bio Merieux | Method for using a test card |
US7276330B2 (en) | 1999-01-28 | 2007-10-02 | Caliper Technologies Corp. | Devices, systems and methods for time domain multiplexing of reagents |
US7282370B2 (en) | 1997-05-23 | 2007-10-16 | Solexa, Inc. | System and apparatus for sequential processing of analytes |
US7303727B1 (en) | 2002-03-06 | 2007-12-04 | Caliper Life Sciences, Inc | Microfluidic sample delivery devices, systems, and methods |
WO2008008284A2 (en) | 2006-07-14 | 2008-01-17 | The Regents Of The University Of California | Cancer biomarkers and methods of use threof |
EP1892306A2 (en) | 2003-10-06 | 2008-02-27 | Bayer HealthCare AG | Methods and kits for investigating cancer |
EP1900827A2 (en) | 2002-05-21 | 2008-03-19 | Bayer HealthCare AG | Methods and compositions for the prediction, diagnosis, prognosis, prevention and treatment of malignant neoplasia |
EP1953243A2 (en) | 2000-06-15 | 2008-08-06 | Novartis Vaccines and Diagnostics, Inc. | Polynucleotides related to colon cancer |
US7419784B2 (en) | 2002-04-02 | 2008-09-02 | Dubrow Robert S | Methods, systems and apparatus for separation and isolation of one or more sample components of a sample biological material |
EP1978098A2 (en) | 1999-12-10 | 2008-10-08 | Invitrogen Corporation | Use of multiple recombination sites with unique specificity in recombinational cloning |
US7497994B2 (en) | 1998-02-24 | 2009-03-03 | Khushroo Gandhi | Microfluidic devices and systems incorporating cover layers |
US7498407B2 (en) | 2001-11-09 | 2009-03-03 | Georgetown University | Vascular endothelial cell growth inhibitor, VEGI-192a |
US7521186B2 (en) | 2000-03-20 | 2009-04-21 | Caliper Lifesciences Inc. | PCR compatible nucleic acid sieving matrix |
US7524456B1 (en) | 1992-05-21 | 2009-04-28 | Biosite Incorporated | Diagnostic devices for the controlled movement of reagents without membranes |
US7550267B2 (en) | 2004-09-23 | 2009-06-23 | University Of Washington | Microscale diffusion immunoassay utilizing multivalent reactants |
EP2075346A2 (en) | 2002-01-08 | 2009-07-01 | Novartis Vaccines and Diagnostics, Inc. | Gene products differentially expressed in cancerous breast cells and their methods of use |
JP2009254384A (en) * | 1997-10-31 | 2009-11-05 | Bbi Bioseq Inc | Method for pressure-enhanced extraction and purification |
EP2090366A3 (en) * | 1997-03-28 | 2009-11-18 | Applera Corporation | Improvements in thermal cycler for PCR |
US7625760B2 (en) | 1999-08-11 | 2009-12-01 | Asahi Kasei Kabushiki Kaisha | Analyzing cartridge and liquid feed control device |
WO2009146204A1 (en) | 2008-04-18 | 2009-12-03 | Tufts Medical Center | Polymorphisms associated with age-related macular degeneration and methods for evaluating patient risk |
EP1196243B2 (en) † | 1999-07-07 | 2009-12-16 | 3M Innovative Properties Company | Detection article having fluid control film with capillary channels |
US7645581B2 (en) | 2002-12-20 | 2010-01-12 | Caliper Life Sciences, Inc. | Determining nucleic acid fragmentation status by coincident detection of two labeled probes |
US7670559B2 (en) | 2001-02-15 | 2010-03-02 | Caliper Life Sciences, Inc. | Microfluidic systems with enhanced detection systems |
US7691333B2 (en) | 2001-11-30 | 2010-04-06 | Fluidigm Corporation | Microfluidic device and methods of using same |
US7700359B2 (en) | 2000-06-02 | 2010-04-20 | Novartis Vaccines And Diagnostics, Inc. | Gene products differentially expressed in cancerous cells |
US7723123B1 (en) | 2001-06-05 | 2010-05-25 | Caliper Life Sciences, Inc. | Western blot by incorporating an affinity purification zone |
US7749737B2 (en) | 2003-04-03 | 2010-07-06 | Fluidigm Corporation | Thermal reaction device and method for using the same |
US7749442B2 (en) | 2001-12-14 | 2010-07-06 | Arkray, Inc. | Sample measuring device |
US7776523B2 (en) | 2000-12-07 | 2010-08-17 | Novartis Vaccines And Diagnostics, Inc. | Endogenous retroviruses up-regulated in prostate cancer |
WO2010111595A2 (en) | 2009-03-27 | 2010-09-30 | Tufts - New England Medical Center | Markers related to age-related macular degeneration and uses therefor |
US7820427B2 (en) | 2001-11-30 | 2010-10-26 | Fluidigm Corporation | Microfluidic device and methods of using same |
US7833708B2 (en) | 2001-04-06 | 2010-11-16 | California Institute Of Technology | Nucleic acid amplification using microfluidic devices |
US7867454B2 (en) | 2003-04-03 | 2011-01-11 | Fluidigm Corporation | Thermal reaction device and method for using the same |
US7867776B2 (en) | 2001-03-02 | 2011-01-11 | Caliper Life Sciences, Inc. | Priming module for microfluidic chips |
US7901881B2 (en) | 2004-04-09 | 2011-03-08 | The United States Of America As Represented By The Department Of Health And Human Services | Diagnostic tool for diagnosing benign versus malignant thyroid lesions |
EP2311530A2 (en) | 2004-10-27 | 2011-04-20 | Vanderbilt University | Mammalian genes involved in infection |
EP2319939A2 (en) | 1999-10-21 | 2011-05-11 | Case Western Reserve University | Gene expression profiling of inflammatory bowel disease |
US8007746B2 (en) | 2003-04-03 | 2011-08-30 | Fluidigm Corporation | Microfluidic devices and methods of using same |
US20110229898A1 (en) * | 2009-06-04 | 2011-09-22 | Lockheed Martin Corporation | DNA analyzer |
US8025853B2 (en) | 2004-12-13 | 2011-09-27 | Canon Kabushiki Kaisha | Biochemical processing apparatus |
WO2011139721A1 (en) | 2010-04-27 | 2011-11-10 | The Regents Of The University Of California | Cancer biomarkers and methods of use thereof |
WO2011146725A1 (en) | 2010-05-19 | 2011-11-24 | Bayer Healthcare Llc | Biomarkers for a multikinase inhibitor |
EP2402460A1 (en) | 2006-02-09 | 2012-01-04 | Caliper Life Sciences, Inc. | Method and apparatus for generating thermal melting curves in a microfluidic device |
USRE43097E1 (en) | 1994-10-13 | 2012-01-10 | Illumina, Inc. | Massively parallel signature sequencing by ligation of encoded adaptors |
US8129176B2 (en) | 2000-06-05 | 2012-03-06 | California Institute Of Technology | Integrated active flux microfluidic devices and methods |
EP2418018A3 (en) * | 2004-12-23 | 2012-03-28 | Abbott Point of Care Inc. | Methods for the separation nucleic acids |
US8168442B2 (en) | 1999-05-28 | 2012-05-01 | Cepheid | Cartridge for conducting a chemical reaction |
US8216852B2 (en) | 2001-07-27 | 2012-07-10 | Caliper Life Sciences, Inc. | Channel cross-section geometry to manipulate dispersion rates |
US8241883B2 (en) | 2002-04-24 | 2012-08-14 | Caliper Life Sciences, Inc. | High throughput mobility shift |
US8249681B2 (en) | 2005-01-31 | 2012-08-21 | Given Imaging Ltd. | Device, system and method for in vivo analysis |
US8275554B2 (en) | 2002-12-20 | 2012-09-25 | Caliper Life Sciences, Inc. | System for differentiating the lengths of nucleic acids of interest in a sample |
US8318109B2 (en) | 2003-01-14 | 2012-11-27 | Micronics, Inc. | Microfluidic devices for fluid manipulation and analysis |
US8518694B2 (en) | 2002-06-13 | 2013-08-27 | Novartis Vaccines And Diagnostics, Inc. | Nucleic acid vector comprising a promoter and a sequence encoding a polypeptide from the endogenous retrovirus PCAV |
EP2636755A1 (en) | 2006-05-26 | 2013-09-11 | AltheaDx Incorporated | Biochemical analysis of partitioned cells |
US8658418B2 (en) | 2002-04-01 | 2014-02-25 | Fluidigm Corporation | Microfluidic particle-analysis systems |
US8759079B2 (en) | 2011-11-15 | 2014-06-24 | Korea Institute Of Machinery & Materials | Device for automatically analyzing nucleic acid |
US8828663B2 (en) | 2005-03-18 | 2014-09-09 | Fluidigm Corporation | Thermal reaction device and method for using the same |
WO2014172661A1 (en) | 2013-04-19 | 2014-10-23 | The Regent Of The University Of California | Lone star virus |
US8871446B2 (en) | 2002-10-02 | 2014-10-28 | California Institute Of Technology | Microfluidic nucleic acid analysis |
US8945884B2 (en) | 2000-12-11 | 2015-02-03 | Life Technologies Corporation | Methods and compositions for synthesis of nucleic acid molecules using multiplerecognition sites |
US8961764B2 (en) | 2010-10-15 | 2015-02-24 | Lockheed Martin Corporation | Micro fluidic optic design |
US9073053B2 (en) | 1999-05-28 | 2015-07-07 | Cepheid | Apparatus and method for cell disruption |
US9101933B2 (en) | 2008-10-10 | 2015-08-11 | University Of Hull | Microfluidic apparatus and method for DNA extraction, amplification and analysis |
US9234244B2 (en) | 2007-08-27 | 2016-01-12 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Diagnostic tool for diagnosing benign versus malignant thyroid lesions |
US9267112B2 (en) | 2011-05-10 | 2016-02-23 | The Regents Of The University Of California | Adenovirus isolated from Titi Monkeys |
US9273949B2 (en) | 2012-05-11 | 2016-03-01 | Vanderbilt University | Backscattering interferometric methods |
US9322054B2 (en) | 2012-02-22 | 2016-04-26 | Lockheed Martin Corporation | Microfluidic cartridge |
US9382590B2 (en) | 2011-03-25 | 2016-07-05 | Florida Agricultural and Mechanical University (FAMU) | Methods and compositions for prostate cancer metastasis |
US9534252B2 (en) | 2003-12-01 | 2017-01-03 | Life Technologies Corporation | Nucleic acid molecules containing recombination sites and methods of using the same |
US9562853B2 (en) | 2011-02-22 | 2017-02-07 | Vanderbilt University | Nonaqueous backscattering interferometric methods |
US9638632B2 (en) | 2010-06-11 | 2017-05-02 | Vanderbilt University | Multiplexed interferometric detection system and method |
US9714443B2 (en) | 2002-09-25 | 2017-07-25 | California Institute Of Technology | Microfabricated structure having parallel and orthogonal flow channels controlled by row and column multiplexors |
US9789481B2 (en) | 1999-05-28 | 2017-10-17 | Cepheid | Device for extracting nucleic acid from a sample |
US9803230B2 (en) | 2013-03-15 | 2017-10-31 | Abbott Molecular Inc. | One-step procedure for the purification of nucleic acids |
US9808472B2 (en) | 2013-08-12 | 2017-11-07 | Tokai Pharmaceuticals, Inc. | Biomarkers for treatment of neoplastic disorders using androgen-targeted therapies |
US9884067B2 (en) | 2013-03-14 | 2018-02-06 | University Of Maryland, Baltimore | Androgen receptor down-regulating agents and uses thereof |
US9943848B2 (en) | 1999-05-28 | 2018-04-17 | Cepheid | Apparatus and method for cell disruption |
US10107797B2 (en) | 2008-10-03 | 2018-10-23 | Micronics, Inc. | Microfluidic apparatus and methods for performing blood typing and crossmatching |
US10202615B2 (en) | 2010-12-10 | 2019-02-12 | Vanderbilt University | Mammalian genes involved in toxicity and infection |
US10221218B2 (en) | 2011-05-10 | 2019-03-05 | The Regents Of The University Of California | Adenovirus isolated from titi monkeys |
US10261013B2 (en) | 2015-01-23 | 2019-04-16 | Vanderbilt University | Robust interferometer and methods of using same |
US10386377B2 (en) | 2013-05-07 | 2019-08-20 | Micronics, Inc. | Microfluidic devices and methods for performing serum separation and blood cross-matching |
US10428377B2 (en) | 2002-12-20 | 2019-10-01 | Caliper Life Sciences, Inc. | Methods of detecting low copy nucleic acids |
US10509018B2 (en) | 2000-11-16 | 2019-12-17 | California Institute Of Technology | Apparatus and methods for conducting assays and high throughput screening |
US10627396B2 (en) | 2016-01-29 | 2020-04-21 | Vanderbilt University | Free-solution response function interferometry |
EP3677336A1 (en) | 2007-09-05 | 2020-07-08 | Caliper Life Sciences Inc. | Microfluidic method and system for enzyme inhibition activity screening |
US10774387B2 (en) | 2014-05-19 | 2020-09-15 | The Johns Hopkins University | Methods for identifying androgen receptor splice variants in subjects having castration resistant prostate cancer |
US10816550B2 (en) | 2012-10-15 | 2020-10-27 | Nanocellect Biomedical, Inc. | Systems, apparatus, and methods for sorting particles |
US10894986B2 (en) | 2008-04-16 | 2021-01-19 | The Johns Hopkins University | Compositions and methods for treating or preventing prostate cancer and for detecting androgen receptor variants |
US10900961B2 (en) | 2007-09-20 | 2021-01-26 | Vanderbilt University | Free solution measurement of molecular interactions by backscattering interferometry |
US10994273B2 (en) | 2004-12-03 | 2021-05-04 | Cytonome/St, Llc | Actuation of parallel microfluidic arrays |
US11027278B2 (en) | 2002-04-17 | 2021-06-08 | Cytonome/St, Llc | Methods for controlling fluid flow in a microfluidic system |
US11345956B2 (en) | 2014-08-25 | 2022-05-31 | The Johns Hopkins University | Methods and compositions related to prostate cancer therapeutics |
EP4019643A1 (en) | 2015-09-23 | 2022-06-29 | Oklahoma Medical Research Foundation | Biomarkers for assessing subjects with multiple sclerosis |
US11543411B2 (en) | 2014-12-05 | 2023-01-03 | Prelude Corporation | DCIS recurrence and invasive breast cancer |
US11821900B2 (en) | 2018-09-14 | 2023-11-21 | Prelude Corporation | Method of selection for treatment of subjects at risk of invasive breast cancer |
US11926817B2 (en) | 2019-08-09 | 2024-03-12 | Nutcracker Therapeutics, Inc. | Microfluidic apparatus and methods of use thereof |
Families Citing this family (1384)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7040653B1 (en) * | 2004-10-27 | 2006-05-09 | Automotive Technologies International, Inc. | Steering wheel assemblies for vehicles |
US20040077074A1 (en) * | 1993-11-01 | 2004-04-22 | Nanogen, Inc. | Multi-chambered analysis device |
US6129828A (en) * | 1996-09-06 | 2000-10-10 | Nanogen, Inc. | Apparatus and methods for active biological sample preparation |
US6319472B1 (en) * | 1993-11-01 | 2001-11-20 | Nanogen, Inc. | System including functionally separated regions in electrophoretic system |
US6638482B1 (en) * | 1993-11-01 | 2003-10-28 | Nanogen, Inc. | Reconfigurable detection and analysis apparatus and method |
US6309602B1 (en) | 1993-11-01 | 2001-10-30 | Nanogen, Inc. | Stacked, reconfigurable system for electrophoretic transport of charged materials |
US6287517B1 (en) * | 1993-11-01 | 2001-09-11 | Nanogen, Inc. | Laminated assembly for active bioelectronic devices |
US6375899B1 (en) * | 1993-11-01 | 2002-04-23 | Nanogen, Inc. | Electrophoretic buss for transport of charged materials in a multi-chamber system |
EP0695941B1 (en) * | 1994-06-08 | 2002-07-31 | Affymetrix, Inc. | Method and apparatus for packaging a chip |
US6287850B1 (en) | 1995-06-07 | 2001-09-11 | Affymetrix, Inc. | Bioarray chip reaction apparatus and its manufacture |
US7857957B2 (en) * | 1994-07-07 | 2010-12-28 | Gamida For Life B.V. | Integrated portable biological detection system |
US6403367B1 (en) * | 1994-07-07 | 2002-06-11 | Nanogen, Inc. | Integrated portable biological detection system |
US6654505B2 (en) | 1994-10-13 | 2003-11-25 | Lynx Therapeutics, Inc. | System and apparatus for sequential processing of analytes |
US5959098A (en) | 1996-04-17 | 1999-09-28 | Affymetrix, Inc. | Substrate preparation process |
US20050100946A1 (en) * | 1995-06-29 | 2005-05-12 | Affymetrix, Inc. | Integrated nucleic acid diagnostic device and method for in-situ confocal microscopy |
US5856174A (en) * | 1995-06-29 | 1999-01-05 | Affymetrix, Inc. | Integrated nucleic acid diagnostic device |
US20020022261A1 (en) * | 1995-06-29 | 2002-02-21 | Anderson Rolfe C. | Miniaturized genetic analysis systems and methods |
US6911183B1 (en) * | 1995-09-15 | 2005-06-28 | The Regents Of The University Of Michigan | Moving microdroplets |
US6048734A (en) | 1995-09-15 | 2000-04-11 | The Regents Of The University Of Michigan | Thermal microvalves in a fluid flow method |
US6057149A (en) * | 1995-09-15 | 2000-05-02 | The University Of Michigan | Microscale devices and reactions in microscale devices |
US20020068357A1 (en) * | 1995-09-28 | 2002-06-06 | Mathies Richard A. | Miniaturized integrated nucleic acid processing and analysis device and method |
US6825047B1 (en) * | 1996-04-03 | 2004-11-30 | Applera Corporation | Device and method for multiple analyte detection |
US7244622B2 (en) * | 1996-04-03 | 2007-07-17 | Applera Corporation | Device and method for multiple analyte detection |
US7235406B1 (en) | 1996-04-03 | 2007-06-26 | Applera Corporation | Nucleic acid analysis device |
US6706875B1 (en) * | 1996-04-17 | 2004-03-16 | Affyemtrix, Inc. | Substrate preparation process |
US6232124B1 (en) | 1996-05-06 | 2001-05-15 | Verification Technologies, Inc. | Automated fingerprint methods and chemistry for product authentication and monitoring |
US6074827A (en) * | 1996-07-30 | 2000-06-13 | Aclara Biosciences, Inc. | Microfluidic method for nucleic acid purification and processing |
CA2301230A1 (en) | 1996-09-20 | 1998-03-26 | Digital Drives, Inc. | Spatially addressable combinatorial chemical arrays in cd-rom format |
DE19648458C1 (en) * | 1996-11-22 | 1998-07-09 | Evotec Biosystems Gmbh | Micromechanical ejection pump for separating the smallest fluid volumes from a flowing sample fluid |
DE19648695C2 (en) * | 1996-11-25 | 1999-07-22 | Abb Patent Gmbh | Device for the automatic and continuous analysis of liquid samples |
DE29724735U1 (en) * | 1996-12-11 | 2003-11-13 | Gesim Ges Fuer Silizium Mikros | Micro-ejection pump - has feed channel found in silicon chip in direction of pump chamber designed at least partly as diffusor element |
CA2281205A1 (en) | 1997-02-12 | 1998-08-13 | Eugene Y. Chan | Methods and products for analyzing polymers |
DE19708472C2 (en) * | 1997-02-20 | 1999-02-18 | Atotech Deutschland Gmbh | Manufacturing process for chemical microreactors |
JP3666604B2 (en) * | 1997-04-16 | 2005-06-29 | アプレラ コーポレーション | Nucleic acid archiving |
US6872527B2 (en) * | 1997-04-16 | 2005-03-29 | Xtrana, Inc. | Nucleic acid archiving |
US6143496A (en) * | 1997-04-17 | 2000-11-07 | Cytonix Corporation | Method of sampling, amplifying and quantifying segment of nucleic acid, polymerase chain reaction assembly having nanoliter-sized sample chambers, and method of filling assembly |
WO1998049344A1 (en) * | 1997-04-28 | 1998-11-05 | Lockheed Martin Energy Research Corporation | Method and apparatus for analyzing nucleic acids |
US6558901B1 (en) * | 1997-05-02 | 2003-05-06 | Biomerieux Vitek | Nucleic acid assays |
IL124275A (en) * | 1997-05-02 | 2002-03-10 | Bio Merieux Vitek Inc | Method for generating nucleic acid sequences |
DE19719862A1 (en) * | 1997-05-12 | 1998-11-19 | Fraunhofer Ges Forschung | Micro diaphragm pump |
US20030013115A1 (en) * | 1997-06-16 | 2003-01-16 | Diversa Corporation, A Delaware Corporation | Capillary array-based sample screening |
GB9715101D0 (en) * | 1997-07-18 | 1997-09-24 | Environmental Sensors Ltd | The production of microstructures for analysis of fluids |
US7214298B2 (en) * | 1997-09-23 | 2007-05-08 | California Institute Of Technology | Microfabricated cell sorter |
US6126804A (en) * | 1997-09-23 | 2000-10-03 | The Regents Of The University Of California | Integrated polymerase chain reaction/electrophoresis instrument |
US6833242B2 (en) * | 1997-09-23 | 2004-12-21 | California Institute Of Technology | Methods for detecting and sorting polynucleotides based on size |
US5993611A (en) * | 1997-09-24 | 1999-11-30 | Sarnoff Corporation | Capacitive denaturation of nucleic acid |
US7473401B1 (en) * | 1997-12-04 | 2009-01-06 | Mds Analytical Technologies (Us) Inc. | Fluidic extraction of microdissected samples |
US8071384B2 (en) | 1997-12-22 | 2011-12-06 | Roche Diagnostics Operations, Inc. | Control and calibration solutions and methods for their use |
AU758407B2 (en) | 1997-12-24 | 2003-03-20 | Cepheid | Integrated fluid manipulation cartridge |
KR20060094541A (en) * | 1998-02-10 | 2006-08-29 | 도요 고한 가부시키가이샤 | Substrates for immobilizing dna |
US6979424B2 (en) | 1998-03-17 | 2005-12-27 | Cepheid | Integrated sample analysis device |
US7188001B2 (en) * | 1998-03-23 | 2007-03-06 | Cepheid | System and method for temperature control |
US6391005B1 (en) * | 1998-03-30 | 2002-05-21 | Agilent Technologies, Inc. | Apparatus and method for penetration with shaft having a sensor for sensing penetration depth |
US6780591B2 (en) | 1998-05-01 | 2004-08-24 | Arizona Board Of Regents | Method of determining the nucleotide sequence of oligonucleotides and DNA molecules |
ATE363339T1 (en) | 1998-05-01 | 2007-06-15 | Gen Probe Inc | STIRRING DEVICE FOR THE FLUID CONTENTS OF A CONTAINER |
US7875440B2 (en) | 1998-05-01 | 2011-01-25 | Arizona Board Of Regents | Method of determining the nucleotide sequence of oligonucleotides and DNA molecules |
US6979728B2 (en) * | 1998-05-04 | 2005-12-27 | Baylor College Of Medicine | Articles of manufacture and methods for array based analysis of biological molecules |
US6761816B1 (en) * | 1998-06-23 | 2004-07-13 | Clinical Micro Systems, Inc. | Printed circuit boards with monolayers and capture ligands |
US6576478B1 (en) * | 1998-07-14 | 2003-06-10 | Zyomyx, Inc. | Microdevices for high-throughput screening of biomolecules |
US6908770B1 (en) * | 1998-07-16 | 2005-06-21 | Board Of Regents, The University Of Texas System | Fluid based analysis of multiple analytes by a sensor array |
US6107038A (en) * | 1998-08-14 | 2000-08-22 | Agilent Technologies Inc. | Method of binding a plurality of chemicals on a substrate by electrophoretic self-assembly |
US6186659B1 (en) * | 1998-08-21 | 2001-02-13 | Agilent Technologies Inc. | Apparatus and method for mixing a film of fluid |
US6572830B1 (en) | 1998-10-09 | 2003-06-03 | Motorola, Inc. | Integrated multilayered microfludic devices and methods for making the same |
US7115422B1 (en) * | 1998-10-23 | 2006-10-03 | Micron Technology, Inc. | Separation apparatus including porous silicon column |
US6762057B1 (en) * | 1998-10-23 | 2004-07-13 | Micron Technology, Inc. | Separation apparatus including porous silicon column |
US6273687B1 (en) * | 1998-11-26 | 2001-08-14 | Aisin Seiki Kabushiki Kaisha | Micromachined pump apparatus |
US7914994B2 (en) | 1998-12-24 | 2011-03-29 | Cepheid | Method for separating an analyte from a sample |
US6261431B1 (en) * | 1998-12-28 | 2001-07-17 | Affymetrix, Inc. | Process for microfabrication of an integrated PCR-CE device and products produced by the same |
US20030180789A1 (en) * | 1998-12-30 | 2003-09-25 | Dale Roderic M.K. | Arrays with modified oligonucleotide and polynucleotide compositions |
US6087112A (en) * | 1998-12-30 | 2000-07-11 | Oligos Etc. Inc. | Arrays with modified oligonucleotide and polynucleotide compositions |
US6056269A (en) * | 1999-01-15 | 2000-05-02 | Hewlett-Packard Company | Microminiature valve having silicon diaphragm |
US6490030B1 (en) | 1999-01-18 | 2002-12-03 | Verification Technologies, Inc. | Portable product authentication device |
US6284195B1 (en) * | 1999-01-25 | 2001-09-04 | Industrial Technology Research Institute | Disposable reaction module |
ATE334197T1 (en) * | 1999-02-19 | 2006-08-15 | Febit Biotech Gmbh | METHOD FOR PRODUCING POLYMERS |
US7150994B2 (en) * | 1999-03-03 | 2006-12-19 | Symyx Technologies, Inc. | Parallel flow process optimization reactor |
US20020042140A1 (en) * | 1999-03-03 | 2002-04-11 | Alfred Hagemeyer | Methods for analysis of heterogeneous catalysts in a multi-variable screening reactor |
EP1159453B1 (en) | 1999-03-10 | 2008-05-28 | ASM Scientific, Inc. | A method for direct nucleic acid sequencing |
ATE399215T1 (en) * | 1999-03-11 | 2008-07-15 | Whatman Inc | SOLID MEDIUM AND METHOD FOR STORAGE AND RAPID PURIFICATION OF NUCLEIC ACIDS |
CN1185492C (en) | 1999-03-15 | 2005-01-19 | 清华大学 | Single-point strobed micro electromagnetic units array chip or electromagnetic biologic chip and application thereof |
TW496775B (en) | 1999-03-15 | 2002-08-01 | Aviva Bioscience Corp | Individually addressable micro-electromagnetic unit array chips |
DE19913451C2 (en) * | 1999-03-25 | 2001-11-22 | Gsf Forschungszentrum Umwelt | Gas inlet for generating a directed and cooled gas jet |
US7250305B2 (en) * | 2001-07-30 | 2007-07-31 | Uab Research Foundation | Use of dye to distinguish salt and protein crystals under microcrystallization conditions |
US20030022383A1 (en) * | 1999-04-06 | 2003-01-30 | Uab Research Foundation | Method for screening crystallization conditions in solution crystal growth |
US7244396B2 (en) * | 1999-04-06 | 2007-07-17 | Uab Research Foundation | Method for preparation of microarrays for screening of crystal growth conditions |
US7247490B2 (en) * | 1999-04-06 | 2007-07-24 | Uab Research Foundation | Method for screening crystallization conditions in solution crystal growth |
ATE357656T1 (en) * | 1999-04-06 | 2007-04-15 | Univ Alabama Res Found | DEVICE FOR SCREENING CRYSTALIZATION CONDITIONS IN CRYSTAL GROWING SOLUTIONS |
US7214540B2 (en) | 1999-04-06 | 2007-05-08 | Uab Research Foundation | Method for screening crystallization conditions in solution crystal growth |
JP4555484B2 (en) * | 1999-04-07 | 2010-09-29 | デニス マイケル コノリー | Method and apparatus for high resolution DNA detection |
US6284465B1 (en) | 1999-04-15 | 2001-09-04 | Agilent Technologies, Inc. | Apparatus, systems and method for locating nucleic acids bound to surfaces |
US20040053290A1 (en) * | 2000-01-11 | 2004-03-18 | Terbrueggen Robert Henry | Devices and methods for biochip multiplexing |
US20020177135A1 (en) * | 1999-07-27 | 2002-11-28 | Doung Hau H. | Devices and methods for biochip multiplexing |
US7312087B2 (en) * | 2000-01-11 | 2007-12-25 | Clinical Micro Sensors, Inc. | Devices and methods for biochip multiplexing |
US6942771B1 (en) * | 1999-04-21 | 2005-09-13 | Clinical Micro Sensors, Inc. | Microfluidic systems in the electrochemical detection of target analytes |
CA2369363A1 (en) * | 1999-04-29 | 2000-11-09 | Marcy Engelstein | Device for rapid dna sample processing with integrated liquid handling, thermocycling, and purification |
US7056661B2 (en) | 1999-05-19 | 2006-06-06 | Cornell Research Foundation, Inc. | Method for sequencing nucleic acid molecules |
US20040200909A1 (en) * | 1999-05-28 | 2004-10-14 | Cepheid | Apparatus and method for cell disruption |
US6635163B1 (en) * | 1999-06-01 | 2003-10-21 | Cornell Research Foundation, Inc. | Entropic trapping and sieving of molecules |
WO2000075377A2 (en) * | 1999-06-03 | 2000-12-14 | Jacques Schrenzel | Non-cognate hybridization system (nchs) |
CA2375197A1 (en) * | 1999-06-08 | 2000-12-14 | Biomicro Systems, Inc. | Laser ablation of doped fluorocarbon materials and applications thereof |
FR2795518B1 (en) * | 1999-06-22 | 2001-12-21 | Biomerieux Sa | DEVICE FOR IMPLEMENTING AN ANALYSIS CARD, ANALYSIS CARD AND METHOD OF IMPLEMENTING THE SAME |
FR2795426A1 (en) * | 1999-06-22 | 2000-12-29 | Commissariat Energie Atomique | Support for genetic analysis comprising reservoir(s) for a medium to be analyzed connected by passage(s) having temperature control device(s) to a test strip with analysis sites having biological probes |
US6200781B1 (en) * | 1999-06-25 | 2001-03-13 | Integrated Genetic Devices, Ltd. | Apparatus, system and method for automated execution and analysis of biological and chemical reactions |
US7144616B1 (en) * | 1999-06-28 | 2006-12-05 | California Institute Of Technology | Microfabricated elastomeric valve and pump systems |
US7217321B2 (en) * | 2001-04-06 | 2007-05-15 | California Institute Of Technology | Microfluidic protein crystallography techniques |
US7501245B2 (en) * | 1999-06-28 | 2009-03-10 | Helicos Biosciences Corp. | Methods and apparatuses for analyzing polynucleotide sequences |
US8709153B2 (en) | 1999-06-28 | 2014-04-29 | California Institute Of Technology | Microfludic protein crystallography techniques |
US6899137B2 (en) * | 1999-06-28 | 2005-05-31 | California Institute Of Technology | Microfabricated elastomeric valve and pump systems |
US6929030B2 (en) * | 1999-06-28 | 2005-08-16 | California Institute Of Technology | Microfabricated elastomeric valve and pump systems |
US7052545B2 (en) * | 2001-04-06 | 2006-05-30 | California Institute Of Technology | High throughput screening of crystallization of materials |
US7306672B2 (en) * | 2001-04-06 | 2007-12-11 | California Institute Of Technology | Microfluidic free interface diffusion techniques |
US8052792B2 (en) * | 2001-04-06 | 2011-11-08 | California Institute Of Technology | Microfluidic protein crystallography techniques |
US7244402B2 (en) * | 2001-04-06 | 2007-07-17 | California Institute Of Technology | Microfluidic protein crystallography |
US7459022B2 (en) * | 2001-04-06 | 2008-12-02 | California Institute Of Technology | Microfluidic protein crystallography |
US8550119B2 (en) * | 1999-06-28 | 2013-10-08 | California Institute Of Technology | Microfabricated elastomeric valve and pump systems |
US20080277007A1 (en) * | 1999-06-28 | 2008-11-13 | California Institute Of Technology | Microfabricated elastomeric valve and pump systems |
CA2721172C (en) * | 1999-06-28 | 2012-04-10 | California Institute Of Technology | Microfabricated elastomeric valve and pump systems |
US7195670B2 (en) * | 2000-06-27 | 2007-03-27 | California Institute Of Technology | High throughput screening of crystallization of materials |
US6818395B1 (en) * | 1999-06-28 | 2004-11-16 | California Institute Of Technology | Methods and apparatus for analyzing polynucleotide sequences |
US6258593B1 (en) * | 1999-06-30 | 2001-07-10 | Agilent Technologies Inc. | Apparatus for conducting chemical or biochemical reactions on a solid surface within an enclosed chamber |
ATE264718T1 (en) * | 1999-07-02 | 2004-05-15 | Clondiag Chip Tech Gmbh | MICROCHIP MATRIX DEVICE FOR THE DUPLICATION AND CHARACTERIZATION OF NUCLEIC ACIDS |
AU5785400A (en) | 1999-07-02 | 2001-01-22 | Symyx Technologies, Inc. | Polymer brushes for immobilizing molecules to a surface or substrate, where the polymers have water-soluble or water-dispersible segments and probes bonded thereto |
US6533914B1 (en) | 1999-07-08 | 2003-03-18 | Shaorong Liu | Microfabricated injector and capillary array assembly for high-resolution and high throughput separation |
US6395232B1 (en) * | 1999-07-09 | 2002-05-28 | Orchid Biosciences, Inc. | Fluid delivery system for a microfluidic device using a pressure pulse |
EP1204859B1 (en) | 1999-07-16 | 2006-11-22 | The Board Of Regents, The University Of Texas System | Method and apparatus for the delivery of samples to a chemical sensor array |
US6660147B1 (en) * | 1999-07-16 | 2003-12-09 | Applera Corporation | High density electrophoresis device and method |
US20050118618A1 (en) * | 1999-08-30 | 2005-06-02 | Dale Roderic M. | Method for detecting nucleic acid sequences |
EP1080785A1 (en) * | 1999-09-04 | 2001-03-07 | F. Hoffmann-La Roche Ag | System for thermocycling of fluids in cartridges |
US6623945B1 (en) | 1999-09-16 | 2003-09-23 | Motorola, Inc. | System and method for microwave cell lysing of small samples |
US6844151B1 (en) | 1999-09-29 | 2005-01-18 | Oligos Etc. Inc. | Methods for production of arrays with modified oligonucleotide and polynucleotide compositions |
GB9922971D0 (en) * | 1999-09-29 | 1999-12-01 | Secr Defence | Reaction system |
US6291180B1 (en) * | 1999-09-29 | 2001-09-18 | American Registry Of Pathology | Ultrasound-mediated high-speed biological reaction and tissue processing |
WO2001026813A2 (en) * | 1999-10-08 | 2001-04-19 | Micronics, Inc. | Microfluidics without electrically of mechanically operated pumps |
US7115423B1 (en) | 1999-10-22 | 2006-10-03 | Agilent Technologies, Inc. | Fluidic structures within an array package |
DE19952723C2 (en) * | 1999-10-26 | 2002-10-31 | Epigenomics Ag | Device and method for hybridizing double-stranded DNA samples on oligomer arrays |
AU1438701A (en) * | 1999-10-27 | 2001-05-08 | Caliper Technologies Corporation | Pressure induced reagent introduction and electrophoretic separation |
US6512580B1 (en) | 1999-10-27 | 2003-01-28 | Verification Technologies, Inc. | Method and apparatus for portable product authentication |
US6958225B2 (en) | 1999-10-27 | 2005-10-25 | Affymetrix, Inc. | Complexity management of genomic DNA |
US6867851B2 (en) * | 1999-11-04 | 2005-03-15 | Regents Of The University Of Minnesota | Scanning of biological samples |
US6784982B1 (en) | 1999-11-04 | 2004-08-31 | Regents Of The University Of Minnesota | Direct mapping of DNA chips to detector arrays |
US6406604B1 (en) * | 1999-11-08 | 2002-06-18 | Norberto A. Guzman | Multi-dimensional electrophoresis apparatus |
US7329388B2 (en) * | 1999-11-08 | 2008-02-12 | Princeton Biochemicals, Inc. | Electrophoresis apparatus having staggered passage configuration |
US6692952B1 (en) * | 1999-11-10 | 2004-02-17 | Massachusetts Institute Of Technology | Cell analysis and sorting apparatus for manipulation of cells |
US6875619B2 (en) * | 1999-11-12 | 2005-04-05 | Motorola, Inc. | Microfluidic devices comprising biochannels |
US6589778B1 (en) | 1999-12-15 | 2003-07-08 | Amersham Biosciences Ab | Method and apparatus for performing biological reactions on a substrate surface |
US6361958B1 (en) * | 1999-11-12 | 2002-03-26 | Motorola, Inc. | Biochannel assay for hybridization with biomaterial |
US6642046B1 (en) * | 1999-12-09 | 2003-11-04 | Motorola, Inc. | Method and apparatus for performing biological reactions on a substrate surface |
CA2290731A1 (en) * | 1999-11-26 | 2001-05-26 | D. Jed Harrison | Apparatus and method for trapping bead based reagents within microfluidic analysis system |
US6432290B1 (en) | 1999-11-26 | 2002-08-13 | The Governors Of The University Of Alberta | Apparatus and method for trapping bead based reagents within microfluidic analysis systems |
US20020119079A1 (en) * | 1999-12-10 | 2002-08-29 | Norbert Breuer | Chemical microreactor and microreactor made by process |
US6878517B1 (en) * | 1999-12-15 | 2005-04-12 | Congra Grocery Products Company | Multispecies food testing and characterization organoleptic properties |
ATE445713T1 (en) * | 1999-12-17 | 2009-10-15 | Bio Merieux | METHOD FOR LABELING A RIBONUCLEIC ACID, AND MARKED RNA FRAGMENTS OBTAINED THEREFROM |
US20030091477A1 (en) * | 1999-12-22 | 2003-05-15 | Paul Eric A. | Flow-thru chip cartridge, chip holder, system & method thereof |
US6612737B1 (en) * | 1999-12-29 | 2003-09-02 | Affymetrix, Inc. | System and method for self-calibrating measurement |
FR2803225B1 (en) * | 1999-12-29 | 2002-06-14 | Biomerieux Sa | ANALYZING APPARATUS WITH VARIABLE GEOMETRY REACTIONAL COMPARTMENT, LIQUID MIXING AND GUIDING METHOD |
US6500620B2 (en) | 1999-12-29 | 2002-12-31 | Mergen Ltd. | Methods for amplifying and detecting multiple polynucleotides on a solid phase support |
AU2788101A (en) * | 2000-01-11 | 2001-07-24 | Maxygen, Inc. | Integrated systems and methods for diversity generation and screening |
US6587579B1 (en) | 2000-01-26 | 2003-07-01 | Agilent Technologies Inc. | Feature quality in array fabrication |
US6458526B1 (en) | 2000-01-28 | 2002-10-01 | Agilent Technologies, Inc. | Method and apparatus to inhibit bubble formation in a fluid |
CA2398107C (en) * | 2000-01-28 | 2013-11-19 | Althea Technologies, Inc. | Methods for analysis of gene expression |
WO2001055702A1 (en) * | 2000-01-31 | 2001-08-02 | Board Of Regents, The University Of Texas System | Portable sensor array system |
WO2001056691A2 (en) * | 2000-02-03 | 2001-08-09 | Deutsches Krebsforschungszentrum Stiftung des öffentlichen Rechts | Method and device for the synthesis and the analysis of support-bound arrays of oligomers, especially of primer pairs for pcr, as well as oligomer-carrying supports |
EP1123739B1 (en) * | 2000-02-11 | 2006-11-29 | STMicroelectronics S.r.l. | Integrated device for microfluid thermoregulation, and manufacturing process thereof |
DE10006214A1 (en) * | 2000-02-11 | 2001-08-16 | Roche Diagnostics Gmbh | System for simple nucleic acid analysis |
US20030017467A1 (en) * | 2000-02-18 | 2003-01-23 | Aclara Biosciences, Inc. | Multiple-site sample-handling apparatus and method |
EP1898210A3 (en) * | 2000-02-23 | 2008-06-25 | Caliper Life Sciences, Inc. | Multi-reservoir pressure control system |
US7230315B2 (en) * | 2000-02-29 | 2007-06-12 | Stmicroelectronics S.R.L. | Integrated chemical microreactor with large area channels and manufacturing process thereof |
US7452713B2 (en) * | 2000-02-29 | 2008-11-18 | Stmicroelectronics S.R.L. | Process for manufacturing a microfluidic device with buried channels |
US7732192B2 (en) * | 2000-02-29 | 2010-06-08 | Stmicroelectronics S.R.L. | Integrated chemical microreactor with large area channels and manufacturing process thereof |
AU2001240040A1 (en) * | 2000-03-03 | 2001-09-17 | California Institute Of Technology | Combinatorial array for nucleic acid analysis |
WO2001066245A2 (en) | 2000-03-07 | 2001-09-13 | Symyx Technologies, Inc. | Parallel flow process optimization reactor |
JP3871846B2 (en) * | 2000-03-10 | 2007-01-24 | 日立ソフトウエアエンジニアリング株式会社 | Hybridization reaction detection method and detection apparatus |
US7485454B1 (en) * | 2000-03-10 | 2009-02-03 | Bioprocessors Corp. | Microreactor |
WO2001069226A1 (en) * | 2000-03-10 | 2001-09-20 | Dna Sciences, Inc. | Cross channel device for serial sample injection |
US20010031495A1 (en) * | 2000-03-13 | 2001-10-18 | Hideji Tajima | Integrated support, integrated minute vessels and permeable membrane and method of making and using same |
US6376191B1 (en) | 2000-03-22 | 2002-04-23 | Mergen, Ltd. | Microarray-based analysis of polynucleotide sequence variations |
US6358387B1 (en) * | 2000-03-27 | 2002-03-19 | Caliper Technologies Corporation | Ultra high throughput microfluidic analytical systems and methods |
US6884578B2 (en) | 2000-03-31 | 2005-04-26 | Affymetrix, Inc. | Genes differentially expressed in secretory versus proliferative endometrium |
US20050118073A1 (en) * | 2003-11-26 | 2005-06-02 | Fluidigm Corporation | Devices and methods for holding microfluidic devices |
US7867763B2 (en) | 2004-01-25 | 2011-01-11 | Fluidigm Corporation | Integrated chip carriers with thermocycler interfaces and methods of using the same |
CA2406707A1 (en) * | 2000-04-06 | 2001-10-18 | Robert Nagle | Microfluidic devices and systems incorporating cover layers |
US6290909B1 (en) * | 2000-04-13 | 2001-09-18 | Sandia Corporation | Sample injector for high pressure liquid chromatography |
US6561208B1 (en) | 2000-04-14 | 2003-05-13 | Nanostream, Inc. | Fluidic impedances in microfluidic system |
US6481453B1 (en) | 2000-04-14 | 2002-11-19 | Nanostream, Inc. | Microfluidic branch metering systems and methods |
US20040000787A1 (en) * | 2000-04-24 | 2004-01-01 | Rakesh Vig | Authentication mark for a product or product package |
US20030112423A1 (en) * | 2000-04-24 | 2003-06-19 | Rakesh Vig | On-line verification of an authentication mark applied to products or product packaging |
CA2406402A1 (en) * | 2000-04-25 | 2001-11-01 | Affymetrix, Inc. | Methods for monitoring the expression of alternatively spliced genes |
AU2001259241A1 (en) * | 2000-04-26 | 2001-11-07 | Arcturus Engineering, Inc. | Laser capture microdissection (lcm) extraction device and device carrier and method for post-lcm fluid processing |
IL152634A0 (en) * | 2000-05-04 | 2003-06-24 | Univ Yale | High density protein arrays for screening of protein activity |
AU2001259770A1 (en) | 2000-05-15 | 2001-11-26 | Biomicro Systems, Inc. | Air flow regulation in microfluidic circuits for pressure control and gaseous exchange |
WO2001089696A2 (en) * | 2000-05-24 | 2001-11-29 | Micronics, Inc. | Microfluidic concentration gradient loop |
EP1161985B1 (en) * | 2000-06-05 | 2005-10-26 | STMicroelectronics S.r.l. | Process for manufacturing integrated chemical microreactors of semiconductor material, and integrated microreactor |
US6875247B2 (en) * | 2000-06-06 | 2005-04-05 | Battelle Memorial Institute | Conditions for fluid separations in microchannels, capillary-driven fluid separations, and laminated devices capable of separating fluids |
US6455007B1 (en) * | 2000-06-13 | 2002-09-24 | Symyx Technologies, Inc. | Apparatus and method for testing compositions in contact with a porous medium |
EP1164201A1 (en) * | 2000-06-14 | 2001-12-19 | Facultés Universitaires Notre-Dame de la Paix | Reverse detection for identification and/or quantification of nucleotide target sequences on biochips |
EP1311346A4 (en) * | 2000-06-19 | 2003-07-30 | Caliper Techn Corp | Methods and devices for enhancing bonded substrate yields and regulating temperature |
US6829753B2 (en) * | 2000-06-27 | 2004-12-07 | Fluidigm Corporation | Microfluidic design automation method and system |
WO2002002301A1 (en) | 2000-06-30 | 2002-01-10 | Verification Technologies Inc. | Copy-protected optical media and method of manufacture thereof |
US6638593B2 (en) * | 2000-06-30 | 2003-10-28 | Verification Technologies, Inc. | Copy-protected optical media and method of manufacture thereof |
US7124944B2 (en) * | 2000-06-30 | 2006-10-24 | Verification Technologies, Inc. | Product packaging including digital data |
US20070172866A1 (en) * | 2000-07-07 | 2007-07-26 | Susan Hardin | Methods for sequence determination using depolymerizing agent |
MXPA02002500A (en) * | 2000-07-07 | 2004-09-10 | Baxter Int | Medical system, method and apparatus employing mems. |
CN101525660A (en) * | 2000-07-07 | 2009-09-09 | 维西根生物技术公司 | An instant sequencing methodology |
US7126688B2 (en) * | 2000-07-11 | 2006-10-24 | Maven Technologies, Llc | Microarray scanning |
US6833920B2 (en) * | 2000-07-11 | 2004-12-21 | Maven Technologies Llc | Apparatus and method for imaging |
US7023547B2 (en) | 2000-07-11 | 2006-04-04 | Maven Technologies, Llc | Apparatus including a biochip for imaging of biological samples and method |
US7193711B2 (en) * | 2000-07-11 | 2007-03-20 | Maven Technologies, Llc | Imaging method and apparatus |
US7518724B2 (en) * | 2000-07-11 | 2009-04-14 | Maven Technologies | Image acquisition, processing, and display |
US6594011B1 (en) | 2000-07-11 | 2003-07-15 | Maven Technologies, Llc | Imaging apparatus and method |
US20070119711A1 (en) * | 2000-08-02 | 2007-05-31 | Caliper Life Sciences, Inc. | High throughput separations based analysis systems and methods |
US7660415B2 (en) * | 2000-08-03 | 2010-02-09 | Selinfreund Richard H | Method and apparatus for controlling access to storage media |
JP2004506189A (en) * | 2000-08-04 | 2004-02-26 | カリパー・テクノロジーズ・コープ. | Control of operating conditions in fluid systems |
US6615856B2 (en) | 2000-08-04 | 2003-09-09 | Biomicro Systems, Inc. | Remote valving for microfluidic flow control |
US20020142618A1 (en) * | 2000-08-04 | 2002-10-03 | Caliper Technologies Corp. | Control of operation conditions within fluidic systems |
AU2001281076A1 (en) * | 2000-08-07 | 2002-02-18 | Nanostream, Inc. | Fluidic mixer in microfluidic system |
US6890093B2 (en) * | 2000-08-07 | 2005-05-10 | Nanostream, Inc. | Multi-stream microfludic mixers |
IL154596A0 (en) | 2000-08-25 | 2003-09-17 | Basf Plant Science Gmbh | Plant polynucleotides encoding novel prenyl proteases |
US8048386B2 (en) | 2002-02-25 | 2011-11-01 | Cepheid | Fluid processing and control |
US6374684B1 (en) | 2000-08-25 | 2002-04-23 | Cepheid | Fluid control and processing system |
FR2813207B1 (en) * | 2000-08-28 | 2002-10-11 | Bio Merieux | REACTIONAL CARD AND USE OF SUCH A CARD |
US7108969B1 (en) | 2000-09-08 | 2006-09-19 | Affymetrix, Inc. | Methods for detecting and diagnosing oral cancer |
US20020031836A1 (en) * | 2000-09-11 | 2002-03-14 | Feldstein Mark J. | Fluidics system |
GB2368809B (en) * | 2000-09-15 | 2004-09-29 | Norchip As | Microfabricated reaction chamber system |
EP1334347A1 (en) | 2000-09-15 | 2003-08-13 | California Institute Of Technology | Microfabricated crossflow devices and methods |
EP2333543B1 (en) | 2000-09-26 | 2018-01-10 | Health Research, Incorporated | Analysis of hiv-1 coreceptor use in the clinical care of hiv-1 infected patients |
DE60032772T2 (en) * | 2000-09-27 | 2007-11-08 | Stmicroelectronics S.R.L., Agrate Brianza | Integrated chemical microreactor with thermally insulated measuring electrodes and method for its production |
CN100495030C (en) * | 2000-09-30 | 2009-06-03 | 清华大学 | Multi-force operator and use thereof |
US7678547B2 (en) * | 2000-10-03 | 2010-03-16 | California Institute Of Technology | Velocity independent analyte characterization |
US7097809B2 (en) * | 2000-10-03 | 2006-08-29 | California Institute Of Technology | Combinatorial synthesis system |
US7258774B2 (en) * | 2000-10-03 | 2007-08-21 | California Institute Of Technology | Microfluidic devices and methods of use |
AU1189702A (en) * | 2000-10-13 | 2002-04-22 | Fluidigm Corp | Microfluidic device based sample injection system for analytical devices |
EP1203945B1 (en) * | 2000-10-26 | 2006-12-20 | Agilent Technologies, Inc. (a Delaware corporation) | Microarray |
WO2002065005A1 (en) * | 2000-11-06 | 2002-08-22 | California Institute Of Technology | Electrostatic valves for microfluidic devices |
EP1334279A1 (en) | 2000-11-06 | 2003-08-13 | Nanostream, Inc. | Uni-directional flow microfluidic components |
EP1410044A2 (en) * | 2000-11-08 | 2004-04-21 | Burstein Technologies, Inc. | Interactive system for analyzing biological samples and processing related information and the use thereof |
GB0027300D0 (en) * | 2000-11-08 | 2000-12-27 | Hybaid Ltd | Chip hybridisation unit |
ATE441110T1 (en) * | 2000-11-09 | 2009-09-15 | Sicel Technologies Inc | IN-VIVO DETECTION OF BIOMOLECULE CONCENTRATIONS USING FLUORESCENCE MARKERS |
US20020150887A1 (en) * | 2000-11-09 | 2002-10-17 | National Institute Of Advanced Industrial Science And Technology | Methods and nucleic acid probes for molecular genetic analysis of polluted environments and environmental samples |
US6653124B1 (en) * | 2000-11-10 | 2003-11-25 | Cytoplex Biosciences Inc. | Array-based microenvironment for cell culturing, cell monitoring and drug-target validation |
AU2002248149A1 (en) * | 2000-11-16 | 2002-08-12 | Fluidigm Corporation | Microfluidic devices for introducing and dispensing fluids from microfluidic systems |
US7087203B2 (en) * | 2000-11-17 | 2006-08-08 | Nagaoka & Co., Ltd. | Methods and apparatus for blood typing with optical bio-disc |
US8641644B2 (en) | 2000-11-21 | 2014-02-04 | Sanofi-Aventis Deutschland Gmbh | Blood testing apparatus having a rotatable cartridge with multiple lancing elements and testing means |
US6521188B1 (en) * | 2000-11-22 | 2003-02-18 | Industrial Technology Research Institute | Microfluidic actuator |
GB0028647D0 (en) * | 2000-11-24 | 2001-01-10 | Nextgen Sciences Ltd | Apparatus for chemical assays |
WO2002044425A2 (en) | 2000-12-01 | 2002-06-06 | Visigen Biotechnologies, Inc. | Enzymatic nucleic acid synthesis: compositions and methods for altering monomer incorporation fidelity |
WO2002046761A2 (en) * | 2000-12-08 | 2002-06-13 | Burstein Technologies, Inc. | Methods for detecting analytes using optical discs and optical disc readers |
US6760298B2 (en) * | 2000-12-08 | 2004-07-06 | Nagaoka & Co., Ltd. | Multiple data layer optical discs for detecting analytes |
JP2002236131A (en) * | 2000-12-08 | 2002-08-23 | Minolta Co Ltd | Microchip |
US20020072111A1 (en) * | 2000-12-13 | 2002-06-13 | Clarkin James P. | Drawn microchannel array devices and method of analysis using same |
US20020123134A1 (en) * | 2000-12-26 | 2002-09-05 | Mingxian Huang | Active and biocompatible platforms prepared by polymerization of surface coating films |
DE60015590T2 (en) * | 2000-12-28 | 2005-11-10 | Roche Diagnostics Gmbh | A method of treating nucleic acid samples by vibration of a portion of a cartridge wall, system and cartridge for performing the same |
US7205161B2 (en) * | 2001-01-10 | 2007-04-17 | Symyx Technologies, Inc. | Polymer brushes for immobilizing molecules to a surface or substrate having improved stability |
US20020108860A1 (en) * | 2001-01-15 | 2002-08-15 | Staats Sau Lan Tang | Fabrication of polymeric microfluidic devices |
JP4505776B2 (en) * | 2001-01-19 | 2010-07-21 | 凸版印刷株式会社 | Gene detection system, gene detection apparatus equipped with the same, detection method, and gene detection chip |
US6878755B2 (en) * | 2001-01-22 | 2005-04-12 | Microgen Systems, Inc. | Automated microfabrication-based biodetector |
US20020098122A1 (en) * | 2001-01-22 | 2002-07-25 | Angad Singh | Active disposable microfluidic system with externally actuated micropump |
JP2004529323A (en) * | 2001-01-31 | 2004-09-24 | ボード・オブ・リージエンツ,ザ・ユニバーシテイ・オブ・テキサス・システム | Method and apparatus for confining material in a micromachined chemical sensor array |
US20030003436A1 (en) * | 2001-02-05 | 2003-01-02 | Willson C. Grant | Use of mesoscale self-assembly and recognition to effect delivery of sensing reagent for arrayed sensors |
WO2002064612A2 (en) | 2001-02-09 | 2002-08-22 | Human Genome Sciences, Inc. | Human g-protein chemokine receptor (ccr5) hdgnr10 |
US6692700B2 (en) | 2001-02-14 | 2004-02-17 | Handylab, Inc. | Heat-reduction methods and systems related to microfluidic devices |
US6913697B2 (en) | 2001-02-14 | 2005-07-05 | Science & Technology Corporation @ Unm | Nanostructured separation and analysis devices for biological membranes |
US20030027135A1 (en) * | 2001-03-02 | 2003-02-06 | Ecker David J. | Method for rapid detection and identification of bioagents |
WO2004060278A2 (en) | 2002-12-06 | 2004-07-22 | Isis Pharmaceuticals, Inc. | Methods for rapid identification of pathogens in humans and animals |
US20040121313A1 (en) | 2002-12-06 | 2004-06-24 | Ecker David J. | Methods for rapid detection and identification of bioagents in organs for transplantation |
US7666588B2 (en) | 2001-03-02 | 2010-02-23 | Ibis Biosciences, Inc. | Methods for rapid forensic analysis of mitochondrial DNA and characterization of mitochondrial DNA heteroplasmy |
US7226739B2 (en) | 2001-03-02 | 2007-06-05 | Isis Pharmaceuticals, Inc | Methods for rapid detection and identification of bioagents in epidemiological and forensic investigations |
US7718354B2 (en) | 2001-03-02 | 2010-05-18 | Ibis Biosciences, Inc. | Methods for rapid identification of pathogens in humans and animals |
US20050196785A1 (en) * | 2001-03-05 | 2005-09-08 | California Institute Of Technology | Combinational array for nucleic acid analysis |
US7118917B2 (en) * | 2001-03-07 | 2006-10-10 | Symyx Technologies, Inc. | Parallel flow reactor having improved thermal control |
US7244232B2 (en) * | 2001-03-07 | 2007-07-17 | Biomed Solutions, Llc | Process for identifying cancerous and/or metastatic cells of a living organism |
US20030060695A1 (en) * | 2001-03-07 | 2003-03-27 | Connelly Patrick R. | Implantable artificial organ devices |
JP4148778B2 (en) * | 2001-03-09 | 2008-09-10 | バイオミクロ システムズ インコーポレイティッド | Microfluidic interface equipment with arrays |
CA2440754A1 (en) * | 2001-03-12 | 2002-09-19 | Stephen Quake | Methods and apparatus for analyzing polynucleotide sequences by asynchronous base extension |
US7316769B2 (en) * | 2001-03-19 | 2008-01-08 | Cornell Research Foundation, Inc. | Length-dependent recoil separation of long molecules |
US7829025B2 (en) | 2001-03-28 | 2010-11-09 | Venture Lending & Leasing Iv, Inc. | Systems and methods for thermal actuation of microfluidic devices |
US6575188B2 (en) | 2001-07-26 | 2003-06-10 | Handylab, Inc. | Methods and systems for fluid control in microfluidic devices |
US8895311B1 (en) | 2001-03-28 | 2014-11-25 | Handylab, Inc. | Methods and systems for control of general purpose microfluidic devices |
US7323140B2 (en) * | 2001-03-28 | 2008-01-29 | Handylab, Inc. | Moving microdroplets in a microfluidic device |
US7192557B2 (en) * | 2001-03-28 | 2007-03-20 | Handylab, Inc. | Methods and systems for releasing intracellular material from cells within microfluidic samples of fluids |
US7270786B2 (en) | 2001-03-28 | 2007-09-18 | Handylab, Inc. | Methods and systems for processing microfluidic samples of particle containing fluids |
US7010391B2 (en) * | 2001-03-28 | 2006-03-07 | Handylab, Inc. | Methods and systems for control of microfluidic devices |
US6852287B2 (en) | 2001-09-12 | 2005-02-08 | Handylab, Inc. | Microfluidic devices having a reduced number of input and output connections |
CA2442978A1 (en) * | 2001-04-04 | 2002-10-17 | Bioprocessors Corp. | System and method for dispensing liquids |
US7670429B2 (en) | 2001-04-05 | 2010-03-02 | The California Institute Of Technology | High throughput screening of crystallization of materials |
US6752922B2 (en) * | 2001-04-06 | 2004-06-22 | Fluidigm Corporation | Microfluidic chromatography |
US20020164816A1 (en) * | 2001-04-06 | 2002-11-07 | California Institute Of Technology | Microfluidic sample separation device |
DE60239328D1 (en) | 2001-04-06 | 2011-04-14 | Fluidigm Corp | POLYMER SURFACE MODIFICATION |
JP2004527247A (en) * | 2001-04-10 | 2004-09-09 | バイオプロセッサーズ コーポレイション | Microfermentor devices and cell-based screening methods |
US20040132166A1 (en) * | 2001-04-10 | 2004-07-08 | Bioprocessors Corp. | Determination and/or control of reactor environmental conditions |
US20040058437A1 (en) * | 2001-04-10 | 2004-03-25 | Rodgers Seth T. | Materials and reactor systems having humidity and gas control |
US20040058407A1 (en) * | 2001-04-10 | 2004-03-25 | Miller Scott E. | Reactor systems having a light-interacting component |
US20050032204A1 (en) * | 2001-04-10 | 2005-02-10 | Bioprocessors Corp. | Microreactor architecture and methods |
US6418968B1 (en) | 2001-04-20 | 2002-07-16 | Nanostream, Inc. | Porous microfluidic valves |
US6727479B2 (en) * | 2001-04-23 | 2004-04-27 | Stmicroelectronics S.R.L. | Integrated device based upon semiconductor technology, in particular chemical microreactor |
KR100438821B1 (en) * | 2001-04-23 | 2004-07-05 | 삼성전자주식회사 | Miniature gene analytical device using multichannel PCR and electrophoresis |
US6645737B2 (en) * | 2001-04-24 | 2003-11-11 | Dade Microscan Inc. | Method for maintaining test accuracy within a microbiological test array |
GB0110476D0 (en) | 2001-04-30 | 2001-06-20 | Secr Defence | Reagent delivery system |
WO2004010099A2 (en) * | 2001-05-16 | 2004-01-29 | Burstein Technologies, Inc. | Variable sampling for rendering pixelization of analysis results in optical bio-disc assembly |
US20050009101A1 (en) * | 2001-05-17 | 2005-01-13 | Motorola, Inc. | Microfluidic devices comprising biochannels |
WO2002095002A2 (en) | 2001-05-22 | 2002-11-28 | University Of Chicago | N4 virion single-stranded dna dependent rna polymerase |
US7294478B1 (en) | 2001-06-06 | 2007-11-13 | Rosetta Inpharmatics Llc | Microarray reaction cartridge |
US6729352B2 (en) | 2001-06-07 | 2004-05-04 | Nanostream, Inc. | Microfluidic synthesis devices and methods |
US6919046B2 (en) * | 2001-06-07 | 2005-07-19 | Nanostream, Inc. | Microfluidic analytical devices and methods |
US6880576B2 (en) * | 2001-06-07 | 2005-04-19 | Nanostream, Inc. | Microfluidic devices for methods development |
US20030009294A1 (en) * | 2001-06-07 | 2003-01-09 | Jill Cheng | Integrated system for gene expression analysis |
US6811695B2 (en) * | 2001-06-07 | 2004-11-02 | Nanostream, Inc. | Microfluidic filter |
US7318912B2 (en) * | 2001-06-07 | 2008-01-15 | Nanostream, Inc. | Microfluidic systems and methods for combining discrete fluid volumes |
US20020186263A1 (en) * | 2001-06-07 | 2002-12-12 | Nanostream, Inc. | Microfluidic fraction collectors |
US20020187564A1 (en) * | 2001-06-08 | 2002-12-12 | Caliper Technologies Corp. | Microfluidic library analysis |
EP1401854A2 (en) * | 2001-06-12 | 2004-03-31 | The Board of Regents of the University of Texas System | Methods of detecting, diagnosing and treating cancer and identifying neoplastic progression |
US7025774B2 (en) | 2001-06-12 | 2006-04-11 | Pelikan Technologies, Inc. | Tissue penetration device |
US9226699B2 (en) * | 2002-04-19 | 2016-01-05 | Sanofi-Aventis Deutschland Gmbh | Body fluid sampling module with a continuous compression tissue interface surface |
DE60234598D1 (en) * | 2001-06-12 | 2010-01-14 | Pelikan Technologies Inc | SELF-OPTIMIZING LANZET DEVICE WITH ADAPTANT FOR TEMPORAL FLUCTUATIONS OF SKIN PROPERTIES |
US7749174B2 (en) | 2001-06-12 | 2010-07-06 | Pelikan Technologies, Inc. | Method and apparatus for lancet launching device intergrated onto a blood-sampling cartridge |
ATE485766T1 (en) * | 2001-06-12 | 2010-11-15 | Pelikan Technologies Inc | ELECTRICAL ACTUATING ELEMENT FOR A LANCET |
US8337419B2 (en) * | 2002-04-19 | 2012-12-25 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
US9795747B2 (en) | 2010-06-02 | 2017-10-24 | Sanofi-Aventis Deutschland Gmbh | Methods and apparatus for lancet actuation |
US7981056B2 (en) | 2002-04-19 | 2011-07-19 | Pelikan Technologies, Inc. | Methods and apparatus for lancet actuation |
US9427532B2 (en) | 2001-06-12 | 2016-08-30 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
US7179423B2 (en) | 2001-06-20 | 2007-02-20 | Cytonome, Inc. | Microfluidic system including a virtual wall fluid interface port for interfacing fluids with the microfluidic system |
US20030015425A1 (en) * | 2001-06-20 | 2003-01-23 | Coventor Inc. | Microfluidic system including a virtual wall fluid interface port for interfacing fluids with the microfluidic system |
US7211442B2 (en) * | 2001-06-20 | 2007-05-01 | Cytonome, Inc. | Microfluidic system including a virtual wall fluid interface port for interfacing fluids with the microfluidic system |
US7217510B2 (en) * | 2001-06-26 | 2007-05-15 | Isis Pharmaceuticals, Inc. | Methods for providing bacterial bioagent characterizing information |
US8073627B2 (en) * | 2001-06-26 | 2011-12-06 | Ibis Biosciences, Inc. | System for indentification of pathogens |
US20050149304A1 (en) * | 2001-06-27 | 2005-07-07 | Fluidigm Corporation | Object oriented microfluidic design method and system |
US20030026705A1 (en) * | 2001-06-27 | 2003-02-06 | Tosoh Corporation | Method for transporting liquid, and microreactor |
US6662091B2 (en) * | 2001-06-29 | 2003-12-09 | Battelle Memorial Institute | Diagnostics/prognostics using wireless links |
US6485918B1 (en) | 2001-07-02 | 2002-11-26 | Packard Bioscience Corporation | Method and apparatus for incubation of a liquid reagent and target spots on a microarray substrate |
CA2452376A1 (en) | 2001-07-02 | 2003-01-16 | Battelle Memorial Institute | Intelligent microsensor module |
US7077152B2 (en) * | 2001-07-07 | 2006-07-18 | Nanostream, Inc. | Microfluidic metering systems and methods |
US7668697B2 (en) * | 2006-02-06 | 2010-02-23 | Andrei Volkov | Method for analyzing dynamic detectable events at the single molecule level |
EP1277438A1 (en) * | 2001-07-10 | 2003-01-22 | Agilent Technologies, Inc. (a Delaware corporation) | System for point of care diagnosis and/or analysis |
US6825127B2 (en) | 2001-07-24 | 2004-11-30 | Zarlink Semiconductor Inc. | Micro-fluidic devices |
WO2003012406A1 (en) * | 2001-07-26 | 2003-02-13 | Handylab, Inc. | Methods and systems for microfluidic processing |
US20030064507A1 (en) * | 2001-07-26 | 2003-04-03 | Sean Gallagher | System and methods for mixing within a microfluidic device |
EP1423506A4 (en) * | 2001-08-06 | 2008-08-06 | Univ Vanderbilt | An apparatus and methods for using biological material to discriminate an agent |
WO2003016547A2 (en) * | 2001-08-13 | 2003-02-27 | Vanderbilt University | Distribution of solutions across a surface |
AU2002335656A1 (en) * | 2001-08-23 | 2003-03-10 | Aclara Biosciences, Inc. | Multiple-site sample-handling apparatus and method |
US6995841B2 (en) * | 2001-08-28 | 2006-02-07 | Rice University | Pulsed-multiline excitation for color-blind fluorescence detection |
US7075162B2 (en) * | 2001-08-30 | 2006-07-11 | Fluidigm Corporation | Electrostatic/electrostrictive actuation of elastomer structures using compliant electrodes |
US20050032060A1 (en) * | 2001-08-31 | 2005-02-10 | Shishir Shah | Arrays comprising pre-labeled biological molecules and methods for making and using these arrays |
US20030059823A1 (en) * | 2001-09-21 | 2003-03-27 | Juki Corporation | Hybridization apparatus and method for detecting nucleic acid in sample using the same |
FR2829948B1 (en) * | 2001-09-21 | 2004-07-09 | Commissariat Energie Atomique | METHOD FOR MOVING A FLUID OF INTEREST INTO A CAPILLARY AND FLUIDIC MICROSYSTEM |
US20030108664A1 (en) * | 2001-10-05 | 2003-06-12 | Kodas Toivo T. | Methods and compositions for the formation of recessed electrical features on a substrate |
DE10149684B4 (en) * | 2001-10-09 | 2005-02-17 | Clondiag Chip Technologies Gmbh | Device for holding a substance library carrier |
US7192629B2 (en) | 2001-10-11 | 2007-03-20 | California Institute Of Technology | Devices utilizing self-assembled gel and method of manufacture |
US20030087289A1 (en) * | 2001-10-12 | 2003-05-08 | Harry Zuzan | Image analysis of high-density synthetic DNA microarrays |
US7439346B2 (en) * | 2001-10-12 | 2008-10-21 | Perkinelmer Las Inc. | Nucleic acids arrays and methods of use therefor |
AU2002334772A1 (en) * | 2001-10-12 | 2003-04-28 | Duke University | Methods for image analysis of high-density synthetic dna microarrays |
JP2005519634A (en) | 2001-10-12 | 2005-07-07 | スペクトラル ジェノミクス、インク. | Nucleic acid compositions and arrays and methods using them |
US20030073089A1 (en) * | 2001-10-16 | 2003-04-17 | Mauze Ganapati R. | Companion cartridge for disposable diagnostic sensing platforms |
US20060134683A1 (en) * | 2001-10-23 | 2006-06-22 | Michael Sogard | Methods and devices for hybridization and binding assays using thermophoresis |
US7244611B2 (en) * | 2001-10-23 | 2007-07-17 | Nikon Research Corporation Of America | Methods and devices for hybridization and binding assays using thermophoresis |
US20030138969A1 (en) * | 2002-01-24 | 2003-07-24 | Jakobsen Mogens Havsteen | Closed substrate platforms suitable for analysis of biomolecules |
US8440093B1 (en) | 2001-10-26 | 2013-05-14 | Fuidigm Corporation | Methods and devices for electronic and magnetic sensing of the contents of microfluidic flow channels |
US20030175947A1 (en) * | 2001-11-05 | 2003-09-18 | Liu Robin Hui | Enhanced mixing in microfluidic devices |
US20030086333A1 (en) * | 2001-11-05 | 2003-05-08 | Constantinos Tsouris | Electrohydrodynamic mixing on microfabricated devices |
EP1451373A4 (en) * | 2001-11-06 | 2005-01-19 | Integrated Nano Tech Llc | System for detecting biological materials in a sample |
US20040028559A1 (en) * | 2001-11-06 | 2004-02-12 | Peter Schuck | Sample delivery system with laminar mixing for microvolume biosensing |
KR100438828B1 (en) * | 2001-11-08 | 2004-07-05 | 삼성전자주식회사 | Micro-electrical detector on-chip |
KR100442836B1 (en) * | 2001-11-10 | 2004-08-02 | 삼성전자주식회사 | System and method for circulating biochemical fluidic solutions around closed two or more temperature zones of chambers |
US20030098271A1 (en) * | 2001-11-26 | 2003-05-29 | Ralph Somack | Capsule and tray systems for combined sample collection, archiving, purification, and PCR |
EP1453758A2 (en) * | 2001-12-06 | 2004-09-08 | Nanostream, Inc. | Adhesiveless microfluidic device fabrication |
EP1317960A1 (en) * | 2001-12-06 | 2003-06-11 | PamGene B.V. | System and method for analyzing a blood sample and disposable cartridge for use in this system or method |
JP2003248008A (en) * | 2001-12-18 | 2003-09-05 | Inst Of Physical & Chemical Res | Method of stirring reaction liquid |
US6739576B2 (en) | 2001-12-20 | 2004-05-25 | Nanostream, Inc. | Microfluidic flow control device with floating element |
KR100408871B1 (en) * | 2001-12-20 | 2003-12-11 | 삼성전자주식회사 | Method of separation or filtration by carbon nanotube in biochip |
US7192560B2 (en) * | 2001-12-20 | 2007-03-20 | 3M Innovative Properties Company | Methods and devices for removal of organic molecules from biological mixtures using anion exchange |
US7347976B2 (en) * | 2001-12-20 | 2008-03-25 | 3M Innovative Properties Company | Methods and devices for removal of organic molecules from biological mixtures using a hydrophilic solid support in a hydrophobic matrix |
US7258839B2 (en) * | 2001-12-21 | 2007-08-21 | Cytonome, Inc. | Temperature controlled microfabricated two-pin liquid sample dispensing system |
WO2003060157A2 (en) * | 2001-12-28 | 2003-07-24 | Norchip As | Fluid manipulation in a microfabricated reaction chamber system |
GB2383546B (en) * | 2001-12-28 | 2006-03-01 | Norchip As | Fluid manipulation in a microfabricated reaction chamber system |
US6889468B2 (en) * | 2001-12-28 | 2005-05-10 | 3M Innovative Properties Company | Modular systems and methods for using sample processing devices |
US6877892B2 (en) * | 2002-01-11 | 2005-04-12 | Nanostream, Inc. | Multi-stream microfluidic aperture mixers |
DE10201463B4 (en) | 2002-01-16 | 2005-07-21 | Clondiag Chip Technologies Gmbh | Reaction vessel for performing array method |
FR2835058B1 (en) * | 2002-01-21 | 2004-03-12 | Centre Nat Rech Scient | METHOD FOR DETECTING AT LEAST ONE CHARACTERISTIC PARAMETER OF PROBE MOLECULES FIXED ON AT LEAST ONE ACTIVE ZONE OF A SENSOR |
WO2003066191A1 (en) * | 2002-02-04 | 2003-08-14 | Colorado School Of Mines | Laminar flow-based separations of colloidal and cellular particles |
US6864058B2 (en) * | 2002-02-06 | 2005-03-08 | Baylor College Of Medicine | Vaccinia topoisomerases I-based assays for detection of specific DNA breaks |
US20050084645A1 (en) * | 2002-02-07 | 2005-04-21 | Selinfreund Richard H. | Method and system for optical disc copy-protection |
US20040109793A1 (en) * | 2002-02-07 | 2004-06-10 | Mcneely Michael R | Three-dimensional microfluidics incorporating passive fluid control structures |
US8271202B1 (en) | 2002-02-11 | 2012-09-18 | Fernandez Dennis S | Modified host bio-data management |
US20030152934A1 (en) * | 2002-02-11 | 2003-08-14 | Industrial Technology Research Institute | High performance nucleic acid hybridization device and process |
US6814859B2 (en) * | 2002-02-13 | 2004-11-09 | Nanostream, Inc. | Frit material and bonding method for microfluidic separation devices |
JP3892743B2 (en) * | 2002-03-01 | 2007-03-14 | 日本碍子株式会社 | Reaction cell and method of use thereof |
US6819027B2 (en) * | 2002-03-04 | 2004-11-16 | Cepheid | Method and apparatus for controlling ultrasonic transducer |
KR100459896B1 (en) * | 2002-03-06 | 2004-12-04 | 삼성전자주식회사 | Thermostatic control Method and apparatus for Driving a PCR(polymerize chain reaction) chip |
US20030170637A1 (en) * | 2002-03-06 | 2003-09-11 | Pirrung Michael C. | Method of analyzing mRNA splice variants |
US20030203384A1 (en) * | 2002-03-08 | 2003-10-30 | Chafin David R. | Multiplex detection of biological materials in a sample |
US6869462B2 (en) * | 2002-03-11 | 2005-03-22 | Battelle Memorial Institute | Methods of contacting substances and microsystem contactors |
AU2003265228A1 (en) * | 2002-03-12 | 2003-12-22 | Surface Logix, Inc. | Assay device that analyzes the absorption, metabolism, permeability and/or toxicity of a candidate compound |
US6916621B2 (en) * | 2002-03-27 | 2005-07-12 | Spectral Genomics, Inc. | Methods for array-based comparitive binding assays |
US7312085B2 (en) * | 2002-04-01 | 2007-12-25 | Fluidigm Corporation | Microfluidic particle-analysis systems |
US20050026134A1 (en) * | 2002-04-10 | 2005-02-03 | Bioprocessors Corp. | Systems and methods for control of pH and other reactor environment conditions |
US6976590B2 (en) * | 2002-06-24 | 2005-12-20 | Cytonome, Inc. | Method and apparatus for sorting particles |
US6808075B2 (en) * | 2002-04-17 | 2004-10-26 | Cytonome, Inc. | Method and apparatus for sorting particles |
US20030198962A1 (en) * | 2002-04-18 | 2003-10-23 | Yung-Chiang Chung | Method and apparatus for nucleic acid hybridization |
US8267870B2 (en) * | 2002-04-19 | 2012-09-18 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for body fluid sampling with hybrid actuation |
US7674232B2 (en) | 2002-04-19 | 2010-03-09 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US20070142748A1 (en) * | 2002-04-19 | 2007-06-21 | Ajay Deshmukh | Tissue penetration device |
US7226461B2 (en) | 2002-04-19 | 2007-06-05 | Pelikan Technologies, Inc. | Method and apparatus for a multi-use body fluid sampling device with sterility barrier release |
US7331931B2 (en) * | 2002-04-19 | 2008-02-19 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US7892183B2 (en) * | 2002-04-19 | 2011-02-22 | Pelikan Technologies, Inc. | Method and apparatus for body fluid sampling and analyte sensing |
CA2481411C (en) | 2002-04-19 | 2016-06-14 | Diversa Corporation | Phospholipases, nucleic acids encoding them and methods for making and using them |
US8702624B2 (en) * | 2006-09-29 | 2014-04-22 | Sanofi-Aventis Deutschland Gmbh | Analyte measurement device with a single shot actuator |
US7892185B2 (en) * | 2002-04-19 | 2011-02-22 | Pelikan Technologies, Inc. | Method and apparatus for body fluid sampling and analyte sensing |
US7909778B2 (en) | 2002-04-19 | 2011-03-22 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US8579831B2 (en) | 2002-04-19 | 2013-11-12 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
US7648468B2 (en) * | 2002-04-19 | 2010-01-19 | Pelikon Technologies, Inc. | Method and apparatus for penetrating tissue |
US8221334B2 (en) * | 2002-04-19 | 2012-07-17 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
US9795334B2 (en) * | 2002-04-19 | 2017-10-24 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
US9314194B2 (en) * | 2002-04-19 | 2016-04-19 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
US7901362B2 (en) * | 2002-04-19 | 2011-03-08 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US7226771B2 (en) | 2002-04-19 | 2007-06-05 | Diversa Corporation | Phospholipases, nucleic acids encoding them and methods for making and using them |
US7547287B2 (en) * | 2002-04-19 | 2009-06-16 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US7976476B2 (en) | 2002-04-19 | 2011-07-12 | Pelikan Technologies, Inc. | Device and method for variable speed lancet |
US8784335B2 (en) | 2002-04-19 | 2014-07-22 | Sanofi-Aventis Deutschland Gmbh | Body fluid sampling device with a capacitive sensor |
US7232451B2 (en) * | 2002-04-19 | 2007-06-19 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US7229458B2 (en) | 2002-04-19 | 2007-06-12 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US7175642B2 (en) * | 2002-04-19 | 2007-02-13 | Pelikan Technologies, Inc. | Methods and apparatus for lancet actuation |
US9248267B2 (en) | 2002-04-19 | 2016-02-02 | Sanofi-Aventis Deustchland Gmbh | Tissue penetration device |
US7491178B2 (en) | 2002-04-19 | 2009-02-17 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
US8360992B2 (en) * | 2002-04-19 | 2013-01-29 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for penetrating tissue |
US7297122B2 (en) * | 2002-04-19 | 2007-11-20 | Pelikan Technologies, Inc. | Method and apparatus for penetrating tissue |
AU2003228711C1 (en) | 2002-04-26 | 2010-01-07 | Board Of Regents, The University Of Texas System | Method and system for the detection of cardiac risk factors |
JPWO2003093835A1 (en) * | 2002-04-30 | 2005-09-08 | アークレイ株式会社 | Temperature control method for analysis tool and analyzer with temperature control function |
US7399449B1 (en) * | 2002-05-14 | 2008-07-15 | Sandia Corporation | Microfabricated diffusion source |
US20030217923A1 (en) * | 2002-05-24 | 2003-11-27 | Harrison D. Jed | Apparatus and method for trapping bead based reagents within microfluidic analysis systems |
WO2003102142A2 (en) * | 2002-05-29 | 2003-12-11 | Henry M. Jackson Foundation For The Advancement Of Military Medicine Inc. | Arrays identifying genomic and proteomic biomarkers for cystic fibrosis |
US20070026528A1 (en) * | 2002-05-30 | 2007-02-01 | Delucas Lawrence J | Method for screening crystallization conditions in solution crystal growth |
US20030224371A1 (en) * | 2002-06-04 | 2003-12-04 | Thomas Bradley S. | Integrated cartridge for sample manipulation |
US20050106714A1 (en) * | 2002-06-05 | 2005-05-19 | Zarur Andrey J. | Rotatable reactor systems and methods |
WO2004001376A2 (en) * | 2002-06-20 | 2003-12-31 | Sention, Inc. | Apparatus for polynucleotide detection and quantitation |
US6780320B2 (en) * | 2002-06-20 | 2004-08-24 | The Regents Of The University Of California | Magnetohydrodynamic fluidic system |
US20060086309A1 (en) * | 2002-06-24 | 2006-04-27 | Fluiding Corporation | Recirculating fluidic network and methods for using the same |
FR2841158B1 (en) * | 2002-06-24 | 2007-02-23 | Bio Merieux | THERMO-PNEUMATICALLY FLEXIBLE FLUID DEVICE ISOLATION AND POSSIBLY AGITATION OF THE CONTENT OF AN OPERATIVE CAVITY |
US7517656B2 (en) * | 2002-07-30 | 2009-04-14 | Trex Enterprises Corp. | Optical sensor and methods for measuring molecular binding interactions |
US20040005247A1 (en) * | 2002-07-03 | 2004-01-08 | Nanostream, Inc. | Microfluidic closed-end metering systems and methods |
US20040007672A1 (en) * | 2002-07-10 | 2004-01-15 | Delucas Lawrence J. | Method for distinguishing between biomolecule and non-biomolecule crystals |
EP1525055A1 (en) * | 2002-07-12 | 2005-04-27 | British Biocell International Limited | Lateral flow assay device and method |
AU2003254093A1 (en) * | 2002-07-19 | 2004-02-09 | Isis Pharmaceuticals, Inc. | Methods for mass spectrometry analysis utilizing an integrated microfluidics sample platform |
US20040011650A1 (en) * | 2002-07-22 | 2004-01-22 | Frederic Zenhausern | Method and apparatus for manipulating polarizable analytes via dielectrophoresis |
JP2005533502A (en) * | 2002-07-24 | 2005-11-10 | ボード オブ レジェンツ,ザ ユニバーシティー オブ テキサス システム | Microbial capture and detection by membrane method |
US20040023397A1 (en) * | 2002-08-05 | 2004-02-05 | Rakesh Vig | Tamper-resistant authentication mark for use in product or product packaging authentication |
JP2004069498A (en) * | 2002-08-06 | 2004-03-04 | Canon Inc | Liquid conveying device and method |
DE10241093A1 (en) * | 2002-09-02 | 2004-03-18 | Siemens Ag | microreactor |
US7094345B2 (en) * | 2002-09-09 | 2006-08-22 | Cytonome, Inc. | Implementation of microfluidic components, including molecular fractionation devices, in a microfluidic system |
US7455770B2 (en) * | 2002-09-09 | 2008-11-25 | Cytonome, Inc. | Implementation of microfluidic components in a microfluidic system |
US6878271B2 (en) * | 2002-09-09 | 2005-04-12 | Cytonome, Inc. | Implementation of microfluidic components in a microfluidic system |
US7279134B2 (en) * | 2002-09-17 | 2007-10-09 | Intel Corporation | Microfluidic devices with porous membranes for molecular sieving, metering, and separations |
ITTO20020808A1 (en) * | 2002-09-17 | 2004-03-18 | St Microelectronics Srl | INTEGRATED DNA ANALYSIS DEVICE. |
ITTO20020809A1 (en) * | 2002-09-17 | 2004-03-18 | St Microelectronics Srl | MICROPUMP, IN PARTICULAR FOR AN INTEGRATED DNA ANALYSIS DEVICE. |
US8220494B2 (en) * | 2002-09-25 | 2012-07-17 | California Institute Of Technology | Microfluidic large scale integration |
CA2497645A1 (en) * | 2002-09-26 | 2004-04-08 | Verification Technologies, Inc. | Authentication of items using transient optical state change materials |
TW590982B (en) * | 2002-09-27 | 2004-06-11 | Agnitio Science & Technology I | Micro-fluid driving device |
ES2375724T3 (en) * | 2002-09-27 | 2012-03-05 | The General Hospital Corporation | MICROFLUDE DEVICE FOR SEPERATION OF CELLS AND ITS USES. |
US20050003369A1 (en) * | 2002-10-10 | 2005-01-06 | Affymetrix, Inc. | Method for depleting specific nucleic acids from a mixture |
US9740817B1 (en) | 2002-10-18 | 2017-08-22 | Dennis Sunga Fernandez | Apparatus for biological sensing and alerting of pharmaco-genomic mutation |
US7932098B2 (en) * | 2002-10-31 | 2011-04-26 | Hewlett-Packard Development Company, L.P. | Microfluidic system utilizing thin-film layers to route fluid |
US20040086872A1 (en) * | 2002-10-31 | 2004-05-06 | Childers Winthrop D. | Microfluidic system for analysis of nucleic acids |
US7010964B2 (en) * | 2002-10-31 | 2006-03-14 | Nanostream, Inc. | Pressurized microfluidic devices with optical detection regions |
JP2004184138A (en) * | 2002-11-29 | 2004-07-02 | Nec Corp | Separator, separation method, and mass spectrometric analysis system |
US20040259111A1 (en) * | 2002-12-10 | 2004-12-23 | Rosetta Inpharmatics Llc | Automated system and method for preparing an assay ready biological sample |
EP1570091B1 (en) * | 2002-12-11 | 2012-02-08 | Centre National De La Recherche Scientifique (Cnrs) | Method for electronically detecting at least one specific interaction between probe molecules and target biomolecules |
EP1578286A4 (en) * | 2002-12-13 | 2009-01-14 | Pelikan Technologies Inc | Method and apparatus for measuring analytes |
US8574895B2 (en) | 2002-12-30 | 2013-11-05 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus using optical techniques to measure analyte levels |
US7445926B2 (en) * | 2002-12-30 | 2008-11-04 | The Regents Of The University Of California | Fluid control structures in microfluidic devices |
US20060133957A1 (en) * | 2003-01-17 | 2006-06-22 | Knapp Merrill A | Device and method for fragmenting material by hydrodynamic shear |
AU2004206250B8 (en) * | 2003-01-21 | 2009-09-17 | Bristol-Myers Squibb Company | Polynucleotide encoding a novel acyl coenzyme a, monoacylglycerol acyltransferase-3 (MGAT3), and uses thereof |
FR2850323A1 (en) * | 2003-01-23 | 2004-07-30 | Neopost Ind | SEPARATOR DEVICE FOR FEEDING MACHINE FEEDER |
US20090186343A1 (en) * | 2003-01-28 | 2009-07-23 | Visigen Biotechnologies, Inc. | Methods for preparing modified biomolecules, modified biomolecules and methods for using same |
US7147955B2 (en) | 2003-01-31 | 2006-12-12 | Societe Bic | Fuel cartridge for fuel cells |
US20050048573A1 (en) * | 2003-02-03 | 2005-03-03 | Plexxikon, Inc. | PDE5A crystal structure and uses |
US20040157343A1 (en) * | 2003-02-06 | 2004-08-12 | Applera Corporation | Devices and methods for biological sample preparation |
US20060203700A1 (en) * | 2003-02-06 | 2006-09-14 | Verification Technologies, Inc. | Method and system for optical disk copy-protection |
EP1604184A4 (en) * | 2003-02-27 | 2010-10-27 | Stephen A Lesko | Standardized evaluation of therapeutic efficacy based on cellular biomarkers |
US20050170431A1 (en) * | 2003-02-28 | 2005-08-04 | Plexxikon, Inc. | PYK2 crystal structure and uses |
CN104388449A (en) | 2003-03-06 | 2015-03-04 | 维莱尼姆公司 | Amylases, nucleic acids encoding them and methods for making and using them |
CA2889013C (en) | 2003-03-07 | 2018-07-17 | Dsm Ip Assets B.V. | Hydrolases, nucleic acids encoding them and methods for making and using them |
US20040179972A1 (en) * | 2003-03-14 | 2004-09-16 | Nanostream, Inc. | Systems and methods for detecting manufacturing defects in microfluidic devices |
US7041481B2 (en) | 2003-03-14 | 2006-05-09 | The Regents Of The University Of California | Chemical amplification based on fluid partitioning |
EP1473085B1 (en) * | 2003-03-31 | 2015-07-22 | Canon Kabushiki Kaisha | Biochemical reaction cartridge |
US20040223874A1 (en) | 2003-03-31 | 2004-11-11 | Canon Kabushiki Kaisha | Biochemical reaction cartridge |
US7666361B2 (en) * | 2003-04-03 | 2010-02-23 | Fluidigm Corporation | Microfluidic devices and methods of using same |
MXPA05010681A (en) | 2003-04-04 | 2005-12-15 | Diversa Corp | Pectate lyases, nucleic acids encoding them and methods for making and using them. |
US20030157503A1 (en) * | 2003-04-04 | 2003-08-21 | Mcgarry Mark W | Compositions and methods for performing biological reactions |
US7178386B1 (en) | 2003-04-10 | 2007-02-20 | Nanostream, Inc. | Parallel fluid processing systems and methods |
WO2004094020A2 (en) * | 2003-04-17 | 2004-11-04 | Fluidigm Corporation | Crystal growth devices and systems, and methods for using same |
US7981600B2 (en) * | 2003-04-17 | 2011-07-19 | 3M Innovative Properties Company | Methods and devices for removal of organic molecules from biological mixtures using an anion exchange material that includes a polyoxyalkylene |
DE10318139B4 (en) * | 2003-04-18 | 2005-02-17 | PRO DESIGN Gesellschaft für Produktentwicklung mbH | Self-configurable biochip |
US8046171B2 (en) * | 2003-04-18 | 2011-10-25 | Ibis Biosciences, Inc. | Methods and apparatus for genetic evaluation |
DE10319045A1 (en) * | 2003-04-25 | 2004-12-09 | november Aktiengesellschaft Gesellschaft für Molekulare Medizin | Device and method for processing liquids containing biopolymers |
WO2004097371A2 (en) * | 2003-04-25 | 2004-11-11 | Board Of Regents, The University Of Texas System | System and method for the detection of analytes |
US8057993B2 (en) | 2003-04-26 | 2011-11-15 | Ibis Biosciences, Inc. | Methods for identification of coronaviruses |
EP1620021A4 (en) * | 2003-05-02 | 2008-06-18 | Pelikan Technologies Inc | Method and apparatus for a tissue penetrating device user interface |
US7074327B2 (en) * | 2003-05-08 | 2006-07-11 | Nanostream, Inc. | Sample preparation for parallel chromatography |
US6948143B2 (en) * | 2003-05-09 | 2005-09-20 | Synopsys, Inc. | Constrained optimization with linear constraints to remove overlap among cells of an integrated circuit |
US7964343B2 (en) * | 2003-05-13 | 2011-06-21 | Ibis Biosciences, Inc. | Method for rapid purification of nucleic acids for subsequent analysis by mass spectrometry by solution capture |
US8158354B2 (en) | 2003-05-13 | 2012-04-17 | Ibis Biosciences, Inc. | Methods for rapid purification of nucleic acids for subsequent analysis by mass spectrometry by solution capture |
US7651850B2 (en) * | 2003-05-16 | 2010-01-26 | Board Of Regents, The University Of Texas System | Image and part recognition technology |
US9317922B2 (en) | 2003-05-16 | 2016-04-19 | Board Of Regents The University Of Texas System | Image and part recognition technology |
CA2526368A1 (en) * | 2003-05-20 | 2004-12-02 | Fluidigm Corporation | Method and system for microfluidic device and imaging thereof |
US7435391B2 (en) * | 2003-05-23 | 2008-10-14 | Lucent Technologies Inc. | Light-mediated micro-chemical reactors |
KR100706464B1 (en) * | 2003-05-30 | 2007-04-10 | 애플라 코포레이션 | Apparatus and method for hybridization and spr detection |
EP1628567B1 (en) | 2003-05-30 | 2010-08-04 | Pelikan Technologies Inc. | Method and apparatus for fluid injection |
EP1628748A2 (en) * | 2003-06-05 | 2006-03-01 | Bioprocessors Corporation | Reactor with memory component |
DK1633235T3 (en) * | 2003-06-06 | 2014-08-18 | Sanofi Aventis Deutschland | Apparatus for sampling body fluid and detecting analyte |
US20040248323A1 (en) | 2003-06-09 | 2004-12-09 | Protometrix, Inc. | Methods for conducting assays for enzyme activity on protein microarrays |
US20050170367A1 (en) * | 2003-06-10 | 2005-08-04 | Quake Stephen R. | Fluorescently labeled nucleoside triphosphates and analogs thereof for sequencing nucleic acids |
WO2006001797A1 (en) | 2004-06-14 | 2006-01-05 | Pelikan Technologies, Inc. | Low pain penetrating |
WO2005006939A2 (en) * | 2003-06-11 | 2005-01-27 | Pelikan Technologies, Inc. | Method and apparatus for body fluid sampling and analyte sensing |
AU2004250131A1 (en) * | 2003-06-13 | 2004-12-29 | The General Hospital Corporation | Microfluidic systems for size based removal of red blood cells and platelets from blood |
US7452457B2 (en) | 2003-06-20 | 2008-11-18 | Roche Diagnostics Operations, Inc. | System and method for analyte measurement using dose sufficiency electrodes |
US7718439B2 (en) | 2003-06-20 | 2010-05-18 | Roche Diagnostics Operations, Inc. | System and method for coding information on a biosensor test strip |
US8058077B2 (en) | 2003-06-20 | 2011-11-15 | Roche Diagnostics Operations, Inc. | Method for coding information on a biosensor test strip |
US7645373B2 (en) | 2003-06-20 | 2010-01-12 | Roche Diagnostic Operations, Inc. | System and method for coding information on a biosensor test strip |
US7488601B2 (en) | 2003-06-20 | 2009-02-10 | Roche Diagnostic Operations, Inc. | System and method for determining an abused sensor during analyte measurement |
US7601545B2 (en) * | 2003-06-20 | 2009-10-13 | Groton Biosystems, Llc | Automated macromolecule sample preparation system |
US8206565B2 (en) | 2003-06-20 | 2012-06-26 | Roche Diagnostics Operation, Inc. | System and method for coding information on a biosensor test strip |
US7645421B2 (en) | 2003-06-20 | 2010-01-12 | Roche Diagnostics Operations, Inc. | System and method for coding information on a biosensor test strip |
US8148164B2 (en) | 2003-06-20 | 2012-04-03 | Roche Diagnostics Operations, Inc. | System and method for determining the concentration of an analyte in a sample fluid |
US20050064465A1 (en) * | 2003-07-02 | 2005-03-24 | Caliper Life Sciences, Inc. | Continuous and non-continuous flow bioreactor |
CN108486086A (en) | 2003-07-02 | 2018-09-04 | 维莱尼姆公司 | Dextranase, encode they nucleic acid and preparation and use their method |
US20050079548A1 (en) * | 2003-07-07 | 2005-04-14 | Plexxikon, Inc. | Ligand development using PDE4B crystal structures |
US7504070B2 (en) * | 2003-07-11 | 2009-03-17 | Ngk Insulators, Ltd. | Micro reactor |
JPWO2005005043A1 (en) * | 2003-07-11 | 2007-09-20 | 日本碍子株式会社 | Microreactor |
ATE531817T1 (en) * | 2003-07-15 | 2011-11-15 | Lukas Bestmann | SAMPLE PREPARATION UNIT |
JP4067463B2 (en) * | 2003-07-18 | 2008-03-26 | トヨタ自動車株式会社 | Control device for hybrid vehicle |
SG145697A1 (en) * | 2003-07-28 | 2008-09-29 | Fluidigm Corp | Image processing method and system for microfluidic devices |
US7335984B2 (en) * | 2003-07-31 | 2008-02-26 | Agency For Science, Technology And Research | Microfluidics chips and methods of using same |
US7731906B2 (en) | 2003-07-31 | 2010-06-08 | Handylab, Inc. | Processing particle-containing samples |
US20050033133A1 (en) * | 2003-08-06 | 2005-02-10 | Clifford Kraft | Implantable chip medical diagnostic device for bodily fluids |
US20050032238A1 (en) * | 2003-08-07 | 2005-02-10 | Nanostream, Inc. | Vented microfluidic separation devices and methods |
WO2005021714A2 (en) | 2003-08-11 | 2005-03-10 | Diversa Corporation | Laccases, nucleic acids encoding them and methods for making and using them |
US7413712B2 (en) * | 2003-08-11 | 2008-08-19 | California Institute Of Technology | Microfluidic rotary flow reactor matrix |
US7111466B2 (en) * | 2003-08-21 | 2006-09-26 | Yamaha Corporation | Microreactor and substance production method therewith |
US8346482B2 (en) * | 2003-08-22 | 2013-01-01 | Fernandez Dennis S | Integrated biosensor and simulation system for diagnosis and therapy |
US20050069895A1 (en) * | 2003-08-29 | 2005-03-31 | Applera Corporation | Compositions, methods, and kits for fabricating coded molecular tags |
US7198900B2 (en) * | 2003-08-29 | 2007-04-03 | Applera Corporation | Multiplex detection compositions, methods, and kits |
US20050048498A1 (en) * | 2003-08-29 | 2005-03-03 | Applera Corporation | Compositions, methods, and kits for assembling probes |
WO2005024043A2 (en) | 2003-09-03 | 2005-03-17 | Government Of The United States Of America, As Represented By Secretary, Department Of Health And Human Services | Methods for identifying, diagnosing, and predicting survival of lymphomas |
US8131475B2 (en) | 2003-09-03 | 2012-03-06 | The United States Of America As Represented By The Secretary, Department Of Health And Human Services | Methods for identifying, diagnosing, and predicting survival of lymphomas |
US20120122096A1 (en) | 2003-09-11 | 2012-05-17 | Rangarajan Sampath | Compositions for use in identification of bacteria |
US20060240412A1 (en) * | 2003-09-11 | 2006-10-26 | Hall Thomas A | Compositions for use in identification of adenoviruses |
US8546082B2 (en) | 2003-09-11 | 2013-10-01 | Ibis Biosciences, Inc. | Methods for identification of sepsis-causing bacteria |
US20080138808A1 (en) * | 2003-09-11 | 2008-06-12 | Hall Thomas A | Methods for identification of sepsis-causing bacteria |
US8097416B2 (en) | 2003-09-11 | 2012-01-17 | Ibis Biosciences, Inc. | Methods for identification of sepsis-causing bacteria |
US20100035239A1 (en) * | 2003-09-11 | 2010-02-11 | Isis Pharmaceuticals, Inc. | Compositions for use in identification of bacteria |
US20050164300A1 (en) * | 2003-09-15 | 2005-07-28 | Plexxikon, Inc. | Molecular scaffolds for kinase ligand development |
WO2005031163A1 (en) * | 2003-09-25 | 2005-04-07 | Cytonome, Inc. | Implementation of microfluidic components in a microfluidic system |
US8282576B2 (en) | 2003-09-29 | 2012-10-09 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for an improved sample capture device |
US20050074784A1 (en) * | 2003-10-07 | 2005-04-07 | Tuan Vo-Dinh | Integrated biochip with continuous sampling and processing (CSP) system |
EP1680014A4 (en) * | 2003-10-14 | 2009-01-21 | Pelikan Technologies Inc | Method and apparatus for a variable user interface |
US7032605B1 (en) | 2003-10-15 | 2006-04-25 | Douglas B. Dority | Dual piston rotary valve |
JP2007515947A (en) * | 2003-10-30 | 2007-06-21 | タフツ−ニュー イングランド メディカル センター | Prenatal diagnosis using acellular fetal DNA in amniotic fluid |
US20050287668A1 (en) * | 2003-11-04 | 2005-12-29 | Cell Therapeutics, Inc. (Cti) | RNA interference compositions and screening methods for the identification of novel genes and biological pathways |
WO2005047881A2 (en) * | 2003-11-05 | 2005-05-26 | Exact Sciences Corporation | Repetitive reversed-field affinity electrophoresis and uses therefor |
CA2563310A1 (en) * | 2003-11-07 | 2005-05-26 | Princeton Biochemicals, Inc. | Multi-dimensional electrophoresis apparatus |
US8030092B2 (en) * | 2003-11-07 | 2011-10-04 | Princeton Biochemicals, Inc. | Controlled electrophoresis method |
US7169560B2 (en) | 2003-11-12 | 2007-01-30 | Helicos Biosciences Corporation | Short cycle methods for sequencing polynucleotides |
DE10353985A1 (en) * | 2003-11-19 | 2005-06-23 | Olympus Biosystems Gmbh | Apparatus for manipulation and analysis of micro-objects, useful particularly for cells or their components, is constructed as a fluidics microsystem and/or microchip |
US7238521B2 (en) * | 2003-11-24 | 2007-07-03 | Biocept, Inc. | Microarray hybridization device having bubble-fracturing elements |
EP1535665A1 (en) * | 2003-11-28 | 2005-06-01 | STMicroelectronics S.r.l. | Integrated chemical microreactor with separated channels for confining liquids inside the channels and manufacturing process thereof |
WO2005054441A2 (en) * | 2003-12-01 | 2005-06-16 | California Institute Of Technology | Device for immobilizing chemical and biomedical species and methods of using same |
US8163895B2 (en) | 2003-12-05 | 2012-04-24 | Ibis Biosciences, Inc. | Compositions for use in identification of orthopoxviruses |
US7651868B2 (en) * | 2003-12-11 | 2010-01-26 | The Board Of Regents Of The University Of Texas System | Method and system for the analysis of saliva using a sensor array |
US20050130177A1 (en) | 2003-12-12 | 2005-06-16 | 3M Innovative Properties Company | Variable valve apparatus and methods |
EP1541991A1 (en) * | 2003-12-12 | 2005-06-15 | STMicroelectronics S.r.l. | Integrated semiconductor chemical microreactor for real-time monitoring of biological reactions |
US7322254B2 (en) * | 2003-12-12 | 2008-01-29 | 3M Innovative Properties Company | Variable valve apparatus and methods |
US20070066641A1 (en) * | 2003-12-19 | 2007-03-22 | Prabha Ibrahim | Compounds and methods for development of RET modulators |
PL1696920T3 (en) * | 2003-12-19 | 2015-03-31 | Plexxikon Inc | Compounds and methods for development of ret modulators |
EP1547688A1 (en) * | 2003-12-23 | 2005-06-29 | STMicroelectronics S.r.l. | Microfluidic device and method of locally concentrating electrically charged substances in a microfluidic device |
US20050161327A1 (en) * | 2003-12-23 | 2005-07-28 | Michele Palmieri | Microfluidic device and method for transporting electrically charged substances through a microchannel of a microfluidic device |
US20050142570A1 (en) * | 2003-12-24 | 2005-06-30 | 3M Innovative Properties Company | Methods for nucleic acid isolation and kits using a microfluidic device and sedimenting reagent |
US7939249B2 (en) * | 2003-12-24 | 2011-05-10 | 3M Innovative Properties Company | Methods for nucleic acid isolation and kits using a microfluidic device and concentration step |
US20050142571A1 (en) * | 2003-12-24 | 2005-06-30 | 3M Innovative Properties Company | Methods for nucleic acid isolation and kits using solid phase material |
US7822454B1 (en) * | 2005-01-03 | 2010-10-26 | Pelikan Technologies, Inc. | Fluid sampling device with improved analyte detecting member configuration |
EP1706026B1 (en) | 2003-12-31 | 2017-03-01 | Sanofi-Aventis Deutschland GmbH | Method and apparatus for improving fluidic flow and sample capture |
JP4246642B2 (en) * | 2004-01-15 | 2009-04-02 | 株式会社日立プラントテクノロジー | Microfluidic system |
US7407799B2 (en) * | 2004-01-16 | 2008-08-05 | California Institute Of Technology | Microfluidic chemostat |
US20050164373A1 (en) * | 2004-01-22 | 2005-07-28 | Oldham Mark F. | Diffusion-aided loading system for microfluidic devices |
WO2005072353A2 (en) * | 2004-01-25 | 2005-08-11 | Fluidigm Corporation | Crystal forming devices and systems and methods for making and using the same |
US8030057B2 (en) | 2004-01-26 | 2011-10-04 | President And Fellows Of Harvard College | Fluid delivery system and method |
PL1776181T3 (en) | 2004-01-26 | 2014-03-31 | Harvard College | Fluid delivery system and method |
US20050170401A1 (en) * | 2004-01-29 | 2005-08-04 | Canon Kabushiki Kaisha | Hybridization apparatus and method |
US20050176135A1 (en) * | 2004-02-06 | 2005-08-11 | Brian Jones | Cassette for isolation, amplification and identification of DNA or protein and method of use |
EP1713926B1 (en) | 2004-02-06 | 2012-08-01 | Bayer HealthCare, LLC | Oxidizable species as an internal reference for biosensors and method of use |
JP4464158B2 (en) * | 2004-02-13 | 2010-05-19 | キヤノン株式会社 | Biochemical reaction cartridge |
US7666592B2 (en) | 2004-02-18 | 2010-02-23 | Ibis Biosciences, Inc. | Methods for concurrent identification and quantification of an unknown bioagent |
EP2248911A1 (en) | 2004-02-19 | 2010-11-10 | Helicos Biosciences Corporation | Methods and kits for analyzing polynucleotide sequences |
US7618811B2 (en) * | 2004-02-24 | 2009-11-17 | Thermal Gradient | Thermal cycling device |
US8043849B2 (en) * | 2004-02-24 | 2011-10-25 | Thermal Gradient | Thermal cycling device |
US20060257941A1 (en) * | 2004-02-27 | 2006-11-16 | Mcdevitt John T | Integration of fluids and reagents into self-contained cartridges containing particle and membrane sensor elements |
US20060257854A1 (en) * | 2004-02-27 | 2006-11-16 | Mcdevitt John T | Membrane assay system including preloaded particles |
US20060046258A1 (en) * | 2004-02-27 | 2006-03-02 | Lapidus Stanley N | Applications of single molecule sequencing |
US7781226B2 (en) * | 2004-02-27 | 2010-08-24 | The Board Of Regents Of The University Of Texas System | Particle on membrane assay system |
US8105849B2 (en) * | 2004-02-27 | 2012-01-31 | Board Of Regents, The University Of Texas System | Integration of fluids and reagents into self-contained cartridges containing sensor elements |
US20060257991A1 (en) * | 2004-02-27 | 2006-11-16 | Mcdevitt John T | Integration of fluids and reagents into self-contained cartridges containing particle-based sensor elements and membrane-based sensor elements |
US8101431B2 (en) | 2004-02-27 | 2012-01-24 | Board Of Regents, The University Of Texas System | Integration of fluids and reagents into self-contained cartridges containing sensor elements and reagent delivery systems |
US20060121624A1 (en) * | 2004-03-03 | 2006-06-08 | Huang Lotien R | Methods and systems for fluid delivery |
US8119336B2 (en) * | 2004-03-03 | 2012-02-21 | Ibis Biosciences, Inc. | Compositions for use in identification of alphaviruses |
WO2005084380A2 (en) * | 2004-03-03 | 2005-09-15 | The General Hospital Corporation | System for delivering a diluted solution |
US7588724B2 (en) * | 2004-03-05 | 2009-09-15 | Bayer Healthcare Llc | Mechanical device for mixing a fluid sample with a treatment solution |
JP4127679B2 (en) * | 2004-03-18 | 2008-07-30 | 株式会社東芝 | Nucleic acid detection cassette and nucleic acid detection apparatus |
US7157233B2 (en) | 2004-03-24 | 2007-01-02 | Tripath Imaging, Inc. | Methods and compositions for the detection of cervical disease |
US7432106B2 (en) | 2004-03-24 | 2008-10-07 | Applied Biosystems Inc. | Liquid processing device including gas trap, and system and method |
US8298759B2 (en) * | 2004-03-25 | 2012-10-30 | The Board Of Trustee Of The Leland Stanford Junior University | Protein expression yield enhancement in cell-free protein synthesis systems by addition of antifoam agents |
US7665303B2 (en) * | 2004-03-31 | 2010-02-23 | Lifescan Scotland, Ltd. | Method of segregating a bolus of fluid using a pneumatic actuator in a fluid handling circuit |
US7059352B2 (en) * | 2004-03-31 | 2006-06-13 | Lifescan Scotland | Triggerable passive valve for use in controlling the flow of fluid |
US20050220630A1 (en) * | 2004-03-31 | 2005-10-06 | Sebastian Bohm | Method of using triggerable passive valves to control the flow of fluid |
US20050217742A1 (en) * | 2004-03-31 | 2005-10-06 | Sebastian Bohm | Microfluidic circuit including an array of triggerable passive valves |
US7156117B2 (en) * | 2004-03-31 | 2007-01-02 | Lifescan Scotland Limited | Method of controlling the movement of fluid through a microfluidic circuit using an array of triggerable passive valves |
US20050220644A1 (en) * | 2004-03-31 | 2005-10-06 | Sebastian Bohm | Pneumatic actuator for bolus generation in a fluid handling circuit |
US7387877B2 (en) * | 2004-04-06 | 2008-06-17 | Oro Grande Technology | Bio-sensor and bio-sensor reporting system |
ATE497837T1 (en) | 2004-04-09 | 2011-02-15 | Vivebio Llc | DEVICES AND METHODS FOR COLLECTION, STORAGE AND TRANSPORTATION OF BIOLOGICAL SAMPLES |
US20050239085A1 (en) * | 2004-04-23 | 2005-10-27 | Buzby Philip R | Methods for nucleic acid sequence determination |
JP4592060B2 (en) * | 2004-04-26 | 2010-12-01 | キヤノン株式会社 | PCR amplification reaction apparatus and PCR amplification reaction method using the apparatus |
US8852862B2 (en) | 2004-05-03 | 2014-10-07 | Handylab, Inc. | Method for processing polynucleotide-containing samples |
AU2005241080B2 (en) * | 2004-05-03 | 2011-08-11 | Handylab, Inc. | Processing polynucleotide-containing samples |
AU2005241523A1 (en) | 2004-05-04 | 2005-11-17 | Bayer Healthcare Llc | Mechanical cartridge with test strip fluid control features for use in a fluid analyte meter |
EP1742627A4 (en) | 2004-05-06 | 2009-08-26 | Plexxikon Inc | Pde4b inhibitors and uses therefor |
JP4784508B2 (en) * | 2004-05-07 | 2011-10-05 | コニカミノルタエムジー株式会社 | Inspection microreactor, inspection apparatus, and inspection method |
AU2016203092B2 (en) * | 2004-05-13 | 2017-10-05 | Nanobiosym, Inc. | Nano-pcr: methods and devices for nucleic acid amplification and detection |
EP1766061B1 (en) * | 2004-05-20 | 2013-07-17 | Quest Diagnostics Investments Incorporated | Single label comparative hybridization |
US8828203B2 (en) * | 2004-05-20 | 2014-09-09 | Sanofi-Aventis Deutschland Gmbh | Printable hydrogels for biosensors |
EP2458619B1 (en) | 2004-05-24 | 2017-08-02 | Ibis Biosciences, Inc. | Mass spectrometry with selective ion filtration by digital thresholding |
US20050260609A1 (en) * | 2004-05-24 | 2005-11-24 | Lapidus Stanley N | Methods and devices for sequencing nucleic acids |
US7476734B2 (en) * | 2005-12-06 | 2009-01-13 | Helicos Biosciences Corporation | Nucleotide analogs |
US20050266411A1 (en) * | 2004-05-25 | 2005-12-01 | Hofstadler Steven A | Methods for rapid forensic analysis of mitochondrial DNA |
US20070117104A1 (en) * | 2005-11-22 | 2007-05-24 | Buzby Philip R | Nucleotide analogs |
WO2006007207A2 (en) * | 2004-05-25 | 2006-01-19 | Helicos Biosciences Corporation | Methods and devices for nucleic acid sequence determination |
US20070117103A1 (en) * | 2005-11-22 | 2007-05-24 | Buzby Philip R | Nucleotide analogs |
US7833709B2 (en) | 2004-05-28 | 2010-11-16 | Wafergen, Inc. | Thermo-controllable chips for multiplex analyses |
US7799553B2 (en) | 2004-06-01 | 2010-09-21 | The Regents Of The University Of California | Microfabricated integrated DNA analysis system |
US7338763B2 (en) * | 2004-06-02 | 2008-03-04 | Eppendorf Array Technologies S.A. | Method and kit for the detection and/or quantification of homologous nucleotide sequences on arrays |
EP1765194A4 (en) | 2004-06-03 | 2010-09-29 | Pelikan Technologies Inc | Method and apparatus for a fluid sampling device |
US9775553B2 (en) | 2004-06-03 | 2017-10-03 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for a fluid sampling device |
US20060024751A1 (en) * | 2004-06-03 | 2006-02-02 | Fluidigm Corporation | Scale-up methods and systems for performing the same |
US20050287673A1 (en) * | 2004-06-07 | 2005-12-29 | Bioprocessors Corp. | Reactor mixing |
JP2008504845A (en) * | 2004-06-07 | 2008-02-21 | バイオプロセッサーズ コーポレイション | Reactor environmental condition control |
US20050277187A1 (en) * | 2004-06-07 | 2005-12-15 | Bioprocessors Corp. | Creation of shear in a reactor |
WO2005121307A2 (en) * | 2004-06-07 | 2005-12-22 | Bioprocessor Corp. | Gas control in a microreactor |
ES2540728T3 (en) | 2004-06-16 | 2015-07-13 | Dsm Ip Assets B.V. | Method for enzymatic discoloration of pheophytin |
WO2006009797A1 (en) * | 2004-06-17 | 2006-01-26 | Plexxikon, Inc. | Azaindoles modulating c-kit activity and uses therefor |
US7498342B2 (en) * | 2004-06-17 | 2009-03-03 | Plexxikon, Inc. | Compounds modulating c-kit activity |
US7569126B2 (en) | 2004-06-18 | 2009-08-04 | Roche Diagnostics Operations, Inc. | System and method for quality assurance of a biosensor test strip |
US8536661B1 (en) | 2004-06-25 | 2013-09-17 | University Of Hawaii | Biosensor chip sensor protection methods |
US7776530B2 (en) * | 2004-06-29 | 2010-08-17 | Wallac Oy | Integrated nucleic acid analysis |
US8965710B2 (en) * | 2004-07-02 | 2015-02-24 | The United States Of America, As Represented By The Secretary Of The Navy | Automated sample-to-microarray apparatus and method |
ITBO20040420A1 (en) | 2004-07-07 | 2004-10-07 | Type S R L | METAL CUTTING AND FORMING MACHINE |
US7615370B2 (en) * | 2004-07-08 | 2009-11-10 | Tecan Trading Ag | System having device for preventing air bubbles in a hybridization chamber and corresponding method |
US7811753B2 (en) | 2004-07-14 | 2010-10-12 | Ibis Biosciences, Inc. | Methods for repairing degraded DNA |
JP4756835B2 (en) * | 2004-07-14 | 2011-08-24 | キヤノン株式会社 | Biochemical reaction cartridge |
US20060024678A1 (en) * | 2004-07-28 | 2006-02-02 | Helicos Biosciences Corporation | Use of single-stranded nucleic acid binding proteins in sequencing |
US20060024206A1 (en) * | 2004-07-29 | 2006-02-02 | Sinha Naveen N | Non-invasive acoustic technique for mixing and segregation of fluid suspensions in microfluidic applications |
US7611840B2 (en) * | 2004-08-03 | 2009-11-03 | Agency For Science, Technology And Research | Method and device for the treatment of biological samples |
US7605168B2 (en) * | 2004-09-03 | 2009-10-20 | Plexxikon, Inc. | PDE4B inhibitors |
EP1794581A2 (en) * | 2004-09-15 | 2007-06-13 | Microchip Biotechnologies, Inc. | Microfluidic devices |
US7170050B2 (en) | 2004-09-17 | 2007-01-30 | Pacific Biosciences Of California, Inc. | Apparatus and methods for optical analysis of molecules |
JP2008513782A (en) * | 2004-09-17 | 2008-05-01 | パシフィック バイオサイエンシーズ オブ カリフォルニア, インコーポレイテッド | Apparatus and method for molecular analysis |
DE102004046618A1 (en) * | 2004-09-25 | 2006-03-30 | Robert Bosch Gmbh | Circuit arrangement for analog / digital conversion |
GB0421529D0 (en) * | 2004-09-28 | 2004-10-27 | Landegren Gene Technology Ab | Microfluidic structure |
JP4621846B2 (en) * | 2004-09-30 | 2011-01-26 | アークレイ株式会社 | Analysis tool |
EP2615160A1 (en) * | 2004-10-06 | 2013-07-17 | Universal Bio Research Co., Ltd. | Reaction vessel and reaction controller |
US7608160B2 (en) | 2004-10-13 | 2009-10-27 | Rheonix, Inc. | Laminated microfluidic structures and method for making |
US7832429B2 (en) * | 2004-10-13 | 2010-11-16 | Rheonix, Inc. | Microfluidic pump and valve structures and fabrication methods |
DE102004050139B4 (en) * | 2004-10-14 | 2008-12-18 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Microfluidic processor and method of conducting a polymerase chain reaction |
DE102004050510B4 (en) * | 2004-10-15 | 2012-01-12 | Siemens Ag | Method for valve control in the thermocyclization of a substance for the purpose of PCR and associated arrangement |
EP1650297B1 (en) * | 2004-10-19 | 2011-04-13 | Samsung Electronics Co., Ltd. | Method and apparatus for the rapid disruption of cells or viruses using micro magnetic beads and laser |
JP3927978B2 (en) | 2004-11-02 | 2007-06-13 | キヤノン株式会社 | Biochemical reaction cartridge and biochemical processing system |
US20090118132A1 (en) * | 2004-11-04 | 2009-05-07 | Roche Molecular Systems, Inc. | Classification of Acute Myeloid Leukemia |
US20060094028A1 (en) * | 2004-11-04 | 2006-05-04 | Welch Allyn, Inc. | Rapid diagnostic assay |
US20080009002A1 (en) * | 2004-11-09 | 2008-01-10 | The Regents Of The University Of California | Analyte Identification Using Electronic Devices |
DE102004056735A1 (en) | 2004-11-09 | 2006-07-20 | Clondiag Chip Technologies Gmbh | Device for performing and analyzing microarray experiments |
US7785785B2 (en) | 2004-11-12 | 2010-08-31 | The Board Of Trustees Of The Leland Stanford Junior University | Charge perturbation detection system for DNA and other molecules |
EP1658898A1 (en) * | 2004-11-20 | 2006-05-24 | Roche Diagnostics GmbH | Nucleic acid preparation |
CN100388967C (en) * | 2004-12-02 | 2008-05-21 | 鸿富锦精密工业(深圳)有限公司 | Particle dispersing method and its device |
US20060118754A1 (en) * | 2004-12-08 | 2006-06-08 | Lapen Daniel C | Stabilizing a polyelectrolyte multilayer |
US7488596B2 (en) | 2004-12-17 | 2009-02-10 | Samsung Electronics Co., Ltd. | Microfluidic device comprising electrolysis device for cell lysis and method for electrochemically lysing cells using the same |
TWI243705B (en) * | 2004-12-22 | 2005-11-21 | Ind Tech Res Inst | Fluid analytical device |
US20090253215A1 (en) * | 2004-12-23 | 2009-10-08 | Koninklijke Philips Electronics, N.V. | Method for controlling the flow of liquids containing biological material by inducing electro- or magneto-rheological effect |
US7220549B2 (en) * | 2004-12-30 | 2007-05-22 | Helicos Biosciences Corporation | Stabilizing a nucleic acid for nucleic acid sequencing |
US8652831B2 (en) | 2004-12-30 | 2014-02-18 | Sanofi-Aventis Deutschland Gmbh | Method and apparatus for analyte measurement test time |
US20080214917A1 (en) * | 2004-12-30 | 2008-09-04 | Dirk Boecker | Method and apparatus for analyte measurement test time |
EP1838875A4 (en) * | 2004-12-30 | 2010-08-25 | Todd M Hauser | Compositions and methods for modulating gene expression using self-protected oligonucleotides |
US20060167382A1 (en) * | 2004-12-30 | 2006-07-27 | Ajay Deshmukh | Method and apparatus for storing an analyte sampling and measurement device |
US20060172328A1 (en) * | 2005-01-05 | 2006-08-03 | Buzby Philip R | Methods and compositions for correcting misincorporation in a nucleic acid synthesis reaction |
US20060171846A1 (en) * | 2005-01-10 | 2006-08-03 | Marr David W M | Microfluidic systems incorporating integrated optical waveguides |
AU2006204858A1 (en) * | 2005-01-13 | 2006-07-20 | Perkinelmer Health Sciences, Inc. | Microfluidic rare cell detection device |
US7391936B2 (en) * | 2005-01-21 | 2008-06-24 | Lucent Technologies, Inc. | Microfluidic sensors and methods for making the same |
DE602006018861D1 (en) * | 2005-01-27 | 2011-01-27 | Quest Diagnostics Invest Inc | FAST COMPARATIVE GENOM HYBRIDIZATION |
US7482120B2 (en) * | 2005-01-28 | 2009-01-27 | Helicos Biosciences Corporation | Methods and compositions for improving fidelity in a nucleic acid synthesis reaction |
US8738106B2 (en) * | 2005-01-31 | 2014-05-27 | Given Imaging, Ltd | Device, system and method for in vivo analysis |
US20060184065A1 (en) * | 2005-02-10 | 2006-08-17 | Ajay Deshmukh | Method and apparatus for storing an analyte sampling and measurement device |
WO2006088907A2 (en) * | 2005-02-15 | 2006-08-24 | University Of Virginia Patent Foundation | Nucleic acid isolation methods and materials and devices thereof |
CA2597947C (en) * | 2005-02-16 | 2014-05-13 | Genetic Technologies Limited | Methods of genetic analysis involving the amplification of complementary duplicons |
WO2006092959A1 (en) * | 2005-03-01 | 2006-09-08 | Rohm Co., Ltd | Microchannel and microfluid chip |
JP4637610B2 (en) * | 2005-03-02 | 2011-02-23 | ローム株式会社 | Microchannel and microchip |
US20060199187A1 (en) * | 2005-03-02 | 2006-09-07 | Meyerhoff Mark E | Enzyme amplified electrochemical DNA detection |
WO2006094238A2 (en) | 2005-03-03 | 2006-09-08 | Isis Pharmaceuticals, Inc. | Compositions for use in identification of adventitious viruses |
US8084207B2 (en) * | 2005-03-03 | 2011-12-27 | Ibis Bioscience, Inc. | Compositions for use in identification of papillomavirus |
US7932081B2 (en) * | 2005-03-10 | 2011-04-26 | Gen-Probe Incorporated | Signal measuring system for conducting real-time amplification assays |
CA2614769A1 (en) | 2005-03-10 | 2006-09-21 | Verenium Corporation | Lyase enzymes, nucleic acids encoding them and methods for making and using them |
BRPI0609140A2 (en) | 2005-03-15 | 2010-02-17 | Verenium Corp | cellulases, nucleic acids that encode them and methods for their production and use |
JP4548174B2 (en) * | 2005-03-24 | 2010-09-22 | コニカミノルタエムジー株式会社 | Microchip for inspection and inspection apparatus using the same |
US20070196820A1 (en) | 2005-04-05 | 2007-08-23 | Ravi Kapur | Devices and methods for enrichment and alteration of cells and other particles |
US20060246576A1 (en) | 2005-04-06 | 2006-11-02 | Affymetrix, Inc. | Fluidic system and method for processing biological microarrays in personal instrumentation |
WO2006113440A2 (en) * | 2005-04-15 | 2006-10-26 | Worcester Polytechnic Institute | Multi-transduction mechanism based microfluidic analyte sensors |
EP1885839B1 (en) * | 2005-04-26 | 2018-08-08 | Life Technologies Corporation | Systems and methods for multiple analyte detection |
TWI274824B (en) * | 2005-05-09 | 2007-03-01 | Li Bing Huan | Method of operating and viewing of liquid in a vacuum or low pressure environment and an apparatus for the same |
WO2006120221A1 (en) * | 2005-05-12 | 2006-11-16 | Stmicroelectronics S.R.L. | Microfluidic device with integrated micropump, in particular biochemical microreactor, and manufacturing method thereof |
AU2006272951A1 (en) | 2005-05-17 | 2007-02-01 | Plexxikon, Inc. | Pyrrol (2,3-b) pyridine derivatives protein kinase inhibitors |
ES2429564T3 (en) | 2005-05-18 | 2013-11-15 | Novartis Ag | Procedures for the diagnosis and treatment of diseases that have an autoimmune and / or inflammatory component |
US20060263790A1 (en) * | 2005-05-20 | 2006-11-23 | Timothy Harris | Methods for improving fidelity in a nucleic acid synthesis reaction |
EP1910824A4 (en) | 2005-05-31 | 2012-11-21 | Labnow Inc | Methods and compositions related to determination and use of white blood cell counts |
US20060280029A1 (en) * | 2005-06-13 | 2006-12-14 | President And Fellows Of Harvard College | Microfluidic mixer |
EP2255880B1 (en) | 2005-06-21 | 2014-05-28 | Tecan Trading AG | System and method to prevent air bubbles in a hybridization chamber |
DK1893612T3 (en) * | 2005-06-22 | 2011-11-21 | Plexxikon Inc | Pyrrole [2,3-B] pyridine derivatives as protein kinase inhibitors |
EP2409767B1 (en) * | 2005-06-23 | 2018-08-08 | Biocartis NV | Modular cartridge, system and method for automated medical diagnosis |
EP2508867A1 (en) * | 2005-06-24 | 2012-10-10 | Board Of Regents, The University Of Texas System | Systems and methods including self-contained cartridges with detection systems and fluid delivery systems |
WO2007005666A2 (en) * | 2005-07-01 | 2007-01-11 | Board Of Regents, The University Of Texas System | System and method of analyte detection using differential receptors |
US7763210B2 (en) * | 2005-07-05 | 2010-07-27 | 3M Innovative Properties Company | Compliant microfluidic sample processing disks |
US7323660B2 (en) | 2005-07-05 | 2008-01-29 | 3M Innovative Properties Company | Modular sample processing apparatus kits and modules |
US7754474B2 (en) * | 2005-07-05 | 2010-07-13 | 3M Innovative Properties Company | Sample processing device compression systems and methods |
US8257964B2 (en) | 2006-01-04 | 2012-09-04 | Cell ASIC | Microwell cell-culture device and fabrication method |
US9388374B2 (en) | 2005-07-07 | 2016-07-12 | Emd Millipore Corporation | Microfluidic cell culture systems |
US9376658B2 (en) | 2008-01-03 | 2016-06-28 | Emd Millipore Corporation | Cell culture array system for automated assays and methods of operation and manufacture thereof |
US9354156B2 (en) | 2007-02-08 | 2016-05-31 | Emd Millipore Corporation | Microfluidic particle analysis method, device and system |
ES2865180T3 (en) | 2005-07-07 | 2021-10-15 | Univ California | Apparatus for cell culture formation |
US9637715B2 (en) | 2005-07-07 | 2017-05-02 | Emd Millipore Corporation | Cell culture and invasion assay method and system |
US7482124B2 (en) * | 2005-07-08 | 2009-01-27 | Bristol-Myers Squibb Company | Method of identifying a PPARgamma-agonist compound having a decreased likelihood of inducing dose-dependent peripheral edema |
US7754873B2 (en) * | 2005-07-16 | 2010-07-13 | Zymo Research Corporation | Isolation of nucleic acid using colored buffers |
ITBO20050481A1 (en) | 2005-07-19 | 2007-01-20 | Silicon Biosystems S R L | METHOD AND APPARATUS FOR THE HANDLING AND / OR IDENTIFICATION OF PARTICLES |
KR101321296B1 (en) | 2005-07-20 | 2013-10-28 | 바이엘 헬스케어 엘엘씨 | Gated amperometry temperature determination |
CA2616281C (en) * | 2005-07-21 | 2014-04-22 | Isis Pharmaceuticals, Inc. | Methods for rapid identification and quantitation of mitochondrial dna variants |
US8921102B2 (en) * | 2005-07-29 | 2014-12-30 | Gpb Scientific, Llc | Devices and methods for enrichment and alteration of circulating tumor cells and other particles |
US20070202512A1 (en) * | 2005-08-19 | 2007-08-30 | Bristol-Myers Squibb Company | Human single nucleotide polymorphisms associated with dose-dependent weight gain and methods of use thereof |
WO2007024778A2 (en) * | 2005-08-22 | 2007-03-01 | Applera Corporation | Device, system and method for depositing processed immiscible-fluid-discrete-volumes |
US7666593B2 (en) | 2005-08-26 | 2010-02-23 | Helicos Biosciences Corporation | Single molecule sequencing of captured nucleic acids |
US7425712B2 (en) * | 2005-09-01 | 2008-09-16 | Contrel Technology Co., Ltd. | Method of operating liquid in the vacuum or low-pressure environment and observing the operation and device for the operation and observation |
US7938573B2 (en) * | 2005-09-02 | 2011-05-10 | Genefluidics, Inc. | Cartridge having variable volume reservoirs |
US7962291B2 (en) * | 2005-09-30 | 2011-06-14 | Affymetrix, Inc. | Methods and computer software for detecting splice variants |
JP5671205B2 (en) | 2005-09-30 | 2015-02-18 | バイエル・ヘルスケア・エルエルシー | Gated voltammetry |
US20070191736A1 (en) * | 2005-10-04 | 2007-08-16 | Don Alden | Method for loading penetrating members in a collection device |
US20070276290A1 (en) * | 2005-10-04 | 2007-11-29 | Dirk Boecker | Tissue Penetrating Apparatus |
JP2009510459A (en) * | 2005-10-06 | 2009-03-12 | テクノロジカル リソーシーズ プロプライエタリー リミテッド | Gravity gradiometer |
WO2007044599A2 (en) * | 2005-10-06 | 2007-04-19 | Hamilton Scott E | Pod connected data monitoring system |
WO2007044917A2 (en) * | 2005-10-11 | 2007-04-19 | Handylab, Inc. | Polynucleotide sample preparation device |
US7754148B2 (en) | 2006-12-27 | 2010-07-13 | Progentech Limited | Instrument for cassette for sample preparation |
US7727473B2 (en) | 2005-10-19 | 2010-06-01 | Progentech Limited | Cassette for sample preparation |
ITBO20050646A1 (en) | 2005-10-26 | 2007-04-27 | Silicon Biosystem S R L | METHOD AND APPARATUS FOR CHARACTERIZATION AND COUNTING OF PARTICLES |
US7947223B2 (en) * | 2005-10-31 | 2011-05-24 | Senzime Ab | Biosensor apparatus for detection of thermal flow |
US20080038714A1 (en) * | 2005-11-02 | 2008-02-14 | Affymetrix, Inc. | Instrument to Pneumatically Control Lab Cards and Method Thereof |
US20080038713A1 (en) * | 2005-11-02 | 2008-02-14 | Affymetrix, Inc. | System and Method for Biological Assay |
US20080311585A1 (en) * | 2005-11-02 | 2008-12-18 | Affymetrix, Inc. | System and method for multiplex liquid handling |
US8075852B2 (en) * | 2005-11-02 | 2011-12-13 | Affymetrix, Inc. | System and method for bubble removal |
US20070099288A1 (en) * | 2005-11-02 | 2007-05-03 | Affymetrix, Inc. | Microfluidic Methods, Devices, and Systems for Fluid Handling |
US8007267B2 (en) * | 2005-11-02 | 2011-08-30 | Affymetrix, Inc. | System and method for making lab card by embossing |
US7817030B2 (en) | 2005-11-09 | 2010-10-19 | Invention Science Fund 1, Llc | Remote controller for in situ reaction device |
US8083710B2 (en) | 2006-03-09 | 2011-12-27 | The Invention Science Fund I, Llc | Acoustically controlled substance delivery device |
US8273071B2 (en) | 2006-01-18 | 2012-09-25 | The Invention Science Fund I, Llc | Remote controller for substance delivery system |
US8992511B2 (en) | 2005-11-09 | 2015-03-31 | The Invention Science Fund I, Llc | Acoustically controlled substance delivery device |
US8998886B2 (en) | 2005-12-13 | 2015-04-07 | The Invention Science Fund I, Llc | Remote control of osmotic pump device |
US7942867B2 (en) | 2005-11-09 | 2011-05-17 | The Invention Science Fund I, Llc | Remotely controlled substance delivery device |
US8936590B2 (en) | 2005-11-09 | 2015-01-20 | The Invention Science Fund I, Llc | Acoustically controlled reaction device |
WO2007142692A2 (en) * | 2005-11-14 | 2007-12-13 | The Government Of The Usa, As Represented By The Secretary Of The Navy | Automated sample-to-microarray system |
US20070141605A1 (en) * | 2005-11-21 | 2007-06-21 | Applera Corporation | Portable preparation, analysis, and detection apparatus for nucleic acid processing |
US20070117102A1 (en) * | 2005-11-22 | 2007-05-24 | Buzby Philip R | Nucleotide analogs |
US8076074B2 (en) | 2005-11-29 | 2011-12-13 | Quest Diagnostics Investments Incorporated | Balanced translocation in comparative hybridization |
US9056291B2 (en) | 2005-11-30 | 2015-06-16 | Micronics, Inc. | Microfluidic reactor system |
WO2008002462A2 (en) * | 2006-06-23 | 2008-01-03 | Micronics, Inc. | Methods and devices for microfluidic point-of-care immunoassays |
US7763453B2 (en) | 2005-11-30 | 2010-07-27 | Micronics, Inc. | Microfluidic mixing and analytic apparatus |
US20070128610A1 (en) * | 2005-12-02 | 2007-06-07 | Buzby Philip R | Sample preparation method and apparatus for nucleic acid sequencing |
EP1969506A1 (en) * | 2005-12-13 | 2008-09-17 | Erasmus University Medical Center Rotterdam | Genetic brain tumor markers |
KR100738085B1 (en) * | 2005-12-21 | 2007-07-12 | 삼성전자주식회사 | A microfluidic device for electrochemically regulating the pH of a fluid therein and method for regulating the pH of a fluid in a microfuidic device using the same |
US20070198653A1 (en) * | 2005-12-30 | 2007-08-23 | Kurt Jarnagin | Systems and methods for remote computer-based analysis of user-provided chemogenomic data |
US8119976B2 (en) * | 2007-07-03 | 2012-02-21 | Colorado School Of Mines | Optical-based cell deformability |
US9885644B2 (en) | 2006-01-10 | 2018-02-06 | Colorado School Of Mines | Dynamic viscoelasticity as a rapid single-cell biomarker |
US9487812B2 (en) | 2012-02-17 | 2016-11-08 | Colorado School Of Mines | Optical alignment deformation spectroscopy |
US9878326B2 (en) * | 2007-09-26 | 2018-01-30 | Colorado School Of Mines | Fiber-focused diode-bar optical trapping for microfluidic manipulation |
SG134186A1 (en) * | 2006-01-12 | 2007-08-29 | Nanyang Polytechnic | Smart nano-integrated system assembly |
CA2658227A1 (en) | 2006-01-17 | 2007-07-26 | Health Research, Inc. | Heteroduplex tracking assay |
CN101375166B (en) * | 2006-01-25 | 2013-07-10 | 皇家飞利浦电子股份有限公司 | Device for analyzing fluids |
WO2007090076A2 (en) | 2006-01-27 | 2007-08-09 | Tripath Imaging, Inc. | Methods for identifying patients with an increased likelihood of having ovarian cancer and compositions therefor |
US7749365B2 (en) | 2006-02-01 | 2010-07-06 | IntegenX, Inc. | Optimized sample injection structures in microfluidic separations |
EP2216403A3 (en) | 2006-02-02 | 2010-11-24 | Verenium Corporation | Esterases and related nucleic acids and methods |
JP5063616B2 (en) | 2006-02-03 | 2012-10-31 | インテジェニックス インコーポレイテッド | Microfluidic device |
NZ595498A (en) | 2006-02-10 | 2013-05-31 | Verenium Corp | Cellulolytic enzymes, nucleic acids encoding them and methods for making and using them |
ES2682284T3 (en) | 2006-02-14 | 2018-09-19 | Bp Corporation North America Inc. | Xylanases, nucleic acids that encode them and methods to make and use them |
JPWO2007097443A1 (en) * | 2006-02-20 | 2009-07-16 | 国立大学法人 北海道大学 | Method for determining DNA base sequence |
US7815868B1 (en) | 2006-02-28 | 2010-10-19 | Fluidigm Corporation | Microfluidic reaction apparatus for high throughput screening |
EP2316962B1 (en) | 2006-03-07 | 2014-07-09 | Cargill, Incorporated | Aldolases, nucleic acids encoding them and methods for making and using them |
CA2645225A1 (en) | 2006-03-07 | 2007-09-13 | Verenium Corporation | Aldolases, nucleic acids encoding them and methods for making and using them |
US7397546B2 (en) * | 2006-03-08 | 2008-07-08 | Helicos Biosciences Corporation | Systems and methods for reducing detected intensity non-uniformity in a laser beam |
US20080309926A1 (en) * | 2006-03-08 | 2008-12-18 | Aaron Weber | Systems and methods for reducing detected intensity non uniformity in a laser beam |
US9423397B2 (en) | 2006-03-10 | 2016-08-23 | Indx Lifecare, Inc. | Waveguide-based detection system with scanning light source |
US7951583B2 (en) * | 2006-03-10 | 2011-05-31 | Plc Diagnostics, Inc. | Optical scanning system |
US9528939B2 (en) | 2006-03-10 | 2016-12-27 | Indx Lifecare, Inc. | Waveguide-based optical scanning systems |
US9976192B2 (en) | 2006-03-10 | 2018-05-22 | Ldip, Llc | Waveguide-based detection system with scanning light source |
US8288157B2 (en) | 2007-09-12 | 2012-10-16 | Plc Diagnostics, Inc. | Waveguide-based optical scanning systems |
WO2007106579A2 (en) * | 2006-03-15 | 2007-09-20 | Micronics, Inc. | Integrated nucleic acid assays |
US7766033B2 (en) * | 2006-03-22 | 2010-08-03 | The Regents Of The University Of California | Multiplexed latching valves for microfluidic devices and processors |
EP2389946A1 (en) | 2006-03-23 | 2011-11-30 | Novartis AG | Anti-tumor cell antigen antibody therapeutics |
US8088616B2 (en) | 2006-03-24 | 2012-01-03 | Handylab, Inc. | Heater unit for microfluidic diagnostic system |
US10900066B2 (en) | 2006-03-24 | 2021-01-26 | Handylab, Inc. | Microfluidic system for amplifying and detecting polynucleotides in parallel |
US8883490B2 (en) | 2006-03-24 | 2014-11-11 | Handylab, Inc. | Fluorescence detector for microfluidic diagnostic system |
US11806718B2 (en) | 2006-03-24 | 2023-11-07 | Handylab, Inc. | Fluorescence detector for microfluidic diagnostic system |
US7998708B2 (en) * | 2006-03-24 | 2011-08-16 | Handylab, Inc. | Microfluidic system for amplifying and detecting polynucleotides in parallel |
JP5415253B2 (en) | 2006-03-24 | 2014-02-12 | ハンディラブ・インコーポレーテッド | Integrated system for processing microfluidic samples and methods of use thereof |
EP1997888A4 (en) * | 2006-03-24 | 2010-07-28 | Toshiba Kk | Nucleic acid detection cassette and nucleic acid detection apparatus |
ITTO20060226A1 (en) | 2006-03-27 | 2007-09-28 | Silicon Biosystem S P A | METHOD AND APPARATUS FOR PROCESSING AND OR ANALYSIS AND OR SELECTION OF PARTICLES, IN PARTICULAR BIOLOGICAL PARTICLES |
US20070232556A1 (en) * | 2006-03-31 | 2007-10-04 | Montine Thomas J | Methods and compositions for the treatment of neurological diseases and disorders |
ATE531199T1 (en) * | 2006-04-03 | 2011-11-15 | Given Imaging Ltd | DEVICE, SYSTEM AND METHOD FOR IN VIVO ANALYSIS |
EP2013795A2 (en) * | 2006-04-03 | 2009-01-14 | Given Imaging Ltd. | Device, system and method for in-vivo analysis |
KR100754399B1 (en) * | 2006-04-05 | 2007-08-31 | 삼성전자주식회사 | Method and apparatus for disrupting cells and purifying nucleic acids using one chamber |
CN101479605A (en) | 2006-04-21 | 2009-07-08 | 纳诺拜希姆公司 | Single-molecule platform for drug discovery: methods and apparatuses for drug discovery, including discovery of anticancer and antiviralagents |
US20070260174A1 (en) * | 2006-05-05 | 2007-11-08 | Searete Llc | Detecting a failure to maintain a regimen |
JP2007301534A (en) * | 2006-05-15 | 2007-11-22 | Ebara Corp | Atomizer |
US8137626B2 (en) | 2006-05-19 | 2012-03-20 | California Institute Of Technology | Fluorescence detector, filter device and related methods |
WO2008000060A1 (en) * | 2006-05-19 | 2008-01-03 | The Governors Of The University Of Alberta | Microfluidic methods for nucleic acid monitoring |
US7641860B2 (en) * | 2006-06-01 | 2010-01-05 | Nanotek, Llc | Modular and reconfigurable multi-stage microreactor cartridge apparatus |
US7998418B1 (en) | 2006-06-01 | 2011-08-16 | Nanotek, Llc | Evaporator and concentrator in reactor and loading system |
GB0611041D0 (en) * | 2006-06-05 | 2006-07-12 | Univ Bristol | Mixing apparatus and method of designing a mixing apparatus |
EP2026075A4 (en) * | 2006-06-06 | 2012-09-19 | Konica Minolta Med & Graphic | Microchip inspection device |
US8137912B2 (en) | 2006-06-14 | 2012-03-20 | The General Hospital Corporation | Methods for the diagnosis of fetal abnormalities |
EP2029779A4 (en) | 2006-06-14 | 2010-01-20 | Living Microsystems Inc | Use of highly parallel snp genotyping for fetal diagnosis |
US20080050739A1 (en) | 2006-06-14 | 2008-02-28 | Roland Stoughton | Diagnosis of fetal abnormalities using polymorphisms including short tandem repeats |
US8372584B2 (en) | 2006-06-14 | 2013-02-12 | The General Hospital Corporation | Rare cell analysis using sample splitting and DNA tags |
US7851028B2 (en) * | 2006-06-30 | 2010-12-14 | The Invention Science Fund I, Llc | Method of combing an elongated molecule |
US7572618B2 (en) | 2006-06-30 | 2009-08-11 | Bristol-Myers Squibb Company | Polynucleotides encoding novel PCSK9 variants |
US7858305B2 (en) * | 2006-06-30 | 2010-12-28 | The Invention Science Fund I, Llc | Method of combing a nucleic acid |
US7642049B2 (en) | 2006-06-30 | 2010-01-05 | Bristol-Myers Squibb Company | Method for identifying HIV-1 protease inhibitors with reduced metabolic affects through detection of human resistin polymorphisms |
US7618771B2 (en) * | 2006-06-30 | 2009-11-17 | Searete Llc | Method of combing a nucleic acid |
KR100790881B1 (en) * | 2006-07-06 | 2008-01-02 | 삼성전자주식회사 | Micro-fluid reaction chip, and method for manufacturing the same |
US7771655B2 (en) * | 2006-07-12 | 2010-08-10 | Bayer Healthcare Llc | Mechanical device for mixing a fluid sample with a treatment solution |
US20080241938A1 (en) * | 2006-07-20 | 2008-10-02 | Visigen Biotechnologies, Inc. | Automated synthesis or sequencing apparatus and method for making and using same |
US20080241951A1 (en) * | 2006-07-20 | 2008-10-02 | Visigen Biotechnologies, Inc. | Method and apparatus for moving stage detection of single molecular events |
US20080091005A1 (en) * | 2006-07-20 | 2008-04-17 | Visigen Biotechnologies, Inc. | Modified nucleotides, methods for making and using same |
US7858363B2 (en) * | 2006-07-22 | 2010-12-28 | Zymo Research Corporation | Plasmid DNA isolation |
ES2688281T3 (en) | 2006-07-28 | 2018-10-31 | Diagnostics For The Real World, Ltd | Device, system and method to process a sample |
EP2444413A1 (en) | 2006-08-04 | 2012-04-25 | Verenium Corporation | Methods for oil or gas well drilling, washing and/or fracturing |
US7854902B2 (en) * | 2006-08-23 | 2010-12-21 | Nanotek, Llc | Modular and reconfigurable multi-stage high temperature microreactor cartridge apparatus and system for using same |
AU2007353877B2 (en) * | 2006-09-14 | 2012-07-19 | Ibis Biosciences, Inc. | Targeted whole genome amplification method for identification of pathogens |
WO2008036614A1 (en) * | 2006-09-18 | 2008-03-27 | California Institute Of Technology | Apparatus for detecting target molecules and related methods |
CA2663962A1 (en) | 2006-09-19 | 2008-03-27 | Asuragen, Inc. | Mir-15, mir-26, mir-31,mir-145, mir-147, mir-188, mir-215, mir-216, mir-331, mmu-mir-292-3p regulated genes and pathways as targets for therapeutic intervention |
WO2008036765A2 (en) | 2006-09-19 | 2008-03-27 | Asuragen, Inc. | Micrornas differentially expressed in pancreatic diseases and uses thereof |
BRPI0716872A2 (en) | 2006-09-21 | 2015-06-16 | Verenium Corp | Phospholipases, nucleic acids encoding them and methods for their manufacture and use |
EP2617819B1 (en) | 2006-09-21 | 2016-04-27 | BASF Enzymes LLC | Phytases, nucleic acids encoding them and methods for making and using them |
US8841116B2 (en) * | 2006-10-25 | 2014-09-23 | The Regents Of The University Of California | Inline-injection microdevice and microfabricated integrated DNA analysis system using same |
US8618248B2 (en) | 2006-10-31 | 2013-12-31 | President And Fellows Of Harvard College | Phosphopeptide compositions and anti-phosphopeptide antibody compositions and methods of detecting phosphorylated peptides |
WO2008066655A2 (en) | 2006-11-02 | 2008-06-05 | Yale University | Assessment of oocyte competence |
JP2008122234A (en) * | 2006-11-13 | 2008-05-29 | Konica Minolta Medical & Graphic Inc | Micro-integrated analysis chip and micro-integrated analysis system |
WO2008061165A2 (en) | 2006-11-14 | 2008-05-22 | Handylab, Inc. | Microfluidic cartridge and method of making same |
JP5266245B2 (en) | 2006-11-15 | 2013-08-21 | バイオファイアー ダイアグノスティックス,インコーポレイテッド | High density built-in biological analysis |
US9102911B2 (en) | 2009-05-15 | 2015-08-11 | Biofire Diagnostics, Llc | High density self-contained biological analysis |
US20100173795A1 (en) * | 2006-11-17 | 2010-07-08 | Yale University | HIV and Hepatitis C Microarray to Detect Drug Resistance |
WO2008063888A2 (en) | 2006-11-22 | 2008-05-29 | Plexxikon, Inc. | Compounds modulating c-fms and/or c-kit activity and uses therefor |
JP4852399B2 (en) * | 2006-11-22 | 2012-01-11 | 富士フイルム株式会社 | Two-component merger |
US20080152543A1 (en) * | 2006-11-22 | 2008-06-26 | Hideyuki Karaki | Temperature regulation method of microfluidic chip, sample analysis system and microfluidic chip |
CA2672315A1 (en) | 2006-12-14 | 2008-06-26 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes using large scale fet arrays |
US11339430B2 (en) | 2007-07-10 | 2022-05-24 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US8349167B2 (en) | 2006-12-14 | 2013-01-08 | Life Technologies Corporation | Methods and apparatus for detecting molecular interactions using FET arrays |
US8262900B2 (en) | 2006-12-14 | 2012-09-11 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
US7932034B2 (en) * | 2006-12-20 | 2011-04-26 | The Board Of Trustees Of The Leland Stanford Junior University | Heat and pH measurement for sequencing of DNA |
PL3101128T3 (en) | 2006-12-21 | 2019-09-30 | Basf Enzymes Llc | Amylases and glucoamylases, nucleic acids encoding them and methods for making and using them |
PE20081581A1 (en) * | 2006-12-21 | 2008-11-12 | Plexxikon Inc | PIRROLO [2,3-b] PYRIDINES COMPOUNDS AS KINASE MODULATORS |
WO2008079909A1 (en) * | 2006-12-21 | 2008-07-03 | Plexxikon, Inc. | Pyrrolo [2,3-b] pyridines as kinase modulators |
EP2094701A2 (en) | 2006-12-21 | 2009-09-02 | Plexxikon, Inc. | Compounds and methods for kinase modulation, and indications therefor |
EP1935496A1 (en) * | 2006-12-22 | 2008-06-25 | Eppendorf Array Technologies SA | Device and/or method for the detection of amplified nucleotides sequences on micro-arrays |
EP1946841A1 (en) * | 2006-12-22 | 2008-07-23 | Eppendorf Array Technologies SA | Device and/or method for the detection of amplified nucleotides sequences on micro-arrays |
CA2677833C (en) | 2007-01-22 | 2016-05-03 | Wafergen, Inc. | Apparatus for high throughput chemical reactions |
US10001496B2 (en) | 2007-01-29 | 2018-06-19 | Gearbox, Llc | Systems for allergen detection |
US20080245740A1 (en) * | 2007-01-29 | 2008-10-09 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Fluidic methods |
US20090050569A1 (en) * | 2007-01-29 | 2009-02-26 | Searete Llc, A Limited Liability Corporation Of The State Of Delaware | Fluidic methods |
NZ610301A (en) | 2007-01-30 | 2015-03-27 | Bp Corp North America Inc | Enzymes for the treatment of lignocellulosics, nucleic acids encoding them and methods for making and using them |
CN101715483A (en) | 2007-02-05 | 2010-05-26 | 微芯片生物工艺学股份有限公司 | microfluidic and nanofluidic devices, systems, and applications |
US20110020797A1 (en) * | 2007-02-09 | 2011-01-27 | Bristol-Myers Squibb Company | Methods For Identifying Patients With An Increased Likelihood Of Responding To DPP-IV Inhibitors |
US7863035B2 (en) * | 2007-02-15 | 2011-01-04 | Osmetech Technology Inc. | Fluidics devices |
US7867783B2 (en) | 2007-02-22 | 2011-01-11 | Maven Technologies, Llc | Apparatus and method for performing ligand binding assays on microarrays in multiwell plates |
US8871471B2 (en) * | 2007-02-23 | 2014-10-28 | Ibis Biosciences, Inc. | Methods for rapid forensic DNA analysis |
US7799656B2 (en) * | 2007-03-15 | 2010-09-21 | Dalsa Semiconductor Inc. | Microchannels for BioMEMS devices |
EP1974815A1 (en) * | 2007-03-23 | 2008-10-01 | Koninklijke Philips Electronics N.V. | Integrated micofluidic device with sensing and control circuits |
WO2008118808A1 (en) | 2007-03-23 | 2008-10-02 | Advion Bioscience, Inc. | Liquid chromatography-mass spectrometry |
EP1974816A1 (en) * | 2007-03-23 | 2008-10-01 | Koninklijke Philips Electronics N.V. | Integrated microfluidic device with integrated circuit |
WO2008117200A2 (en) * | 2007-03-23 | 2008-10-02 | Koninklijke Philips Electronics N.V. | Integrated microfluidic device with reduced peak power consumption |
WO2008118809A1 (en) * | 2007-03-23 | 2008-10-02 | Ibis Biosciences, Inc. | Compositions for use in identification of mixed populations of bioagents |
JP4489088B2 (en) * | 2007-03-23 | 2010-06-23 | 株式会社東芝 | Nucleic acid detection device |
JP4922808B2 (en) * | 2007-03-30 | 2012-04-25 | 富士フイルム株式会社 | Specimen detection method and detection apparatus |
KR101530943B1 (en) | 2007-04-04 | 2015-06-23 | 네트바이오, 인코포레이티드 | Integrated nucleic acid analysis |
US7863037B1 (en) | 2007-04-04 | 2011-01-04 | Maven Technologies, Llc | Ligand binding assays on microarrays in closed multiwell plates |
WO2008131039A2 (en) * | 2007-04-16 | 2008-10-30 | Board Of Regents, The University Of Texas System | Cardibioindex/cardibioscore and utility of salivary proteome in cardiovascular diagnostics |
EP2140001A2 (en) * | 2007-04-25 | 2010-01-06 | 3M Innovative Properties Company | Methods for nucleic acid amplification |
CN103555735B (en) | 2007-04-27 | 2016-03-09 | 加利福尼亚大学董事会 | Plant CO 2sensor, encode their nucleic acid and manufacture and their method of use |
ES2687620T3 (en) | 2007-05-04 | 2018-10-26 | Opko Diagnostics, Llc | Device and method for analysis in microfluidic systems |
US20090041633A1 (en) * | 2007-05-14 | 2009-02-12 | Dultz Shane C | Apparatus and method for performing ligand binding assays on microarrays in multiwell plates |
US7799558B1 (en) | 2007-05-22 | 2010-09-21 | Dultz Shane C | Ligand binding assays on microarrays in closed multiwell plates |
US9598724B2 (en) | 2007-06-01 | 2017-03-21 | Ibis Biosciences, Inc. | Methods and compositions for multiple displacement amplification of nucleic acids |
US20090047191A1 (en) * | 2007-06-08 | 2009-02-19 | Gafur Zainiev | Closed space disposable micro-reactor and uses thereof |
US9457497B2 (en) | 2007-06-14 | 2016-10-04 | University Of Rochester | Microfluidic device and method of manufacturing the microfluidic device |
US9346197B2 (en) | 2007-06-14 | 2016-05-24 | University Of Rochester | Microfluidic device and method of manufacturing the microfluidic device |
US20090075361A1 (en) * | 2007-06-14 | 2009-03-19 | University Of Rochester | Microfluidic Device and Method of Manufacturing the Microfluidic Device |
WO2009002511A1 (en) * | 2007-06-26 | 2008-12-31 | Applera Corporation | Nucleic acid sample preparation by exclusion of dna |
US20090011470A1 (en) * | 2007-06-26 | 2009-01-08 | Lakdawalla Abizar A | Nucleic acid sample preparation by exclusion of DNA |
US20090017528A1 (en) * | 2007-07-12 | 2009-01-15 | Pei-Tai Chen | Nucleic Acid Hybridization Device |
US9618139B2 (en) | 2007-07-13 | 2017-04-11 | Handylab, Inc. | Integrated heater and magnetic separator |
US9186677B2 (en) | 2007-07-13 | 2015-11-17 | Handylab, Inc. | Integrated apparatus for performing nucleic acid extraction and diagnostic testing on multiple biological samples |
USD621060S1 (en) | 2008-07-14 | 2010-08-03 | Handylab, Inc. | Microfluidic cartridge |
US8105783B2 (en) * | 2007-07-13 | 2012-01-31 | Handylab, Inc. | Microfluidic cartridge |
US8133671B2 (en) | 2007-07-13 | 2012-03-13 | Handylab, Inc. | Integrated apparatus for performing nucleic acid extraction and diagnostic testing on multiple biological samples |
US20090136385A1 (en) * | 2007-07-13 | 2009-05-28 | Handylab, Inc. | Reagent Tube |
WO2009012185A1 (en) | 2007-07-13 | 2009-01-22 | Handylab, Inc. | Polynucleotide capture materials, and methods of using same |
US8287820B2 (en) | 2007-07-13 | 2012-10-16 | Handylab, Inc. | Automated pipetting apparatus having a combined liquid pump and pipette head system |
US8182763B2 (en) | 2007-07-13 | 2012-05-22 | Handylab, Inc. | Rack for sample tubes and reagent holders |
MX2010000617A (en) | 2007-07-17 | 2010-05-17 | Plexxikon Inc | Compounds and methods for kinase modulation, and indications therefor. |
ES2717940T3 (en) * | 2007-07-23 | 2019-06-26 | Alere Tech Gmbh | essays |
WO2009015296A1 (en) * | 2007-07-24 | 2009-01-29 | The Regents Of The University Of California | Microfabricated dropley generator |
US7507539B2 (en) * | 2007-07-30 | 2009-03-24 | Quest Diagnostics Investments Incorporated | Substractive single label comparative hybridization |
JP5852781B2 (en) | 2007-07-31 | 2016-02-03 | マイクロニクス, インコーポレイテッド | Hygienic swab collection system, microfluidic assay device and method for diagnostic assays |
US20110212491A1 (en) * | 2007-08-03 | 2011-09-01 | Enigma Diagnostics Limited | Reaction vessel |
GB0715170D0 (en) * | 2007-08-03 | 2007-09-12 | Enigma Diagnostics Ltd | Reaction vessel |
ITBO20070588A1 (en) | 2007-08-13 | 2009-02-14 | Silicon Biosystems Spa | METHOD TO BOND A SILICON LAYER TO A METHACRYLIC POLYMER SUBSTRATE |
GB2456079B (en) | 2007-08-17 | 2010-07-14 | Diagnostics For The Real World | Device, system and method for processing a sample |
US9492826B2 (en) | 2007-08-29 | 2016-11-15 | Canon U.S. Life Sciences, Inc. | Microfluidic devices with integrated resistive heater electrodes including systems and methods for controlling and measuring the temperatures of such heater electrodes |
US10722250B2 (en) | 2007-09-04 | 2020-07-28 | Colorado School Of Mines | Magnetic-field driven colloidal microbots, methods for forming and using the same |
US20090062828A1 (en) * | 2007-09-04 | 2009-03-05 | Colorado School Of Mines | Magnetic field-based colloidal atherectomy |
US8778663B2 (en) * | 2007-09-18 | 2014-07-15 | Lawrence Livermore National Security, Llc. | Thermal cycler |
CN110577945A (en) | 2007-10-03 | 2019-12-17 | 维莱尼姆公司 | xylanases, nucleic acids encoding them, and methods for making and using them |
EP2265375A1 (en) * | 2007-10-12 | 2010-12-29 | Rheonix, Inc. | Integrated microfluidic device and methods |
US7811810B2 (en) | 2007-10-25 | 2010-10-12 | Industrial Technology Research Institute | Bioassay system including optical detection apparatuses, and method for detecting biomolecules |
US7767441B2 (en) * | 2007-10-25 | 2010-08-03 | Industrial Technology Research Institute | Bioassay system including optical detection apparatuses, and method for detecting biomolecules |
ITTO20070771A1 (en) | 2007-10-29 | 2009-04-30 | Silicon Biosystems Spa | METHOD AND APPARATUS FOR IDENTIFICATION AND HANDLING OF PARTICLES |
US8381169B2 (en) * | 2007-10-30 | 2013-02-19 | International Business Machines Corporation | Extending unified process and method content to include dynamic and collaborative content |
EP2212437A4 (en) * | 2007-11-07 | 2011-09-28 | Univ British Columbia | Microfluidic device and method of using same |
US9656271B2 (en) * | 2007-12-04 | 2017-05-23 | Headway Technologies, Inc. | Guided transport of magnetically labeled biological molecules and cells |
WO2009076302A1 (en) | 2007-12-10 | 2009-06-18 | Bayer Healthcare Llc | Control markers for auto-detection of control solution and methods of use |
EP2072115A1 (en) * | 2007-12-21 | 2009-06-24 | Corning Incorporated | Microreactor assembly incorporating an interconnecting element |
CN104651381A (en) | 2008-01-03 | 2015-05-27 | 巴斯夫酶有限责任公司 | Transferases and oxidoreductases, nucleic acids encoding them and methods for making and using them |
DE102008004139B3 (en) * | 2008-01-14 | 2009-06-04 | Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. | Liquid moving device for moving liquid back and forth over sensor surface of analytic sensor utilized in bio analytics field, has channel designed in such manner that counter pressure difference opposite to pressure difference is produced |
US20090209883A1 (en) * | 2008-01-17 | 2009-08-20 | Michael Higgins | Tissue penetrating apparatus |
US9138700B2 (en) * | 2008-01-18 | 2015-09-22 | The Regents Of The University Of California | Accurate and rapid micromixer for integrated microfluidic devices |
WO2009108260A2 (en) | 2008-01-22 | 2009-09-03 | Microchip Biotechnologies, Inc. | Universal sample preparation system and use in an integrated analysis system |
US20090203022A1 (en) * | 2008-02-07 | 2009-08-13 | Arizona Board Of Regents For And On Behalf Of Arizona State University | Analysis |
CA2716337C (en) * | 2008-02-20 | 2017-11-14 | Streck, Inc. | Thermocycler and sample vessel for rapid amplification of dna |
WO2009111316A2 (en) * | 2008-02-29 | 2009-09-11 | Northwestern University | Barriers for facilitating biological reactions |
WO2009120372A2 (en) | 2008-03-28 | 2009-10-01 | Pacific Biosciences Of California, Inc. | Compositions and methods for nucleic acid sequencing |
US8192371B2 (en) * | 2008-03-31 | 2012-06-05 | The Invention Science Fund I, Llc | Systems and methods for obtaining analytes from a body |
EP2107125A1 (en) | 2008-03-31 | 2009-10-07 | Eppendorf Array Technologies SA (EAT) | Real-time PCR of targets on a micro-array |
WO2009126900A1 (en) * | 2008-04-11 | 2009-10-15 | Pelikan Technologies, Inc. | Method and apparatus for analyte detecting device |
EP2285491A1 (en) | 2008-04-25 | 2011-02-23 | Claros Diagnostics, Inc. | Flow control in microfluidic systems |
US20090269800A1 (en) * | 2008-04-29 | 2009-10-29 | Todd Covey | Device and method for processing cell samples |
WO2009137369A1 (en) * | 2008-05-03 | 2009-11-12 | Tufts Medical Center, Inc. | Neonatal salivary genomics |
WO2009140685A2 (en) * | 2008-05-16 | 2009-11-19 | Bristol-Myers Squibb Company | Methods for identifying subjects with an increased likelihood of responding to dpp-iv inhibitors |
US7981664B1 (en) | 2008-05-22 | 2011-07-19 | Maven Technologies, Llc | Apparatus and method for performing ligand binding assays on microarrays in multiwell plates |
US8039270B2 (en) * | 2008-05-22 | 2011-10-18 | Maven Technologies, Llc | Apparatus and method for performing ligand binding assays on microarrays in multiwell plates |
WO2009158143A1 (en) | 2008-05-30 | 2009-12-30 | The University Of North Carolina At Chapel Hill | Gene expression profiles to predict breast cancer outcomes |
US20110195064A1 (en) | 2008-06-06 | 2011-08-11 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Serv | Survival predictor for diffuse large b cell lymphoma |
GB2461026B (en) | 2008-06-16 | 2011-03-09 | Plc Diagnostics Inc | System and method for nucleic acids sequencing by phased synthesis |
US8216526B2 (en) * | 2008-06-17 | 2012-07-10 | The United States of America, as represented by the Secretary of Commerce, The National Institute of Standards and Technology | Method and device for generating diffusive gradients in a microfluidic chamber |
US8470164B2 (en) | 2008-06-25 | 2013-06-25 | Life Technologies Corporation | Methods and apparatus for measuring analytes using large scale FET arrays |
WO2010002890A2 (en) * | 2008-06-30 | 2010-01-07 | The Washington University | Methods of promoting weight loss and associated arrays |
US20100014741A1 (en) * | 2008-07-10 | 2010-01-21 | Banville Steven C | Methods and apparatus related to gate boundaries within a data space |
US9183237B2 (en) | 2008-07-10 | 2015-11-10 | Nodality, Inc. | Methods and apparatus related to gate boundaries within a data space |
US20100030719A1 (en) * | 2008-07-10 | 2010-02-04 | Covey Todd M | Methods and apparatus related to bioinformatics data analysis |
GB2474613A (en) * | 2008-07-10 | 2011-04-20 | Nodality Inc | Methods and apparatus related to management of experiments |
US20100009351A1 (en) * | 2008-07-11 | 2010-01-14 | Handylab, Inc. | Polynucleotide Capture Materials, and Method of Using Same |
USD618820S1 (en) | 2008-07-11 | 2010-06-29 | Handylab, Inc. | Reagent holder |
USD787087S1 (en) | 2008-07-14 | 2017-05-16 | Handylab, Inc. | Housing |
US7976789B2 (en) * | 2008-07-22 | 2011-07-12 | The Board Of Trustees Of The University Of Illinois | Microfluidic device for preparing mixtures |
ES2581774T3 (en) | 2008-08-29 | 2016-09-07 | Janssen Biotech, Inc. | Markers and methods of evaluation and treatment of ulcerative colitis and related disorders using a panel of 20 genes |
US8357503B2 (en) | 2008-08-29 | 2013-01-22 | Bunge Oils, Inc. | Hydrolases, nucleic acids encoding them and methods for making and using them |
US8153391B2 (en) | 2008-08-29 | 2012-04-10 | Bunge Oils, Inc. | Hydrolases, nucleic acids encoding them and methods for making and using them |
US8198062B2 (en) | 2008-08-29 | 2012-06-12 | Dsm Ip Assets B.V. | Hydrolases, nucleic acids encoding them and methods for making and using them |
CN102203288A (en) | 2008-09-03 | 2011-09-28 | 康特姆斯集团有限公司 | Methods and kits for nucleic acid sequencing |
US10759824B2 (en) | 2008-09-03 | 2020-09-01 | Quantumdx Group Limited | Design, synthesis and use of synthetic nucleotides comprising charge mass tags |
EP3002288B1 (en) * | 2008-09-03 | 2019-12-04 | Quantumdx Group Limited | Design, synthesis and use of synthetic nucleotides comprising ionic reporter groups |
EP2344893B1 (en) | 2008-09-16 | 2014-10-15 | Ibis Biosciences, Inc. | Microplate handling systems and methods |
WO2010033599A2 (en) | 2008-09-16 | 2010-03-25 | Ibis Biosciences, Inc. | Mixing cartridges, mixing stations, and related kits, systems, and methods |
US8148163B2 (en) * | 2008-09-16 | 2012-04-03 | Ibis Biosciences, Inc. | Sample processing units, systems, and related methods |
EP2334812B1 (en) | 2008-09-20 | 2016-12-21 | The Board of Trustees of The Leland Stanford Junior University | Noninvasive diagnosis of fetal aneuploidy by sequencing |
US8633015B2 (en) * | 2008-09-23 | 2014-01-21 | Bio-Rad Laboratories, Inc. | Flow-based thermocycling system with thermoelectric cooler |
US9417190B2 (en) | 2008-09-23 | 2016-08-16 | Bio-Rad Laboratories, Inc. | Calibrations and controls for droplet-based assays |
US9132394B2 (en) | 2008-09-23 | 2015-09-15 | Bio-Rad Laboratories, Inc. | System for detection of spaced droplets |
US9289765B2 (en) * | 2008-09-23 | 2016-03-22 | Samsung Electronics Co., Ltd. | Micro-fluidic device and sample testing apparatus using the same |
US9598725B2 (en) * | 2010-03-02 | 2017-03-21 | Bio-Rad Laboratories, Inc. | Emulsion chemistry for encapsulated droplets |
US9764322B2 (en) | 2008-09-23 | 2017-09-19 | Bio-Rad Laboratories, Inc. | System for generating droplets with pressure monitoring |
US9492797B2 (en) | 2008-09-23 | 2016-11-15 | Bio-Rad Laboratories, Inc. | System for detection of spaced droplets |
US11130128B2 (en) | 2008-09-23 | 2021-09-28 | Bio-Rad Laboratories, Inc. | Detection method for a target nucleic acid |
US10512910B2 (en) | 2008-09-23 | 2019-12-24 | Bio-Rad Laboratories, Inc. | Droplet-based analysis method |
US8663920B2 (en) | 2011-07-29 | 2014-03-04 | Bio-Rad Laboratories, Inc. | Library characterization by digital assay |
US8951939B2 (en) | 2011-07-12 | 2015-02-10 | Bio-Rad Laboratories, Inc. | Digital assays with multiplexed detection of two or more targets in the same optical channel |
US9156010B2 (en) | 2008-09-23 | 2015-10-13 | Bio-Rad Laboratories, Inc. | Droplet-based assay system |
US8709762B2 (en) | 2010-03-02 | 2014-04-29 | Bio-Rad Laboratories, Inc. | System for hot-start amplification via a multiple emulsion |
US20100301398A1 (en) | 2009-05-29 | 2010-12-02 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
US20100137143A1 (en) | 2008-10-22 | 2010-06-03 | Ion Torrent Systems Incorporated | Methods and apparatus for measuring analytes |
EP2350673B1 (en) * | 2008-10-24 | 2022-05-11 | Leica Biosystems Richmond, Inc. | Modular system for performing laboratory protocols and associated methods |
US9034257B2 (en) | 2008-10-27 | 2015-05-19 | Nodality, Inc. | High throughput flow cytometry system and method |
WO2010051318A2 (en) * | 2008-10-31 | 2010-05-06 | Abbott Laboratories | Genomic classification of colorectal cancer based on patterns of gene copy number alterations |
CA2739462A1 (en) * | 2008-10-31 | 2010-05-06 | Abbott Laboratories | Methods for assembling panels of cancer cell lines for use in testing the efficacy of one or more pharmaceutical compositions |
JP5632382B2 (en) * | 2008-10-31 | 2014-11-26 | アッヴィ・インコーポレイテッド | Genomic classification of non-small cell lung cancer based on gene copy number change patterns |
CN102203789B (en) * | 2008-10-31 | 2015-06-03 | Abbvie公司 | Genomic classification of malignant melanoma based on patterns of gene copy number alterations |
US10895575B2 (en) | 2008-11-04 | 2021-01-19 | Menarini Silicon Biosystems S.P.A. | Method for identification, selection and analysis of tumour cells |
IT1391619B1 (en) | 2008-11-04 | 2012-01-11 | Silicon Biosystems Spa | METHOD FOR THE IDENTIFICATION, SELECTION AND ANALYSIS OF TUMOR CELLS |
EP2352998A4 (en) | 2008-11-07 | 2011-09-21 | Centocor Ortho Biotech Inc | Markers and methods for assessing and treating lupus patients susceptible to photoprovocation |
US8309306B2 (en) * | 2008-11-12 | 2012-11-13 | Nodality, Inc. | Detection composition |
CH699853A1 (en) * | 2008-11-13 | 2010-05-14 | Tecan Trading Ag | Meter and method for determining provided by a laboratory fluid system parameters. |
US8703358B2 (en) * | 2008-11-20 | 2014-04-22 | Mti Microfuel Cells, Inc. | Fuel cell feed systems |
DK2376226T3 (en) | 2008-12-18 | 2018-10-15 | Opko Diagnostics Llc | IMPROVED REAGENT STORAGE IN MICROFLUIDIC SYSTEMS AND RELATED ARTICLES AND PROCEDURES |
US8448499B2 (en) | 2008-12-23 | 2013-05-28 | C A Casyso Ag | Cartridge device for a measuring system for measuring viscoelastic characteristics of a sample liquid, a corresponding measuring system, and a corresponding method |
US8672532B2 (en) | 2008-12-31 | 2014-03-18 | Integenx Inc. | Microfluidic methods |
US7927904B2 (en) | 2009-01-05 | 2011-04-19 | Dalsa Semiconductor Inc. | Method of making BIOMEMS devices |
US20100184623A1 (en) * | 2009-01-22 | 2010-07-22 | Suz-Kai Hsiung | Gene-array operation chip device |
US8100293B2 (en) * | 2009-01-23 | 2012-01-24 | Formulatrix, Inc. | Microfluidic dispensing assembly |
GB0901593D0 (en) | 2009-01-30 | 2009-03-11 | Touchlight Genetics Ltd | Production of closed linear DNA |
US9375169B2 (en) * | 2009-01-30 | 2016-06-28 | Sanofi-Aventis Deutschland Gmbh | Cam drive for managing disposable penetrating member actions with a single motor and motor and control system |
WO2010087999A1 (en) | 2009-02-02 | 2010-08-05 | Claros Diagnostics, Inc. | Structures for controlling light interaction with microfluidic devices |
EP2393941A2 (en) * | 2009-02-09 | 2011-12-14 | Frederic Zenhausern | Improvements in and relating to microfluidic devices for processing a sample |
EP2396803A4 (en) | 2009-02-12 | 2016-10-26 | Ibis Biosciences Inc | Ionization probe assemblies |
ES2661310T3 (en) * | 2009-03-09 | 2018-03-28 | Bioatla, Llc | Mirac proteins |
ITBO20090153A1 (en) * | 2009-03-17 | 2010-09-18 | Silicon Biosystems Spa | APPARATUS FOR PARTICLE ISOLATION |
CN102427883B (en) | 2009-03-17 | 2014-08-20 | 硅生物系统股份公司 | Microfluidic device for isolation of cells |
US9447461B2 (en) | 2009-03-24 | 2016-09-20 | California Institute Of Technology | Analysis devices, kits, and related methods for digital quantification of nucleic acids and other analytes |
AU2010229490B2 (en) | 2009-03-24 | 2015-02-12 | University Of Chicago | Slip chip device and methods |
US9464319B2 (en) | 2009-03-24 | 2016-10-11 | California Institute Of Technology | Multivolume devices, kits and related methods for quantification of nucleic acids and other analytes |
US10196700B2 (en) | 2009-03-24 | 2019-02-05 | University Of Chicago | Multivolume devices, kits and related methods for quantification and detection of nucleic acids and other analytes |
WO2010114928A2 (en) * | 2009-04-03 | 2010-10-07 | F.Hoffmann-La Roche Ag | Compositions and uses thereof |
RU2549443C2 (en) | 2009-04-14 | 2015-04-27 | Биокартис Нв | Cavitation induced by high-intensity focused ultrasound with reduced power threshold |
WO2010118541A1 (en) | 2009-04-15 | 2010-10-21 | Biocartis Sa | OPTICAL DETECTION SYSTEM FOR MONITORING rtPCR REACTION |
AU2010237533B2 (en) | 2009-04-15 | 2014-09-25 | Biocartis Nv | Protection of bioanalytical sample chambers |
CN102460254B (en) | 2009-04-29 | 2015-05-06 | Plc诊断股份有限公司 | Waveguide-based detection system with scanning light source |
ES2540118T3 (en) | 2009-05-06 | 2015-07-08 | Biocartis Nv | Device for cutting a sample holder |
CA2761943A1 (en) * | 2009-05-14 | 2010-11-18 | Streck, Inc. | Sample processing cassette, system, and method |
MX355638B (en) | 2009-05-21 | 2018-03-26 | Verenium Corp | Phytases, nucleic acids encoding them and methods for making and using them. |
US20120261274A1 (en) | 2009-05-29 | 2012-10-18 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US8776573B2 (en) | 2009-05-29 | 2014-07-15 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US8574835B2 (en) | 2009-05-29 | 2013-11-05 | Life Technologies Corporation | Scaffolded nucleic acid polymer particles and methods of making and using |
US8673627B2 (en) * | 2009-05-29 | 2014-03-18 | Life Technologies Corporation | Apparatus and methods for performing electrochemical reactions |
CA2764158A1 (en) | 2009-06-01 | 2010-12-09 | Halo-Bio Rnai Therapeutics, Inc. | Polynucleotides for multivalent rna interference, compositions and methods of use thereof |
CN102459565A (en) | 2009-06-02 | 2012-05-16 | 尹特根埃克斯有限公司 | Fluidic devices with diaphragm valves |
JP2012529268A (en) | 2009-06-05 | 2012-11-22 | インテジェンクス,インコーポレイテッド | Use of universal sample preparation system and integrated analysis system |
WO2010147654A2 (en) | 2009-06-15 | 2010-12-23 | Netbio Inc. | Improved methods for forensic dna quantitation |
US9194877B2 (en) | 2009-07-17 | 2015-11-24 | Ibis Biosciences, Inc. | Systems for bioagent indentification |
WO2011008971A1 (en) * | 2009-07-17 | 2011-01-20 | Ibis Biosciences, Inc. | Lift and mount apparatus |
US8445201B2 (en) * | 2009-07-31 | 2013-05-21 | Affymetrix, Inc. | Hybridization device, methods, and system using mixing beads |
US8329724B2 (en) | 2009-08-03 | 2012-12-11 | Hoffmann-La Roche Inc. | Process for the manufacture of pharmaceutically active compounds |
CA2767056C (en) * | 2009-09-02 | 2018-12-04 | Bio-Rad Laboratories, Inc. | System for mixing fluids by coalescence of multiple emulsions |
KR20110027419A (en) * | 2009-09-10 | 2011-03-16 | 삼성전자주식회사 | Fluid receiving chamber, microfluidic device with fluid receiving chamber, and fluid mixing method |
JP5570600B2 (en) * | 2009-09-10 | 2014-08-13 | ロンザ バイオロジクス ピーエルシー | Methods and systems for polypeptide purification |
CN102630250A (en) | 2009-09-25 | 2012-08-08 | 基因诊断测试公司 | Multiplex (+/-) stranded arrays and assays for detecting chromosomal abnormalities associated with cancer and other diseases |
US20110091882A1 (en) * | 2009-10-02 | 2011-04-21 | Ibis Biosciences, Inc. | Determination of methylation status of polynucleotides |
EP2486151B1 (en) | 2009-10-06 | 2016-04-13 | Shire Human Genetic Therapies, Inc. | Assays for agents affecting megakaryocyte development |
EP2957641B1 (en) * | 2009-10-15 | 2017-05-17 | Ibis Biosciences, Inc. | Multiple displacement amplification |
UA109884C2 (en) | 2009-10-16 | 2015-10-26 | A POLYPEPTIDE THAT HAS THE ACTIVITY OF THE PHOSPHATIDYLINOSYTOL-SPECIFIC PHOSPHOLIPASE C, NUCLEIC ACID, AND METHOD OF METHOD | |
UA111708C2 (en) | 2009-10-16 | 2016-06-10 | Бандж Ойлз, Інк. | METHOD OF OIL REFINING |
WO2011048498A2 (en) | 2009-10-19 | 2011-04-28 | Stichting Het Nederlands Kanker Instituut | Differentiation between brca2-associated tumours and sporadic tumours via array comparative genomic hybridization |
WO2011048495A1 (en) | 2009-10-19 | 2011-04-28 | Stichting Het Nederlands Kanker Instituut | Predicting benefit of anti-cancer therapy via array comparative genomic hybridization |
US20120277112A1 (en) | 2009-10-19 | 2012-11-01 | Stichting Het Nederlands Kanker Instituut | Predicting response to anti-cancer therapy via array comparative genomic hybridization |
KR20110046867A (en) * | 2009-10-29 | 2011-05-06 | 삼성전자주식회사 | Microfluidic device comprising gas providing unit, and method for mixing liquids and generate emulsion using the same |
NZ629615A (en) | 2009-11-06 | 2016-01-29 | Plexxikon Inc | Compounds and methods for kinase modulation, and indications therefor |
USD638550S1 (en) | 2009-11-13 | 2011-05-24 | 3M Innovative Properties Company | Sample processing disk cover |
USD667561S1 (en) | 2009-11-13 | 2012-09-18 | 3M Innovative Properties Company | Sample processing disk cover |
US8834792B2 (en) | 2009-11-13 | 2014-09-16 | 3M Innovative Properties Company | Systems for processing sample processing devices |
US20110117607A1 (en) * | 2009-11-13 | 2011-05-19 | 3M Innovative Properties Company | Annular compression systems and methods for sample processing devices |
USD638951S1 (en) | 2009-11-13 | 2011-05-31 | 3M Innovative Properties Company | Sample processing disk cover |
US9700889B2 (en) | 2009-11-23 | 2017-07-11 | Cyvek, Inc. | Methods and systems for manufacture of microarray assay systems, conducting microfluidic assays, and monitoring and scanning to obtain microfluidic assay results |
US9500645B2 (en) | 2009-11-23 | 2016-11-22 | Cyvek, Inc. | Micro-tube particles for microfluidic assays and methods of manufacture |
US9216412B2 (en) | 2009-11-23 | 2015-12-22 | Cyvek, Inc. | Microfluidic devices and methods of manufacture and use |
US9759718B2 (en) | 2009-11-23 | 2017-09-12 | Cyvek, Inc. | PDMS membrane-confined nucleic acid and antibody/antigen-functionalized microlength tube capture elements, and systems employing them, and methods of their use |
WO2011062557A1 (en) * | 2009-11-23 | 2011-05-26 | Haiqing Gong | Improved microfluidic device and method |
US10065403B2 (en) | 2009-11-23 | 2018-09-04 | Cyvek, Inc. | Microfluidic assay assemblies and methods of manufacture |
US9651568B2 (en) | 2009-11-23 | 2017-05-16 | Cyvek, Inc. | Methods and systems for epi-fluorescent monitoring and scanning for microfluidic assays |
JP5701894B2 (en) | 2009-11-23 | 2015-04-15 | サイヴェク・インコーポレイテッド | Method and apparatus for performing an assay |
US9855735B2 (en) | 2009-11-23 | 2018-01-02 | Cyvek, Inc. | Portable microfluidic assay devices and methods of manufacture and use |
PT2504105T (en) | 2009-11-24 | 2021-03-31 | Opko Diagnostics Llc | Fluid mixing and delivery in microfluidic systems |
US8584703B2 (en) | 2009-12-01 | 2013-11-19 | Integenx Inc. | Device with diaphragm valve |
US8187979B2 (en) * | 2009-12-23 | 2012-05-29 | Varian Semiconductor Equipment Associates, Inc. | Workpiece patterning with plasma sheath modulation |
US8355133B2 (en) | 2009-12-30 | 2013-01-15 | Maven Technologies, Llc | Biological testing with sawtooth-shaped prisms |
US9353342B2 (en) | 2010-01-21 | 2016-05-31 | Emd Millipore Corporation | Cell culture and gradient migration assay methods and devices |
WO2011094577A2 (en) | 2010-01-29 | 2011-08-04 | Micronics, Inc. | Sample-to-answer microfluidic cartridge |
JP5691187B2 (en) * | 2010-02-10 | 2015-04-01 | ソニー株式会社 | Microchip for nucleic acid amplification reaction and method for producing the same |
AU2014224115B2 (en) * | 2010-02-23 | 2015-07-09 | Luminex Corporation | Apparatus and methods for integrated sample preparation, reaction and detection |
JP6058399B2 (en) | 2010-02-23 | 2017-01-11 | レオニックス,インコーポレイテッド | Self-contained biological assay device, method and application |
EP2539426B1 (en) | 2010-02-23 | 2016-11-09 | Luminex Corporation | Apparatus for integrated sample preparation, reaction and detection |
TWI421340B (en) * | 2010-03-16 | 2014-01-01 | Nat Univ Tsing Hua | Microfluidic chip and method using the same |
CA2767182C (en) | 2010-03-25 | 2020-03-24 | Bio-Rad Laboratories, Inc. | Droplet generation for droplet-based assays |
EP2556170A4 (en) | 2010-03-25 | 2014-01-01 | Quantalife Inc | Droplet transport system for detection |
CA2767113A1 (en) | 2010-03-25 | 2011-09-29 | Bio-Rad Laboratories, Inc. | Detection system for droplet-based assays |
US8965476B2 (en) | 2010-04-16 | 2015-02-24 | Sanofi-Aventis Deutschland Gmbh | Tissue penetration device |
EP2558203A1 (en) | 2010-04-16 | 2013-02-20 | Opko Diagnostics, LLC | Systems and devices for analysis of samples |
ITTO20100068U1 (en) * | 2010-04-20 | 2011-10-21 | Eltek Spa | MICROFLUID AND / OR EQUIPMENT DEVICES FOR MICROFLUID DEVICES |
AU2011249913B2 (en) | 2010-05-06 | 2014-09-11 | Ibis Biosciences, Inc. | Integrated sample preparation systems and stabilized enzyme mixtures |
USD645971S1 (en) | 2010-05-11 | 2011-09-27 | Claros Diagnostics, Inc. | Sample cassette |
US8512538B2 (en) | 2010-05-28 | 2013-08-20 | Integenx Inc. | Capillary electrophoresis device |
CA2800913C (en) | 2010-06-03 | 2019-07-23 | Pharmacyclics, Inc. | The use of inhibitors of bruton's tyrosine kinase (btk) |
US20110312763A1 (en) * | 2010-06-17 | 2011-12-22 | Geneasys Pty Ltd | Genetic analysis loc with in-loc storage of all required reagents |
US8731847B2 (en) | 2010-06-30 | 2014-05-20 | Life Technologies Corporation | Array configuration and readout scheme |
AU2011226767B1 (en) | 2010-06-30 | 2011-11-10 | Life Technologies Corporation | Ion-sensing charge-accumulation circuits and methods |
JP5952813B2 (en) | 2010-06-30 | 2016-07-13 | ライフ テクノロジーズ コーポレーション | Method and apparatus for testing ISFET arrays |
US11307166B2 (en) | 2010-07-01 | 2022-04-19 | Life Technologies Corporation | Column ADC |
EP2589065B1 (en) | 2010-07-03 | 2015-08-19 | Life Technologies Corporation | Chemically sensitive sensor with lightly doped drains |
CN102985823B (en) * | 2010-07-05 | 2015-09-30 | 皇家飞利浦电子股份有限公司 | With the check system that sample is cultivated |
EP2409765A1 (en) * | 2010-07-21 | 2012-01-25 | F. Hoffmann-La Roche AG | Microfluidic system and process for mixing liquid fluids |
EP3100786A1 (en) * | 2010-07-22 | 2016-12-07 | Gencell Biosystems Limited | Composite liquid cells |
CN103551212B (en) | 2010-07-23 | 2016-01-20 | 贝克曼考尔特公司 | Kit |
ITBO20100502A1 (en) * | 2010-08-04 | 2012-02-05 | Silicon Biosystems Spa | MICROFLUID SYSTEM |
ITBO20100504A1 (en) * | 2010-08-04 | 2012-02-05 | Silicon Biosystems Spa | MICROFLUID SYSTEM |
ITBO20100503A1 (en) * | 2010-08-04 | 2012-02-05 | Silicon Biosystems Spa | MICROFLUID SYSTEM |
GB201013153D0 (en) | 2010-08-04 | 2010-09-22 | Touchlight Genetics Ltd | Primer for production of closed linear DNA |
ITBO20100505A1 (en) * | 2010-08-04 | 2012-02-05 | Silicon Biosystems Spa | MICROFLUID SYSTEM |
US9121058B2 (en) | 2010-08-20 | 2015-09-01 | Integenx Inc. | Linear valve arrays |
US8763642B2 (en) | 2010-08-20 | 2014-07-01 | Integenx Inc. | Microfluidic devices with mechanically-sealed diaphragm valves |
KR101228725B1 (en) * | 2010-09-03 | 2013-02-01 | 삼성전기주식회사 | A microfluidic ejecting device and a method for manufacturing the same |
WO2012036679A1 (en) | 2010-09-15 | 2012-03-22 | Life Technologies Corporation | Methods and apparatus for measuring analytes |
US20140018251A1 (en) | 2010-09-20 | 2014-01-16 | Stichting Het Nederlands Kanker Instituut | Methods for Predicting Response to Anti-Cancer Therapy in Cancer Patients |
EP2619564B1 (en) | 2010-09-24 | 2016-03-16 | Life Technologies Corporation | Matched pair transistor circuits |
US20120077184A1 (en) * | 2010-09-28 | 2012-03-29 | Starkdx Incorporated | Electromagnetic multiplex assay biosensor |
WO2012051055A2 (en) | 2010-10-06 | 2012-04-19 | Bp Corporation North America Inc. | Variant cbh i polypeptides |
US8460607B2 (en) | 2010-10-22 | 2013-06-11 | Abbott Laboratories | Microfluidic device having a flow channel |
WO2012058532A2 (en) | 2010-10-28 | 2012-05-03 | Yale University | Methods and compositions for assessing and treating cancer |
EP3574990B1 (en) | 2010-11-01 | 2022-04-06 | Bio-Rad Laboratories, Inc. | System for forming emulsions |
US9308255B2 (en) | 2010-11-24 | 2016-04-12 | Yale University | Methods of administering D-dopachrome tautomerase (D-DT) to treat ischemia-reperfusion injury |
EA029673B1 (en) | 2010-12-17 | 2018-04-30 | Биджиэс Айпи Лимитэд | Microplate for polymerase chain reaction (pcr) |
IT1403518B1 (en) | 2010-12-22 | 2013-10-31 | Silicon Biosystems Spa | MICROFLUID DEVICE FOR PARTICLE HANDLING |
CN103703143B (en) | 2011-01-31 | 2016-12-14 | 爱普瑞斯生物公司 | The method of the multiple epi-positions in identification of cell |
JP5941069B2 (en) | 2011-02-07 | 2016-06-29 | プレキシコン インコーポレーテッドPlexxikon Inc. | Compounds and methods for kinase regulation and indications therefor |
AR085279A1 (en) | 2011-02-21 | 2013-09-18 | Plexxikon Inc | SOLID FORMS OF {3- [5- (4-CHLORINE-PHENYL) -1H-PIRROLO [2,3-B] PIRIDINA-3-CARBONIL] -2,4-DIFLUOR-PHENIL} -AMIDE OF PROPANE ACID-1- SULFONIC |
CA2830240A1 (en) | 2011-03-15 | 2012-09-20 | The University Of North Carolina At Chapell Hill | Methods of treating breast cancer with anthracycline therapy |
CN103534360A (en) | 2011-03-18 | 2014-01-22 | 伯乐生命医学产品有限公司 | Multiplexed digital assays with combinatorial use of signals |
WO2012134813A1 (en) | 2011-03-31 | 2012-10-04 | St. Jude Children's Research Hospital | Methods and compositions for identifying minimal residual disease in acute lymphoblastic leukemia |
US10526572B2 (en) | 2011-04-01 | 2020-01-07 | EMD Millipore Corporaticn | Cell culture and invasion assay method and system |
CN106190806B (en) | 2011-04-15 | 2018-11-06 | 贝克顿·迪金森公司 | Scan real-time microfluid thermal cycler and the method for synchronous thermal cycle and scanning optical detection |
JP2014512826A (en) | 2011-04-25 | 2014-05-29 | バイオ−ラド ラボラトリーズ インコーポレイテッド | Methods and compositions for nucleic acid analysis |
CA2834790C (en) | 2011-05-04 | 2019-04-09 | Luminex Corporation | Apparatus and methods for integrated sample preparation, reaction and detection |
EP2707396B1 (en) | 2011-05-12 | 2018-11-14 | Gnosis S.p.A. | Biotechnological sulphated chondroitin sulphate at position 4 or 6 on the same polysaccharide chain, and process for the preparation thereof |
RU2631487C2 (en) | 2011-05-17 | 2017-09-22 | Плексксикон Инк. | Kinases modulation and indications for its use |
USD672467S1 (en) | 2011-05-18 | 2012-12-11 | 3M Innovative Properties Company | Rotatable sample processing disk |
BR112013027990B1 (en) | 2011-05-18 | 2020-11-03 | Diasorin S.P.A. | valve structure in a sample processing device and method for operating valves in a sample processing device |
AU2012255144B2 (en) | 2011-05-18 | 2015-01-29 | Diasorin Italia S.P.A. | Systems and methods for volumetric metering on a sample processing device |
WO2012158997A1 (en) | 2011-05-18 | 2012-11-22 | 3M Innovative Properties Company | Systems and methods for detecting the presence of a selected volume of material in a sample processing device |
PL2710043T3 (en) | 2011-05-20 | 2016-11-30 | Shark-like chondroitin sulphate and process for the preparation thereof | |
CA2835654A1 (en) | 2011-06-01 | 2012-12-06 | Streck, Inc. | Rapid thermocycler system for rapid amplification of nucleic acids and related methods |
KR20120134461A (en) * | 2011-06-02 | 2012-12-12 | 삼성전자주식회사 | Micro-fluid supplying device having gas bubble trapping function |
WO2013009705A2 (en) | 2011-07-09 | 2013-01-17 | The Trustees Of Columbia University In The City Of New York | Biomarkers, methods, and compositions for inhibiting a multi-cancer mesenchymal transition mechanism |
WO2013040251A2 (en) | 2011-09-13 | 2013-03-21 | Asurgen, Inc. | Methods and compositions involving mir-135b for distinguishing pancreatic cancer from benign pancreatic disease |
USD692162S1 (en) | 2011-09-30 | 2013-10-22 | Becton, Dickinson And Company | Single piece reagent holder |
KR102121853B1 (en) | 2011-09-30 | 2020-06-12 | 벡톤 디킨슨 앤드 컴퍼니 | Unitized reagent strip |
US20150136604A1 (en) | 2011-10-21 | 2015-05-21 | Integenx Inc. | Sample preparation, processing and analysis systems |
US10865440B2 (en) | 2011-10-21 | 2020-12-15 | IntegenX, Inc. | Sample preparation, processing and analysis systems |
WO2013063519A1 (en) | 2011-10-26 | 2013-05-02 | Asuragen, Inc. | Methods and compositions involving mirna expression levels for distinguishing pancreatic cysts |
US20130142728A1 (en) | 2011-10-27 | 2013-06-06 | Asuragen, Inc. | Mirnas as diagnostic biomarkers to distinguish benign from malignant thyroid tumors |
ITTO20110990A1 (en) | 2011-10-28 | 2013-04-29 | Silicon Biosystems Spa | METHOD AND APPARATUS FOR OPTICAL ANALYSIS OF LOW TEMPERATURE PARTICLES |
US9138714B2 (en) * | 2011-10-31 | 2015-09-22 | General Electric Company | Microfluidic chip and a related method thereof |
CN104040238B (en) | 2011-11-04 | 2017-06-27 | 汉迪拉布公司 | Polynucleotides sample preparation apparatus |
BR112014011035A2 (en) | 2011-11-07 | 2017-06-13 | Beckman Coulter, Inc. | aliquot system and workflow |
ES2844324T3 (en) | 2011-11-07 | 2021-07-21 | Beckman Coulter Inc | Robotic arm |
WO2013070755A2 (en) | 2011-11-07 | 2013-05-16 | Beckman Coulter, Inc. | Centrifuge system and workflow |
KR20140091032A (en) | 2011-11-07 | 2014-07-18 | 베크만 컬터, 인코포레이티드 | Magnetic damping for specimen transport system |
EP2776848B1 (en) | 2011-11-07 | 2019-12-25 | Beckman Coulter, Inc. | System and method for transporting sample containers |
JP6062449B2 (en) | 2011-11-07 | 2017-01-18 | ベックマン コールター, インコーポレイテッド | Specimen container detection |
WO2013074885A1 (en) * | 2011-11-17 | 2013-05-23 | Rheonix, Inc. | Microfluidic apparatus, method, and applications |
US9970984B2 (en) | 2011-12-01 | 2018-05-15 | Life Technologies Corporation | Method and apparatus for identifying defects in a chemical sensor array |
CN104245917B (en) | 2011-12-03 | 2017-07-21 | Emd密理博公司 | Miniature culture system and method for Microfluidic cell culture |
TW201326814A (en) * | 2011-12-21 | 2013-07-01 | Nat Univ Tsing Hua | Microfluidic chip device for selecting a cell aptamer and method thereof |
ITBO20110766A1 (en) | 2011-12-28 | 2013-06-29 | Silicon Biosystems Spa | DEVICES, EQUIPMENT, KITS AND METHOD FOR THE TREATMENT OF A BIOLOGICAL SAMPLE |
JP6190822B2 (en) | 2012-01-09 | 2017-08-30 | マイクロニクス, インコーポレイテッド | Microfluidic reactor system |
US8747748B2 (en) | 2012-01-19 | 2014-06-10 | Life Technologies Corporation | Chemical sensor with conductive cup-shaped sensor surface |
US8821798B2 (en) | 2012-01-19 | 2014-09-02 | Life Technologies Corporation | Titanium nitride as sensing layer for microwell structure |
WO2013112216A1 (en) | 2012-01-24 | 2013-08-01 | Cd Diagnostics, Llc | System for detecting infection in synovial fluid |
JP5912582B2 (en) * | 2012-01-27 | 2016-04-27 | ローム株式会社 | Microchip with built-in liquid reagent containing packaging material and method of using the same |
CN107881219B (en) | 2012-02-03 | 2021-09-10 | 贝克顿·迪金森公司 | External file for molecular diagnostic test assignment and compatibility determination between tests |
US9637775B2 (en) * | 2012-02-13 | 2017-05-02 | Neumodx Molecular, Inc. | System and method for processing biological samples |
US11931740B2 (en) | 2012-02-13 | 2024-03-19 | Neumodx Molecular, Inc. | System and method for processing and detecting nucleic acids |
US9050594B2 (en) | 2012-02-13 | 2015-06-09 | Neumodx Molecular, Inc. | System and method for processing and detecting nucleic acids |
US11485968B2 (en) | 2012-02-13 | 2022-11-01 | Neumodx Molecular, Inc. | Microfluidic cartridge for processing and detecting nucleic acids |
US9604213B2 (en) | 2012-02-13 | 2017-03-28 | Neumodx Molecular, Inc. | System and method for processing and detecting nucleic acids |
BR112014020499A2 (en) | 2012-02-22 | 2019-09-24 | Univ Pennsylvania | isolated nucleic acid sequence, t-cell, vector, and persistent t-cell population |
CN104364788B (en) | 2012-03-05 | 2018-02-06 | 阿克蒂克合伙公司 | Predict prostate cancer risk and the device of prostate gland volume |
EP2822688B1 (en) | 2012-03-08 | 2019-09-25 | Cyvek, Inc. | Microfluidic assay assemblies and methods of manufacture |
US9062342B2 (en) | 2012-03-16 | 2015-06-23 | Stat-Diagnostica & Innovation, S.L. | Test cartridge with integrated transfer module |
WO2013154213A1 (en) * | 2012-04-10 | 2013-10-17 | Lg Electronics Inc. | Diagnostic cartridge |
WO2013155531A2 (en) | 2012-04-13 | 2013-10-17 | Bio-Rad Laboratories, Inc. | Sample holder with a well having a wicking promoter |
EA031833B1 (en) | 2012-04-27 | 2019-02-28 | Цефеид | Apparatus with heterogeneous processing modules |
EP2852689B1 (en) | 2012-05-22 | 2019-12-11 | Nanostring Technologies, Inc. | Nano46 genes and methods to predict breast cancer outcome |
EP2855019A1 (en) | 2012-05-24 | 2015-04-08 | BJS IP Limited | Clamp for fast pcr heating |
US8786331B2 (en) | 2012-05-29 | 2014-07-22 | Life Technologies Corporation | System for reducing noise in a chemical sensor array |
US9150570B2 (en) | 2012-05-31 | 2015-10-06 | Plexxikon Inc. | Synthesis of heterocyclic compounds |
US20130331298A1 (en) * | 2012-06-06 | 2013-12-12 | Great Basin Scientific | Analyzer and disposable cartridge for molecular in vitro diagnostics |
EP2877598A1 (en) | 2012-07-24 | 2015-06-03 | Pharmacyclics, Inc. | Mutations associated with resistance to inhibitors of bruton's tyrosine kinase (btk) |
EP2882868B1 (en) | 2012-08-08 | 2019-07-31 | H. Hoffnabb-La Roche Ag | Increasing dynamic range for identifying multiple epitopes in cells |
CA2879638A1 (en) | 2012-08-10 | 2014-02-13 | Streck, Inc. | Real-time optical system for polymerase chain reaction |
US10752949B2 (en) | 2012-08-14 | 2020-08-25 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US11591637B2 (en) | 2012-08-14 | 2023-02-28 | 10X Genomics, Inc. | Compositions and methods for sample processing |
US10584381B2 (en) | 2012-08-14 | 2020-03-10 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10273541B2 (en) | 2012-08-14 | 2019-04-30 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10221442B2 (en) | 2012-08-14 | 2019-03-05 | 10X Genomics, Inc. | Compositions and methods for sample processing |
US10323279B2 (en) | 2012-08-14 | 2019-06-18 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
CA2881685C (en) | 2012-08-14 | 2023-12-05 | 10X Genomics, Inc. | Microcapsule compositions and methods |
US9701998B2 (en) | 2012-12-14 | 2017-07-11 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US9951386B2 (en) | 2014-06-26 | 2018-04-24 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US9580679B2 (en) | 2012-09-21 | 2017-02-28 | California Institute Of Technology | Methods and devices for sample lysis |
US20140100124A1 (en) | 2012-10-04 | 2014-04-10 | Asuragen, Inc. | Diagnostic mirnas for differential diagnosis of incidental pancreatic cystic lesions |
US20140120544A1 (en) | 2012-10-25 | 2014-05-01 | Neumodx Molecular, Inc. | Method and materials for isolation of nucleic acid materials |
US9776182B2 (en) | 2012-11-27 | 2017-10-03 | Gencell Biosystems Ltd. | Handling liquid samples |
US10533221B2 (en) | 2012-12-14 | 2020-01-14 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
EP3567116A1 (en) | 2012-12-14 | 2019-11-13 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
WO2014100732A1 (en) | 2012-12-21 | 2014-06-26 | Micronics, Inc. | Fluidic circuits and related manufacturing methods |
JP2016509206A (en) | 2012-12-21 | 2016-03-24 | マイクロニクス, インコーポレイテッド | Portable fluorescence detection system and microassay cartridge |
KR20150096788A (en) | 2012-12-21 | 2015-08-25 | 마이크로닉스 인코포레이티드. | Low elasticity films for microfluidic use |
US9080968B2 (en) | 2013-01-04 | 2015-07-14 | Life Technologies Corporation | Methods and systems for point of use removal of sacrificial material |
US9841398B2 (en) | 2013-01-08 | 2017-12-12 | Life Technologies Corporation | Methods for manufacturing well structures for low-noise chemical sensors |
US8962366B2 (en) | 2013-01-28 | 2015-02-24 | Life Technologies Corporation | Self-aligned well structures for low-noise chemical sensors |
EP2954065B1 (en) | 2013-02-08 | 2021-07-28 | 10X Genomics, Inc. | Partitioning and processing of analytes and other species |
US9267171B2 (en) | 2013-02-28 | 2016-02-23 | New York University | DNA photolithography with cinnamate crosslinkers |
US8963216B2 (en) | 2013-03-13 | 2015-02-24 | Life Technologies Corporation | Chemical sensor with sidewall spacer sensor surface |
ES2741001T3 (en) | 2013-03-13 | 2020-02-07 | Opko Diagnostics Llc | Mixing fluids in fluid systems |
US8841217B1 (en) | 2013-03-13 | 2014-09-23 | Life Technologies Corporation | Chemical sensor with protruded sensor surface |
US10234425B2 (en) | 2013-03-15 | 2019-03-19 | Qorvo Us, Inc. | Thin film bulk acoustic resonator with signal enhancement |
CN105051525B (en) | 2013-03-15 | 2019-07-26 | 生命科技公司 | Chemical device with thin conducting element |
US10933417B2 (en) | 2013-03-15 | 2021-03-02 | Nanobiosym, Inc. | Systems and methods for mobile device analysis of nucleic acids and proteins |
EP2970909A4 (en) | 2013-03-15 | 2017-02-15 | The University of Chicago | Methods and compositions related to t-cell activity |
CN105264366B (en) | 2013-03-15 | 2019-04-16 | 生命科技公司 | Chemical sensor with consistent sensor surface area |
US9116117B2 (en) | 2013-03-15 | 2015-08-25 | Life Technologies Corporation | Chemical sensor with sidewall sensor surface |
CN105283758B (en) | 2013-03-15 | 2018-06-05 | 生命科技公司 | Chemical sensor with consistent sensor surface area |
US9835585B2 (en) | 2013-03-15 | 2017-12-05 | Life Technologies Corporation | Chemical sensor with protruded sensor surface |
US20140295441A1 (en) * | 2013-03-27 | 2014-10-02 | Zygem Corporation Ltd. | Cartridge interface module |
MX365092B (en) | 2013-04-15 | 2019-05-22 | Becton Dickinson Co | Biological fluid separation device and biological fluid separation and testing system. |
ES2755490T3 (en) * | 2013-04-15 | 2020-04-22 | Becton Dickinson Co | Biological Fluid Extraction Device and Biological Fluid Separation System |
JP6568843B2 (en) | 2013-04-15 | 2019-08-28 | ベクトン・ディキンソン・アンド・カンパニーBecton, Dickinson And Company | Body fluid sampling device and body fluid sampling and collection assembly |
ES2663791T3 (en) | 2013-04-15 | 2018-04-17 | Becton, Dickinson And Company | Blood sample transfer device |
JP6339663B2 (en) | 2013-04-15 | 2018-06-06 | ベクトン・ディキンソン・アンド・カンパニーBecton, Dickinson And Company | Biological fluid collection device and biological fluid collection inspection system |
MX2015014478A (en) | 2013-04-15 | 2016-02-05 | Becton Dickinson Co | Biological fluid transfer device and biological fluid sampling system. |
EP2986384B1 (en) | 2013-04-15 | 2019-07-17 | Becton, Dickinson and Company | Biological fluid sampling transfer device and biological fluid separation and testing system |
BR112015026246B1 (en) | 2013-04-15 | 2022-10-18 | Becton, Dickinson And Company | BLOOD COLLECTION TRANSFER DEVICE, BLOOD SEPARATION AND TESTING SYSTEM AND BLOOD COLLECTION TRANSFER SYSTEM |
US9408568B2 (en) | 2013-04-15 | 2016-08-09 | Becton, Dickinson And Company | Biological fluid sampling device |
JP6367923B2 (en) | 2013-04-15 | 2018-08-01 | ベクトン・ディキンソン・アンド・カンパニーBecton, Dickinson And Company | Body fluid collection device and body fluid separation and inspection system |
WO2014172236A1 (en) | 2013-04-15 | 2014-10-23 | Becton, Dickinson And Company | Biological fluid separation device and biological fluid separation and testing system |
WO2014172234A1 (en) * | 2013-04-15 | 2014-10-23 | Becton, Dickinson And Company | Biological fluid collection device and biological fluid separation and testing system |
BR112015026139B1 (en) | 2013-04-15 | 2022-12-06 | Becton, Dickinson And Company | BIOLOGICAL FLUID COLLECTION DEVICE, BIOLOGICAL FLUID SEPARATION DEVICE AND BIOLOGICAL FLUID SEPARATION AND TESTING SYSTEM |
CA2909263C (en) | 2013-04-15 | 2020-01-28 | Becton, Dickinson And Company | Biological fluid sampling transfer device and biological fluid separation and testing system |
WO2014182847A1 (en) | 2013-05-07 | 2014-11-13 | Micronics, Inc. | Device for preparation and analysis of nucleic acids |
US10190153B2 (en) | 2013-05-07 | 2019-01-29 | Micronics, Inc. | Methods for preparation of nucleic acid-containing samples using clay minerals and alkaline solutions |
US20140336063A1 (en) | 2013-05-09 | 2014-11-13 | Life Technologies Corporation | Windowed Sequencing |
DK2999959T3 (en) | 2013-05-23 | 2021-10-11 | Qorvo Us Inc | FLUID DEVICE IN TWO PARTS |
CN110632171B (en) | 2013-05-23 | 2022-07-22 | Qorvo美国公司 | Sensor, method and apparatus for forming sensor |
CN105682802B (en) * | 2013-05-27 | 2018-03-16 | 星阵私人有限公司 | A kind of micro fluidic device and the method for controlling its flow of fluid |
US10458942B2 (en) | 2013-06-10 | 2019-10-29 | Life Technologies Corporation | Chemical sensor array having multiple sensors per well |
WO2014210593A1 (en) | 2013-06-28 | 2014-12-31 | Streck, Inc. | Devices for real-time polymerase chain reaction |
US20160137963A1 (en) | 2013-06-28 | 2016-05-19 | Danmarks Tekniske Universitet | A Microfluidic Device with a Diffusion Barrier |
EP3013475A1 (en) | 2013-06-28 | 2016-05-04 | Danmarks Tekniske Universitet | A microfluidic device with pillars |
US10395758B2 (en) | 2013-08-30 | 2019-08-27 | 10X Genomics, Inc. | Sequencing methods |
AU2014317843A1 (en) | 2013-09-09 | 2016-03-24 | British Columbia Cancer Agency Branch | Methods and kits for predicting outcome and methods and kits for treating breast cancer with radiation therapy |
ITMI20131541A1 (en) * | 2013-09-19 | 2015-03-20 | Eugenio Iannone | DIAGNOSIS DEVICE, PARTICULARLY OF THE LAB-ON-CHIP TYPE. |
US10920283B2 (en) | 2013-11-01 | 2021-02-16 | Washington University | Methods to establish and restore normal gut microbiota function of subject in need thereof |
CN106232831B (en) | 2013-11-06 | 2021-02-26 | 美国卫生和人力服务部 | Method for subtype classification of lymphoma types by expression profiling |
WO2015073999A1 (en) | 2013-11-18 | 2015-05-21 | Integenx Inc. | Cartridges and instruments for sample analysis |
US9824068B2 (en) | 2013-12-16 | 2017-11-21 | 10X Genomics, Inc. | Methods and apparatus for sorting data |
EP3105326A4 (en) | 2014-02-10 | 2018-01-10 | Gencell Biosystems Limited | Composite liquid cell (clc) mediated nucleic acid library preparation device, and methods for using the same |
KR20150101316A (en) * | 2014-02-26 | 2015-09-03 | 삼성전자주식회사 | Fluid analysis cartridge |
US10018566B2 (en) | 2014-02-28 | 2018-07-10 | Ldip, Llc | Partially encapsulated waveguide based sensing chips, systems and methods of use |
WO2015138343A1 (en) | 2014-03-10 | 2015-09-17 | Click Diagnostics, Inc. | Cartridge-based thermocycler |
WO2015143400A1 (en) | 2014-03-20 | 2015-09-24 | Pharmacyclics, Inc. | Phospholipase c gamma 2 and resistance associated mutations |
DE102014205728B3 (en) | 2014-03-27 | 2015-03-05 | Robert Bosch Gmbh | A chip laboratory cartridge for a microfluidic system for analyzing a sample of biological material, a microfluidic system for analyzing a sample of biological material, and a method and apparatus for analyzing a sample of biological material |
JP2015188377A (en) * | 2014-03-28 | 2015-11-02 | セイコーエプソン株式会社 | Cartridge for nucleic acid amplification reaction and nucleic acid amplification device |
AU2015243445B2 (en) | 2014-04-10 | 2020-05-28 | 10X Genomics, Inc. | Fluidic devices, systems, and methods for encapsulating and partitioning reagents, and applications of same |
DE102014221616A1 (en) * | 2014-04-25 | 2015-10-29 | Robert Bosch Gmbh | Microfluidic device and method for analyzing a sample of biological material |
ES2913205T3 (en) | 2014-05-13 | 2022-06-01 | Bioatla Inc | Conditionally active biological proteins |
GB2544198B (en) | 2014-05-21 | 2021-01-13 | Integenx Inc | Fluidic cartridge with valve mechanism |
US10829819B2 (en) | 2014-05-30 | 2020-11-10 | Genecentric Therapeutics, Inc. | Methods for typing of lung cancer |
WO2015187849A2 (en) | 2014-06-04 | 2015-12-10 | Lucigen Corporation | Sample collection and analysis devices |
WO2015195636A1 (en) * | 2014-06-16 | 2015-12-23 | Siemens Healthcare Diagnostics Inc. | Fluidic device and degassing method |
WO2015195949A2 (en) | 2014-06-18 | 2015-12-23 | Clear Gene, Inc. | Methods, compositions, and devices for rapid analysis of biological markers |
CN106795553B (en) | 2014-06-26 | 2021-06-04 | 10X基因组学有限公司 | Methods of analyzing nucleic acids from individual cells or cell populations |
CN106575322B (en) | 2014-06-26 | 2019-06-18 | 10X基因组学有限公司 | The method and system of nucleic acid sequence assembly |
JP6501866B2 (en) * | 2014-08-05 | 2019-04-17 | ザ チャールズ スターク ドレイパー ラボラトリー インク | Fluid circulation system incorporating fluid leveling device |
JP2017529199A (en) | 2014-08-12 | 2017-10-05 | ネクストジェン ジェイン, インコーポレイテッド | System and method for monitoring health based on collected body fluid |
AU2015308818B2 (en) | 2014-08-28 | 2021-02-25 | Bioatla Llc | Conditionally active chimeric antigen receptors for modified T-cells |
JP2017532019A (en) | 2014-09-03 | 2017-11-02 | バイオアトラ、エルエルシー | Discovery and production of conditionally active biological proteins in the same eukaryotic cell production host |
GB201415789D0 (en) | 2014-09-05 | 2014-10-22 | Touchlight Genetics Ltd | Synthesis of DNA |
EP3000528B1 (en) * | 2014-09-25 | 2020-12-16 | European Molecular Biology Laboratory | Microfluidic device for the generation of combinatorial samples |
CN107106983B (en) | 2014-10-22 | 2021-04-16 | 尹特根埃克斯有限公司 | Systems and methods for sample preparation, processing, and analysis |
KR20170073667A (en) | 2014-10-29 | 2017-06-28 | 10엑스 제노믹스, 인크. | Methods and compositions for targeted nucleic acid sequencing |
US9975122B2 (en) | 2014-11-05 | 2018-05-22 | 10X Genomics, Inc. | Instrument systems for integrated sample processing |
KR101878655B1 (en) * | 2014-12-09 | 2018-07-16 | 포-캉 린 | Photosynthesis microfluidic channel chamber and photosynthesis method |
EP3229963B1 (en) | 2014-12-12 | 2023-08-23 | Opko Diagnostics, LLC | Fluidic systems comprising an incubation channel, including fluidic systems formed by molding, and method |
KR102593647B1 (en) | 2014-12-18 | 2023-10-26 | 라이프 테크놀로지스 코포레이션 | High data rate integrated circuit with transmitter configuration |
US10077472B2 (en) | 2014-12-18 | 2018-09-18 | Life Technologies Corporation | High data rate integrated circuit with power management |
EP3234575B1 (en) | 2014-12-18 | 2023-01-25 | Life Technologies Corporation | Apparatus for measuring analytes using large scale fet arrays |
EP4029606A1 (en) | 2014-12-31 | 2022-07-20 | Visby Medical, Inc. | Molecular diagnostic testing |
CN112126675B (en) | 2015-01-12 | 2022-09-09 | 10X基因组学有限公司 | Method and system for preparing nucleic acid sequencing library and library prepared by using same |
CN107209814B (en) | 2015-01-13 | 2021-10-15 | 10X基因组学有限公司 | System and method for visualizing structural variation and phase information |
US10450594B2 (en) * | 2015-01-22 | 2019-10-22 | Po-Kang Lin | Photosynthetic device with microfluid chamber for causing photosynthesis therein and method thereof |
WO2016123185A2 (en) * | 2015-01-28 | 2016-08-04 | Opti Medicalsystems, Inc. | Cartridges, analyzers, and systems for analyzing samples |
EP3250910B1 (en) * | 2015-01-30 | 2021-03-03 | Hewlett-Packard Development Company, L.P. | Diagnostic chip |
CA2975529A1 (en) | 2015-02-09 | 2016-08-18 | 10X Genomics, Inc. | Systems and methods for determining structural variation and phasing using variant call data |
EP3822361A1 (en) | 2015-02-20 | 2021-05-19 | Takara Bio USA, Inc. | Method for rapid accurate dispensing, visualization and analysis of single cells |
WO2016137973A1 (en) | 2015-02-24 | 2016-09-01 | 10X Genomics Inc | Partition processing methods and systems |
EP3262188B1 (en) | 2015-02-24 | 2021-05-05 | 10X Genomics, Inc. | Methods for targeted nucleic acid sequence coverage |
CA3225013A1 (en) | 2015-02-24 | 2016-09-01 | Bioatla, Llc | Conditionally active proteins |
US11181479B2 (en) | 2015-02-27 | 2021-11-23 | Ldip, Llc | Waveguide-based detection system with scanning light source |
US10160755B2 (en) | 2015-04-08 | 2018-12-25 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
TWI582240B (en) | 2015-05-19 | 2017-05-11 | 鄭鴻鈞 | Prediction of local and regional recurrence and response to radiotherapy in breast cancer by genomic prognostic kits |
JPWO2016199437A1 (en) * | 2015-06-12 | 2018-03-29 | 株式会社ソシオネクスト | Semiconductor device |
US10233491B2 (en) | 2015-06-19 | 2019-03-19 | IntegenX, Inc. | Valved cartridge and system |
US10894980B2 (en) | 2015-07-17 | 2021-01-19 | President And Fellows Of Harvard College | Methods of amplifying nucleic acid sequences mediated by transposase/transposon DNA complexes |
US10775370B2 (en) * | 2015-07-17 | 2020-09-15 | Stat-Diagnostica & Innovation, S.L. | Fluidic system for performing assays |
US10829484B2 (en) | 2015-07-28 | 2020-11-10 | Plexxikon Inc. | Compounds and methods for kinase modulation, and indications therefor |
EP3331572A4 (en) | 2015-08-04 | 2019-05-01 | CD Diagnostics, Inc. | Methods for detecting adverse local tissue reaction (altr) necrosis |
USD804682S1 (en) | 2015-08-10 | 2017-12-05 | Opko Diagnostics, Llc | Multi-layered sample cassette |
CN108366966A (en) | 2015-08-24 | 2018-08-03 | 光环生物干扰疗法公司 | Polynucleotides nano particle and application thereof for adjusting gene expression |
BR112018003614A2 (en) * | 2015-08-26 | 2018-09-25 | EMULATE, Inc. | infusion dispenser set |
US10228367B2 (en) | 2015-12-01 | 2019-03-12 | ProteinSimple | Segmented multi-use automated assay cartridge |
US10774370B2 (en) | 2015-12-04 | 2020-09-15 | 10X Genomics, Inc. | Methods and compositions for nucleic acid analysis |
RU2018123825A (en) | 2015-12-07 | 2020-01-15 | Плексксикон Инк. | COMPOUNDS AND METHODS FOR MODULATION OF KINASES, AND INDICATIONS FOR THIS |
US10852310B2 (en) | 2015-12-11 | 2020-12-01 | Opko Diagnostics, Llc | Fluidic systems involving incubation of samples and/or reagents |
WO2017106790A1 (en) | 2015-12-18 | 2017-06-22 | Clear Gene, Inc. | Methods, compositions, kits and devices for rapid analysis of biological markers |
JP2019503174A (en) | 2016-01-04 | 2019-02-07 | クァンタムディーエックス グループ リミテッドQuantumdx Group Limited | Design, synthesis, and use of synthetic nucleotides containing charge tags |
EP3932555A1 (en) | 2016-02-04 | 2022-01-05 | Massachusetts Institute Of Technology | Modular organ microphysiological system with integrated pumping, leveling, and sensing |
SG11201806757XA (en) | 2016-02-11 | 2018-09-27 | 10X Genomics Inc | Systems, methods, and media for de novo assembly of whole genome sequence data |
WO2017146744A1 (en) * | 2016-02-27 | 2017-08-31 | Hewlett-Packard Development Company, L.P. | Sample preparation system |
US9659838B1 (en) * | 2016-03-28 | 2017-05-23 | Lockheed Martin Corporation | Integration of chip level micro-fluidic cooling in chip packages for heat flux removal |
WO2017180909A1 (en) | 2016-04-13 | 2017-10-19 | Nextgen Jane, Inc. | Sample collection and preservation devices, systems and methods |
CA3021569A1 (en) | 2016-04-20 | 2017-10-26 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Evaluation of mantle cell lymphoma and methods related thereto |
US10987674B2 (en) | 2016-04-22 | 2021-04-27 | Visby Medical, Inc. | Printed circuit board heater for an amplification module |
WO2017197040A1 (en) | 2016-05-11 | 2017-11-16 | Click Diagnostics, Inc. | Devices and methods for nucleic acid extraction |
WO2017197338A1 (en) | 2016-05-13 | 2017-11-16 | 10X Genomics, Inc. | Microfluidic systems and methods of use |
EP3458611B1 (en) | 2016-05-17 | 2023-11-08 | Genecentric Therapeutics, Inc. | Methods for subtyping of lung squamous cell carcinoma |
CA3024747A1 (en) | 2016-05-17 | 2017-11-23 | Genecentric Therapeutics, Inc. | Methods for subtyping of lung adenocarcinoma |
EP3260552A1 (en) | 2016-06-20 | 2017-12-27 | Istituto Europeo di Oncologia (IEO) | Methods and kits comprising gene signatures for stratifying breast cancer patients |
USD800331S1 (en) | 2016-06-29 | 2017-10-17 | Click Diagnostics, Inc. | Molecular diagnostic device |
WO2018005710A1 (en) | 2016-06-29 | 2018-01-04 | Click Diagnostics, Inc. | Devices and methods for the detection of molecules using a flow cell |
USD800914S1 (en) | 2016-06-30 | 2017-10-24 | Click Diagnostics, Inc. | Status indicator for molecular diagnostic device |
USD800913S1 (en) | 2016-06-30 | 2017-10-24 | Click Diagnostics, Inc. | Detection window for molecular diagnostic device |
CA3020629A1 (en) | 2016-07-21 | 2018-01-25 | Takara Bio Usa, Inc. | Multi-z imaging and dispensing with multi-well devices |
SG11201900782UA (en) * | 2016-08-15 | 2019-02-27 | Univ Tasmania | Inorganic ion detection system and methods |
WO2018053228A1 (en) | 2016-09-15 | 2018-03-22 | The Regents Of The University Of California | Biomarkers for bipolar disorder and schizophrenia |
TW201815766A (en) | 2016-09-22 | 2018-05-01 | 美商普雷辛肯公司 | Compounds and methods for IDO and TDO modulation, and indications therefor |
CA3038063A1 (en) * | 2016-09-23 | 2018-03-29 | ArcherDX, Inc. | System for nucleic acid preparation |
WO2018098241A1 (en) | 2016-11-22 | 2018-05-31 | University Of Rochester | Methods of assessing risk of recurrent prostate cancer |
WO2018106931A1 (en) * | 2016-12-07 | 2018-06-14 | Progenity Inc. | Gastrointestinal tract detection methods, devices and systems |
US10427162B2 (en) | 2016-12-21 | 2019-10-01 | Quandx Inc. | Systems and methods for molecular diagnostics |
US10011872B1 (en) | 2016-12-22 | 2018-07-03 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10815525B2 (en) | 2016-12-22 | 2020-10-27 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
US10550429B2 (en) | 2016-12-22 | 2020-02-04 | 10X Genomics, Inc. | Methods and systems for processing polynucleotides |
WO2018136202A2 (en) | 2016-12-23 | 2018-07-26 | Plexxikon Inc. | Compounds and methods for cdk8 modulation and indications therefor |
GB201700340D0 (en) * | 2017-01-09 | 2017-02-22 | Gsg Tech Ltd | fluid manipulation cartridge and controller mechanism |
WO2018140966A1 (en) | 2017-01-30 | 2018-08-02 | 10X Genomics, Inc. | Methods and systems for droplet-based single cell barcoding |
WO2018213690A1 (en) | 2017-05-18 | 2018-11-22 | The Rockefeller University | Compositions and methods for diagnosing and treating diseases and disorders associated with mutant kcnj5 |
EP3625715A4 (en) | 2017-05-19 | 2021-03-17 | 10X Genomics, Inc. | Systems and methods for analyzing datasets |
US10844372B2 (en) | 2017-05-26 | 2020-11-24 | 10X Genomics, Inc. | Single cell analysis of transposase accessible chromatin |
EP4230746A3 (en) | 2017-05-26 | 2023-11-01 | 10X Genomics, Inc. | Single cell analysis of transposase accessible chromatin |
US11602750B2 (en) | 2017-05-30 | 2023-03-14 | Roche Molecular Systems, Inc. | Customizable sample processing device |
US10428067B2 (en) | 2017-06-07 | 2019-10-01 | Plexxikon Inc. | Compounds and methods for kinase modulation |
CA3066247A1 (en) | 2017-06-07 | 2018-12-13 | University Of Maryland, Baltimore County | Factory-on-a-chip for production of biologically derived medicines/biopharmaceuticals/biologics/ biotherapeutics |
WO2018231589A1 (en) | 2017-06-14 | 2018-12-20 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Method for determining lymphoma type |
US11739386B2 (en) | 2017-07-21 | 2023-08-29 | Genecentric Therapeutics, Inc. | Methods for determining response to PARP inhibitors |
DE102017218117A1 (en) * | 2017-10-11 | 2019-04-11 | Robert Bosch Gmbh | Microfluidic device, process for its production and injection-compression molding device |
WO2019084351A1 (en) | 2017-10-27 | 2019-05-02 | The Regents Of The University Of California | Salivary extracellular rna biomarkers for gingivitis |
US10532356B2 (en) * | 2017-11-09 | 2020-01-14 | International Business Machines Corporation | pH control for analyte detection |
SG11202002931VA (en) | 2017-11-09 | 2020-04-29 | Visby Medical Inc | Portable molecular diagnostic device and methods for the detection of target viruses |
EP3954782A1 (en) | 2017-11-15 | 2022-02-16 | 10X Genomics, Inc. | Functionalized gel beads |
US10829815B2 (en) | 2017-11-17 | 2020-11-10 | 10X Genomics, Inc. | Methods and systems for associating physical and genetic properties of biological particles |
JP7052044B2 (en) | 2017-12-19 | 2022-04-11 | エフ.ホフマン-ラ ロシュ アーゲー | How to make a brittle seal in a sample processing device |
US10046322B1 (en) * | 2018-03-22 | 2018-08-14 | Talis Biomedical Corporation | Reaction well for assay device |
CN112262218A (en) | 2018-04-06 | 2021-01-22 | 10X基因组学有限公司 | System and method for quality control in single cell processing |
WO2019209776A1 (en) | 2018-04-27 | 2019-10-31 | Corning Incorporated | Microfluidic devices and methods for manufacturing microfluidic devices |
DE102018210069A1 (en) * | 2018-06-21 | 2019-12-24 | Robert Bosch Gmbh | Microfluidic device, process for its manufacture and use |
EP3818371A4 (en) | 2018-07-06 | 2022-03-23 | Qorvo Us, Inc. | Bulk acoustic wave resonator with increased dynamic range |
US11801509B2 (en) * | 2018-08-10 | 2023-10-31 | Hewlett-Packard Development Company, L.P. | Serial cellular analytics |
WO2020061515A1 (en) | 2018-09-20 | 2020-03-26 | Cepheid | System, device and methods of sample processing using semiconductor detection chips |
WO2020076897A1 (en) | 2018-10-09 | 2020-04-16 | Genecentric Therapeutics, Inc. | Detecting cancer cell of origin |
GB2578528B (en) | 2018-12-04 | 2021-02-24 | Omniome Inc | Mixed-phase fluids for nucleic acid sequencing and other analytical assays |
KR20210104091A (en) | 2018-12-14 | 2021-08-24 | 세페이드 | Diagnostic detection chip device, manufacturing and assembly method thereof |
CN114207448A (en) | 2019-06-07 | 2022-03-18 | 蜂巢生物技术公司 | Cell cartridge for collecting, storing and analyzing biological samples |
GB2587844A (en) * | 2019-06-07 | 2021-04-14 | Blue White Ind Ltd | Flow sensor devices and systems |
US10820847B1 (en) | 2019-08-15 | 2020-11-03 | Talis Biomedical Corporation | Diagnostic system |
CN114514422A (en) * | 2019-10-01 | 2022-05-17 | 基础科学公司 | Automated online preparation and degassing of volatile samples for online analysis |
EP4085149A4 (en) | 2020-01-03 | 2024-03-06 | Visby Medical Inc | Devices and methods for antibiotic susceptibility testing |
CA3172154C (en) | 2020-04-28 | 2023-09-19 | Peter Paulicka | Acoustophoretic lysis devices and methods |
EP3907301A1 (en) | 2020-05-08 | 2021-11-10 | Istituto Europeo di Oncologia S.r.l. | Methods and kits for determining the risk of breast cancer recurrence |
WO2021229582A1 (en) * | 2020-05-14 | 2021-11-18 | Technion Research And Development Foundation Ltd. | Device, systems, kits and methods for rapid and simple detection of pathogens |
US20220072547A1 (en) * | 2020-09-08 | 2022-03-10 | Dartmouth Ocean Technologies Inc. | Microfluidic chip, systems, and methods for capturing of environmental dna |
JP2023545363A (en) | 2020-09-14 | 2023-10-30 | エンクイスト テクノロジーズ インコーポレイテッド | Process technology for the production and downstream purification of biological products |
US20230332998A1 (en) * | 2020-09-29 | 2023-10-19 | Nok Corporation | Particle analysis device and method for producing same |
EP4291506A2 (en) * | 2021-02-13 | 2023-12-20 | Aptitude Medical Systems, Inc. | Systems and methods for sample analysis |
AU2022264249A1 (en) * | 2021-04-30 | 2023-10-26 | University Of Tasmania | Sample transfer method and system |
WO2023122758A1 (en) | 2021-12-22 | 2023-06-29 | Cornell University | Prognostic/predictive epigenetic breast cancer signature |
DE102022208510A1 (en) | 2022-08-17 | 2024-02-22 | Cellcentric Gmbh & Co. Kg | Device for producing a contamination-free dispersion |
Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4426451A (en) * | 1981-01-28 | 1984-01-17 | Eastman Kodak Company | Multi-zoned reaction vessel having pressure-actuatable control means between zones |
US5252294A (en) * | 1988-06-01 | 1993-10-12 | Messerschmitt-Bolkow-Blohm Gmbh | Micromechanical structure |
WO1994005414A1 (en) * | 1992-08-31 | 1994-03-17 | The Regents Of The University Of California | Microfabricated reactor |
US5304487A (en) * | 1992-05-01 | 1994-04-19 | Trustees Of The University Of Pennsylvania | Fluid handling in mesoscale analytical devices |
US5384261A (en) * | 1991-11-22 | 1995-01-24 | Affymax Technologies N.V. | Very large scale immobilized polymer synthesis using mechanically directed flow paths |
US5498392A (en) * | 1992-05-01 | 1996-03-12 | Trustees Of The University Of Pennsylvania | Mesoscale polynucleotide amplification device and method |
Family Cites Families (65)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3631654A (en) * | 1968-10-03 | 1972-01-04 | Pall Corp | Gas purge device |
US3614856A (en) * | 1968-11-29 | 1971-10-26 | Perkin Elmer Corp | Gas transfer device |
FR2106918A5 (en) * | 1970-09-29 | 1972-05-05 | Rhone Poulenc Sa | |
CA1238900A (en) * | 1982-11-15 | 1988-07-05 | Stephen Saros | Single channel continuous slug flow mixing of discrete fluid components |
US4490216A (en) | 1983-02-03 | 1984-12-25 | Molecular Devices Corporation | Lipid membrane electroanalytical elements and method of analysis therewith |
US5500188A (en) | 1984-03-01 | 1996-03-19 | Molecular Devices Corporation | Device for photoresponsive detection and discrimination |
US4591550A (en) | 1984-03-01 | 1986-05-27 | Molecular Devices Corporation | Device having photoresponsive electrode for determining analytes including ligands and antibodies |
US4883579A (en) | 1984-04-27 | 1989-11-28 | Molecular Devices Corporation | Photoresponsive redox detection and discrimination |
US4849330A (en) | 1984-04-27 | 1989-07-18 | Molecular Devices Corporation | Photoresponsive redox detection and discrimination |
US4704353A (en) | 1984-04-27 | 1987-11-03 | Molecular Devices Corporation | Photoresponsive redox detection and discrimination |
US4676274A (en) * | 1985-02-28 | 1987-06-30 | Brown James F | Capillary flow control |
EP0213825A3 (en) | 1985-08-22 | 1989-04-26 | Molecular Devices Corporation | Multiple chemically modulated capacitance |
US4790640A (en) | 1985-10-11 | 1988-12-13 | Nason Frederic L | Laboratory slide |
US4789628A (en) | 1986-06-16 | 1988-12-06 | Vxr, Inc. | Devices for carrying out ligand/anti-ligand assays, methods of using such devices and diagnostic reagents and kits incorporating such devices |
US4911794A (en) | 1986-06-20 | 1990-03-27 | Molecular Devices Corporation | Measuring with zero volume cell |
US4915812A (en) | 1986-06-20 | 1990-04-10 | Molecular Devices Corporation | Zero volume cell |
US4758786A (en) | 1986-08-06 | 1988-07-19 | Molecular Devices Corporation | Method of analyzing semiconductor systems |
US4963815A (en) | 1987-07-10 | 1990-10-16 | Molecular Devices Corporation | Photoresponsive electrode for determination of redox potential |
US4946795A (en) * | 1987-08-27 | 1990-08-07 | Biotrack, Inc. | Apparatus and method for dilution and mixing of liquid samples |
US4858883A (en) * | 1987-12-11 | 1989-08-22 | Integrated Fluidics, Inc. | Valve with flexible sheet member |
US5700637A (en) * | 1988-05-03 | 1997-12-23 | Isis Innovation Limited | Apparatus and method for analyzing polynucleotide sequences and method of generating oligonucleotide arrays |
US5281516A (en) * | 1988-08-02 | 1994-01-25 | Gene Tec Corporation | Temperature control apparatus and method |
US5188963A (en) * | 1989-11-17 | 1993-02-23 | Gene Tec Corporation | Device for processing biological specimens for analysis of nucleic acids |
US5382511A (en) * | 1988-08-02 | 1995-01-17 | Gene Tec Corporation | Method for studying nucleic acids within immobilized specimens |
DE68922390T2 (en) | 1988-10-21 | 1995-10-05 | Molecular Devices Corp | METHOD AND APPARATUS FOR MEASURING THE EFFECTS OF CELL EFFECTIVE AGENTS ON LIVING CELLS. |
SE462408B (en) * | 1988-11-10 | 1990-06-18 | Pharmacia Ab | OPTICAL BIOSENSOR SYSTEM USING SURFACE MONITORING RESONSE FOR THE DETECTION OF A SPECIFIC BIOMOLIC CYCLE, TO CALIBRATE THE SENSOR DEVICE AND TO CORRECT FOUND BASELINE OPERATION IN THE SYSTEM |
US5229297A (en) | 1989-02-03 | 1993-07-20 | Eastman Kodak Company | Containment cuvette for PCR and method of use |
US5424186A (en) * | 1989-06-07 | 1995-06-13 | Affymax Technologies N.V. | Very large scale immobilized polymer synthesis |
US5871928A (en) * | 1989-06-07 | 1999-02-16 | Fodor; Stephen P. A. | Methods for nucleic acid analysis |
US5143854A (en) * | 1989-06-07 | 1992-09-01 | Affymax Technologies N.V. | Large scale photolithographic solid phase synthesis of polypeptides and receptor binding screening thereof |
US5346672A (en) * | 1989-11-17 | 1994-09-13 | Gene Tec Corporation | Devices for containing biological specimens for thermal processing |
US5171132A (en) * | 1989-12-27 | 1992-12-15 | Seiko Epson Corporation | Two-valve thin plate micropump |
US5126022A (en) * | 1990-02-28 | 1992-06-30 | Soane Tecnologies, Inc. | Method and device for moving molecules by the application of a plurality of electrical fields |
US5053060A (en) * | 1990-06-29 | 1991-10-01 | Molecular Devices Corporation | Device and method for degassing, gassing and debubbling liquids |
DE69107813T2 (en) * | 1990-07-10 | 1995-11-09 | Westonbridge Int Ltd | Valve, method of making this valve and micropump equipped with this valve. |
DE69111591T2 (en) * | 1990-08-31 | 1996-02-29 | Westonbridge Int Ltd | VALVE WITH POSITION DETECTOR AND MICROPUMP WITH IT. |
ES2142805T3 (en) * | 1990-10-11 | 2000-05-01 | Advanced Res & Tech Inst | PROCESS AND APPARATUS FOR FRAGMENTING BIOLOGICAL MATERIALS. |
ES2155822T3 (en) * | 1990-12-06 | 2001-06-01 | Affymetrix Inc | COMPOUNDS AND ITS USE IN A BINARY SYNTHESIS STRATEGY. |
US5230866A (en) * | 1991-03-01 | 1993-07-27 | Biotrack, Inc. | Capillary stop-flow junction having improved stability against accidental fluid flow |
US5846708A (en) * | 1991-11-19 | 1998-12-08 | Massachusetts Institiute Of Technology | Optical and electrical methods and apparatus for molecule detection |
AU675054B2 (en) * | 1991-11-22 | 1997-01-23 | Affymetrix, Inc. | Combinatorial strategies for polymer synthesis |
US5486335A (en) * | 1992-05-01 | 1996-01-23 | Trustees Of The University Of Pennsylvania | Analysis based on flow restriction |
US5587128A (en) * | 1992-05-01 | 1996-12-24 | The Trustees Of The University Of Pennsylvania | Mesoscale polynucleotide amplification devices |
JP3558294B2 (en) * | 1992-05-01 | 2004-08-25 | トラスティーズ・オブ・ザ・ユニバーシティ・オブ・ペンシルベニア | Polynucleotide amplification analysis using microfabrication equipment |
US5296375A (en) * | 1992-05-01 | 1994-03-22 | Trustees Of The University Of Pennsylvania | Mesoscale sperm handling devices |
US5726026A (en) | 1992-05-01 | 1998-03-10 | Trustees Of The University Of Pennsylvania | Mesoscale sample preparation device and systems for determination and processing of analytes |
DE4220077A1 (en) * | 1992-06-19 | 1993-12-23 | Bosch Gmbh Robert | Micro-pump for delivery of gases - uses working chamber warmed by heating element and controlled by silicon wafer valves. |
WO1994003791A1 (en) | 1992-07-31 | 1994-02-17 | Molecular Devices Corporation | Metabolic monitoring of cells in a microplate reader |
US5503980A (en) * | 1992-11-06 | 1996-04-02 | Trustees Of Boston University | Positional sequencing by hybridization |
WO1994011489A1 (en) * | 1992-11-06 | 1994-05-26 | Biolog, Inc. | Testing device for liquid and liquid suspended samples |
US5503985A (en) * | 1993-02-18 | 1996-04-02 | Cathey; Cheryl A. | Disposable device for diagnostic assays |
WO1994020831A1 (en) | 1993-03-08 | 1994-09-15 | Norman Wainwright | Aligned fiber diagnostic chromatography |
SE501713C2 (en) * | 1993-09-06 | 1995-05-02 | Pharmacia Biosensor Ab | Diaphragm-type valve, especially for liquid handling blocks with micro-flow channels |
EP1157743B1 (en) | 1993-10-28 | 2009-03-11 | Houston Advanced Research Center | Microfabricated, flowthrough porous apparatus for discrete detection of binding reactions |
US5580523A (en) | 1994-04-01 | 1996-12-03 | Bard; Allen J. | Integrated chemical synthesizers |
US6001229A (en) | 1994-08-01 | 1999-12-14 | Lockheed Martin Energy Systems, Inc. | Apparatus and method for performing microfluidic manipulations for chemical analysis |
US5707799A (en) | 1994-09-30 | 1998-01-13 | Abbott Laboratories | Devices and methods utilizing arrays of structures for analyte capture |
US5585069A (en) * | 1994-11-10 | 1996-12-17 | David Sarnoff Research Center, Inc. | Partitioned microelectronic and fluidic device array for clinical diagnostics and chemical synthesis |
US5856174A (en) * | 1995-06-29 | 1999-01-05 | Affymetrix, Inc. | Integrated nucleic acid diagnostic device |
US6130098A (en) * | 1995-09-15 | 2000-10-10 | The Regents Of The University Of Michigan | Moving microdroplets |
US5863801A (en) | 1996-06-14 | 1999-01-26 | Sarnoff Corporation | Automated nucleic acid isolation |
US5976336A (en) | 1997-04-25 | 1999-11-02 | Caliper Technologies Corp. | Microfluidic devices incorporating improved channel geometries |
WO1998052691A1 (en) | 1997-05-16 | 1998-11-26 | Alberta Research Council | Microfluidic system and methods of use |
US6001231A (en) | 1997-07-15 | 1999-12-14 | Caliper Technologies Corp. | Methods and systems for monitoring and controlling fluid flow rates in microfluidic systems |
JPH11137907A (en) * | 1997-11-11 | 1999-05-25 | Moore Kk | Deaerator |
-
1996
- 1996-01-19 US US08/589,027 patent/US5856174A/en not_active Expired - Lifetime
- 1996-06-27 US US08/671,928 patent/US5922591A/en not_active Expired - Lifetime
- 1996-06-27 JP JP9505261A patent/JPH11509094A/en not_active Ceased
- 1996-06-27 EP EP03000459A patent/EP1304388B1/en not_active Expired - Lifetime
- 1996-06-27 AT AT96923572T patent/ATE235559T1/en active
- 1996-06-27 AT AT03000459T patent/ATE386590T1/en active
- 1996-06-27 DE DE69637443T patent/DE69637443T2/en not_active Expired - Lifetime
- 1996-06-27 EP EP96923572A patent/EP0843734B1/en not_active Expired - Lifetime
- 1996-06-27 WO PCT/US1996/011147 patent/WO1997002357A1/en active IP Right Grant
- 1996-06-27 AU AU64049/96A patent/AU6404996A/en not_active Abandoned
- 1996-06-27 DE DE69626988T patent/DE69626988T2/en not_active Expired - Lifetime
-
1998
- 1998-12-11 US US09/210,025 patent/US6043080A/en not_active Expired - Lifetime
-
1999
- 1999-04-19 US US09/294,700 patent/US6197595B1/en not_active Expired - Lifetime
-
2000
- 2000-03-10 US US09/523,417 patent/US6326211B1/en not_active Expired - Lifetime
- 2000-12-31 US US09/751,658 patent/US6830936B2/en not_active Expired - Fee Related
-
2004
- 2004-12-13 US US11/010,841 patent/US20050250199A1/en not_active Abandoned
Patent Citations (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4426451A (en) * | 1981-01-28 | 1984-01-17 | Eastman Kodak Company | Multi-zoned reaction vessel having pressure-actuatable control means between zones |
US5252294A (en) * | 1988-06-01 | 1993-10-12 | Messerschmitt-Bolkow-Blohm Gmbh | Micromechanical structure |
US5384261A (en) * | 1991-11-22 | 1995-01-24 | Affymax Technologies N.V. | Very large scale immobilized polymer synthesis using mechanically directed flow paths |
US5304487A (en) * | 1992-05-01 | 1994-04-19 | Trustees Of The University Of Pennsylvania | Fluid handling in mesoscale analytical devices |
US5498392A (en) * | 1992-05-01 | 1996-03-12 | Trustees Of The University Of Pennsylvania | Mesoscale polynucleotide amplification device and method |
WO1994005414A1 (en) * | 1992-08-31 | 1994-03-17 | The Regents Of The University Of California | Microfabricated reactor |
Non-Patent Citations (1)
Title |
---|
PROC. NATL. ACAD. SCI. U.S.A., November 1994, Vol. 91, WOOLLEY et al., "Ultra-High Speed DNA Fragment Separations Using Microfabricated Capillary Array Electrophoresis Chips", pages 11348-11352. * |
Cited By (405)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6767510B1 (en) | 1992-05-21 | 2004-07-27 | Biosite, Inc. | Diagnostic devices and apparatus for the controlled movement of reagents without membranes |
US7524456B1 (en) | 1992-05-21 | 2009-04-28 | Biosite Incorporated | Diagnostic devices for the controlled movement of reagents without membranes |
US6271040B1 (en) | 1992-05-21 | 2001-08-07 | Biosite Diagnostics Incorporated | Diagnostic devices method and apparatus for the controlled movement of reagents without membranes |
US6905882B2 (en) | 1992-05-21 | 2005-06-14 | Biosite, Inc. | Diagnostic devices and apparatus for the controlled movement of reagents without membranes |
USRE43097E1 (en) | 1994-10-13 | 2012-01-10 | Illumina, Inc. | Massively parallel signature sequencing by ligation of encoded adaptors |
US6454945B1 (en) | 1995-06-16 | 2002-09-24 | University Of Washington | Microfabricated devices and methods |
US6274091B1 (en) | 1995-09-22 | 2001-08-14 | Berlex Laboratories, Inc. | Apparatus and process for multiple chemical reactions |
US5888830A (en) * | 1995-09-22 | 1999-03-30 | Berlex Laboratories, Inc. | Apparatus and process for multiple chemical reactions |
US6171865B1 (en) | 1996-03-29 | 2001-01-09 | University Of Washington | Simultaneous analyte determination and reference balancing in reference T-sensor devices |
US7271007B2 (en) | 1996-03-29 | 2007-09-18 | University Of Washington | Microscale diffusion immunoassay |
US6541213B1 (en) | 1996-03-29 | 2003-04-01 | University Of Washington | Microscale diffusion immunoassay |
US6582963B1 (en) | 1996-03-29 | 2003-06-24 | University Of Washington | Simultaneous analyte determination and reference balancing in reference T-sensor devices |
US5972710A (en) * | 1996-03-29 | 1999-10-26 | University Of Washington | Microfabricated diffusion-based chemical sensor |
US6514399B1 (en) | 1996-04-16 | 2003-02-04 | Caliper Technologies Corp. | Controlled fluid transport in microfabricated polymeric substrates |
US6156181A (en) * | 1996-04-16 | 2000-12-05 | Caliper Technologies, Corp. | Controlled fluid transport microfabricated polymeric substrates |
US6787088B2 (en) | 1996-04-16 | 2004-09-07 | Caliper Life Science, Inc. | Controlled fluid transport in microfabricated polymeric substrates |
US6409900B1 (en) | 1996-04-16 | 2002-06-25 | Caliper Technologies Corp. | Controlled fluid transport in microfabricated polymeric substrates |
US6238538B1 (en) | 1996-04-16 | 2001-05-29 | Caliper Technologies, Corp. | Controlled fluid transport in microfabricated polymeric substrates |
US6303288B1 (en) * | 1996-05-08 | 2001-10-16 | Regents Of The University Of Minnesota | Integrated microchip genetic testing system |
US6054277A (en) * | 1996-05-08 | 2000-04-25 | Regents Of The University Of Minnesota | Integrated microchip genetic testing system |
US6630353B1 (en) | 1996-06-28 | 2003-10-07 | Caliper Technologies Corp. | High throughput screening assay systems in microscale fluidic devices |
US5942443A (en) * | 1996-06-28 | 1999-08-24 | Caliper Technologies Corporation | High throughput screening assay systems in microscale fluidic devices |
US5958203A (en) * | 1996-06-28 | 1999-09-28 | Caliper Technologies Corportion | Electropipettor and compensation means for electrophoretic bias |
US6547942B1 (en) | 1996-06-28 | 2003-04-15 | Caliper Technologies Corp. | Electropipettor and compensation means for electrophoretic bias |
US6080295A (en) * | 1996-06-28 | 2000-06-27 | Caliper Technologies Corporation | Electropipettor and compensation means for electrophoretic bias |
US5779868A (en) * | 1996-06-28 | 1998-07-14 | Caliper Technologies Corporation | Electropipettor and compensation means for electrophoretic bias |
US6267858B1 (en) | 1996-06-28 | 2001-07-31 | Caliper Technologies Corp. | High throughput screening assay systems in microscale fluidic devices |
US5972187A (en) * | 1996-06-28 | 1999-10-26 | Caliper Technologies Corporation | Electropipettor and compensation means for electrophoretic bias |
US6399389B1 (en) | 1996-06-28 | 2002-06-04 | Caliper Technologies Corp. | High throughput screening assay systems in microscale fluidic devices |
US6558944B1 (en) | 1996-06-28 | 2003-05-06 | Caliper Technologies Corp. | High throughput screening assay systems in microscale fluidic devices |
US6429025B1 (en) | 1996-06-28 | 2002-08-06 | Caliper Technologies Corp. | High-throughput screening assay systems in microscale fluidic devices |
US6287520B1 (en) | 1996-06-28 | 2001-09-11 | Caliper Technologies Corp. | Electropipettor and compensation means for electrophoretic bias |
EP1145760A2 (en) * | 1996-06-28 | 2001-10-17 | Caliper Technologies Corp. | High-throughput screening assay systems in microscale fluidic devices |
US5880071A (en) * | 1996-06-28 | 1999-03-09 | Caliper Technologies Corporation | Electropipettor and compensation means for electrophoretic bias |
US6274337B1 (en) | 1996-06-28 | 2001-08-14 | Caliper Technologies Corp. | High throughput screening assay systems in microscale fluidic devices |
US6150180A (en) * | 1996-06-28 | 2000-11-21 | Caliper Technologies Corp. | High throughput screening assay systems in microscale fluidic devices |
US6042709A (en) * | 1996-06-28 | 2000-03-28 | Caliper Technologies Corp. | Microfluidic sampling system and methods |
US7001496B2 (en) | 1996-06-28 | 2006-02-21 | Caliper Life Sciences, Inc. | Electropipettor and compensation means for electrophoretic bias |
US6046056A (en) * | 1996-06-28 | 2000-04-04 | Caliper Technologies Corporation | High throughput screening assay systems in microscale fluidic devices |
EP1145760A3 (en) * | 1996-06-28 | 2003-05-14 | Caliper Technologies Corp. | High-throughput screening assay systems in microscale fluidic devices |
AU754363B2 (en) * | 1996-06-28 | 2002-11-14 | Caliper Life Sciences, Inc. | Microfluidic device and method |
US6558960B1 (en) | 1996-06-28 | 2003-05-06 | Caliper Technologies Corp. | High throughput screening assay systems in microscale fluidic devices |
US6482364B2 (en) | 1996-06-28 | 2002-11-19 | Caliper Technologies Corp. | Microfluidic systems including pipettor elements |
US6306659B1 (en) | 1996-06-28 | 2001-10-23 | Caliper Technologies Corp. | High throughput screening assay systems in microscale fluidic devices |
US6413401B1 (en) | 1996-07-03 | 2002-07-02 | Caliper Technologies Corp. | Variable control of electroosmotic and/or electrophoretic forces within a fluid-containing structure via electrical forces |
US5800690A (en) * | 1996-07-03 | 1998-09-01 | Caliper Technologies Corporation | Variable control of electroosmotic and/or electrophoretic forces within a fluid-containing structure via electrical forces |
US5965001A (en) * | 1996-07-03 | 1999-10-12 | Caliper Technologies Corporation | Variable control of electroosmotic and/or electrophoretic forces within a fluid-containing structure via electrical forces |
US8173001B2 (en) | 1996-09-25 | 2012-05-08 | California Institute Of Technology | Method and apparatus for analysis and sorting of polynucleotides based on size |
US6221654B1 (en) | 1996-09-25 | 2001-04-24 | California Institute Of Technology | Method and apparatus for analysis and sorting of polynucleotides based on size |
US6964736B2 (en) | 1996-09-25 | 2005-11-15 | California Institute Of Technology | Method and apparatus for analysis and sorting of polynucleotides based on size |
US7670471B2 (en) | 1996-09-25 | 2010-03-02 | California Institute Of Technology | Method and apparatus for analysis and sorting of polynucleotides based on size |
US9383337B2 (en) | 1996-09-25 | 2016-07-05 | California Institute Of Technology | Method and apparatus for analysis and sorting of polynucleotides based on size |
US6344325B1 (en) | 1996-09-25 | 2002-02-05 | California Institute Of Technology | Methods for analysis and sorting of polynucleotides |
US6465257B1 (en) | 1996-11-19 | 2002-10-15 | Caliper Technologies Corp. | Microfluidic systems |
US6447727B1 (en) | 1996-11-19 | 2002-09-10 | Caliper Technologies Corp. | Microfluidic systems |
US6379974B1 (en) | 1996-11-19 | 2002-04-30 | Caliper Technologies Corp. | Microfluidic systems |
WO1998043739A3 (en) * | 1997-03-27 | 2001-06-07 | Biosite Diagnostics Inc | Diagnostic devices and apparatus for the controlled movement of reagents without membranes |
WO1998043739A2 (en) * | 1997-03-27 | 1998-10-08 | Biosite Diagnostics Incorporated | Diagnostic devices and apparatus for the controlled movement of reagents without membranes |
EP2090366A3 (en) * | 1997-03-28 | 2009-11-18 | Applera Corporation | Improvements in thermal cycler for PCR |
US5948684A (en) * | 1997-03-31 | 1999-09-07 | University Of Washington | Simultaneous analyte determination and reference balancing in reference T-sensor devices |
US6444461B1 (en) | 1997-04-04 | 2002-09-03 | Caliper Technologies Corp. | Microfluidic devices and methods for separation |
US6440722B1 (en) | 1997-04-04 | 2002-08-27 | Caliper Technologies Corp. | Microfluidic devices and methods for optimizing reactions |
US6849411B2 (en) | 1997-04-04 | 2005-02-01 | Caliper Life Sciences, Inc. | Microfluidic sequencing methods |
US6670133B2 (en) | 1997-04-04 | 2003-12-30 | Caliper Technologies Corp. | Microfluidic device for sequencing by hybridization |
US6391622B1 (en) | 1997-04-04 | 2002-05-21 | Caliper Technologies Corp. | Closed-loop biochemical analyzers |
US6129826A (en) * | 1997-04-04 | 2000-10-10 | Caliper Technologies Corp. | Methods and systems for enhanced fluid transport |
US6471841B1 (en) | 1997-04-04 | 2002-10-29 | Caliper Technologies Corp. | Methods and systems for enhanced fluid transport |
US7238323B2 (en) | 1997-04-04 | 2007-07-03 | Caliper Life Sciences, Inc. | Microfluidic sequencing systems |
US6403338B1 (en) | 1997-04-04 | 2002-06-11 | Mountain View | Microfluidic systems and methods of genotyping |
US6235471B1 (en) | 1997-04-04 | 2001-05-22 | Caliper Technologies Corp. | Closed-loop biochemical analyzers |
US6406893B1 (en) | 1997-04-04 | 2002-06-18 | Caliper Technologies Corp. | Microfluidic methods for non-thermal nucleic acid manipulations |
US5964995A (en) * | 1997-04-04 | 1999-10-12 | Caliper Technologies Corp. | Methods and systems for enhanced fluid transport |
US5885470A (en) * | 1997-04-14 | 1999-03-23 | Caliper Technologies Corporation | Controlled fluid transport in microfabricated polymeric substrates |
US6068752A (en) * | 1997-04-25 | 2000-05-30 | Caliper Technologies Corp. | Microfluidic devices incorporating improved channel geometries |
US6153073A (en) * | 1997-04-25 | 2000-11-28 | Caliper Technologies Corp. | Microfluidic devices incorporating improved channel geometries |
US7033474B1 (en) | 1997-04-25 | 2006-04-25 | Caliper Life Sciences, Inc. | Microfluidic devices incorporating improved channel geometries |
US5976336A (en) * | 1997-04-25 | 1999-11-02 | Caliper Technologies Corp. | Microfluidic devices incorporating improved channel geometries |
US6235175B1 (en) | 1997-04-25 | 2001-05-22 | Caliper Technologies Corp. | Microfluidic devices incorporating improved channel geometries |
US9562260B2 (en) | 1997-05-02 | 2017-02-07 | Biomerieux, Inc. | Nucleic acid amplification reaction station for disposable test devices |
EP0875291A3 (en) * | 1997-05-02 | 2000-05-24 | bioMerieux Vitek, Inc. | Dual chamber disposable reaction vessel for amplification reactions, reaction processing station therefor, and methods of use |
US7807449B2 (en) | 1997-05-02 | 2010-10-05 | Biomerieux, Inc. | Nucleic acid amplification reaction station for disposable test devices |
US6429007B1 (en) | 1997-05-02 | 2002-08-06 | BIOMéRIEUX, INC. | Nucleic acid amplification reaction station for disposable test devices |
US6949376B2 (en) | 1997-05-02 | 2005-09-27 | Biomerieux, Inc. | Nucleic acid amplification reaction station for disposable test devices |
US6410275B1 (en) | 1997-05-02 | 2002-06-25 | Biomerieux, Inc. | Disposable test devices for performing nucleic acid amplification reactions |
US7214529B2 (en) | 1997-05-02 | 2007-05-08 | BIOMéRIEUX, INC. | Nucleic acid amplification reaction station for disposable test devices |
EP0875291A2 (en) * | 1997-05-02 | 1998-11-04 | bioMerieux Vitek, Inc. | Dual chamber disposable reaction vessel for amplification reactions, reaction processing station therefor, and methods of use |
WO1998050154A1 (en) * | 1997-05-08 | 1998-11-12 | University Of Minnesota | Integrated microchip genetic testing system |
US8361713B2 (en) | 1997-05-23 | 2013-01-29 | Illumina, Inc. | System and apparatus for sequential processing of analytes |
US9273354B2 (en) | 1997-05-23 | 2016-03-01 | Illumina, Inc. | System and apparatus for sequential processing of analytes |
EP0985142A4 (en) * | 1997-05-23 | 2006-09-13 | Lynx Therapeutics Inc | System and apparaus for sequential processing of analytes |
EP0985142A2 (en) * | 1997-05-23 | 2000-03-15 | Lynx Therapeutics, Inc. | System and apparaus for sequential processing of analytes |
US7282370B2 (en) | 1997-05-23 | 2007-10-16 | Solexa, Inc. | System and apparatus for sequential processing of analytes |
US7399448B2 (en) | 1997-06-06 | 2008-07-15 | Sundberg Steven A | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
US7364915B2 (en) | 1997-06-06 | 2008-04-29 | Sundberg Steven A | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
US7364705B2 (en) | 1997-06-06 | 2008-04-29 | Sundberg Steven A | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
US7259020B2 (en) | 1997-06-06 | 2007-08-21 | Applera Corporation | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
US7364706B2 (en) | 1997-06-06 | 2008-04-29 | Sundberg Steven A | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
US7364703B2 (en) | 1997-06-06 | 2008-04-29 | Sundberg Steven A | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
US7364916B2 (en) | 1997-06-06 | 2008-04-29 | Sundberg Steven A | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
US6709559B2 (en) | 1997-06-06 | 2004-03-23 | Caliper Technologies Corp. | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
US6451188B1 (en) | 1997-06-06 | 2002-09-17 | Caliper Technologies Corp. | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
US7364704B2 (en) | 1997-06-06 | 2008-04-29 | Sundberg Steven A | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
US6090251A (en) * | 1997-06-06 | 2000-07-18 | Caliper Technologies, Inc. | Microfabricated structures for facilitating fluid introduction into microfluidic devices |
US6149870A (en) * | 1997-06-09 | 2000-11-21 | Caliper Technologies Corp. | Apparatus for in situ concentration and/or dilution of materials in microfluidic systems |
US6004515A (en) * | 1997-06-09 | 1999-12-21 | Calipher Technologies Corp. | Methods and apparatus for in situ concentration and/or dilution of materials in microfluidic systems |
US6613512B1 (en) | 1997-06-09 | 2003-09-02 | Caliper Technologies Corp. | Apparatus and method for correcting for variable velocity in microfluidic systems |
US6524790B1 (en) | 1997-06-09 | 2003-02-25 | Caliper Technologies Corp. | Apparatus and methods for correcting for variable velocity in microfluidic systems |
US6703205B2 (en) | 1997-06-09 | 2004-03-09 | Caliper Technologies Corp. | Apparatus and methods for correcting for variable velocity in microfluidic systems |
US5869004A (en) * | 1997-06-09 | 1999-02-09 | Caliper Technologies Corp. | Methods and apparatus for in situ concentration and/or dilution of materials in microfluidic systems |
US6182733B1 (en) | 1997-06-18 | 2001-02-06 | Caliper Technologies Corp. | Methods of manufacturing microfabricated substrates |
US6425972B1 (en) | 1997-06-18 | 2002-07-30 | Calipher Technologies Corp. | Methods of manufacturing microfabricated substrates |
US5882465A (en) * | 1997-06-18 | 1999-03-16 | Caliper Technologies Corp. | Method of manufacturing microfluidic devices |
EP1520621A3 (en) * | 1997-07-21 | 2006-06-07 | Ysi Incorporated | Microfluidic analyzer module |
US6293012B1 (en) | 1997-07-21 | 2001-09-25 | Ysi Incorporated | Method of making a fluid flow module |
WO1999003584A1 (en) * | 1997-07-21 | 1999-01-28 | Ysi Incorporated | Microfluidic analyzer module |
US6073482A (en) * | 1997-07-21 | 2000-06-13 | Ysi Incorporated | Fluid flow module |
US5932799A (en) * | 1997-07-21 | 1999-08-03 | Ysi Incorporated | Microfluidic analyzer module |
EP1520621A2 (en) * | 1997-07-21 | 2005-04-06 | Ysi Incorporated | Microfluidic analyzer module |
US5876675A (en) * | 1997-08-05 | 1999-03-02 | Caliper Technologies Corp. | Microfluidic devices and systems |
US6534013B1 (en) | 1997-08-05 | 2003-03-18 | Caliper Technologies Corp. | Microfluidic devices and systems |
US6048498A (en) * | 1997-08-05 | 2000-04-11 | Caliper Technologies Corp. | Microfluidic devices and systems |
US6582576B1 (en) | 1997-08-29 | 2003-06-24 | Caliper Technologies Corp. | Controller/detector interfaces for microfluidic systems |
US6827831B1 (en) | 1997-08-29 | 2004-12-07 | Callper Life Sciences, Inc. | Controller/detector interfaces for microfluidic systems |
US5989402A (en) * | 1997-08-29 | 1999-11-23 | Caliper Technologies Corp. | Controller/detector interfaces for microfluidic systems |
US6537799B2 (en) | 1997-09-02 | 2003-03-25 | Caliper Technologies Corp. | Electrical current for controlling fluid parameters in microchannels |
US5965410A (en) * | 1997-09-02 | 1999-10-12 | Caliper Technologies Corp. | Electrical current for controlling fluid parameters in microchannels |
US6016712A (en) * | 1997-09-18 | 2000-01-25 | Accumetrics | Device for receiving and processing a sample |
US6540895B1 (en) | 1997-09-23 | 2003-04-01 | California Institute Of Technology | Microfabricated cell sorter for chemical and biological materials |
US6012902A (en) * | 1997-09-25 | 2000-01-11 | Caliper Technologies Corp. | Micropump |
US6394759B1 (en) | 1997-09-25 | 2002-05-28 | Caliper Technologies Corp. | Micropump |
US6568910B1 (en) | 1997-09-25 | 2003-05-27 | Caliper Technologies Corp. | Micropump |
US6171067B1 (en) | 1997-09-25 | 2001-01-09 | Caliper Technologies Corp. | Micropump |
US6186660B1 (en) | 1997-10-09 | 2001-02-13 | Caliper Technologies Corp. | Microfluidic systems incorporating varied channel dimensions |
US6517234B1 (en) | 1997-10-09 | 2003-02-11 | Caliper Technologies Corp. | Microfluidic systems incorporating varied channel dimensions |
US5842787A (en) * | 1997-10-09 | 1998-12-01 | Caliper Technologies Corporation | Microfluidic systems incorporating varied channel dimensions |
US5957579A (en) * | 1997-10-09 | 1999-09-28 | Caliper Technologies Corp. | Microfluidic systems incorporating varied channel dimensions |
US6316201B1 (en) | 1997-10-16 | 2001-11-13 | Caliper Technologies Corp. | Apparatus and methods for sequencing nucleic acids in microfluidic systems |
US6107044A (en) * | 1997-10-16 | 2000-08-22 | Caliper Technologies Corp. | Apparatus and methods for sequencing nucleic acids in microfluidic systems |
US5958694A (en) * | 1997-10-16 | 1999-09-28 | Caliper Technologies Corp. | Apparatus and methods for sequencing nucleic acids in microfluidic systems |
JP2009254384A (en) * | 1997-10-31 | 2009-11-05 | Bbi Bioseq Inc | Method for pressure-enhanced extraction and purification |
US6174675B1 (en) | 1997-11-25 | 2001-01-16 | Caliper Technologies Corp. | Electrical current for controlling fluid parameters in microchannels |
US6042710A (en) * | 1997-12-17 | 2000-03-28 | Caliper Technologies Corp. | Methods and compositions for performing molecular separations |
US7081190B2 (en) | 1997-12-17 | 2006-07-25 | Caliper Life Sciences, Inc. | Methods and compositions for performing molecular separations |
US6440284B1 (en) | 1997-12-17 | 2002-08-27 | Caliper Technologies Corp. | Methods and compositions for performing molecular separations |
US5948227A (en) * | 1997-12-17 | 1999-09-07 | Caliper Technologies Corp. | Methods and systems for performing electrophoretic molecular separations |
US6648015B1 (en) | 1998-01-20 | 2003-11-18 | Caliper Technologies Corp. | Multi-layer microfluidic devices |
US6494230B2 (en) | 1998-01-20 | 2002-12-17 | Caliper Technologies Corp. | Multi-layer microfluidic devices |
US6857449B1 (en) | 1998-01-20 | 2005-02-22 | Caliper Life Sciences, Inc. | Multi-layer microfluidic devices |
US6321791B1 (en) | 1998-01-20 | 2001-11-27 | Caliper Technologies Corp. | Multi-layer microfluidic devices |
US6167910B1 (en) | 1998-01-20 | 2001-01-02 | Caliper Technologies Corp. | Multi-layer microfluidic devices |
US6413766B2 (en) | 1998-01-29 | 2002-07-02 | University Of Pittsburgh Of The Commonwealth System | Rapid thermocycling for sample analysis |
WO1999039005A1 (en) * | 1998-01-29 | 1999-08-05 | University Of Pittsburgh | Rapid thermocycling for sample analysis |
WO1999039120A1 (en) * | 1998-01-29 | 1999-08-05 | University Of Pittsburgh | Thermal expansion-induced fluid control for microfluidic devices |
US6210882B1 (en) | 1998-01-29 | 2001-04-03 | Mayo Foundation For Medical Education And Reseach | Rapid thermocycling for sample analysis |
US6420143B1 (en) | 1998-02-13 | 2002-07-16 | Caliper Technologies Corp. | Methods and systems for performing superheated reactions in microscale fluidic systems |
US6498353B2 (en) | 1998-02-24 | 2002-12-24 | Caliper Technologies | Microfluidic devices and systems incorporating integrated optical elements |
US6251343B1 (en) | 1998-02-24 | 2001-06-26 | Caliper Technologies Corp. | Microfluidic devices and systems incorporating cover layers |
US6756019B1 (en) | 1998-02-24 | 2004-06-29 | Caliper Technologies Corp. | Microfluidic devices and systems incorporating cover layers |
US6100541A (en) * | 1998-02-24 | 2000-08-08 | Caliper Technologies Corporation | Microfluidic devices and systems incorporating integrated optical elements |
US6488897B2 (en) | 1998-02-24 | 2002-12-03 | Caliper Technologies Corp. | Microfluidic devices and systems incorporating cover layers |
US7497994B2 (en) | 1998-02-24 | 2009-03-03 | Khushroo Gandhi | Microfluidic devices and systems incorporating cover layers |
US6316781B1 (en) | 1998-02-24 | 2001-11-13 | Caliper Technologies Corporation | Microfluidic devices and systems incorporating integrated optical elements |
WO1999052633A1 (en) * | 1998-04-14 | 1999-10-21 | Ivd Systems | Test cartridge with a single inlet port |
US6123798A (en) * | 1998-05-06 | 2000-09-26 | Caliper Technologies Corp. | Methods of fabricating polymeric structures incorporating microscale fluidic elements |
US7138032B2 (en) | 1998-05-06 | 2006-11-21 | Caliper Life Sciences, Inc. | Methods of fabricating polymeric structures incorporating microscale fluidic elements |
US6576194B1 (en) | 1998-05-18 | 2003-06-10 | University Of Washington | Sheath flow assembly |
US6537501B1 (en) | 1998-05-18 | 2003-03-25 | University Of Washington | Disposable hematology cartridge |
US6656431B2 (en) | 1998-05-18 | 2003-12-02 | University Of Washington | Sample analysis instrument |
US6551836B1 (en) | 1998-06-08 | 2003-04-22 | Caliper Technologies Corp. | Microfluidic devices, systems and methods for performing integrated reactions and separations |
US6274089B1 (en) | 1998-06-08 | 2001-08-14 | Caliper Technologies Corp. | Microfluidic devices, systems and methods for performing integrated reactions and separations |
US6375871B1 (en) | 1998-06-18 | 2002-04-23 | 3M Innovative Properties Company | Methods of manufacturing microfluidic articles |
US6907921B2 (en) | 1998-06-18 | 2005-06-21 | 3M Innovative Properties Company | Microchanneled active fluid heat exchanger |
WO1999065664A1 (en) * | 1998-06-18 | 1999-12-23 | 3M Innovative Properties Company | Microfluidic articles and method of manufacturing same |
US6381846B2 (en) | 1998-06-18 | 2002-05-07 | 3M Innovative Properties Company | Microchanneled active fluid heat exchanger method |
US6514412B1 (en) | 1998-06-18 | 2003-02-04 | 3M Innovative Properties Company | Microstructured separation device |
US6431695B1 (en) | 1998-06-18 | 2002-08-13 | 3M Innovative Properties Company | Microstructure liquid dispenser |
US6540896B1 (en) | 1998-08-05 | 2003-04-01 | Caliper Technologies Corp. | Open-Field serial to parallel converter |
US7208320B2 (en) | 1998-08-05 | 2007-04-24 | Caliper Life Sciences, Inc. | Open-field serial to parallel converter |
WO2000009991A1 (en) * | 1998-08-10 | 2000-02-24 | Biotul Ag | Method and device for mixing samples near the interface in biosensor systems |
US6132685A (en) * | 1998-08-10 | 2000-10-17 | Caliper Technologies Corporation | High throughput microfluidic systems and methods |
US6495369B1 (en) | 1998-08-10 | 2002-12-17 | Caliper Technologies Corp. | High throughput microfluidic systems and methods |
US6296020B1 (en) | 1998-10-13 | 2001-10-02 | Biomicro Systems, Inc. | Fluid circuit components based upon passive fluid dynamics |
US6591852B1 (en) | 1998-10-13 | 2003-07-15 | Biomicro Systems, Inc. | Fluid circuit components based upon passive fluid dynamics |
US6637463B1 (en) | 1998-10-13 | 2003-10-28 | Biomicro Systems, Inc. | Multi-channel microfluidic system design with balanced fluid flow distribution |
US6601613B2 (en) | 1998-10-13 | 2003-08-05 | Biomicro Systems, Inc. | Fluid circuit components based upon passive fluid dynamics |
US6447661B1 (en) | 1998-10-14 | 2002-09-10 | Caliper Technologies Corp. | External material accession systems and methods |
US6149787A (en) * | 1998-10-14 | 2000-11-21 | Caliper Technologies Corp. | External material accession systems and methods |
US6680193B1 (en) | 1998-10-16 | 2004-01-20 | Commissariat A L'energie Atomique | Device for chemical and/or biological analysis with analysis support |
WO2000023190A1 (en) * | 1998-10-16 | 2000-04-27 | Commissariat A L'energie Atomique | Device for chemical and/or biological analysis with analysis support |
US6086740A (en) * | 1998-10-29 | 2000-07-11 | Caliper Technologies Corp. | Multiplexed microfluidic devices and systems |
US6488895B1 (en) | 1998-10-29 | 2002-12-03 | Caliper Technologies Corp. | Multiplexed microfluidic devices, systems, and methods |
EP1144092A1 (en) * | 1998-12-23 | 2001-10-17 | Nanogen, Inc. | Integrated portable biological detection system |
EP1144092A4 (en) * | 1998-12-23 | 2002-10-29 | Nanogen Inc | Integrated portable biological detection system |
US6987018B2 (en) | 1998-12-24 | 2006-01-17 | Cepheid | Container for holding cells or viruses for disruption |
US6887693B2 (en) | 1998-12-24 | 2005-05-03 | Cepheid | Device and method for lysing cells, spores, or microorganisms |
US6511853B1 (en) | 1999-01-19 | 2003-01-28 | Caliper Technologies Corp. | Optimized high-throughput analytical system |
US6150119A (en) * | 1999-01-19 | 2000-11-21 | Caliper Technologies Corp. | Optimized high-throughput analytical system |
US7276330B2 (en) | 1999-01-28 | 2007-10-02 | Caliper Technologies Corp. | Devices, systems and methods for time domain multiplexing of reagents |
US6475364B1 (en) | 1999-02-02 | 2002-11-05 | Caliper Technologies Corp. | Methods, devices and systems for characterizing proteins |
US9101928B2 (en) | 1999-02-23 | 2015-08-11 | Caliper Life Sciences, Inc. | Manipulation of microparticles in microfluidic systems |
US6632655B1 (en) | 1999-02-23 | 2003-10-14 | Caliper Technologies Corp. | Manipulation of microparticles in microfluidic systems |
US7566538B2 (en) | 1999-02-23 | 2009-07-28 | Caliper Lifesciences Inc. | Sequencing by incorporation |
US7105300B2 (en) | 1999-02-23 | 2006-09-12 | Caliper Life Sciences, Inc. | Sequencing by incorporation |
US6613513B1 (en) | 1999-02-23 | 2003-09-02 | Caliper Technologies Corp. | Sequencing by incorporation |
US7344865B2 (en) | 1999-02-23 | 2008-03-18 | Caliper Life Sciences, Inc. | Sequencing by incorporation |
US6541274B2 (en) | 1999-03-08 | 2003-04-01 | Caliper Technologies Corp. | Integrated devices and method of use for performing temperature controlled reactions and analyses |
US6171850B1 (en) | 1999-03-08 | 2001-01-09 | Caliper Technologies Corp. | Integrated devices and systems for performing temperature controlled reactions and analyses |
US6337212B1 (en) | 1999-03-08 | 2002-01-08 | Caliper Technologies Corp. | Methods and integrated devices and systems for performing temperature controlled reactions and analyses |
US6148508A (en) * | 1999-03-12 | 2000-11-21 | Caliper Technologies Corp. | Method of making a capillary for electrokinetic transport of materials |
US6773567B1 (en) | 1999-03-12 | 2004-08-10 | Caliper Life Sciences, Inc. | High-throughput analytical microfluidic systems and methods of making same |
WO2000055362A1 (en) | 1999-03-16 | 2000-09-21 | Institut Pasteur | Deleted sequences in m. bovis bcg/m. bovis or m. tuberculosis, method for detecting mycobacteria using said sequences and vaccines |
US6500323B1 (en) | 1999-03-26 | 2002-12-31 | Caliper Technologies Corp. | Methods and software for designing microfluidic devices |
US6524830B2 (en) | 1999-04-06 | 2003-02-25 | Caliper Technologies Corp. | Microfluidic devices and systems for performing inefficient fast PCR |
US6303343B1 (en) | 1999-04-06 | 2001-10-16 | Caliper Technologies Corp. | Inefficient fast PCR |
US6322683B1 (en) | 1999-04-14 | 2001-11-27 | Caliper Technologies Corp. | Alignment of multicomponent microfabricated structures |
US6506609B1 (en) | 1999-05-17 | 2003-01-14 | Caliper Technologies Corp. | Focusing of microparticles in microfluidic systems |
US6592821B1 (en) | 1999-05-17 | 2003-07-15 | Caliper Technologies Corp. | Focusing of microparticles in microfluidic systems |
US9789481B2 (en) | 1999-05-28 | 2017-10-17 | Cepheid | Device for extracting nucleic acid from a sample |
US9943848B2 (en) | 1999-05-28 | 2018-04-17 | Cepheid | Apparatus and method for cell disruption |
US8168442B2 (en) | 1999-05-28 | 2012-05-01 | Cepheid | Cartridge for conducting a chemical reaction |
US9073053B2 (en) | 1999-05-28 | 2015-07-07 | Cepheid | Apparatus and method for cell disruption |
US8709363B2 (en) | 1999-05-28 | 2014-04-29 | Cepheid | Cartridge for conducting a chemical reaction |
US9322052B2 (en) | 1999-05-28 | 2016-04-26 | Cepheid | Cartridge for conducting a chemical reaction |
US6649358B1 (en) | 1999-06-01 | 2003-11-18 | Caliper Technologies Corp. | Microscale assays and microfluidic devices for transporter, gradient induced, and binding activities |
US6878540B2 (en) | 1999-06-25 | 2005-04-12 | Cepheid | Device for lysing cells, spores, or microorganisms |
US7064844B2 (en) | 1999-07-05 | 2006-06-20 | Novartis Ag | Sensor platform, apparatus incorporating the platform and process using the platform |
US6867869B2 (en) | 1999-07-05 | 2005-03-15 | Novartis Ag | Sensor platform, apparatus incorporating the platform, and process using the platform |
US6771376B2 (en) | 1999-07-05 | 2004-08-03 | Novartis Ag | Sensor platform, apparatus incorporating the platform, and process using the platform |
US6707561B1 (en) | 1999-07-05 | 2004-03-16 | Novartis Ag | Sensor platform, apparatus incorporating platform, and process using the platform |
US6870630B2 (en) | 1999-07-05 | 2005-03-22 | Novartis Ag | Sensor platform, apparatus incorporating the platform, and process using the same |
US7820106B2 (en) | 1999-07-05 | 2010-10-26 | Novartis Ag | Sensor platform, apparatus incorporating the platform and process using the platform |
EP1196243B2 (en) † | 1999-07-07 | 2009-12-16 | 3M Innovative Properties Company | Detection article having fluid control film with capillary channels |
US6864050B2 (en) | 1999-07-30 | 2005-03-08 | Affymetrix, Inc. | Single-phase amplification of nucleic acids |
US7625760B2 (en) | 1999-08-11 | 2009-12-01 | Asahi Kasei Kabushiki Kaisha | Analyzing cartridge and liquid feed control device |
US6495104B1 (en) | 1999-08-19 | 2002-12-17 | Caliper Technologies Corp. | Indicator components for microfluidic systems |
US6858185B1 (en) | 1999-08-25 | 2005-02-22 | Caliper Life Sciences, Inc. | Dilutions in high throughput systems with a single vacuum source |
US6613581B1 (en) | 1999-08-26 | 2003-09-02 | Caliper Technologies Corp. | Microfluidic analytic detection assays, devices, and integrated systems |
US6752966B1 (en) | 1999-09-10 | 2004-06-22 | Caliper Life Sciences, Inc. | Microfabrication methods and devices |
US6537771B1 (en) | 1999-10-08 | 2003-03-25 | Caliper Technologies Corp. | Use of nernstein voltage sensitive dyes in measuring transmembrane voltage |
US6759191B2 (en) | 1999-10-08 | 2004-07-06 | Caliper Life Sciences, Inc. | Use of nernstein voltage sensitive dyes in measuring transmembrane voltage |
US6979553B2 (en) | 1999-10-08 | 2005-12-27 | Caliper Life Sciences, Inc. | Use of Nernstein voltage sensitive dyes in measuring transmembrane voltage |
EP2319939A2 (en) | 1999-10-21 | 2011-05-11 | Case Western Reserve University | Gene expression profiling of inflammatory bowel disease |
EP2210948A2 (en) | 1999-12-10 | 2010-07-28 | Life Technologies Corporation | Use of multiple recombination sites with unique specificity in recombinational cloning |
EP1978098A2 (en) | 1999-12-10 | 2008-10-08 | Invitrogen Corporation | Use of multiple recombination sites with unique specificity in recombinational cloning |
AU778696B2 (en) * | 1999-12-15 | 2004-12-16 | Ge Healthcare Bio-Sciences Ab | Compositions and methods for performing biological reactions |
US6569674B1 (en) * | 1999-12-15 | 2003-05-27 | Amersham Biosciences Ab | Method and apparatus for performing biological reactions on a substrate surface |
US6431476B1 (en) | 1999-12-21 | 2002-08-13 | Cepheid | Apparatus and method for rapid ultrasonic disruption of cells or viruses |
US6379884B2 (en) | 2000-01-06 | 2002-04-30 | Caliper Technologies Corp. | Methods and systems for monitoring intracellular binding reactions |
US6468761B2 (en) | 2000-01-07 | 2002-10-22 | Caliper Technologies, Corp. | Microfluidic in-line labeling method for continuous-flow protease inhibition analysis |
US6632629B2 (en) | 2000-01-07 | 2003-10-14 | Caliper Technologies Corp. | Microfluidic in-line labeling method of continuous-flow protease inhibition analysis |
US7037416B2 (en) | 2000-01-14 | 2006-05-02 | Caliper Life Sciences, Inc. | Method for monitoring flow rate using fluorescent markers |
US6915679B2 (en) | 2000-02-23 | 2005-07-12 | Caliper Life Sciences, Inc. | Multi-reservoir pressure control system |
US7040144B2 (en) | 2000-02-23 | 2006-05-09 | Caliper Life Sciences, Inc. | Microfluidic viscometer |
US6990851B2 (en) | 2000-02-23 | 2006-01-31 | Caliper Life Sciences, Inc. | Microfluidic viscometer |
US7259021B2 (en) | 2000-03-07 | 2007-08-21 | Bio Merieux | Method for using a test card |
US7521186B2 (en) | 2000-03-20 | 2009-04-21 | Caliper Lifesciences Inc. | PCR compatible nucleic acid sieving matrix |
US6733645B1 (en) | 2000-04-18 | 2004-05-11 | Caliper Technologies Corp. | Total analyte quantitation |
US7264702B1 (en) | 2000-04-18 | 2007-09-04 | Caliper Life Sciences, Inc. | Total analyte quantitation |
US6669831B2 (en) | 2000-05-11 | 2003-12-30 | Caliper Technologies Corp. | Microfluidic devices and methods to regulate hydrodynamic and electrical resistance utilizing bulk viscosity enhancers |
US6777184B2 (en) | 2000-05-12 | 2004-08-17 | Caliper Life Sciences, Inc. | Detection of nucleic acid hybridization by fluorescence polarization |
US7700359B2 (en) | 2000-06-02 | 2010-04-20 | Novartis Vaccines And Diagnostics, Inc. | Gene products differentially expressed in cancerous cells |
US8221983B2 (en) | 2000-06-02 | 2012-07-17 | Novartis Vaccines And Diagnostics, Inc. | Gene products differentially expressed in cancerous cells |
US8129176B2 (en) | 2000-06-05 | 2012-03-06 | California Institute Of Technology | Integrated active flux microfluidic devices and methods |
US8257666B2 (en) | 2000-06-05 | 2012-09-04 | California Institute Of Technology | Integrated active flux microfluidic devices and methods |
EP1953243A2 (en) | 2000-06-15 | 2008-08-06 | Novartis Vaccines and Diagnostics, Inc. | Polynucleotides related to colon cancer |
US9926521B2 (en) | 2000-06-27 | 2018-03-27 | Fluidigm Corporation | Microfluidic particle-analysis systems |
EP1314024A4 (en) * | 2000-08-02 | 2007-04-11 | Caliper Life Sciences Inc | High throughput separations based analysis systems |
EP1314024A1 (en) * | 2000-08-02 | 2003-05-28 | Caliper Technologies Corp. | High throughput separations based analysis systems |
US7192559B2 (en) | 2000-08-03 | 2007-03-20 | Caliper Life Sciences, Inc. | Methods and devices for high throughput fluid delivery |
WO2002011887A1 (en) | 2000-08-03 | 2002-02-14 | Caliper Technologies Corp. | Methods and devices for high throughput fluid delivery |
US9309520B2 (en) | 2000-08-21 | 2016-04-12 | Life Technologies Corporation | Methods and compositions for synthesis of nucleic acid molecules using multiple recognition sites |
US6670153B2 (en) | 2000-09-14 | 2003-12-30 | Caliper Technologies Corp. | Microfluidic devices and methods for performing temperature mediated reactions |
US7153673B2 (en) | 2000-09-14 | 2006-12-26 | Caliper Life Sciences, Inc. | Microfluidic devices and methods for performing temperature mediated reactions |
US6623860B2 (en) | 2000-10-10 | 2003-09-23 | Aclara Biosciences, Inc. | Multilevel flow structures |
US9983155B2 (en) | 2000-11-16 | 2018-05-29 | Canon U.S. Life Sciences, Inc. | Method and apparatus for generating thermal melting curves in a microfluidic device |
US9376718B2 (en) | 2000-11-16 | 2016-06-28 | Caliper Life Sciences, Inc. | Method and apparatus for generating thermal melting curves in a microfluidic device |
US11162910B2 (en) | 2000-11-16 | 2021-11-02 | Caliper Life Sciences, Inc. | Method and apparatus for generating thermal melting curves in a microfluidic device |
US8900811B2 (en) | 2000-11-16 | 2014-12-02 | Caliper Life Sciences, Inc. | Method and apparatus for generating thermal melting curves in a microfluidic device |
EP1343973B2 (en) † | 2000-11-16 | 2020-09-16 | California Institute Of Technology | Apparatus and methods for conducting assays and high throughput screening |
US10509018B2 (en) | 2000-11-16 | 2019-12-17 | California Institute Of Technology | Apparatus and methods for conducting assays and high throughput screening |
US10871460B2 (en) | 2000-11-16 | 2020-12-22 | Canon U.S.A., Inc. | Method and apparatus for generating thermal melting curves in a microfluidic device |
US7776523B2 (en) | 2000-12-07 | 2010-08-17 | Novartis Vaccines And Diagnostics, Inc. | Endogenous retroviruses up-regulated in prostate cancer |
EP2339035A1 (en) | 2000-12-07 | 2011-06-29 | Novartis Vaccines and Diagnostics, Inc. | Endogenous retroviruses up-regulated in prostate cancer |
EP2336368A1 (en) | 2000-12-07 | 2011-06-22 | Novartis Vaccines and Diagnostics, Inc. | Endogenous retroviruses up-regulated in prostate cancer |
US8945884B2 (en) | 2000-12-11 | 2015-02-03 | Life Technologies Corporation | Methods and compositions for synthesis of nucleic acid molecules using multiplerecognition sites |
US6681788B2 (en) | 2001-01-29 | 2004-01-27 | Caliper Technologies Corp. | Non-mechanical valves for fluidic systems |
US6779559B2 (en) | 2001-01-29 | 2004-08-24 | Caliper Life Sciences, Inc. | Non-mechanical valves for fluidic systems |
US7670559B2 (en) | 2001-02-15 | 2010-03-02 | Caliper Life Sciences, Inc. | Microfluidic systems with enhanced detection systems |
US6720148B1 (en) | 2001-02-22 | 2004-04-13 | Caliper Life Sciences, Inc. | Methods and systems for identifying nucleotides by primer extension |
US7867776B2 (en) | 2001-03-02 | 2011-01-11 | Caliper Life Sciences, Inc. | Priming module for microfluidic chips |
US7150999B1 (en) | 2001-03-09 | 2006-12-19 | Califer Life Sciences, Inc. | Process for filling microfluidic channels |
US7833708B2 (en) | 2001-04-06 | 2010-11-16 | California Institute Of Technology | Nucleic acid amplification using microfluidic devices |
US8486636B2 (en) | 2001-04-06 | 2013-07-16 | California Institute Of Technology | Nucleic acid amplification using microfluidic devices |
US8936764B2 (en) | 2001-04-06 | 2015-01-20 | California Institute Of Technology | Nucleic acid amplification using microfluidic devices |
US7723123B1 (en) | 2001-06-05 | 2010-05-25 | Caliper Life Sciences, Inc. | Western blot by incorporating an affinity purification zone |
US8592141B2 (en) | 2001-06-05 | 2013-11-26 | Caliper Life Sciences, Inc. | Western blot by incorporating an affinity purification zone |
US8007738B2 (en) | 2001-06-05 | 2011-08-30 | Caliper Life Sciences, Inc. | Western blot by incorporating an affinity purification zone |
US6977163B1 (en) | 2001-06-13 | 2005-12-20 | Caliper Life Sciences, Inc. | Methods and systems for performing multiple reactions by interfacial mixing |
US8216852B2 (en) | 2001-07-27 | 2012-07-10 | Caliper Life Sciences, Inc. | Channel cross-section geometry to manipulate dispersion rates |
US7060171B1 (en) | 2001-07-31 | 2006-06-13 | Caliper Life Sciences, Inc. | Methods and systems for reducing background signal in assays |
US7498407B2 (en) | 2001-11-09 | 2009-03-03 | Georgetown University | Vascular endothelial cell growth inhibitor, VEGI-192a |
US7750133B2 (en) | 2001-11-09 | 2010-07-06 | Georgetown University | Vascular endothelial cell growth inhibitor, VEGI-192a |
US7247274B1 (en) | 2001-11-13 | 2007-07-24 | Caliper Technologies Corp. | Prevention of precipitate blockage in microfluidic channels |
US7069952B1 (en) | 2001-11-14 | 2006-07-04 | Caliper Life Sciences, Inc. | Microfluidic devices and methods of their manufacture |
US7820427B2 (en) | 2001-11-30 | 2010-10-26 | Fluidigm Corporation | Microfluidic device and methods of using same |
US9643178B2 (en) | 2001-11-30 | 2017-05-09 | Fluidigm Corporation | Microfluidic device with reaction sites configured for blind filling |
US8163492B2 (en) | 2001-11-30 | 2012-04-24 | Fluidign Corporation | Microfluidic device and methods of using same |
US7691333B2 (en) | 2001-11-30 | 2010-04-06 | Fluidigm Corporation | Microfluidic device and methods of using same |
US7837946B2 (en) | 2001-11-30 | 2010-11-23 | Fluidigm Corporation | Microfluidic device and methods of using same |
US8343442B2 (en) | 2001-11-30 | 2013-01-01 | Fluidigm Corporation | Microfluidic device and methods of using same |
US7749442B2 (en) | 2001-12-14 | 2010-07-06 | Arkray, Inc. | Sample measuring device |
EP2075346A2 (en) | 2002-01-08 | 2009-07-01 | Novartis Vaccines and Diagnostics, Inc. | Gene products differentially expressed in cancerous breast cells and their methods of use |
US7160423B2 (en) | 2002-03-05 | 2007-01-09 | Caliper Life Sciences, Inc. | Mixed mode microfluidic systems |
US7303727B1 (en) | 2002-03-06 | 2007-12-04 | Caliper Life Sciences, Inc | Microfluidic sample delivery devices, systems, and methods |
US8658418B2 (en) | 2002-04-01 | 2014-02-25 | Fluidigm Corporation | Microfluidic particle-analysis systems |
US7419784B2 (en) | 2002-04-02 | 2008-09-02 | Dubrow Robert S | Methods, systems and apparatus for separation and isolation of one or more sample components of a sample biological material |
US11027278B2 (en) | 2002-04-17 | 2021-06-08 | Cytonome/St, Llc | Methods for controlling fluid flow in a microfluidic system |
US9683994B2 (en) | 2002-04-24 | 2017-06-20 | Caliper Life Sciences, Inc. | High throughput mobility shift |
US8241883B2 (en) | 2002-04-24 | 2012-08-14 | Caliper Life Sciences, Inc. | High throughput mobility shift |
EP1900827A2 (en) | 2002-05-21 | 2008-03-19 | Bayer HealthCare AG | Methods and compositions for the prediction, diagnosis, prognosis, prevention and treatment of malignant neoplasia |
US7161356B1 (en) | 2002-06-05 | 2007-01-09 | Caliper Life Sciences, Inc. | Voltage/current testing equipment for microfluidic devices |
US8518694B2 (en) | 2002-06-13 | 2013-08-27 | Novartis Vaccines And Diagnostics, Inc. | Nucleic acid vector comprising a promoter and a sequence encoding a polypeptide from the endogenous retrovirus PCAV |
US9714443B2 (en) | 2002-09-25 | 2017-07-25 | California Institute Of Technology | Microfabricated structure having parallel and orthogonal flow channels controlled by row and column multiplexors |
US9579650B2 (en) | 2002-10-02 | 2017-02-28 | California Institute Of Technology | Microfluidic nucleic acid analysis |
US10940473B2 (en) | 2002-10-02 | 2021-03-09 | California Institute Of Technology | Microfluidic nucleic acid analysis |
US10328428B2 (en) | 2002-10-02 | 2019-06-25 | California Institute Of Technology | Apparatus for preparing cDNA libraries from single cells |
US8871446B2 (en) | 2002-10-02 | 2014-10-28 | California Institute Of Technology | Microfluidic nucleic acid analysis |
US8275554B2 (en) | 2002-12-20 | 2012-09-25 | Caliper Life Sciences, Inc. | System for differentiating the lengths of nucleic acids of interest in a sample |
US10428377B2 (en) | 2002-12-20 | 2019-10-01 | Caliper Life Sciences, Inc. | Methods of detecting low copy nucleic acids |
US7645581B2 (en) | 2002-12-20 | 2010-01-12 | Caliper Life Sciences, Inc. | Determining nucleic acid fragmentation status by coincident detection of two labeled probes |
US8557198B2 (en) | 2003-01-14 | 2013-10-15 | Micronics, Inc. | Microfluidic devices for fluid manipulation and analysis |
US8318109B2 (en) | 2003-01-14 | 2012-11-27 | Micronics, Inc. | Microfluidic devices for fluid manipulation and analysis |
US8697009B2 (en) | 2003-01-14 | 2014-04-15 | Micronics, Inc. | Microfluidic devices for fluid manipulation and analysis |
US7867454B2 (en) | 2003-04-03 | 2011-01-11 | Fluidigm Corporation | Thermal reaction device and method for using the same |
US7749737B2 (en) | 2003-04-03 | 2010-07-06 | Fluidigm Corporation | Thermal reaction device and method for using the same |
US8007746B2 (en) | 2003-04-03 | 2011-08-30 | Fluidigm Corporation | Microfluidic devices and methods of using same |
US9150913B2 (en) | 2003-04-03 | 2015-10-06 | Fluidigm Corporation | Thermal reaction device and method for using the same |
US10131934B2 (en) | 2003-04-03 | 2018-11-20 | Fluidigm Corporation | Thermal reaction device and method for using the same |
US8247178B2 (en) | 2003-04-03 | 2012-08-21 | Fluidigm Corporation | Thermal reaction device and method for using the same |
EP1892306A2 (en) | 2003-10-06 | 2008-02-27 | Bayer HealthCare AG | Methods and kits for investigating cancer |
US9534252B2 (en) | 2003-12-01 | 2017-01-03 | Life Technologies Corporation | Nucleic acid molecules containing recombination sites and methods of using the same |
US7901881B2 (en) | 2004-04-09 | 2011-03-08 | The United States Of America As Represented By The Department Of Health And Human Services | Diagnostic tool for diagnosing benign versus malignant thyroid lesions |
US7550267B2 (en) | 2004-09-23 | 2009-06-23 | University Of Washington | Microscale diffusion immunoassay utilizing multivalent reactants |
EP2311530A2 (en) | 2004-10-27 | 2011-04-20 | Vanderbilt University | Mammalian genes involved in infection |
US10994273B2 (en) | 2004-12-03 | 2021-05-04 | Cytonome/St, Llc | Actuation of parallel microfluidic arrays |
US8025853B2 (en) | 2004-12-13 | 2011-09-27 | Canon Kabushiki Kaisha | Biochemical processing apparatus |
US8831783B2 (en) | 2004-12-13 | 2014-09-09 | Canon Kabushiki Kaisha | Biochemical processing apparatus |
EP2418018A3 (en) * | 2004-12-23 | 2012-03-28 | Abbott Point of Care Inc. | Methods for the separation nucleic acids |
US8883487B2 (en) | 2004-12-23 | 2014-11-11 | Abbott Point Of Care Inc. | Molecular diagnostics system and methods |
US8249681B2 (en) | 2005-01-31 | 2012-08-21 | Given Imaging Ltd. | Device, system and method for in vivo analysis |
US8828663B2 (en) | 2005-03-18 | 2014-09-09 | Fluidigm Corporation | Thermal reaction device and method for using the same |
WO2007016367A2 (en) | 2005-07-29 | 2007-02-08 | Bayer Healthcare Llc | Neoplastic disease-related methods, kits, systems and databases |
EP2402460A1 (en) | 2006-02-09 | 2012-01-04 | Caliper Life Sciences, Inc. | Method and apparatus for generating thermal melting curves in a microfluidic device |
EP2636755A1 (en) | 2006-05-26 | 2013-09-11 | AltheaDx Incorporated | Biochemical analysis of partitioned cells |
EP2442109A1 (en) | 2006-07-14 | 2012-04-18 | The Regents of the University of California | Cancer biomarkers and methods of use thereof |
EP2442108A1 (en) | 2006-07-14 | 2012-04-18 | The Regents of the University of California | Cancer biomarkers and methods of use thereof |
EP2450710A2 (en) | 2006-07-14 | 2012-05-09 | The Regents of the University of California | Cancer biomarkers and methods of use thereof |
EP3796002A1 (en) | 2006-07-14 | 2021-03-24 | The Regents of The University of California | Cancer biomarkers and methods of use thereof |
WO2008008284A2 (en) | 2006-07-14 | 2008-01-17 | The Regents Of The University Of California | Cancer biomarkers and methods of use threof |
US9234244B2 (en) | 2007-08-27 | 2016-01-12 | The United States Of America, As Represented By The Secretary, Department Of Health And Human Services | Diagnostic tool for diagnosing benign versus malignant thyroid lesions |
EP3677336A1 (en) | 2007-09-05 | 2020-07-08 | Caliper Life Sciences Inc. | Microfluidic method and system for enzyme inhibition activity screening |
US10900961B2 (en) | 2007-09-20 | 2021-01-26 | Vanderbilt University | Free solution measurement of molecular interactions by backscattering interferometry |
US10894986B2 (en) | 2008-04-16 | 2021-01-19 | The Johns Hopkins University | Compositions and methods for treating or preventing prostate cancer and for detecting androgen receptor variants |
WO2009146204A1 (en) | 2008-04-18 | 2009-12-03 | Tufts Medical Center | Polymorphisms associated with age-related macular degeneration and methods for evaluating patient risk |
US10107797B2 (en) | 2008-10-03 | 2018-10-23 | Micronics, Inc. | Microfluidic apparatus and methods for performing blood typing and crossmatching |
US9101933B2 (en) | 2008-10-10 | 2015-08-11 | University Of Hull | Microfluidic apparatus and method for DNA extraction, amplification and analysis |
EP2894229A1 (en) | 2009-03-27 | 2015-07-15 | Tufts Medical Center, Inc. | Markers related to age-related macular degeneration and uses therefor |
WO2010111595A2 (en) | 2009-03-27 | 2010-09-30 | Tufts - New England Medical Center | Markers related to age-related macular degeneration and uses therefor |
US9067207B2 (en) | 2009-06-04 | 2015-06-30 | University Of Virginia Patent Foundation | Optical approach for microfluidic DNA electrophoresis detection |
US9656261B2 (en) | 2009-06-04 | 2017-05-23 | Leidos Innovations Technology, Inc. | DNA analyzer |
US9649631B2 (en) | 2009-06-04 | 2017-05-16 | Leidos Innovations Technology, Inc. | Multiple-sample microfluidic chip for DNA analysis |
US20110229898A1 (en) * | 2009-06-04 | 2011-09-22 | Lockheed Martin Corporation | DNA analyzer |
EP3508854A1 (en) | 2010-04-27 | 2019-07-10 | The Regents of The University of California | Cancer biomarkers and methods of use thereof |
WO2011139721A1 (en) | 2010-04-27 | 2011-11-10 | The Regents Of The University Of California | Cancer biomarkers and methods of use thereof |
WO2011146725A1 (en) | 2010-05-19 | 2011-11-24 | Bayer Healthcare Llc | Biomarkers for a multikinase inhibitor |
US9638632B2 (en) | 2010-06-11 | 2017-05-02 | Vanderbilt University | Multiplexed interferometric detection system and method |
US8961764B2 (en) | 2010-10-15 | 2015-02-24 | Lockheed Martin Corporation | Micro fluidic optic design |
US10202615B2 (en) | 2010-12-10 | 2019-02-12 | Vanderbilt University | Mammalian genes involved in toxicity and infection |
US9562853B2 (en) | 2011-02-22 | 2017-02-07 | Vanderbilt University | Nonaqueous backscattering interferometric methods |
US9382590B2 (en) | 2011-03-25 | 2016-07-05 | Florida Agricultural and Mechanical University (FAMU) | Methods and compositions for prostate cancer metastasis |
US9914976B2 (en) | 2011-03-25 | 2018-03-13 | Florida Agricultural And Mechanical University (Fa | Methods and compositions for prostate cancer metastasis |
US10221218B2 (en) | 2011-05-10 | 2019-03-05 | The Regents Of The University Of California | Adenovirus isolated from titi monkeys |
US9267112B2 (en) | 2011-05-10 | 2016-02-23 | The Regents Of The University Of California | Adenovirus isolated from Titi Monkeys |
US8759079B2 (en) | 2011-11-15 | 2014-06-24 | Korea Institute Of Machinery & Materials | Device for automatically analyzing nucleic acid |
US9322054B2 (en) | 2012-02-22 | 2016-04-26 | Lockheed Martin Corporation | Microfluidic cartridge |
US9988676B2 (en) | 2012-02-22 | 2018-06-05 | Leidos Innovations Technology, Inc. | Microfluidic cartridge |
US9273949B2 (en) | 2012-05-11 | 2016-03-01 | Vanderbilt University | Backscattering interferometric methods |
US10816550B2 (en) | 2012-10-15 | 2020-10-27 | Nanocellect Biomedical, Inc. | Systems, apparatus, and methods for sorting particles |
US9884067B2 (en) | 2013-03-14 | 2018-02-06 | University Of Maryland, Baltimore | Androgen receptor down-regulating agents and uses thereof |
US9803230B2 (en) | 2013-03-15 | 2017-10-31 | Abbott Molecular Inc. | One-step procedure for the purification of nucleic acids |
WO2014172661A1 (en) | 2013-04-19 | 2014-10-23 | The Regent Of The University Of California | Lone star virus |
US11016108B2 (en) | 2013-05-07 | 2021-05-25 | Perkinelmer Health Sciences, Inc. | Microfluidic devices and methods for performing serum separation and blood cross-matching |
US10386377B2 (en) | 2013-05-07 | 2019-08-20 | Micronics, Inc. | Microfluidic devices and methods for performing serum separation and blood cross-matching |
US9808472B2 (en) | 2013-08-12 | 2017-11-07 | Tokai Pharmaceuticals, Inc. | Biomarkers for treatment of neoplastic disorders using androgen-targeted therapies |
US10774387B2 (en) | 2014-05-19 | 2020-09-15 | The Johns Hopkins University | Methods for identifying androgen receptor splice variants in subjects having castration resistant prostate cancer |
US11866787B2 (en) | 2014-05-19 | 2024-01-09 | The Johns Hopkins University | Methods for identifying androgen receptor splice variants in subjects having castration resistant prostate cancer |
US11345956B2 (en) | 2014-08-25 | 2022-05-31 | The Johns Hopkins University | Methods and compositions related to prostate cancer therapeutics |
US11543411B2 (en) | 2014-12-05 | 2023-01-03 | Prelude Corporation | DCIS recurrence and invasive breast cancer |
US10261013B2 (en) | 2015-01-23 | 2019-04-16 | Vanderbilt University | Robust interferometer and methods of using same |
US11293863B2 (en) | 2015-01-23 | 2022-04-05 | Vanderbilt University | Robust interferometer and methods of using same |
EP4019643A1 (en) | 2015-09-23 | 2022-06-29 | Oklahoma Medical Research Foundation | Biomarkers for assessing subjects with multiple sclerosis |
US11143649B2 (en) | 2016-01-29 | 2021-10-12 | Vanderbilt University | Free-solution response function interferometry |
US10627396B2 (en) | 2016-01-29 | 2020-04-21 | Vanderbilt University | Free-solution response function interferometry |
US11821900B2 (en) | 2018-09-14 | 2023-11-21 | Prelude Corporation | Method of selection for treatment of subjects at risk of invasive breast cancer |
US11926817B2 (en) | 2019-08-09 | 2024-03-12 | Nutcracker Therapeutics, Inc. | Microfluidic apparatus and methods of use thereof |
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EP0843734B1 (en) | 2003-03-26 |
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