CA2356634A1 - Improved biosensor device and method of manufacturing same - Google Patents
Improved biosensor device and method of manufacturing same Download PDFInfo
- Publication number
- CA2356634A1 CA2356634A1 CA002356634A CA2356634A CA2356634A1 CA 2356634 A1 CA2356634 A1 CA 2356634A1 CA 002356634 A CA002356634 A CA 002356634A CA 2356634 A CA2356634 A CA 2356634A CA 2356634 A1 CA2356634 A1 CA 2356634A1
- Authority
- CA
- Canada
- Prior art keywords
- fibers
- fiber
- biosensor
- devices
- manufacturing
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
Classifications
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
- B01L3/5085—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates
- B01L3/50857—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above for multiple samples, e.g. microtitration plates using arrays or bundles of open capillaries for holding samples
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0046—Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/75—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated
- G01N21/77—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator
- G01N21/7703—Systems in which material is subjected to a chemical reaction, the progress or the result of the reaction being investigated by observing the effect on a chemical indicator using reagent-clad optical fibres or optical waveguides
-
- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B6/00—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings
- G02B6/04—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings formed by bundles of fibres
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00513—Essentially linear supports
- B01J2219/00524—Essentially linear supports in the shape of fiber bundles
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00277—Apparatus
- B01J2219/00497—Features relating to the solid phase supports
- B01J2219/00527—Sheets
- B01J2219/00536—Sheets in the shape of disks
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00585—Parallel processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00596—Solid-phase processes
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00612—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports the surface being inorganic
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00614—Delimitation of the attachment areas
- B01J2219/00621—Delimitation of the attachment areas by physical means, e.g. trenches, raised areas
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00605—Making arrays on substantially continuous surfaces the compounds being directly bound or immobilised to solid supports
- B01J2219/00623—Immobilisation or binding
- B01J2219/00626—Covalent
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00659—Two-dimensional arrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00583—Features relative to the processes being carried out
- B01J2219/00603—Making arrays on substantially continuous surfaces
- B01J2219/00673—Slice arrays
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00718—Type of compounds synthesised
- B01J2219/0072—Organic compounds
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00718—Type of compounds synthesised
- B01J2219/0072—Organic compounds
- B01J2219/00722—Nucleotides
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00274—Sequential or parallel reactions; Apparatus and devices for combinatorial chemistry or for making arrays; Chemical library technology
- B01J2219/00718—Type of compounds synthesised
- B01J2219/0072—Organic compounds
- B01J2219/0074—Biological products
-
- C—CHEMISTRY; METALLURGY
- C40—COMBINATORIAL TECHNOLOGY
- C40B—COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES
- C40B40/00—Libraries per se, e.g. arrays, mixtures
- C40B40/04—Libraries containing only organic compounds
- C40B40/06—Libraries containing nucleotides or polynucleotides, or derivatives thereof
-
- G—PHYSICS
- G02—OPTICS
- G02B—OPTICAL ELEMENTS, SYSTEMS OR APPARATUS
- G02B6/00—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings
- G02B6/04—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings formed by bundles of fibres
- G02B6/06—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings formed by bundles of fibres the relative position of the fibres being the same at both ends, e.g. for transporting images
- G02B6/08—Light guides; Structural details of arrangements comprising light guides and other optical elements, e.g. couplings formed by bundles of fibres the relative position of the fibres being the same at both ends, e.g. for transporting images with fibre bundle in form of plate
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/14—Heterocyclic carbon compound [i.e., O, S, N, Se, Te, as only ring hetero atom]
- Y10T436/142222—Hetero-O [e.g., ascorbic acid, etc.]
- Y10T436/143333—Saccharide [e.g., DNA, etc.]
Abstract
A new biosensor device (10) and biosensor device manufacturing method improv es upon the prior art by providing high reliability devices that can be manufactured on an extremely cost basis and which are amenable to quality control procedures, which can be performed on individual fibers as well as t he devices themselves. The improved biosensor devices are manufactured by first synthesizing a plurality of functional moieties onto a plurality of fibers (100), which may be solid and/or hollow, wherein at least one fiber receives one moiety. Once the functional moieties are synthesized onto the fibers, th e fibers are bundled in a predetermined arrangement (120). The bundled fibers are then bonded or fused together to fix their predetermined arrangement (130). Finally, the bonded fiber bundle is sliced into a plurality of individual devices or chips (140).
Description
IMPROVED BIOSENSOR DEVICE AND METHOD OF MANUFACTURING SAME
FIELD OF THE INVENTION
This invention relates to a device which can serve as a _ biosensor device and which is useful for separation and detection of micro quantities of proteins and similar types of genetic materials and organic molecules and to a method of manufacturing such a device, which can be implemented as microarrays which may be used for high throughput screening applications, bioremediation and detection and quantification.
BACKGROUND OF THE INVENTION
There exists a need for reliable, low cost analytical devices that allow for the rapid separation and detection of micro quantities of cellular tissue, genetic material, organic molecules, sequencing, etc. for use in research as well as in the diagnosis of diseases) or the existence of certain predetermined conditions. DNA analysis is an effective approach for the detection and identification of viruses, bacteria, and other microbes and is essential to the identification of genetic disorders. The ability to detect DNA
with a high level of specificity entails high resolution separation of RNA or DNA fragments, appropriate labeling chemistry for such fragments and the adaptation of high sensitivity sensors that are specific for the labeling chemistry employed. DNA probe technology is now an established tool of the molecular biologist for revealing the presence of diagnostically significant cells, whether they be diseased cells from the subject or infectious micro organisms.
Recently, DNA analysis devices have experienced a miniaturization trend similar to that experienced in the electronics industry with the advent of integrated circuits.
Many of the same principles that have led to smaller and smaller micro processor devices have shrunk the size of a chemistry lab to a device no larger than the size of a dime.
The techniques are all aimed at producing a device having different, discreet areas that are sensitive to different genetic sequences. These areas, or probes, are formed using a number of techniques, including photo patterning methods, such _ as photolithography, which is a direct descendant from techniques used in the manufacture of micro processor chips;
micro machining, where tiny channels are machined into a chip to hold various test media; and other methods of precisely depositing test media upon chips in a precisely defined pattern.
While these methods do allow for the manufacture of acceptable biosensor chips, they do have a number of drawbacks.
One significant drawback is the sophistication and expense of photo patterning, micro machining and micro-media deposition devices that are capable of producing biosensor chips including hundreds or thousands of individual probes. Additionally, the use of these prior art methods requires extreme precision in the deposition of test materials since their deposition involves microscopic quantities and positions. This also leads to significant quality control issues, since a single biosensor chip can have literally thousands of separate probes, each of which requires testing or verification.
Due to these drawbacks and limitations, biosensor chips are expensive to manufacture and although they provide significant improvements in the state of the art, they have not yet experienced wide scale implementation. In addition, the technology is too expensive for implementation with respect to low cost diagnostic tests.
Accordingly, there is a need for an improved biosensor chip or device and method of manufacturing the same, which can result in inexpensive biosensor devices that can be manufactured using cost effective machinery. Additionally, there is a need for a biosensor device that can be highly reliable due to improved quality assurance procedures performed during the manufacture thereof. Finally, a biosensor device is needed that can utilize the same manufacturing methods for a wide variety of analysis protocols including both sophisticated and simple analytical procedures.
SUMMARY OF THE INVENTION
The disclosed invention provides a new biosensor device which improves upon the prior art by providing high reliability sensors that can be manufactured on an extremely low cost basis. The improved biosensor devices are manufactured by first synthesizing a plurality of functional moieties onto a plurality of fibers, wherein each fiber receives one moiety.
Once the functional-moieties are synthesized onto the fibers, the fibers are bundled in a predetermined arrangement. The bundled fibers are then bonded together to fix their predetermined arrangement. Finally, the bonded fiber bundle is "sliced" into a plurality of devices (chips). In one preferred embodiment, the fibers comprise glass fibers.
DESCRIPTION OF THE DRAWINGS
These and other features and advantages of the present invention will be better understood by reading the following detailed description, taken together with the drawings wherein:
Fig. 1 is a flow diagram showing the steps included in the disclosed method of manufacturing a biosensor device;
Fig. 2 is a detailed block diagram of a method of synthesizing DNA onto fibers to be included in the biosensor device of the present invention;
Fig. 3 is a functio nal block diagram of the disclosed method of manufacturing biosensor devices; and Fig. 4 is a top view of a biosensor device manufactured according to the principles of the present invention.
FIELD OF THE INVENTION
This invention relates to a device which can serve as a _ biosensor device and which is useful for separation and detection of micro quantities of proteins and similar types of genetic materials and organic molecules and to a method of manufacturing such a device, which can be implemented as microarrays which may be used for high throughput screening applications, bioremediation and detection and quantification.
BACKGROUND OF THE INVENTION
There exists a need for reliable, low cost analytical devices that allow for the rapid separation and detection of micro quantities of cellular tissue, genetic material, organic molecules, sequencing, etc. for use in research as well as in the diagnosis of diseases) or the existence of certain predetermined conditions. DNA analysis is an effective approach for the detection and identification of viruses, bacteria, and other microbes and is essential to the identification of genetic disorders. The ability to detect DNA
with a high level of specificity entails high resolution separation of RNA or DNA fragments, appropriate labeling chemistry for such fragments and the adaptation of high sensitivity sensors that are specific for the labeling chemistry employed. DNA probe technology is now an established tool of the molecular biologist for revealing the presence of diagnostically significant cells, whether they be diseased cells from the subject or infectious micro organisms.
Recently, DNA analysis devices have experienced a miniaturization trend similar to that experienced in the electronics industry with the advent of integrated circuits.
Many of the same principles that have led to smaller and smaller micro processor devices have shrunk the size of a chemistry lab to a device no larger than the size of a dime.
The techniques are all aimed at producing a device having different, discreet areas that are sensitive to different genetic sequences. These areas, or probes, are formed using a number of techniques, including photo patterning methods, such _ as photolithography, which is a direct descendant from techniques used in the manufacture of micro processor chips;
micro machining, where tiny channels are machined into a chip to hold various test media; and other methods of precisely depositing test media upon chips in a precisely defined pattern.
While these methods do allow for the manufacture of acceptable biosensor chips, they do have a number of drawbacks.
One significant drawback is the sophistication and expense of photo patterning, micro machining and micro-media deposition devices that are capable of producing biosensor chips including hundreds or thousands of individual probes. Additionally, the use of these prior art methods requires extreme precision in the deposition of test materials since their deposition involves microscopic quantities and positions. This also leads to significant quality control issues, since a single biosensor chip can have literally thousands of separate probes, each of which requires testing or verification.
Due to these drawbacks and limitations, biosensor chips are expensive to manufacture and although they provide significant improvements in the state of the art, they have not yet experienced wide scale implementation. In addition, the technology is too expensive for implementation with respect to low cost diagnostic tests.
Accordingly, there is a need for an improved biosensor chip or device and method of manufacturing the same, which can result in inexpensive biosensor devices that can be manufactured using cost effective machinery. Additionally, there is a need for a biosensor device that can be highly reliable due to improved quality assurance procedures performed during the manufacture thereof. Finally, a biosensor device is needed that can utilize the same manufacturing methods for a wide variety of analysis protocols including both sophisticated and simple analytical procedures.
SUMMARY OF THE INVENTION
The disclosed invention provides a new biosensor device which improves upon the prior art by providing high reliability sensors that can be manufactured on an extremely low cost basis. The improved biosensor devices are manufactured by first synthesizing a plurality of functional moieties onto a plurality of fibers, wherein each fiber receives one moiety.
Once the functional-moieties are synthesized onto the fibers, the fibers are bundled in a predetermined arrangement. The bundled fibers are then bonded together to fix their predetermined arrangement. Finally, the bonded fiber bundle is "sliced" into a plurality of devices (chips). In one preferred embodiment, the fibers comprise glass fibers.
DESCRIPTION OF THE DRAWINGS
These and other features and advantages of the present invention will be better understood by reading the following detailed description, taken together with the drawings wherein:
Fig. 1 is a flow diagram showing the steps included in the disclosed method of manufacturing a biosensor device;
Fig. 2 is a detailed block diagram of a method of synthesizing DNA onto fibers to be included in the biosensor device of the present invention;
Fig. 3 is a functio nal block diagram of the disclosed method of manufacturing biosensor devices; and Fig. 4 is a top view of a biosensor device manufactured according to the principles of the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT
Turning now to the Figures, and in particular Figs 1 and 3, an improved method of manufacturing a biosensor device is disclosed. Method 100 begins by synthesizing functional moieties onto a plurality of fibers, step 110. The fibers can be various diameters and may be solid or hollow. At least one fiber receives several moieties of the same species. However, as will become evident below, more than one fiber may receive the same functional moiety. The functional moieties selected will be dependent upon the specific testing protocol or protocols for which the biosensor device is designed.
For example, functional moieties may include DNA
oligonucleotides for DNA testing biosensor devices.
Alternatively, the functional moieties may include proteins, peptides, antibodies or other chemical functional groups. In the preferred embodiment, the fibers comprise glass fibers.
However, the principles of the invention are equally applicable to polymer fibers or other similar elongated fibers.
Once the fibers are synthesized with their respective functional moieties, the fibers are bundled into a predetermined arrangement, step 120, such as a circle, square, etc. The bundled fibers are then bonded to fix the predetermined arrangement, step 130. Bonding may include fiber fusion or any one of a number of well known biologically inert bonding adhesives such as polysulfone adhesive available from Huls of Germany under the brand name glassclad, or other biologically inert adhesive used in the biopharmaceutical industry. The bio logically inert bonding medium thus fills the interstices intermediate the plurality of fibers, thereby separating the functional moieties on the plurality of fibers included in the bundle.
Once the bundled fibers are adequately bonded and their predetermined arrangement is fixed, the fiber bundle is sliced, step 140, to form a plurality of individual "chips" or devices.
Turning now to the Figures, and in particular Figs 1 and 3, an improved method of manufacturing a biosensor device is disclosed. Method 100 begins by synthesizing functional moieties onto a plurality of fibers, step 110. The fibers can be various diameters and may be solid or hollow. At least one fiber receives several moieties of the same species. However, as will become evident below, more than one fiber may receive the same functional moiety. The functional moieties selected will be dependent upon the specific testing protocol or protocols for which the biosensor device is designed.
For example, functional moieties may include DNA
oligonucleotides for DNA testing biosensor devices.
Alternatively, the functional moieties may include proteins, peptides, antibodies or other chemical functional groups. In the preferred embodiment, the fibers comprise glass fibers.
However, the principles of the invention are equally applicable to polymer fibers or other similar elongated fibers.
Once the fibers are synthesized with their respective functional moieties, the fibers are bundled into a predetermined arrangement, step 120, such as a circle, square, etc. The bundled fibers are then bonded to fix the predetermined arrangement, step 130. Bonding may include fiber fusion or any one of a number of well known biologically inert bonding adhesives such as polysulfone adhesive available from Huls of Germany under the brand name glassclad, or other biologically inert adhesive used in the biopharmaceutical industry. The bio logically inert bonding medium thus fills the interstices intermediate the plurality of fibers, thereby separating the functional moieties on the plurality of fibers included in the bundle.
Once the bundled fibers are adequately bonded and their predetermined arrangement is fixed, the fiber bundle is sliced, step 140, to form a plurality of individual "chips" or devices.
The slices may be along an axis perpendicular to a longitudinal axis of the fibers. Thus, each individual biosensor device may include a portion of each fiber included in the fiber bundle.
Of course, different slicing orientations will result in biosensor devices having different configurations. In fact, the invention contemplates linearly aligned fibers, which are _ bonded in their linear arrangement. The linearly arranged fiber bundle can then be cut to form wafers having linearly orientated fibers upon which the various functional moieties are synthesized.
Since the arrangement of the fibers is determined during the bundling process, a wide variety of devices may be implemented according to the invention. For example, a device may include many fibers that have the same functional moiety synthesized thereupon. These like fibers can be arranged to form a large region responsive to certain chemicals. Thus, larger, macroscopic biosensor devices can be produced.
On the other extreme, the biosensor devices manufactured according to the principles of the present invention could include literally thousands of fibers synthesized with distinct functional moieties. In this case, analysis of such a biosensor device after it is exposed to a sample would require sophisticated readers and processors, such as lasers, micro computers and optical recognition devices.
In the preferred embodiment, the glass fibers used are selected from the group consisting of lead borosilicate, soda-lime, rare earth lead, rare earth crown, flint, short flint, crown, silica, fused silica and borosilicate. However, the invention is not limited to these specific types of glass.
Fig. 2 shows, in detail, one embodiment of the step of the invention wherein the functional moieties are synthesized onto the fibers. In the example shown, the fibers include glass fibers and the functional moieties synthesized thereupon comprise DNA oligonucleotides. If the invention is practiced using plastic or polymer fibers, the method 200 would begin with step 225.
In the embodiment of the invention utilizing glass fibers, the method 200 begins by treating each glass fiber in generally a 35 percent and 40 percent HC1 solution at substantially 100°C for substantially three hours, step 205. _ This step exposes the hydroxy group of the glass fibers. In step 210, each HC1 treated glass fiber is washed with deionized water until its pH reaches substantially 6.5. Next, each washed fiber is baked at substantially 120°C for substantially two hours, step 215.
Thereafter, each fiber is cooled to substantially ambient temperature, step 220. At this point, one can directly go to the synthesis column step 225 or a cleavable linkage may be added to the hydroxyl groups, step 228, which allows for the DNA to be cleaved and analyzed after synthesis, for quality control purposes and the like. Then, in step 225, each glass fiber is packed into a synthesis column, such as a one " Etmole"
column manufactured by PerSeptive Biosystems. The fiber is then ready to accept the syntheses of a DNA oligonucleotide.
A DNA oligonucleotide is synthesized onto the fiber , step 230, using a n automated DNA synthesizer such as those available from PerSeptive Biosystems or Perkin Elmer . This is accomplished with either the standard protocol or with a minor variation to the manufacturer's standard synthesis protocol namely, an increased coupling time . The standard protocol typically has three (3) coupling steps or stages totaling 5 minutes coupling time. The present invention contemplates three (3) coupling stages of 10 minu tes, 4 minutes and 1 minute respectively, although this is not a limitation of the present invention. Coupling time is a factor of the fiber type used and whether or not the fibers are hollow or not.
After the DNA synthesis is completed, the column is dried under a vacuum for substantially ten minutes, step 235. As indicated earlier, if quality control measures are to be implemented to the synthesized fibers, then, in optional step 240, the fiber, which now includes a DNA oligonucleotide synthesized thereupon is treated with a one ml concentrated ammonium hydroxide solution at a temperature of substantially 55°C for a period of substantially six hours. This step will cleave the DNA ologonucleotide (the functional moiety) from the fiber so that it can be analyzed for quality control purposes.
Analytical testing, such as absorption measurement of the ammonium hydroxide solution at 260 nm indicates that there is no loss of the DNA oligonucleotide from the glass fiber or if a cleavable linker was added then absorption at 260 nm indicates the presence of DNA.
One of the important improvements over the prior art offered by the disclosed method of making biosensor devices is that they can be manufactured at a low cost, when compared to current manufacturing methods. Another advance, which is again significant is the ability to test the individual fibers before they are formed into a bundle for quality assurance purposes.
Testing can be performed by cleaving a functional moiety off of an individual fiber sample and quality control can be performed on the cleaved functional moiety. This is not possible with present biosensor chips, which utilize photolithography or other techniques to bond a plurality of different functional moieties to different locations upon the chip.
Fig. 4 shows a biosensor device 10 manufactured according to the principles of the present invention. The biosensor device 10 is comprised of a plurality of individual fibers 12 upon which functional moieties have been synthesized. As explained earlier, the fibers are arranged and bonded in their arrangement using a bonding medium 14, which substantially fills the interstitial spaces intermediate the individual fibers and thereafter allows the fiber bundle to be sliced into individual chips, (step 140, Fig. 3). Step 140 may also be accomplished by glass fusion, as is well know in the art, which serves to "bond" the fibers together.
Thus, the disclosed invention provides a significant improvement over the prior art in providing a cost effective, quality determinative biosensor device and method of their manufacture.
Modifications and substitutions by one of ordinary skill in the art are considered to be within the scope of the present invention which is not to be limited except by the claims which follow.
Of course, different slicing orientations will result in biosensor devices having different configurations. In fact, the invention contemplates linearly aligned fibers, which are _ bonded in their linear arrangement. The linearly arranged fiber bundle can then be cut to form wafers having linearly orientated fibers upon which the various functional moieties are synthesized.
Since the arrangement of the fibers is determined during the bundling process, a wide variety of devices may be implemented according to the invention. For example, a device may include many fibers that have the same functional moiety synthesized thereupon. These like fibers can be arranged to form a large region responsive to certain chemicals. Thus, larger, macroscopic biosensor devices can be produced.
On the other extreme, the biosensor devices manufactured according to the principles of the present invention could include literally thousands of fibers synthesized with distinct functional moieties. In this case, analysis of such a biosensor device after it is exposed to a sample would require sophisticated readers and processors, such as lasers, micro computers and optical recognition devices.
In the preferred embodiment, the glass fibers used are selected from the group consisting of lead borosilicate, soda-lime, rare earth lead, rare earth crown, flint, short flint, crown, silica, fused silica and borosilicate. However, the invention is not limited to these specific types of glass.
Fig. 2 shows, in detail, one embodiment of the step of the invention wherein the functional moieties are synthesized onto the fibers. In the example shown, the fibers include glass fibers and the functional moieties synthesized thereupon comprise DNA oligonucleotides. If the invention is practiced using plastic or polymer fibers, the method 200 would begin with step 225.
In the embodiment of the invention utilizing glass fibers, the method 200 begins by treating each glass fiber in generally a 35 percent and 40 percent HC1 solution at substantially 100°C for substantially three hours, step 205. _ This step exposes the hydroxy group of the glass fibers. In step 210, each HC1 treated glass fiber is washed with deionized water until its pH reaches substantially 6.5. Next, each washed fiber is baked at substantially 120°C for substantially two hours, step 215.
Thereafter, each fiber is cooled to substantially ambient temperature, step 220. At this point, one can directly go to the synthesis column step 225 or a cleavable linkage may be added to the hydroxyl groups, step 228, which allows for the DNA to be cleaved and analyzed after synthesis, for quality control purposes and the like. Then, in step 225, each glass fiber is packed into a synthesis column, such as a one " Etmole"
column manufactured by PerSeptive Biosystems. The fiber is then ready to accept the syntheses of a DNA oligonucleotide.
A DNA oligonucleotide is synthesized onto the fiber , step 230, using a n automated DNA synthesizer such as those available from PerSeptive Biosystems or Perkin Elmer . This is accomplished with either the standard protocol or with a minor variation to the manufacturer's standard synthesis protocol namely, an increased coupling time . The standard protocol typically has three (3) coupling steps or stages totaling 5 minutes coupling time. The present invention contemplates three (3) coupling stages of 10 minu tes, 4 minutes and 1 minute respectively, although this is not a limitation of the present invention. Coupling time is a factor of the fiber type used and whether or not the fibers are hollow or not.
After the DNA synthesis is completed, the column is dried under a vacuum for substantially ten minutes, step 235. As indicated earlier, if quality control measures are to be implemented to the synthesized fibers, then, in optional step 240, the fiber, which now includes a DNA oligonucleotide synthesized thereupon is treated with a one ml concentrated ammonium hydroxide solution at a temperature of substantially 55°C for a period of substantially six hours. This step will cleave the DNA ologonucleotide (the functional moiety) from the fiber so that it can be analyzed for quality control purposes.
Analytical testing, such as absorption measurement of the ammonium hydroxide solution at 260 nm indicates that there is no loss of the DNA oligonucleotide from the glass fiber or if a cleavable linker was added then absorption at 260 nm indicates the presence of DNA.
One of the important improvements over the prior art offered by the disclosed method of making biosensor devices is that they can be manufactured at a low cost, when compared to current manufacturing methods. Another advance, which is again significant is the ability to test the individual fibers before they are formed into a bundle for quality assurance purposes.
Testing can be performed by cleaving a functional moiety off of an individual fiber sample and quality control can be performed on the cleaved functional moiety. This is not possible with present biosensor chips, which utilize photolithography or other techniques to bond a plurality of different functional moieties to different locations upon the chip.
Fig. 4 shows a biosensor device 10 manufactured according to the principles of the present invention. The biosensor device 10 is comprised of a plurality of individual fibers 12 upon which functional moieties have been synthesized. As explained earlier, the fibers are arranged and bonded in their arrangement using a bonding medium 14, which substantially fills the interstitial spaces intermediate the individual fibers and thereafter allows the fiber bundle to be sliced into individual chips, (step 140, Fig. 3). Step 140 may also be accomplished by glass fusion, as is well know in the art, which serves to "bond" the fibers together.
Thus, the disclosed invention provides a significant improvement over the prior art in providing a cost effective, quality determinative biosensor device and method of their manufacture.
Modifications and substitutions by one of ordinary skill in the art are considered to be within the scope of the present invention which is not to be limited except by the claims which follow.
Claims (21)
1. A method of manufacturing biosensor device comprising synthesizing one or more functional moiety onto a plurality of fibers, wherein at least one fiber receives one moiety;
bundling said plurality of fibers in a predetermined arrangement; bonding or fixing said bundled plurality of fibers to fix the predetermined arrangement; and slicing said bundled fiber bundle into a plurality of biosensor devices.
bundling said plurality of fibers in a predetermined arrangement; bonding or fixing said bundled plurality of fibers to fix the predetermined arrangement; and slicing said bundled fiber bundle into a plurality of biosensor devices.
2. The method of manufacturing biosensor devices of Claim 1 wherein the step of slicing said bonded fiber bundle comprises cutting the bundle at an angle such that a portion of each fiber included in the bundle is included in each biosensor device.
3. The method of manufacturing biosensor devices of Claim 2, wherein said angle is substantially 90° with respect to a longitudinal axis of the bundled fibers.
4. The method of manufacturing biosensor devices of Claim 1, wherein said at least one functional moiety synthesized onto said fibers comprises DNA oligonucleotides.
5. The method of manufacturing biosensor devices of Claim 1, wherein said at least one functional moiety comprise proteins.
6. The method of manufacturing biosensor devices of Claim 1, wherein said functional moieties comprise peptides.
7. The method of manufacturing biosensor devices of Claim 1, wherein said functional moieties comprise antibodies.
8. The method of manufacturing biosensor devices of Claim 1, wherein said functional moieties comprise chemical functional groups.
9. The method of manufacturing biosensor devices of Claim 4, wherein said step of synthesizing said DNA
oligonucleotide onto said fibers comprises:
treating each fiber in substantially between a 35 and 40 percent HCl solution at substantially 100°C for substantially three hours;
washing each treated fiber with deionized water until the pH of each glass fiber is substantially 6.5;
baking each washed fiber at substantially 120°C for substantially two hours;
cooling each fiber to substantially ambient temperature;
packing each fiber into a 1 µ mole column;
synthesizing a DNA oligonucleotide onto said fiber using an automated DNA synthesizer; and drying said fiber under vacuum for substantially ten minutes.
oligonucleotide onto said fibers comprises:
treating each fiber in substantially between a 35 and 40 percent HCl solution at substantially 100°C for substantially three hours;
washing each treated fiber with deionized water until the pH of each glass fiber is substantially 6.5;
baking each washed fiber at substantially 120°C for substantially two hours;
cooling each fiber to substantially ambient temperature;
packing each fiber into a 1 µ mole column;
synthesizing a DNA oligonucleotide onto said fiber using an automated DNA synthesizer; and drying said fiber under vacuum for substantially ten minutes.
10. The method of manufacturing biosensor devices of Claim 9, further comprising the step of treating said fiber with 1 ml concentrated ammonium hydroxide at substantially 55°C for substantially six hours.
11. The method of manufacturing biosensor devices of Claim 1, wherein said step of bonding said plurality of fibers comprises chemically bonding said fibers using a biologically inert chemical bonding agent, said bonding agent forming biologically inert interstices intermediate the fibers arranging the bundle and thereby separating the functional moieties included on the manufactured biosensor device.
12. The method of manufacturing biosensor devices of Claim 1, wherein said fibers are glass fibers, and further wherein said step of bonding said plurality of fibers comprises glass fusing said glass fibers.
13. A method of manufacturing biosensor devices comprising: applying a plurality of functional moieties onto a plurality of fibers, each of said fibers including a single functional moiety;
arranging said plurality of fibers into a bundle, wherein each said fiber is in a predetermined position;
fixing said fiber arrangement in said bundle using a chemical bonding technique; and slicing said fiber bundle into individual biosensor devices.
arranging said plurality of fibers into a bundle, wherein each said fiber is in a predetermined position;
fixing said fiber arrangement in said bundle using a chemical bonding technique; and slicing said fiber bundle into individual biosensor devices.
14. An improved biosensor device comprising an individual slice of a plurality of individual fibers, each individual fiber having applied thereto a functional moiety, said individual fibers being arranged in a predetermined fashion, and the arrangement fixed by bonding said fibers together.
15. The improved biosensor device of Claim 14, wherein said fibers comprise glass fibers.
16. The improved biosensor device of Claim 14, wherein said fibers comprise plastic fibers.
17. The improved biosensor device of Claim 15, wherein said fibers comprise quartz fibers.
18. The improved biosensor device of Claim 14, wherein the glass fibers are selected from the group consisting of lead borosilicate, soda lime, borosilicate, rare earth lead, rare earth crown, flint, short flint, crown, silica, and fused silica.
19. The improved biosensor device of Claim 14, wherein said fibers comprise polymer fibers.
20. The improved biosensor device of Claim 14, wherein said fibers comprise hollow fibers.
21. The improved biosensor device of Claim 14, wherein said fibers comprise solid fibers.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/213,587 | 1998-12-17 | ||
US09/213,587 US6129896A (en) | 1998-12-17 | 1998-12-17 | Biosensor chip and manufacturing method |
PCT/US1999/029965 WO2000040942A2 (en) | 1998-12-17 | 1999-12-15 | Improved biosensor device and method of manufacturing same |
Publications (1)
Publication Number | Publication Date |
---|---|
CA2356634A1 true CA2356634A1 (en) | 2000-07-13 |
Family
ID=22795684
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002356634A Abandoned CA2356634A1 (en) | 1998-12-17 | 1999-12-15 | Improved biosensor device and method of manufacturing same |
Country Status (7)
Country | Link |
---|---|
US (1) | US6129896A (en) |
EP (1) | EP1166077A4 (en) |
JP (1) | JP2002534672A (en) |
AU (1) | AU4324100A (en) |
CA (1) | CA2356634A1 (en) |
MX (1) | MXPA01006126A (en) |
WO (1) | WO2000040942A2 (en) |
Families Citing this family (39)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7019827B2 (en) * | 1997-06-16 | 2006-03-28 | Diversa Corporation | GigaMatrix holding tray having through-hole wells |
ATE423314T1 (en) | 1998-06-24 | 2009-03-15 | Illumina Inc | DECODING OF MATRIXED SENSORS BY MICROPARTICLES |
AU2830400A (en) * | 1999-03-05 | 2000-09-28 | Mitsubishi Rayon Company Limited | Carriers having biological substance |
US20030134330A1 (en) * | 1999-04-15 | 2003-07-17 | Ilya Ravkin | Chemical-library composition and method |
US7253435B2 (en) * | 1999-04-15 | 2007-08-07 | Millipore Corporation | Particles with light-polarizing codes |
US20030207249A1 (en) * | 1999-04-15 | 2003-11-06 | Beske Oren E. | Connection of cells to substrates using association pairs |
US20040018485A1 (en) * | 1999-04-15 | 2004-01-29 | Ilya Ravkin | Multiplexed analysis of cells |
US6908737B2 (en) * | 1999-04-15 | 2005-06-21 | Vitra Bioscience, Inc. | Systems and methods of conducting multiplexed experiments |
US20030129654A1 (en) * | 1999-04-15 | 2003-07-10 | Ilya Ravkin | Coded particles for multiplexed analysis of biological samples |
JP3957118B2 (en) * | 1999-05-18 | 2007-08-15 | 富士フイルム株式会社 | Test piece and image information reading device from the test piece |
US6713309B1 (en) * | 1999-07-30 | 2004-03-30 | Large Scale Proteomics Corporation | Microarrays and their manufacture |
US20020015952A1 (en) * | 1999-07-30 | 2002-02-07 | Anderson Norman G. | Microarrays and their manufacture by slicing |
US6770441B2 (en) | 2000-02-10 | 2004-08-03 | Illumina, Inc. | Array compositions and methods of making same |
EP1257805B1 (en) * | 2000-02-10 | 2015-10-14 | Illumina, Inc. | Composition comprising a substrate with multiple assay locations for bead-based simultaneous processing of multiple samples, apparatus comprising the composition, and manufacturing method for the composition |
US20030162232A1 (en) * | 2000-02-28 | 2003-08-28 | Derya Ozkan | Component comprising a plurality of fiber elements and sample molecules that are immobilized on said fiber elements |
KR100359941B1 (en) * | 2000-04-14 | 2002-11-07 | 엘지전자 주식회사 | method for fabricating the biochip |
JP3510882B2 (en) * | 2000-06-20 | 2004-03-29 | 三菱レイヨン株式会社 | Biologically related substance microarray and manufacturing method thereof |
DE10034570A1 (en) * | 2000-07-14 | 2002-01-31 | Max Delbrueck Centrum | Process for the production of microarray chips with nucleic acids, proteins or other test substances |
GB0024276D0 (en) * | 2000-10-04 | 2000-11-15 | Univ Cranfield | Substrate specific materials |
JP2004537712A (en) * | 2000-10-18 | 2004-12-16 | バーチャル・アレイズ・インコーポレーテッド | Multiple cell analysis system |
DE10110511C1 (en) | 2001-02-28 | 2002-10-10 | Attomol Gmbh Molekulare Diagno | Method for producing an array for the detection of components from a biological sample |
US20020129889A1 (en) * | 2001-03-15 | 2002-09-19 | Anderson Norman G. | Method and apparatus for making fibers for sectioned arrays |
DE10117135A1 (en) * | 2001-04-05 | 2002-10-17 | Biotechnolog Forschung Gmbh | Method for making a plurality of identical copies of a planar test assembly of probe molecules |
US20030022394A1 (en) * | 2001-07-27 | 2003-01-30 | Dumas David P. | Biochips and methods of making same |
US20030219800A1 (en) * | 2001-10-18 | 2003-11-27 | Beske Oren E. | Multiplexed cell transfection using coded carriers |
WO2003076588A2 (en) * | 2002-03-05 | 2003-09-18 | Vitra Bioscience, Inc. | Multiplexed cell transfection using coded carriers |
AU2003213790A1 (en) * | 2002-03-05 | 2003-09-22 | Vitra Bioscience, Inc. | Multiplexed analysis of cell-substrate interactions |
US8048623B1 (en) | 2002-04-24 | 2011-11-01 | The University Of North Carolina At Greensboro | Compositions, products, methods and systems to monitor water and other ecosystems |
US8383342B2 (en) | 2002-04-24 | 2013-02-26 | The University Of North Carolina At Greensboro | Compositions, products, methods and systems to monitor water and other ecosystems |
US9126165B1 (en) | 2002-04-24 | 2015-09-08 | The University Of North Carolina At Greensboro | Nucleic acid arrays to monitor water and other ecosystems |
US20040126773A1 (en) * | 2002-05-23 | 2004-07-01 | Beske Oren E. | Assays with coded sensor particles to sense assay conditions |
CA2513985C (en) | 2003-01-21 | 2012-05-29 | Illumina Inc. | Chemical reaction monitor |
US20070101549A1 (en) * | 2003-05-19 | 2007-05-10 | Mitsubishi Rayon Co., Ltd. | Yarn arrangement device and method for yarn arrangement using the device, yarn arrangement tool, method of manufacturing yarn arranged body, and method of manufacturing living body-related substance immobilizing micro array |
US20050208468A1 (en) * | 2003-09-15 | 2005-09-22 | Beske Oren E | Assays with primary cells |
US7488451B2 (en) * | 2003-09-15 | 2009-02-10 | Millipore Corporation | Systems for particle manipulation |
EP2407242A1 (en) | 2010-07-13 | 2012-01-18 | Dublin City University | Direct clone analysis and selection technology |
JP5660468B2 (en) * | 2011-03-15 | 2015-01-28 | 三菱レイヨン株式会社 | Method for producing gel microarray for detecting bio-related substances |
US20160266106A1 (en) * | 2013-10-28 | 2016-09-15 | Seoul National University R&Db Foundation | Multiplex bioassay platform using cut fiber bundle |
EP3933374A4 (en) * | 2019-02-27 | 2022-12-07 | Beijing Center For Physical And Chemical Analysis | Carbon fibre bundle sample and preparation method therefor |
Family Cites Families (16)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4103064A (en) * | 1976-01-09 | 1978-07-25 | Dios, Inc. | Microdevice substrate and method for making micropattern devices |
US4302530A (en) * | 1977-12-08 | 1981-11-24 | University Of Pennsylvania | Method for making substance-sensitive electrical structures by processing substance-sensitive photoresist material |
GB8314523D0 (en) * | 1983-05-25 | 1983-06-29 | Lowe C R | Diagnostic device |
US4908112A (en) * | 1988-06-16 | 1990-03-13 | E. I. Du Pont De Nemours & Co. | Silicon semiconductor wafer for analyzing micronic biological samples |
US5200051A (en) * | 1988-11-14 | 1993-04-06 | I-Stat Corporation | Wholly microfabricated biosensors and process for the manufacture and use thereof |
US5244636A (en) * | 1991-01-25 | 1993-09-14 | Trustees Of Tufts College | Imaging fiber optic array sensors, apparatus, and methods for concurrently detecting multiple analytes of interest in a fluid sample |
US5320814A (en) * | 1991-01-25 | 1994-06-14 | Trustees Of Tufts College | Fiber optic array sensors, apparatus, and methods for concurrently visualizing and chemically detecting multiple analytes of interest in a fluid sample |
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 |
US5736257A (en) * | 1995-04-25 | 1998-04-07 | Us Navy | Photoactivatable polymers for producing patterned biomolecular assemblies |
US5690894A (en) * | 1995-05-23 | 1997-11-25 | The Regents Of The University Of California | High density array fabrication and readout method for a fiber optic biosensor |
US5545531A (en) * | 1995-06-07 | 1996-08-13 | Affymax Technologies N.V. | Methods for making a device for concurrently processing multiple biological chip assays |
US5661028A (en) * | 1995-09-29 | 1997-08-26 | Lockheed Martin Energy Systems, Inc. | Large scale DNA microsequencing device |
US5837196A (en) * | 1996-01-26 | 1998-11-17 | The Regents Of The University Of California | High density array fabrication and readout method for a fiber optic biosensor |
US5760130A (en) * | 1997-05-13 | 1998-06-02 | Molecular Dynamics, Inc. | Aminosilane/carbodiimide coupling of DNA to glass substrate |
US6037186A (en) * | 1997-07-16 | 2000-03-14 | Stimpson; Don | Parallel production of high density arrays |
EP0955084B1 (en) * | 1998-04-27 | 2006-07-26 | Corning Incorporated | Method of depositing an array of biological samples using a redrawn capillary reservoir |
-
1998
- 1998-12-17 US US09/213,587 patent/US6129896A/en not_active Expired - Fee Related
-
1999
- 1999-12-15 WO PCT/US1999/029965 patent/WO2000040942A2/en not_active Application Discontinuation
- 1999-12-15 MX MXPA01006126A patent/MXPA01006126A/en not_active Application Discontinuation
- 1999-12-15 EP EP99972833A patent/EP1166077A4/en not_active Withdrawn
- 1999-12-15 JP JP2000592611A patent/JP2002534672A/en active Pending
- 1999-12-15 CA CA002356634A patent/CA2356634A1/en not_active Abandoned
- 1999-12-15 AU AU43241/00A patent/AU4324100A/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
EP1166077A2 (en) | 2002-01-02 |
MXPA01006126A (en) | 2002-09-18 |
JP2002534672A (en) | 2002-10-15 |
US6129896A (en) | 2000-10-10 |
AU4324100A (en) | 2000-07-24 |
EP1166077A4 (en) | 2002-03-20 |
WO2000040942A2 (en) | 2000-07-13 |
WO2000040942A3 (en) | 2000-09-21 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US6129896A (en) | Biosensor chip and manufacturing method | |
US6875620B1 (en) | Tiling process for constructing a chemical array | |
US6309831B1 (en) | Method of manufacturing biological chips | |
US5607646A (en) | Device for separating polynucleotides having a plurality of electrode-containing cells and movable collecting capillary | |
AU2002232193B2 (en) | Microchip | |
US7964388B2 (en) | Chemical reaction device, chemical reaction system, and chemical reaction method | |
US5936730A (en) | Bio-molecule analyzer with detector array and filter device | |
EP1250954B1 (en) | Microchannel device, method for producing the microchannel device and use of the same | |
KR20020042632A (en) | Microarrays and their manufacture | |
US20080254997A1 (en) | Kit, Device and Method For Analyzing Biological Substance | |
JP2003532123A (en) | Microarray evanescent wave fluorescence detector | |
JP2000515632A (en) | Discs, devices for performing assays, assay elements, and assay components | |
KR20000071894A (en) | Multipurpose diagnostic systems using protein chips | |
JP3533374B2 (en) | How to bind biomolecules to test sites | |
KR100848636B1 (en) | Selectively hybridizable substance immobilization fiber, fiber array comprising bundle of such fibers, selective hybridizing method, device therefor, and base | |
EP1229129A2 (en) | Affinity detecting/analytical chip, method for production thereof, detection method and detection system using same | |
JP2008134188A (en) | Probe solidifying reaction array and manufacturing method of array | |
AT524623B1 (en) | Solid support comprising a set of protein arrays | |
EP1271149A2 (en) | Structure with immobilized biological material and method for manufacturing the same | |
US20040197787A1 (en) | Affinity reaction probe detection/analysis chips and detection system and apparatus using the same | |
US20040265838A1 (en) | Method of manufacturing | |
US20020168655A1 (en) | Method of manufacturing | |
JP2002139494A (en) | Method for fixing microorganism, nucleic acid, and protein and its series and method for analysis | |
MXPA99007981A (en) | Laboratory in a disk |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
FZDE | Discontinued |