WO2002090770A2 - Method and apparatus for propelling a fluid - Google Patents

Method and apparatus for propelling a fluid Download PDF

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Publication number
WO2002090770A2
WO2002090770A2 PCT/IL2002/000357 IL0200357W WO02090770A2 WO 2002090770 A2 WO2002090770 A2 WO 2002090770A2 IL 0200357 W IL0200357 W IL 0200357W WO 02090770 A2 WO02090770 A2 WO 02090770A2
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WO
WIPO (PCT)
Prior art keywords
fluid
microfluidics
distribution unit
accordance
work fluid
Prior art date
Application number
PCT/IL2002/000357
Other languages
French (fr)
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WO2002090770A3 (en
Inventor
Amit Shacham
Shay Kaplan
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Nanolab Ltd.
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Filing date
Publication date
Application filed by Nanolab Ltd. filed Critical Nanolab Ltd.
Priority to AU2002302937A priority Critical patent/AU2002302937A1/en
Publication of WO2002090770A2 publication Critical patent/WO2002090770A2/en
Publication of WO2002090770A3 publication Critical patent/WO2002090770A3/en

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Classifications

    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04BPOSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/20Other positive-displacement pumps
    • F04B19/24Pumping by heat expansion of pumped fluid
    • FMECHANICAL ENGINEERING; LIGHTING; HEATING; WEAPONS; BLASTING
    • F04POSITIVE - DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS FOR LIQUIDS OR ELASTIC FLUIDS
    • F04BPOSITIVE-DISPLACEMENT MACHINES FOR LIQUIDS; PUMPS
    • F04B19/00Machines or pumps having pertinent characteristics not provided for in, or of interest apart from, groups F04B1/00 - F04B17/00
    • F04B19/006Micropumps

Definitions

  • This invention relates to microfluidics. More particularly, the invention relates to a method and apparatus for liquid propulsion in a nanoscale device, using non-mechanically-induced volumetric changes for propelling the liquid.
  • Microfluidics systems and devices known in the art often propel fluids such as liquids or gasses by moving the fluids through channels or passages formed within various substrates.
  • the moving of the fluids may be achieved by capillary effects or by using suitable micropumps and/or other material transport devices or sub-systems.
  • Such micropumps may operate, inter alia, by using piezoelectric effects, electrostatic effects, electro-osmotic effects, mechanical effects or electromagnetic effects.
  • the construction of such micropumps may require costly manufacturing methods.
  • Certain types of mechanical or electromechanical micropumps such as, for example valve or diaphragm operated micropumps may move or propel fluids within fluidic channels by controilably and actively producing positive or negative pressure within parts of such fluidic channels in the fluidic system to induce a pressure gradient within different portions of the fluidic system for pushing or pulling fluids in a desired direction within a flow channel.
  • the amounts of fluids pumped by known micropumps may depend, inter alia, on the type of fluid pumped. Often, in mechanically or valve based micropumps the amount of fluid pumped may depend on the number of pump strokes. In some micropumps it may be necessary to count and calibrate pump strokes for different types of pumped fluids, or to use flow sensors or detectors for quantitating or monitoring the pumped fluid volume or the fluid's flow or position.
  • Integrated microfluidics systems may also be connected through suitable ports or channels to one or more external sources of positive and/or negative pressure for propelling one or more fluids within one or more flow channels included in the system.
  • micropumps may involve further design considerations which take into account dead volume and pump priming. Integration of such micropumps with other components to form entire systems therefore may often be complicated, costly and cumbersome.
  • the flow of the liquids is achieved by either capillary effects or by micropumps operated by piezoelectric, electrostatic or electromagnetic effects. These require costly manufacturing techniques and the amount of liquid pumped is derived from the liquid type and pump strokes that have to be counted and calibrated for different liquids or with flow sensors.
  • a sample solution is forced into the end of the capillary furthest from the detector.
  • Sample volumes often range from .1-100 ml.
  • the most frequently used injection mode is to dip the capillary into the sample solution vial. A volume of solution is then drawn into the capillary, mostly under the influence of capillary action forces.
  • a less popular sample injection procedure is to dip the capillary and electrode into the sample solution vial and to apply a voltage. If the sample is ionized and the appropriate voltage polarity is used then sample ions will migrate into the capillary. This type of injection is known as electrokinetic sampling.
  • the piezoelectric micropump for example, relies on a membrane actuator which is deflected by a piezoelectric plate. The actuation is done by the piezoelectric membrane actuator, which changes the chamber volume periodically. When the chamber volume increases, liquid is sucked through the inlet into the chamber. At the point when the chamber volume decreases, the fluid is pressed through the outlet.
  • this approach requires a difference in flow resistance between inlet and outlet for different flow directions. Such a behavior is realized, for example, with passive cantilever valves among others, which show a large flowrate in forward direction and low leakage rates in reverse operation.
  • Electromagnetic effects are embodied by another electrokinetic phenomenon known as "electrophoresis,” which occurs in the channels of movement. This is the movement of charged molecules or particles in an electric field. Electrophoresis is often used in conventional laboratories for analyzing molecules since they move differently according to their physical make-up. Electrophoresis can be used to move molecules in solution, or to separate molecules with very subtle differences.
  • Pressure can also be used to move fluid in the channels.
  • small amounts of pressure produce highly predictable and reproducible fluid flow.
  • Both computer-controlled pressure and electrokinetic forces are used to gain precise control over fluid flow in the microfluidic channel network.
  • Dead volume is the total volume of the liquid phase in the column.
  • Miniaturized micropumps combine the ability of dosing very small amounts of fluids with low manufacturing costs and small overall size. In the laboratory a major concern is the ease of handling equipment. Pump priming can be laborious.
  • an exemplary embodiment of the present invention consisting of a chamber with two electrodes.
  • the flow of fluids is achieved by electrolysis of minute quantities of the fluid, which in most cases is solution of some materials in water, to form gas.
  • the propelling fluid can be just water that pushes other liquid.
  • the liquid can be isolated from the water by air/gas bubble.
  • the volume of the gas is much larger than the volume of the liquid from which it was formed. Since the current is easily controllable, the exact volume of gas formed is controlled as well.
  • the volume of fluid dispensed is linear with the electrical charge and is limited by the original volume of liquid in the chamber that can decompose.
  • the propulsion method comprises vaporizing at least part of the liquid that needs to be propelled such that the rest of the fluid is propelled in a controllable manner.
  • the propelling liquid can be a different liquid from the sample fluid that needs to be pushed.
  • this can be accomplished either by choosing a propelling fluid which is not soluble in the sample fluid solvent.
  • motive force for directing substances through the microcapillary network of the microfluidics lab-on-a- chip is accomplished by generating some volumetric expansion of a substance, that substance being either initially present or brought into being by activation of the device (for example by electrically-catalyzed chemical or combustive reaction of one or more solids). This in turn creates pressure changes in the microcapillary network and applies motive force to the substances which need to be moved from one reaction point to another.
  • FIG. 1 is a schematic illustration of a chamber cross-section of the electrolysis embodiment of the present invention
  • FIG. 2 is a schematic illustration of a detailed top-view of a T-shape chamber of the electrolysis embodiment of the present invention
  • FIG. 3 is a schematic illustration of a refillable configuration for the electrolysis embodiment of the present invention.
  • FIG. 4 is a schematic illustration of a chamber cross-section of the liquid evaporation embodiment of the present invention.
  • FIG. 5 is a schematic illustration of a top-view of an evaporation chamber of the liquid evaporation embodiment of the present invention.
  • FIG. 6 is a schematic illustration of a sequence of resistors in an evaporation chamber of the liquid evaporation embodiment of the present invention.
  • FIG. 7 is a schematic illustration of a refillable evaporation chamber of the liquid evaporation embodiment of the present invention.
  • FIG. 8 is a schematic illustration of a microfluidics system constructed in accordance with an exemplary embodiment of the present invention.
  • FIG. 9 is a schematic illustration of a microfluidics system constructed in accordance with an exemplary embodiment of the present invention.
  • the present invention is an innovative method for propelling fluid through microfluidics devices and to devices which incorporate the propulsive method for motivating sample fluids through a series of nanoscale reaction chambers connected to one another by tiny channels or capillaries which together comprises a microfluidics environment.
  • a generic device which could incorporate the propulsive mechanism of the present invention would typically comprise microcapillaries or channels provided in a substrate or housing, the microcapillaries having a port for introducing a sample fluid, reaction chambers connected by the microcapillaries in which test or reaction reagents are located, reservoirs for holding expandable fluids and means for moving test fluid through the microcapillaries in a controlled fashion for example by causing expansion of the expandable fluids held in the reservoirs, and a controller for controlling the means for moving the test fluid.
  • the motive providing expandable fluid may be generated within the reservoirs or capillaries by the chemical or combustive reaction of one or more solid agents, (e.g.
  • the propulsion of fluid in the present invention is performed by creating a positive pressure gradient positioned in the microcapillary system with respect to the test sample such that the sample of test fluid is motivated through the channels of the microfluidics testing device.
  • the pressure gradient is created by the expansion of an expandable fluid using one or more of several possible means for expansion, examples of which will be discussed hereinbelow, resulting in the propulsion of the test fluid.
  • said method of expansion of the expandable fluid is controlled by a controller. In an alternate embodiment of the present invention, said method of expansion is controlled manually.
  • the method of expansion is electrolysis. Electrodes 13 are provided in properly arranged areas of a chamber 11 filled with the expandable fluid, in this case a fluid which is selected for its ease of undergoing hydrolysis, for example, water. Upon activation of the electrodes by activating a circuit which charges the electrodes, electrolysis of the expandable fluid occurs and the gases formed by the electrolytic process create a pressure by their expansion. Because the volume of 1 mole of gaseous products of electrolysis at 1 atmosphere is much greater than the volume of 1 mole of the liquid at 1 atmosphere, the expandable fluid is pushed against the sample fluid in the direction of a reaction chamber 62, for example.
  • the expandable fluid is pushed against the sample fluid in the direction of a reaction chamber 62, for example.
  • an easily expandible fluid might be used, for example alcohol, which is easily expanded by simply applying heat.
  • the method of fluid expansion is fluid phase changing. This is performed by heating the expandable fluid, thereby causing it to evaporate. During the evaporation process, liquid vapors are formed from the heated fluid. The volume of the liquid vapors is larger than the volume of the fluid in its liquid state. This difference in the volume of the expandable fluid, a result of the heating process, causes the work fluid to be expelled from the liquid reservoir 11.
  • FIG. 1 With reference to Fig. 1, there is seen in cross-section a view of a chamber useful with the electrolysis embodiment of the present invention.
  • the device comprises the following components:
  • a microfluidics chip 10 has formed thereon an expandable fluid reservoir 11, capillaries or channels 14, electrodes 13 and conductors 15 all sandwiched between a cover layer 12 and a substrate or base layer 18.
  • a nitride layer 17 is deposited on a silicon wafer 10, which comprises a channel layer 18 having a uniform height.
  • a photolithographic process defines the channel(s) on wafer 10 by removing portions of nitride layer 17.
  • the silicon of channel layer 18 is then etched, where it has been photolithographically exposed, thereby forming channel 14 at a reduced height in silicon wafer 10 as shown.
  • a conductive layer 19 is deposited on top of nitride layer 17, and is patterned to form electrodes 13 and conductors 15.
  • the lower portions of a cover and chamber layer 21, with a hole that defines expandable fluid reservoir 11, is then bonded to wafer 10. Expandable fluid reservoir 11 is then filled with fluid, and glass cover 12 is bonded as shown.
  • Electrodes 13 are connected via two conductors 15 to a controller (not shown) that applies voltage when there is a need to push the test fluid.
  • the material used for electrodes 13 needs to be selected according to the properties of the liquid used, so as not to adversely affect the required process.
  • Chamber 11 extends to the left over the inlet of channel 14 and to the right over electrodes 13 as shown.
  • Fig. 1a there is seen an alternative embodiment of a manufacturing process.
  • Starting material is a silicon wafer topped with a layer 19 of silicon oxide at a thickness of 300 angstrom and silicon nitride at a thickness of 1200 angstrom.
  • the capillaries are defined and etched into silicon nitride and silicon oxide using Reactive Ion Etching (hereinafter RIE).
  • RIE Reactive Ion Etching
  • the silicon is then wet etched in potassium hydroxide or etched by using RIE.
  • a polyimide film 12 such as KaptonTM film, product of the Dupont Co., that has been cut by a laser to define nozzles of the channels, is attached by glueing.
  • This polyimide layer forms the upper half structure of the channels.
  • a second polyimide layer 12 is then attached on the first.
  • This layer has been cut by laser to form spaces for the expandable fluid reservoirs.
  • the last layer is a Kapton with copper layer. First the layer is cut to form the sampling port and openings to air. Then electrodes are defined by a photolithographic method and etched. Finally this layer is glued with metal facing the previous layer.
  • the first layer thickness is 25 micron of polyimide.
  • the second and third layers are 50 microns of polyimide.
  • the adhesive adds to the thickness of the layers.
  • an exemplary embodiment could have features with specifications as follows:
  • channels can be 100-micron wide and V-grooved in the silicon of channel layer; • conductive layer might be a 1 micron thick layer of aluminum;
  • • electrodes could be about 2 mm apart, although this might vary depending on the electrochemical nature of the liquid medium being expanded;
  • chamber layer might consist of a 0.5 mm thick Pyrex wafer, it might be drilled with a 1 mm drill and bonded to wafer to form a chamber;
  • resistors might be provided having dimensions a width of 45 microns and lengths of 835 microns.
  • FIG. 2 there is seen a schematic illustration of a detailed top-view 20 of an exemplary embodiment of the present invention useful with the electrolysis embodiment of the present invention.
  • a chamber, or reservoir 11 contains both the work fluid to be ejected and the expandable fluid.
  • An ejection port 14 through which the work fluid is dispensed extends from the chamber 11.
  • Electrodes 13, attached to conductors 15, are situated within the chamber 11 for electrolysis of the expandable fluid.
  • chamber 11 can be formed in the shape of a T as shown.
  • the oxygen accumulates at one wing 22 of the T while the hydrogen accumulates at the other wing 24.
  • the remaining fluid separates the two gases from each other so long as unelectrolysed fluid remains.
  • Refillable propulsive mechanism 30 is suitable either for initial filling of chamber 11, or for refilling of chamber 11 after electrolysis of all the liquid.
  • Refillable propulsive mechanism 30 includes an inlet channel 32 with active valve 34 attached to one wing 22 of T chamber 11.
  • Device 40 comprises identical components to microfluidics chip 10 with the exception that device 40 includes resistors 42 in place of conductors 13 of microfluidics chip 10.
  • Optional additional cell 44 serves to separate the heated fluid from the fluid dispensed into the system.
  • Conductors 15 lead from a controller (not shown) to a resistor 42 which, upon activation, serves to heat the expandable fluid located in chamber 11 until at least a portion thereof undergoes a change of phase.
  • Resistor 42 can be comprised of various types of metal.
  • FIG. 6 there is seen a schematic illustration of a detailed top-view 60 of an alternate embodiment of the propulsive mechanism of the present invention useful with the fluid phase-changing embodiment of the present invention.
  • This embodiment additionally comprises a sequence of resistors 46 in place of the solitary resistor 42 of device 50 of Fig. 5.
  • the additional resistors provide for a more accurate control of the fluid dispensation, as well as allowing for the heating to vaporization of, and therefore dispensation of, larger quantities of fluid.
  • the resistors can be activated in sequence.
  • Refillable propulsive mechanism 70 is seen here consisting of a plurality of resistors 46. In an alternate embodiment only one resistor may be used, as seen in Fig. 5.
  • the components of refillable propulsive mechanism 70 are identical to those of device 60, save for inlet channel 32 leading to, and outlet channel 36 leading from, chamber 11.
  • active valve 34 allowing fluid to enter chamber 11, but not to exit from it.
  • outlet channel 36 is situated an active valve 38, allowing fluid to exit chamber 11 upon activation, but preventing fluid from entering chamber 11 through outlet channel 36.
  • FIG. 8 there is seen a schematic illustration 80 of an exemplary embodiment of a sample testing unit, incorporating the propulsive mechanism of the present invention.
  • an active valve 52 allows the flow of the sample from sampling port 48 through channel 54 towards reaction chamber 62 by capillary forces.
  • reaction chamber 62 Within reaction chamber 62 is a dry reagent.
  • the valve 52 is closed, so as to prevent the sample from receding back towards sampling port 48.
  • Activation of the first propelling mechanism 56 pushes the fluid in channel 54 between channels intersection 68 and the first reaction chamber 62 into reaction chamber 62.
  • Activation of the second propelling mechanism 58 will push the fluid from the first reaction chamber 62 through channel 64 and into the second reaction chamber 66.
  • a similar multi-staged effect can be achieved by multi-staged heating or electrolysis.
  • a sample testing unit incorporating the propulsive mechanism of the present invention, in which the expandable fluid and the propelled fluid are the same.
  • a sample fluid flows from sampling port 72 towards reaction chamber 82.
  • reaction chamber 82 Located within reaction chamber 82 is a test or reaction reagent.
  • Propulsive mechanism 76 and channel 78 are filled with expandable fluid, water, for instance.
  • the expandable fluid located in propulsive mechanism 76 begins to expand, pushing the sample fluid in channel 78.
  • the expansion in the direction of reaction chamber 82 is permitted because of pressure relief channel 86.
  • a device 80 consisting of a means for sensing reaction between a test or reaction reagent and a sample fluid, incorporating the propulsive mechanism of the present invention, 56 can indicate biochemical properties of the sample fluid or of the reaction between the sample fluid and a test or reaction reagent.
  • a device 80 consisting of a means for sensing reaction between a test or reaction reagent and a sample fluid, incorporating the propulsive mechanism of the present invention 56, can indicate chemical properties of the sample fluid or of the reaction between the sample fluid and a test or reaction reagent.
  • a device 80 consisting of a means for sensing reaction between a test or reaction reagent and a sample fluid, incorporating the propulsive mechanism of the present invention 56, can indicate electrical properties of the sample fluid or of the reaction between the sample fluid and a test or reaction reagent.
  • a device 80 consisting of a means for sensing reaction between a test or reaction reagent and a sample fluid, incorporating the propulsive mechanism of the present invention 56, can indicate enzymatic properties of the sample fluid or of the reaction between the sample fluid and a test or reaction reagent.
  • a device 80 consisting of a means for sensing reaction between a test or reaction reagent and a sample fluid, incorporating the propulsive mechanism of the present invention 56 can indicate measurable physical properties of the sample fluid or of the reaction between the sample fluid and a test or reaction reagent.

Abstract

A microfluidics liquid dispensing unit comprises: a housing containing a liquid reservoir, the liquid reservoir having an ejection port. The liquid reservoir contains a test fluid in fluid contact with ejection port and further contains an expandable fluid or means for generating an expanding fluid. Activation of means for actively generating or expanding the expandable fluid, provides force generated by the expansion of expanded fluid which force is transmitted to dispensing fluid thereby ejecting and dispensing fluid through an ejection port.

Description

METHOD AND APPARATUS FOR PROPELLING A FLUID
Field of Invention
This invention relates to microfluidics. More particularly, the invention relates to a method and apparatus for liquid propulsion in a nanoscale device, using non-mechanically-induced volumetric changes for propelling the liquid.
Background Of The Invention
Microfluidics systems and devices known in the art often propel fluids such as liquids or gasses by moving the fluids through channels or passages formed within various substrates. Typically, in such microfluidics systems, the moving of the fluids may be achieved by capillary effects or by using suitable micropumps and/or other material transport devices or sub-systems. Such micropumps may operate, inter alia, by using piezoelectric effects, electrostatic effects, electro-osmotic effects, mechanical effects or electromagnetic effects. The construction of such micropumps may require costly manufacturing methods. Certain types of mechanical or electromechanical micropumps, such as, for example valve or diaphragm operated micropumps may move or propel fluids within fluidic channels by controilably and actively producing positive or negative pressure within parts of such fluidic channels in the fluidic system to induce a pressure gradient within different portions of the fluidic system for pushing or pulling fluids in a desired direction within a flow channel.
Examples of microfluidic systems, components thereof and their uses are described in the following US Patents: 6,197,595 to Anderson et al.; 6,168,948 to Anderson et al.; 6,114,122 to Besemer et al.; 5,922,591 to Anderson et al.; 6,090,545 to Wohlstadter et al.; 6,090,251 to Sundberg et al.; 6,086,825 to Sundberg et al.; 6,086,740 to Kennedy; 6048734 to Burns et al.; 6,042,710 to Dubrow; 5,810,325 to Carr; and 5,681 ,024 to Lisec et al. These patents disclose examples of the technology discussed in brief hereinbelow and are incorporated herein by reference as indicative and explanatory of the state of the art of the technology prior to the invention herein.
Typically, the amounts of fluids pumped by known micropumps may depend, inter alia, on the type of fluid pumped. Often, in mechanically or valve based micropumps the amount of fluid pumped may depend on the number of pump strokes. In some micropumps it may be necessary to count and calibrate pump strokes for different types of pumped fluids, or to use flow sensors or detectors for quantitating or monitoring the pumped fluid volume or the fluid's flow or position.
Integrated microfluidics systems may also be connected through suitable ports or channels to one or more external sources of positive and/or negative pressure for propelling one or more fluids within one or more flow channels included in the system.
In addition, the operation of some micropumps may involve further design considerations which take into account dead volume and pump priming. Integration of such micropumps with other components to form entire systems therefore may often be complicated, costly and cumbersome.
In most microfluidics systems, the flow of the liquids is achieved by either capillary effects or by micropumps operated by piezoelectric, electrostatic or electromagnetic effects. These require costly manufacturing techniques and the amount of liquid pumped is derived from the liquid type and pump strokes that have to be counted and calibrated for different liquids or with flow sensors.
In the case of capillary effects, a sample solution is forced into the end of the capillary furthest from the detector. Sample volumes often range from .1-100 ml. The most frequently used injection mode is to dip the capillary into the sample solution vial. A volume of solution is then drawn into the capillary, mostly under the influence of capillary action forces. As an alternative, a less popular sample injection procedure is to dip the capillary and electrode into the sample solution vial and to apply a voltage. If the sample is ionized and the appropriate voltage polarity is used then sample ions will migrate into the capillary. This type of injection is known as electrokinetic sampling.
The piezoelectric micropump, for example, relies on a membrane actuator which is deflected by a piezoelectric plate. The actuation is done by the piezoelectric membrane actuator, which changes the chamber volume periodically. When the chamber volume increases, liquid is sucked through the inlet into the chamber. At the point when the chamber volume decreases, the fluid is pressed through the outlet. However, this approach requires a difference in flow resistance between inlet and outlet for different flow directions. Such a behavior is realized, for example, with passive cantilever valves among others, which show a large flowrate in forward direction and low leakage rates in reverse operation.
Electromagnetic effects are embodied by another electrokinetic phenomenon known as "electrophoresis," which occurs in the channels of movement. This is the movement of charged molecules or particles in an electric field. Electrophoresis is often used in conventional laboratories for analyzing molecules since they move differently according to their physical make-up. Electrophoresis can be used to move molecules in solution, or to separate molecules with very subtle differences.
Pressure can also be used to move fluid in the channels. On the microfluidic scale, small amounts of pressure produce highly predictable and reproducible fluid flow. Both computer-controlled pressure and electrokinetic forces are used to gain precise control over fluid flow in the microfluidic channel network.
Additional care needs to be taken to solve issues regarding dead volume, and priming. Dead volume is the total volume of the liquid phase in the column. Miniaturized micropumps combine the ability of dosing very small amounts of fluids with low manufacturing costs and small overall size. In the laboratory a major concern is the ease of handling equipment. Pump priming can be laborious.
State-of the-art microfluidic lab-on-a-chip technology represents a revolution in laboratory experimentation, potentially bringing the benefits of miniaturization, integration and automation to many research-based industries. Such products are created by combining manufacturing methods from the microchip industry with expertise in fluid dynamics, biochemistry and software and hardware engineering to develop miniature, integrated biochemical processing systems.
There is therefore a long felt need for simple methods and devices for moving or propelling fluids in microfluidics systems and other fluidic systems which may be easily integrated into, or fabricated within, or added to such systems, using standard manufacturing and/or microfabrication techniques and which may allow for controilably propelling fluids such as liquids or gasses within such fluidic systems and/or microfluidics systems and other fluidic systems.
Summary Of The Invention
It is an object of the present invention to provide methods and apparatus for lower cost and smaller size of fluid propulsion mechanisms, yet maintaining a high degree of accuracy.
It is another object of the present invention to provide methods and apparatus for a propulsion mechanism that is straightforward to fabricate with very few steps.
These objects, and others not specified hereinabove, are achieved by an exemplary embodiment of the present invention, consisting of a chamber with two electrodes. The flow of fluids is achieved by electrolysis of minute quantities of the fluid, which in most cases is solution of some materials in water, to form gas. The propelling fluid can be just water that pushes other liquid. The liquid can be isolated from the water by air/gas bubble.
The volume of the gas is much larger than the volume of the liquid from which it was formed. Since the current is easily controllable, the exact volume of gas formed is controlled as well.
The volume of fluid dispensed is linear with the electrical charge and is limited by the original volume of liquid in the chamber that can decompose.
In one alternative exemplary embodiment of the present invention, the propulsion method comprises vaporizing at least part of the liquid that needs to be propelled such that the rest of the fluid is propelled in a controllable manner.
Alternatively, the propelling liquid can be a different liquid from the sample fluid that needs to be pushed. In such a scenario, if it is desirable to prevent mixing of the propelling fluid and the sample fluid, this can be accomplished either by choosing a propelling fluid which is not soluble in the sample fluid solvent. Alternatively, it may be possible to isolate the propellant fluid from the sample fluid by providing an insulating bubble of air/gas between them.
The devices which can achieve the above objectives according to the present invention are straightforward to fabricate, require few steps and therefore are economical to manufacture, while still enabling accurate volume dispensation.
In all of the exemplary embodiments, motive force for directing substances through the microcapillary network of the microfluidics lab-on-a- chip, is accomplished by generating some volumetric expansion of a substance, that substance being either initially present or brought into being by activation of the device (for example by electrically-catalyzed chemical or combustive reaction of one or more solids). This in turn creates pressure changes in the microcapillary network and applies motive force to the substances which need to be moved from one reaction point to another.
The present invention will be more fully understood from the following detailed description of the preferred embodiments thereof, taken together with the drawings, in which:
Brief Description Of the Drawings
FIG. 1 is a schematic illustration of a chamber cross-section of the electrolysis embodiment of the present invention;
FIG. 2 is a schematic illustration of a detailed top-view of a T-shape chamber of the electrolysis embodiment of the present invention;
FIG. 3 is a schematic illustration of a refillable configuration for the electrolysis embodiment of the present invention;
FIG. 4 is a schematic illustration of a chamber cross-section of the liquid evaporation embodiment of the present invention;
FIG. 5 is a schematic illustration of a top-view of an evaporation chamber of the liquid evaporation embodiment of the present invention;
FIG. 6 is a schematic illustration of a sequence of resistors in an evaporation chamber of the liquid evaporation embodiment of the present invention;
FIG. 7 is a schematic illustration of a refillable evaporation chamber of the liquid evaporation embodiment of the present invention;
FIG. 8 is a schematic illustration of a microfluidics system constructed in accordance with an exemplary embodiment of the present invention; and
FIG. 9 is a schematic illustration of a microfluidics system constructed in accordance with an exemplary embodiment of the present invention.
Description of Exemplary Embodiments The present invention is an innovative method for propelling fluid through microfluidics devices and to devices which incorporate the propulsive method for motivating sample fluids through a series of nanoscale reaction chambers connected to one another by tiny channels or capillaries which together comprises a microfluidics environment. A generic device which could incorporate the propulsive mechanism of the present invention would typically comprise microcapillaries or channels provided in a substrate or housing, the microcapillaries having a port for introducing a sample fluid, reaction chambers connected by the microcapillaries in which test or reaction reagents are located, reservoirs for holding expandable fluids and means for moving test fluid through the microcapillaries in a controlled fashion for example by causing expansion of the expandable fluids held in the reservoirs, and a controller for controlling the means for moving the test fluid. It should be noted that exemplary embodiments of the present invention may be designed wherein the motive providing expandable fluid may be generated within the reservoirs or capillaries by the chemical or combustive reaction of one or more solid agents, (e.g. applying electrical current to a laminate of solid materals to induce an expanding-gas-producing reaction). Other features which are often found in such devices are valves and sensing means or display means for sensing the results of reactions or displaying the results of reactions to the device operator. In general, the propulsion of fluid in the present invention is performed by creating a positive pressure gradient positioned in the microcapillary system with respect to the test sample such that the sample of test fluid is motivated through the channels of the microfluidics testing device. The pressure gradient is created by the expansion of an expandable fluid using one or more of several possible means for expansion, examples of which will be discussed hereinbelow, resulting in the propulsion of the test fluid.
In one possible embodiment of the present invention, said method of expansion of the expandable fluid is controlled by a controller. In an alternate embodiment of the present invention, said method of expansion is controlled manually.
In a preferred embodiment of the present invention, the method of expansion is electrolysis. Electrodes 13 are provided in properly arranged areas of a chamber 11 filled with the expandable fluid, in this case a fluid which is selected for its ease of undergoing hydrolysis, for example, water. Upon activation of the electrodes by activating a circuit which charges the electrodes, electrolysis of the expandable fluid occurs and the gases formed by the electrolytic process create a pressure by their expansion. Because the volume of 1 mole of gaseous products of electrolysis at 1 atmosphere is much greater than the volume of 1 mole of the liquid at 1 atmosphere, the expandable fluid is pushed against the sample fluid in the direction of a reaction chamber 62, for example.
In other exemplary embodiments, other means of chemical dissociation or chemical reaction may be employed in place of electrolysis to create a situation where gas is expanded or alternatively, an easily expandible fluid might be used, for example alcohol, which is easily expanded by simply applying heat.
In an additional preferred ambodiment of the present invention, the method of fluid expansion is fluid phase changing. This is performed by heating the expandable fluid, thereby causing it to evaporate. During the evaporation process, liquid vapors are formed from the heated fluid. The volume of the liquid vapors is larger than the volume of the fluid in its liquid state. This difference in the volume of the expandable fluid, a result of the heating process, causes the work fluid to be expelled from the liquid reservoir 11.
In alternate embodiments of the present invention, different means of achieving liquid phase change other than heating may be employed.
With reference to Fig. 1, there is seen in cross-section a view of a chamber useful with the electrolysis embodiment of the present invention. The device comprises the following components:
A microfluidics chip 10 has formed thereon an expandable fluid reservoir 11, capillaries or channels 14, electrodes 13 and conductors 15 all sandwiched between a cover layer 12 and a substrate or base layer 18.
One example of a process by which such a device is manufactured is as follows: A nitride layer 17 is deposited on a silicon wafer 10, which comprises a channel layer 18 having a uniform height. A photolithographic process defines the channel(s) on wafer 10 by removing portions of nitride layer 17. The silicon of channel layer 18 is then etched, where it has been photolithographically exposed, thereby forming channel 14 at a reduced height in silicon wafer 10 as shown.
A conductive layer 19 is deposited on top of nitride layer 17, and is patterned to form electrodes 13 and conductors 15. The lower portions of a cover and chamber layer 21, with a hole that defines expandable fluid reservoir 11, is then bonded to wafer 10. Expandable fluid reservoir 11 is then filled with fluid, and glass cover 12 is bonded as shown.
The distance between electrodes 13 needs to be appropriate for the intended voltage deemed necessary for electrolysis to take place. Electrodes 13 are connected via two conductors 15 to a controller (not shown) that applies voltage when there is a need to push the test fluid. The material used for electrodes 13 needs to be selected according to the properties of the liquid used, so as not to adversely affect the required process.
Chamber 11 extends to the left over the inlet of channel 14 and to the right over electrodes 13 as shown.
With reference to Fig. 1a there is seen an alternative embodiment of a manufacturing process. Starting material is a silicon wafer topped with a layer 19 of silicon oxide at a thickness of 300 angstrom and silicon nitride at a thickness of 1200 angstrom. With standard photolithographic methods, the capillaries are defined and etched into silicon nitride and silicon oxide using Reactive Ion Etching (hereinafter RIE). The silicon is then wet etched in potassium hydroxide or etched by using RIE.
After the wet etching, a polyimide film 12 such as Kapton™ film, product of the Dupont Co., that has been cut by a laser to define nozzles of the channels, is attached by glueing. This polyimide layer forms the upper half structure of the channels. A second polyimide layer 12 is then attached on the first. This layer has been cut by laser to form spaces for the expandable fluid reservoirs. The last layer is a Kapton with copper layer. First the layer is cut to form the sampling port and openings to air. Then electrodes are defined by a photolithographic method and etched. Finally this layer is glued with metal facing the previous layer.
The first layer thickness is 25 micron of polyimide. The second and third layers are 50 microns of polyimide. The adhesive adds to the thickness of the layers.
As an example, an exemplary embodiment could have features with specifications as follows:
• channels can be 100-micron wide and V-grooved in the silicon of channel layer; • conductive layer might be a 1 micron thick layer of aluminum;
• electrodes could be about 2 mm apart, although this might vary depending on the electrochemical nature of the liquid medium being expanded; • chamber layer might consist of a 0.5 mm thick Pyrex wafer, it might be drilled with a 1 mm drill and bonded to wafer to form a chamber;
• colored water might be used to prefill a chamber; and
• 4 volts might be the voltage applied to the electrodes, though this might depend on the liquid being electrolysed or the material from which the electrodes are made.
• Where the expansion is being caused by phase change, described further hereinbelow, then resistors might be provided having dimensions a width of 45 microns and lengths of 835 microns.
With reference to Fig. 2, there is seen a schematic illustration of a detailed top-view 20 of an exemplary embodiment of the present invention useful with the electrolysis embodiment of the present invention. A chamber, or reservoir 11, contains both the work fluid to be ejected and the expandable fluid. An ejection port 14 through which the work fluid is dispensed extends from the chamber 11. Electrodes 13, attached to conductors 15, are situated within the chamber 11 for electrolysis of the expandable fluid. For safety considerations chamber 11 can be formed in the shape of a T as shown. Upon electrolysis, the oxygen accumulates at one wing 22 of the T while the hydrogen accumulates at the other wing 24. The remaining fluid separates the two gases from each other so long as unelectrolysed fluid remains.
With reference to Fig. 3, there is seen a schematic illustration of a detailed top-view 30 of an alternate embodiment of the present invention useful with the electrolysis embodiment of the present invention. Refillable propulsive mechanism 30 is suitable either for initial filling of chamber 11, or for refilling of chamber 11 after electrolysis of all the liquid. Refillable propulsive mechanism 30 includes an inlet channel 32 with active valve 34 attached to one wing 22 of T chamber 11. An outlet channel 36 equipped with an active valve 38, which can be closed during the operation of the device, is attached to the other wing 24 of T chamber 11. In this configuration, as all the liquid is electrolysed, chamber 11 can be emptied through the draining of any remaining liquid through channel 36, allowing for the refilling of chamber 11 through channel 32, and the subsequent reuse of refillable propulsive mechanism 30.
With reference to Fig. 4, there is seen in cross-section a view of a chamber useful with the fluid phase changing embodiment of the present invention. Device 40 comprises identical components to microfluidics chip 10 with the exception that device 40 includes resistors 42 in place of conductors 13 of microfluidics chip 10.
With reference to Fig. 5, there is seen a schematic illustration of a detailed top-view 50 of an exemplary embodiment of the propulsive mechanism of the present invention useful with the fluid phase changing embodiment of the present invention. Extending from chamber 11, in which the expandable fluid is located, is ejection channel 14. At the other end of ejection channel 14 is an optional additional cell 44. Optional additional cell 44 serves to separate the heated fluid from the fluid dispensed into the system. Conductors 15 lead from a controller (not shown) to a resistor 42 which, upon activation, serves to heat the expandable fluid located in chamber 11 until at least a portion thereof undergoes a change of phase. Resistor 42 can be comprised of various types of metal.
With reference to Fig. 6, there is seen a schematic illustration of a detailed top-view 60 of an alternate embodiment of the propulsive mechanism of the present invention useful with the fluid phase-changing embodiment of the present invention. This embodiment additionally comprises a sequence of resistors 46 in place of the solitary resistor 42 of device 50 of Fig. 5. The additional resistors provide for a more accurate control of the fluid dispensation, as well as allowing for the heating to vaporization of, and therefore dispensation of, larger quantities of fluid. The resistors can be activated in sequence.
With reference to Fig. 7, there is seen a schematic illustration of a detailed top-view of a refillable propulsive mechanism 70 useful with the fluid phase changing embodiment of the present invention. Refillable propulsive mechanism 70 is seen here consisting of a plurality of resistors 46. In an alternate embodiment only one resistor may be used, as seen in Fig. 5. The components of refillable propulsive mechanism 70 are identical to those of device 60, save for inlet channel 32 leading to, and outlet channel 36 leading from, chamber 11. Along inlet channel 32 is situated active valve 34, allowing fluid to enter chamber 11, but not to exit from it. Likewise, along outlet channel 36 is situated an active valve 38, allowing fluid to exit chamber 11 upon activation, but preventing fluid from entering chamber 11 through outlet channel 36.
With reference to Fig. 8, there is seen a schematic illustration 80 of an exemplary embodiment of a sample testing unit, incorporating the propulsive mechanism of the present invention. When open, an active valve 52 allows the flow of the sample from sampling port 48 through channel 54 towards reaction chamber 62 by capillary forces. Within reaction chamber 62 is a dry reagent. Once the sample has passed valve 52, the valve 52 is closed, so as to prevent the sample from receding back towards sampling port 48. Activation of the first propelling mechanism 56 pushes the fluid in channel 54 between channels intersection 68 and the first reaction chamber 62 into reaction chamber 62. Activation of the second propelling mechanism 58 will push the fluid from the first reaction chamber 62 through channel 64 and into the second reaction chamber 66. In the alternative, a similar multi-staged effect can be achieved by multi-staged heating or electrolysis.
With reference to Fig. 9, there is seen an alternate embodiment of a sample testing unit incorporating the propulsive mechanism of the present invention, in which the expandable fluid and the propelled fluid are the same. Upon opening of active valve 74 a sample fluid flows from sampling port 72 towards reaction chamber 82. Located within reaction chamber 82 is a test or reaction reagent. Propulsive mechanism 76 and channel 78 are filled with expandable fluid, water, for instance. When propulsive mechanism 76 is activated, the expandable fluid located in propulsive mechanism 76 begins to expand, pushing the sample fluid in channel 78. The expansion in the direction of reaction chamber 82 is permitted because of pressure relief channel 86.
In an alternate embodiment of the present invention, a device 80 consisting of a means for sensing reaction between a test or reaction reagent and a sample fluid, incorporating the propulsive mechanism of the present invention, 56 can indicate biochemical properties of the sample fluid or of the reaction between the sample fluid and a test or reaction reagent.
In an additional alternate embodiment of the present invention, a device 80 consisting of a means for sensing reaction between a test or reaction reagent and a sample fluid, incorporating the propulsive mechanism of the present invention 56, can indicate chemical properties of the sample fluid or of the reaction between the sample fluid and a test or reaction reagent.
In an additional alternate embodiment of the present invention, a device 80 consisting of a means for sensing reaction between a test or reaction reagent and a sample fluid, incorporating the propulsive mechanism of the present invention 56, can indicate electrical properties of the sample fluid or of the reaction between the sample fluid and a test or reaction reagent.
In an additional alternate embodiment of the present invention, a device 80 consisting of a means for sensing reaction between a test or reaction reagent and a sample fluid, incorporating the propulsive mechanism of the present invention 56, can indicate enzymatic properties of the sample fluid or of the reaction between the sample fluid and a test or reaction reagent. In an additional alternate embodiment of the present invention, a device 80 consisting of a means for sensing reaction between a test or reaction reagent and a sample fluid, incorporating the propulsive mechanism of the present invention 56, can indicate measurable physical properties of the sample fluid or of the reaction between the sample fluid and a test or reaction reagent.

Claims

What is claimed is:
In a microfluidics distribution unit comprising a housing and having at least one microchannel and a test sample, means for moving said test sample from a first location in said microfluidics unit to a second location in said microfluidics unit, said means for moving said test sample comprising a work fluid within said microfluidics unit and further comprising non-mechanical means for changing the volume of said work fluid.
A microfluidics distribution unit in accordance with claim 1 , wherein said work fluid is said test sample.
3. A microfluidics distribution unit in accordance with claim 1 , wherein said work fluid is provided by chemically modifying at least one substrate.
4. A microfluidics distribution unit in accordance with claim 1 , wherein said work fluid is provided by changing the phase of at least one substrate.
5. A microfluidics distribution unit in accordance with claim 1 , wherein said work fluid is provided by initiating a reaction of at least one reactant which produces at least one product having a different volume than the volume of said at least one reactant.
6. A microfluidics distribution unit in accordance with claim 5, wherein said reaction is a dissociative reaction.
7. A microfluidics distribution unit in accordance with claim 5, wherein said reaction is a combustive reaction.
8. A microfluidics distribution unit in accordance with claim 3, wherein said chemical modification of said at least one substrate produces a fluid having a volume which may be changed.
9. A microfluidics distribution unit in accordance with claim 6, wherein said dissociative reaction is an electrolytic reaction.
10. A microfluidics distribution unit in accordance with claim 1 , wherein said work fluid is a liquid.
11. A microfluidics distribution unit in accordance with claim 1 , wherein said work fluid is a gas.
12. A microfluidics distribution unit in accordance with claim 1 , wherein said means for expanding said work fluid is by the addition of heat.
13. A microfluidics distribution unit in accordance with claim 1 , wherein said means for changing the volume of said work fluid is by removal of heat.
14. A microfluidics distribution unit in accordance with claim 1 , wherein said housing is formed from the group comprising at least one of silicon, glass and plastic.
15. A method for moving a test sample in the microchannels of a microfluidics distribution unit, said method comprising providing a work fluid in said microfluidics distribution unit and non-mechanically changing the volume of said work fluid.
16. A method for moving a test sample in the microchannels of a microfluidics distribution unit in accordance with claim 15, further comprising changing the volume of said work fluid by causing a phase change in said work fluid.
17. A method for moving a test sample in the microchannels of a microfluidics distribution unit in accordance with claim 15, further comprising expanding said expandable fluid by adding heat to said expandable fluid.
18. A method for moving a test sample in the microchannels of a microfluidics distribution unit in accordance with claim 15, further comprising changing the volume of said work fluid by removing heat from said work fluid.
19. A method for moving a test sample in the microchannels of a microfluidics distribution unit in accordance with claim 15, further comprising providing said work fluid by chemically modifying at least one reactant.
20. A method for moving a test sample in the microchannels of a microfluidics distribution unit in accordance with claim 15, further comprising changing the volume of said work fluid by causing a chemical change in said work fluid.
21. A method for moving a test sample in the microchannels of a microfluidics distribution unit in accordance with claim 15, further comprising changing the volume of said work fluid by causing a dissociative reaction in said work fluid.
PCT/IL2002/000357 2001-05-07 2002-05-07 Method and apparatus for propelling a fluid WO2002090770A2 (en)

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US6033544A (en) * 1996-10-11 2000-03-07 Sarnoff Corporation Liquid distribution system
US6117396A (en) * 1998-02-18 2000-09-12 Orchid Biocomputer, Inc. Device for delivering defined volumes

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5178190A (en) * 1990-12-22 1993-01-12 Robert Bosch Gmbh Microvalve
US6033546A (en) * 1994-08-01 2000-03-07 Lockheed Martin Energy Research Corporation Apparatus and method for performing microfluidic manipulations for chemical analysis and synthesis
US5846396A (en) * 1994-11-10 1998-12-08 Sarnoff Corporation Liquid distribution system
US5872010A (en) * 1995-07-21 1999-02-16 Northeastern University Microscale fluid handling system
US5879632A (en) * 1996-04-09 1999-03-09 Sarnoff Corporation Apportioning system
US6033544A (en) * 1996-10-11 2000-03-07 Sarnoff Corporation Liquid distribution system
US6117396A (en) * 1998-02-18 2000-09-12 Orchid Biocomputer, Inc. Device for delivering defined volumes

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