Abstract:
In one embodiment, a fluidic module, such as a microfluidic module, has a fluid-flow channel, an electroosmotic flow membrane positioned in the channel, and a cathode located on one side and an anode located on the other side of the membrane so that an electrolyte in the channel is transported through the membrane in the presence of a voltage. In another embodiment, the channel has a port, a flexible and fluid-impermeable diaphragm is added, the electrolyte is contained in a reservoir, and the membrane moves the bladder which acts as a valve for fluid leaving the channel through the port. In a further embodiment, electrolyte in a first reservoir is transported through the membrane to move the bladder to force fluid out of a second reservoir.

Description:
CROSS-REFERENCE TO RELATED APPLICATION 
     The present application claims priority from U.S. Provisional Application No. 60/136,886, filed Jun. 1, 1999, the entire disclosure of which is incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     The present invention relates to a valving mechanism for microfluidic devices and more particularly to a valving mechanism which is controlled or actuated by electroosmotic flow (EOF). The invention also relates to a device for delivering fluid reagents which is actuated by EOF. 
     One example of a valving mechanism for a microfluidic device is described in U.S. Pat. Nos. 4,304,257; 4,858,883 and 5,660,370 to Webster and others. That mechanism employs a flexible sheet or diaphragm which is moved toward or away from a flat non-flexing sheet member having a pair of fluid ports such that flow between the ports is easily regulated. In one embodiment disclosed in U.S. Pat. No. 5,660,370, the diaphragm is attached to the plunger head of a solenoid which is operated to move the diaphragm between blocking and non-blocking positions to activate the valve. In another embodiment disclosed in U.S. Pat. No. 4,858,883, the diaphragm overlies a concavity which is connected to a source of vacuum or pressure which controls the valve. Other microvalve constructions useful in microfluidic devises are described in International Application WO 97/21090. These constructions include a piezoelectric element in which an applied voltage is used to deform the element and block fluid flow; a diaphragm which includes a bimetallic element which is resistively heated to proportionately deflect the diaphragm; an electrostatically activated plunger which is moved into a gap in the microfluidic; and a single-use valve fashioned from polymers which are stretched under defined condition such that when the polymer is subsequently heated, the polymer chains relax and thereby actuate the valve. 
     SUMMARY OF THE INVENTION 
     Electroosmotic flow (EOF) has been proposed as a means for moving solutions within a microfluidic device. In accordance with the present invention, two valve constructions are proposed for valves which utilize EOF to control the flow of a fluid between two ports. In one embodiment EOF is used to generate sufficient pressure to actuate a diaphragm valve. In another embodiment, EOF is used to control flow through a membrane which functions as a gate which is opened and closed electrokinetically. Another manifestation of the invention is a fluid delivery device in which EOF is used to move a diaphragm into a reservoir containing a reagent and in turn to meter the reagent into a microfluidic device. 
    
    
     BRIEF DESCRIPTION OF THE DRAWINGS 
     FIG. 1 schematically illustrates a valve construction in the passive state in accordance with one manifestation of the present invention. 
     FIG. 2 schematically illustrates a valve construction in the de-energized state in accordance with one manifestation of the present invention. 
     FIG. 3 schematicaly illustrates a valve construction in the energized state in accordance with one manifestation of the present invention. 
     FIG. 4 is an exploded view of a valve construction in accordance with one embodiment of the invention in which the electrodes have the design shown. 
     FIG. 5 is an overhead view of a valve construction in which the electrodes have the design shown in accordance with one embodiment of the invention. 
     FIG. 6 is a schematic illustration of a valve construction in accordance with another embodiment of the invention in which the EOF membrane controls the flow of fluid through a microfluidic device 
     FIG. 7 is an overhead view of a valve construction in which the electrodes have the design shown in accordance with another embodiment of the invention. 
     FIG. 8 is a schematic illustration in which the EOF membrane is used in a fluid delivery device for metering fluid from a reservoir to a microfluidic or other device. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     P. H. Paul, D. W. Arnold, D. J. Rakestraw, Electrokinetic Generation of High Pressures Using Porous Microstructures, Proceedings of the μTAS&#39;98 Workshop Banff, Canada, 13-16 October 1998 p.49 reports that up to 8,000 psi pressure can be generated electrokinetically through a porous media and shows that there is a log-linear relationship between pressure per volt and bead diameter and a linear relationship between pressure and applied voltage. In accordance with the present invention these electrokinetic pressures are used to operate a diaphragm valve. A microfluidic device is provided which includes a valve body having first and second fluid passageways which intersect the surface of the valve body at spaced locations and a valve diaphragm having a surface for making engagement with said valve body surface. A porous membrane is provided between a pair of electrodes and is operatively associated with the diaphragm member and a reservoir of an electrolyte such that when a voltage is applied between the electrodes, the electrolyte is transported through the membrane to effect a change in pressure between the diaphragm and the membrane. The change in pressure actuates the valve. In one embodiment of the invention the EOF of the electrolyte results in application of a positive pressure which closes the valve. In another embodiment the applied voltage causes the electrolyte to move away from the diaphragm and thereby opens the valve. 
     The valve body and diaphragm can be constructed from materials and using manufacturing techniques that have previously been used in the construction of microfluidic devices with the addition of an EOF membrane and electrodes as described herein. The channel size in the microfluidic devices of the present invention can range from about 50 to 500 microns. 
     The EOF membrane can be one having an open porous network in which the pore size may range from about 30 angstroms to about 25 microns. The membrane may be about 2 microns to about 25 microns thick and is more typically about 2 to 12 microns thick. The pore size and thickness of the membrane are selected such that an EOF adequate to operate the valve can be established without using voltages which cause electrolysis. Water electrolyzes at about 1.2 to 1.5 volts depending on the electrode. However, by selecting an electrode with a high over-potential (e.g., a boron doped diamond electrode), voltages as high as about 2 volts can be used without electrolysis. 
     The EOF velocity is usually very small, e.g., about 0.0001 m/sec and is a function of the membrane, the fluid and the voltage. Accordingly, the valve is designed and structured such that the small EOF velocities generate pressures sufficient to operate the valve, e.g., about 10 to 30 psi in conventional microfluidic devices. The valves will not actuate immediately but rather upon application of the electric field, the field will force electrolyte to flow through the membrane. The valve will open or close (depending on the valve design) when sufficient fluid has been pumped through the membrane to generate enough pressure to actuate the valve. 
     The EOF membrane will be formed by a material which can carry a charge upon the inner surfaces of the walls of its pores such that when it is placed in and ionic solution it will create an electric double layer which is characteristic of electroosmotic. Most substances will acquire a surface electric charge when brought into contact with an aqueous medium via a charging mechanism such as ionization, ion adsorption, or ion dissolution. Additionally, the membrane must be inert to the fluids with which the microfluidic is used and is desirable a material that can be readily bonded to the valve body. Preferably the membrane will be bonded within the microfluidic device using an adhesive or a bonding technique such as heat sealing, but mechanical constructions using clips and other fasteners could also be used for some applications. Two materials which are commercially available and have been used experimentally are track etched polycarbonate and track etched polyimide. If the membrane is so thin that it is not able to maintain enough pressure to actuate the valve, e.g., the membrane flexes readily under pressures less than 20 psi, a contiguous structural supporting material such as cellulosic or synthetic paper, a metal or synthetic wire mesh may be used in conjunction with the membrane to prevent the membrane from yielding to the EOF pressure. 
     In order to generate the EOF, an electric field is deployed across the membrane. Typically this field can run from about 100 v/cm to 1000 v/cm but those skilled in the art will recognize that the field controls the EOF velocity and weaker fields could be used but the valve will operate more slowly and stronger fields could be used provided that they do not result in electrolysis. As explained above, due to the electrolytic limits of water, the electric field generally must be effected using less than 2 volts. This field is most conveniently established using thin film electrodes of a type known in the art. An electrode is preferably selected which does not result in dendrite formation or the formation of precipitates and which does not produce appreciable gas through electrolysis. Silver or platinum electrodes are well known and can be used but other electrodes having a higher overpotential which can be sputter deposited may prove to be more desirable for use. 
     FIGS. 1-3 schematically illustrate one embodiment of the invention wherein a microfluidic device  10  contains a first channel  12  and a second channel  14  having respectively ports  16  and  18  which open on a valve area  20  on one surface of the microfluidic  10 . The microfluidic is constructed from interfacing lower element  30  and upper element  32  which have been micromachined at the interface to provide the channels  12  and  14 . A diaphragm  22  overlies the ports  16  and  18 . The diaphragm  22  is a fluid impermeable but flexible partition such as a polyimide or a polyurethane film. Juxtaposed with the diaphragm is the EOF membrane  24 . This EOF membrane seals a reservoir  26  containing an electrolyte. In FIG. 1, the valve is shown in a passive state in which no fluid is flowing in the microfluidic. When a fluid is pumped through the microfluidic as shown in FIG. 2, the fluid easily deflects the diaphragm/EOF membrane construction  22 / 24  and passes between the first and second channels  12  and  14  through the ports  16  and  18 . The microfluidic includes a pair of electrodes which is not shown in FIGS. 1-3. In the illustrated in FIG. 3 when an electric field is applied by means of the electrodes, the electrolyte in reservoir  26  is transported through the EOF membrane  24  and because the diaphragm is impermeable, the electrolyte accumulates in the space  28  between the diaphragm and the membrane and produces a positive pressure on the fluid impermeable diaphragm  22  forcing it to seal the ports  16  and  18 . To open the valve, the electric field can be reversed such that electrolyte is transported back into the reservoir  26  so that fluid pressure in channels  12  and  14  moves the diaphragm away from the ports  16  and  18 . 
     FIG. 4 is an exploded view of a valve construction in accordance with this embodiment of the invention showing that the reservoir is formed from a electrolyte containment layer  33  which may be formed from the same material as the microfluidic halves  30  and  32  or from a different dimensionally stable and inert material, and a flexible containment layer  35  which is conveniently formed of a material such as a polyester or polyimide film. The containment layer  35  is preferably sufficiently flexible so that a negative pressure which interferes with electroosmotic flow is not produced in the electrolyte chamber as the electrolyte moves from the reservoir  26  into the space  28 . In lieu of a flexible containment layer, the reservoir could be vented. 
     The EOF membrane  24  is sandwiched between a pair of thin film electrodes. These electrodes are formed from materials and in a manner that is well known in the art. In the illustrated embodiment, one electrode  34  is located on the side of the EOF membrane  24  which faces the reservoir and the other electrode  36  is affixed to the diaphragm  22 . The electrodes can be shaped as shown in top view in FIG. 5 in which one is annular (electrode  34 ) and the other  36  is a disk or they can be shaped differently provided that they generate an electric field across the EOF membrane which transports fluid. The electrodes will include tabs  38  for connecting them to an external power supply. The electrolyte is preferably an aqueous solution of a monovalent salt such as sodium borate. Typically a concentration less than about 0.1 μM to 1.0 mM is used. 
     The microfluidic halves, the diaphragm, the EOF membrane and the reservoir can be assembled using one or a combination of techniques known in the art including using adhesives, self bonding films, melt flow or mechanical clamping. 
     In another embodiment of the invention as schematically illustrated in FIG. 6, the diaphragm is omitted and the EOF membrane is interposed in the channel as a “gate” that is opened, partially opened or closed using the electric field strength. For this embodiment of the invention, the fluid passing through the microfluidic must have a weakly ionic character. In this embodiment of the invention a microfluidic device  100  includes a first channel  102  and a second channel  104  which open onto each other at common ports  106  and  108 . Interposed between these ports is an EOF membrane  110  which includes electrodes  114  and  112  (FIG. 7) on each side thereof. The electrodes can have the same construction as shown in FIG.  5 . When the electric field is zero or very low, essentially no fluid passes through the membrane. When an electric field is applied, the EOF membrane  110  transports fluid across the membrane and enables flow between the channels  102  and  104 . In theory, by varying the field strength one should be able to control the rate of flow through the membrane. 
     In another embodiment of the invention an EOF membrane is used as an actuator for a fluid delivery system. This embodiment is illustrated in FIG.  8 . The dispenser  200  includes a reservoir of electrolyte  202 , which is formed by a containment layer  204  and a pair of flexible bladder diaphragms  206 / 207 . An EOF membrane  208  is provided inside the electrolyte reservoir  202  on the electrolyte reservoir side of the bladder diaphragm  207 . A second reservoir  210  contains a solution, such as a solution of a reagent, that is to be delivered. This reservoir includes a small outlet  212  which may feed a microfluidic or a reagent delivery device. As in the other embodiments of the invention, the EOF membrane  208  is used in conjunction with a pair of electrodes analogous to FIGS. 5 and 7. By applying a voltage across the anode and cathode, the electrolyte is transported from the reservoir  202  across the EOF membrane  208  into the space  214  between the EOF membrane  208  and the bladder diaphragm  207 . This results in a fluid pressure being applied to the diaphragm  207  which causes the diaphragm to expand into the reservoir  210  thereby forcing the fluid from the reservoir via the outlet  212 . At the same time, the bladder  206  and the EOF membrane  208  are drawn together as shown in FIG.  8 ( b ). While the embodiment of FIG. 8 shows the electrolyte chamber being formed from two flexible bladder members, this is not an essential element of the invention. The electrolyte chamber could be formed using a single flexible bladder or the electrolyte chamber could be vented so that a negative pressure which would interfere with the EOF flow is not created in the electrolyte chamber as the electrolyte is transported. 
     In summary, one manifestation of the invention is a microfluidic module having fluid flow channels therein, at least one fluid flow channel being in communication with a diaphragm valve, said diaphragm valve including a flexible fluid impermeable diaphragm and a fluid permeable member contiguous with said fluid impermeable diaphragm, a reservoir of an electrolyte in fluid communication with said fluid permeable member, a cathode positioned on one side of said fluid permeable member and an anode positioned on the opposite side of said fluid permeable member such that when a voltage is applied to said electrodes, said electrolyte is transported through said fluid permeable member and said transported electrolyte applies fluid pressure to said diaphragm thereby closing said valve. 
     In a more particular manifestation of the invention, the fluid permeable member is a porous membrane which is interposed between said fluid impermeable diaphragm and said reservoir such that when a voltage is applied between said electrodes, electrolyte is transported from said reservoir to said diaphragm where fluid pressure is applied to close said valve. 
     Another manifestation of the invention is a module having fluid flow channels therein, at least one fluid flow channel having a fluid permeable membrane situated therein such that fluid passing through said channel must flow through said membrane, said membrane having a cathode on one side thereof and an anode on the other side such that when a voltage is applied to said electrodes, fluid flows selectively through said channel and when no voltage is applied to said electrodes, essentially no fluid flows through said channel whereby the flow of fluid through said channel is controlled electrokinetically by said membrane. 
     Still another manifestation of the invention is a fluid delivery system which includes a first reservoir of an electrolyte, a second reservoir of a fluid to be delivered by said delivery system, an outlet in said second reservoir, a flexible fluid impermeable diaphragm and a fluid permeable diaphragm interposed between said first and second reservoirs, said fluid permeable diaphragm having electrodes positioned on each side thereof wherein by applying a voltage to said electrodes, said electrolyte is transported from said first reservoir through said membrane and said electrolyte expands said fluid impermeable membrane into said second reservoir containing said deliverable fluid thereby forcing said fluid through the outlet in said second reservoir.