US20050205816A1 - Pneumatic valve interface for use in microfluidic structures - Google Patents

Abstract

A pneumatic valve for use in laminated plastic microfluidic structures. This zero or low dead volume valve allows flow through microfluidic channels for use in mixing, dilution, particulate suspension and other techniques necessary for flow control in analytical devices.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS
• This patent application claims benefit from U.S. provisional Patent Application Ser. No. 60/281,114, filed Apr. 3, 2001, which application is incorporated herein by reference.
BACKGROUND OF THE INVENTION
• 1. Field of the Invention
• This invention relates generally to microscale devices for performing analytical testing and, in particular, to a valve interface for use in laminated microfluidic structures.
• 2. Description of the Prior Art
• Microfluidic devices have recently become popular for performing analytical testing. Using tools developed by the semiconductor industry to miniaturize electronics, it has become possible to fabricate intricate fluid systems which can be inexpensively mass produced. Systems have been developed to perform a variety of analytical techniques for the acquisition of information for the medical field.
• Microfluidic devices may be constructed in a multi-layer laminated structure where each layer has channels and structures fabricated from a laminate material to form microscale voids or channels where fluids flow. A microscale channel is generally defined as a fluid passage which has at least one internal cross-sectional dimension that is less than 500 μm and typically between about 0.1 μm and about 500 μm. The control and pumping of fluids through these channels is affected by either external pressurized fluid forced into the laminate, or by structures located within the laminate.
• U.S. Pat. No. 5,716,852 teaches a method for analyzing the presence and concentration of small particles in a flow cell using diffusion principles. This patent, the disclosure of which is incorporated herein by reference, discloses a channel cell system for detecting the presence of analyte particles in a sample stream using a laminar flow channel having at least two inlet means which provide an indicator stream and a sample stream, where the laminar flow channel has a depth sufficiently small to allow laminar flow of the streams and length sufficient to allow diffusion of particles of the analyte into the indicator stream to form a detection area, and having an outlet out of the channel to form a single mixed stream. This device, which is known at a T-Sensor, may contain an external detecting means for detecting changes in the indicator stream. This detecting means may be provided by any means known in the art, including optical means such as optical spectroscopy, or absorption spectroscopy of fluorescence.
• U.S. Pat. No. 5,932,100, which patent is also incorporated herein by reference, teaches another method for analyzing particles within microfluidic channels using diffusion principles. A mixture of particles suspended in a sample stream enters an extraction channel from one upper arm of a structure, which comprises microchannels in the shape of an “H”. An extraction stream (a dilution stream) enters from the lower arm on the same side of the extraction channel and due to the size of the microfluidic extraction channel, the flow is laminar and the streams do not mix. The sample stream exits as a by-product stream at the upper arm at the end of the extraction channel, while the extraction stream exits as a product stream at the lower arm. While the streams are in parallel laminar flow in the extraction channel, particles having a greater diffusion coefficient (smaller particles such as albumin, sugars, and small ions) have time to diffuse into the extraction stream, while the larger particles (blood cells) remain in the sample stream. Particles in the exiting extraction stream (now called the product stream) may be analyzed without interference from the larger particles. This microfluidic structure, commonly known as an “H-Filter,” can be used for extracting desired particles from a sample stream containing those particles.
• Several types of valves are commonly used for fluid management in flow systems. Flap valves, ball-in-socket valves, and tapered wedge valves are a few of the valve types existing in the macroscale domain of fluid control. However, in the microscale field, where flow channels are often the size of a human hair (approximately 100 microns in diameter), there are special needs and uses for valves which are unique to microscale systems, especially microfluidic devices incorporating fluids with various concentrations of particulates in suspension. Special challenges involve mixing, dilution, fluidic circuit isolation, and anti-sediment techniques when employing microscale channels within a device. The incorporation of a simple compact microfluidic valve within microscale devices addresses these potential problems while maintaining high density of fluidic structure within the device, and eliminating the need for active valve actuation in many cases.
• Many different types of valves for use in controlling fluids in microscale devices have been developed. U.S. Pat. No. 4,895,500, which issued on Jan. 23, 1990, describes a silicon micromechanical non-reverse valve which consists of a cantilever beam extending over a cavity and integrally formed with the silicon wafer such that the beam can be shifted to control flow within channels of the microfluidic structure.
• U.S. Pat. No. 5,443,890, which issued Aug. 22, 1995 to Pharmacia Biosensor AB, describes a sealing device in a microfluidic channel assembly having first and second flat surface members which when pressed against each other define at least part of a microfluidic channel system between them.
• U.S. Pat. No. 5,593,130, which issued on Jan. 14, 1997 to Pharmacia Biosensor AB, describes a valve for use in microfluidic structures in which the material fatigue of the flexible valve membrane and the valve seat is minimized by a two-step seat construction and the fact that both the membrane and the seat are constructed from elastic material.
• U.S. Pat. No. 5,932,799, which issued Aug. 3, 1999 to YSI Incorporated, teaches a microfluidic analyzer module having a plurality of channel forming laminate layers which are directly bonded together without adhesives, with a valve containing layer directly adhesivelessly bonded over the channel containing layers and a flexible valve member integral with the valve layer to open and close communication between feed and sensor channels of the network.
• U.S. Pat. No. 5,962,081, which issued Oct. 5, 1999 to Pharmacia Biotech AB, describes a method for the manufacturer of polymer membrane-containing microstructures such as valves by combining polymer spin deposition methods with semiconductor manufacturing techniques.
• U.S. Pat. No. 5,977,355, which issued on Oct. 26, 1999 to Xerox Corporation, describes a valve array system for microdevices based on microelectro-mechanical systems (MEMS) technology consisting of a dielectric material forming a laminate which is embedded within multiple laminate layers.
• U.S. Pat. No. 6,068,751, which issued on May 30, 2000, describes a microfluidic delivery system using elongated capillaries that are enclosed along one surface by a layer of malleable material which is shifted by a valve having a electrically-powered actuator.
SUMMARY OF THE INVENTION
• It is therefore an object of the present invention to provide an efficient valve suitable for use in a microfluidic system.
• It is a further object of the present invention is to provide a microfluidic valve which can be integrated into a cartridge constructed of multi-layer laminates.
• It is a further object of the present invention is to provide an array of microfluidic valves which can be integrated into a cartridge constructed of multi-layer laminates.
• These and other objects of the present invention will be more readily apparent in the description and drawings which follow.
BRIEF DESCRIPTION OF THE DRAWINGS
• FIG. 1 is a perspective view of a microfluidic valve according to the present invention;
• FIG. 2 is a fragmentary cross-sectional view of an alternative valve according to the present invention;
• FIG. 3 is a fragmentary cross-sectional view of the valve ofFIG. 2 shown in its activated position;
• FIG. 4 is a fragmentary top view, partly in phantom, of the valve ofFIG. 2;
• FIG. 5 is a fragmentary cross-sectional view of another alternative valve according to the present invention;
• FIG. 6 is a fragmentary cross-sectional view of the valve ofFIG. 5 shown in its activated position;
• andFIG. 7 is a perspective view of an array which uses valves according to the present invention.
DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
• A basic zero dead volume valve according to the present invention is shown inFIG. 1. Referring now toFIG. 1, a valve generally indicated at10 consists of amembrane layer12 which covers aflat surface13 coupled to aninput channel14, which is connected to a flow channel16 and also anoutput channel18 connected to aflow channel20. Abovelayer12 is anair chamber22 which is coupled to apneumatic source24 by ashort air channel26. In operation, zerodead volume valve10 works as follows: a liquid30 enters channel16 and travels intochannel14 where itcontacts membrane layer12. Under atmospheric conditions withinair chamber22, membrane lines flat against surface orseat13, causingliquid30 to stop inchannel14. However, if the fluid pressure withinchannel14 exceeds the elastic force contained inmembrane13,membrane13 will bulge out intochamber22, allowingliquid30 to pass undermembrane13 and flow out throughchannel18 and intochannel20, as shown by the arrows inFIG. 1.Valve10 shown inFIG. 1 may operate as a zero volume valve, as it is a normally closed valve in which sufficient fluid pressure moves the membrane away from its sealing position to open with only atmospheric pressure withinchamber22.
• When in operation within a microfluidic circuit, pneumatic pressure withinchannel24 is used to open andclose valve10. If it is desirable to keepvalve10 in its closed position, positive air pressure is applied throughsource24 intochannel26, when it fillsair chamber22, which forcesmembrane12 againstseat13. It has been found that applying +1.0 psi air pressure withinsource24 will adequately keepvalve10 closed. It is desirable to openvalve10, a negative pressure of −55 mm Hg creates a vacuum withinchamber22 to completely liftmembrane12 away fromseat13 to allow liquid30 to travel fromchannel14 acrosssurface13 out ofchannel18. Pressure fromsource24 can also be varied to vary the flow throughvalve10.
• FIGS. 2-4 show an alternate embodiment in which avalve40 is constructed as a normally open valve. Referring now toFIG. 2, a latexrubber diaphragm membrane50 is held between two spacinglayers54 of a laminated microfluidic structure.Valve40 is fabricated from a series oflaminar sheets60 which are preferably MYLAR® or a similar plastic sheet. Channels are constructed withinvalve40 by cutout spaces within spacing layers54 betweensheets60. InFIG. 2 is in its relaxed state, which allows liquid to enter aflow inlet62, and pass through a channel64 into a lower chamber66 belowmembrane50. The liquid can flow out ofvalve40 from chamber66 through a channel68 and out through aflow outlet70. Flow throughvalve40 is controlled by pneumatic pressure which is supplied by a valveair supply channel72 through achannel74 into anupper chamber76.
• Operation ofvalve40 is clearly shown inFIG. 3. Referring now toFIG. 3, sufficient air pressure is supplied viachannel72 throughchannel74 and intoupper chamber76. This pressure forcesmembrane50 to flex downwardly into lower chamber66, blocking channels64 and68, preventing fluid flow betweeninlet62 andoutlet70.
• FIGS. 5 and 6 show another embodiment of the valve of the present invention. Referring now toFIG. 5, which shows the normal “on” state of the valve, avalve80 is constructed from a pair of laminar MYLAR®sheets82 which are separated by a series of spacing layers84. Channels are formed in spacing layers84 by cutout sections which form a flow structure. Aflexible membrane86 is held between two spacinglayers84 in its relaxed state. Afluid input channel90 is connected to channel92 and to anupper chamber94. Afluid output chamber96 is also coupled toupper chamber94. Apneumatic supply channel98 is connected to alower chamber100. In its normal inactivated state,valve80 is “on,” allowing liquid to flow frominlet90 tooutlet96. When it is desirable to turnvalve80 “off,” sufficient air pressure is supplied to supplychannel98, fillinglower chamber100 with pressurized air and forcingmembrane86 upwardly intoupper chamber94, sealing scaling channel92 such that the flow passage frominlet90 tooutlet96 is blocked, closingvalve80, as can be seen inFIG. 6.
• FIG. 7 shows an array110 in which a plurality ofvalves80 can be constructed. Array110 includes a plurality ofinput air ports112 along with a plurality ofinput fluid ports114. Each ofvalves80 can be selectively operated to control fluid flow through a microfluidic device. Such an array of microfluidic valves can be integrated into a cartridge constructed of multi-layer laminates, and can be used to control multiple parallel fluidic processes, or a single process at multiple locations in a microfluidic circuit. Such a system may have applications in drug discovery processes, or in the analysis of multiple samples.
• While the present invention has been shown and described in terms of preferred embodiments thereof, it will be understood that this invention is not limited to any particular embodiment and that changes and modifications may be made without departing from the true spirit and scope of the invention as defined in the appended claims.

Claims (3)

1. A device for controlling flow in microfluidic devices comprising:

a first substrate having at least one microfluidic structure manufactured therein;

a first flexible sheet placed on top of at least a portion of said microfluidic structure; and

means for creating a pressure differential onto said first flexible sheet such that a portion of said sheet moves in relationship to said microfluidic structure wherein the cross-section of said microfluidic structure is altered at least in one dimension such that the fluid resistance in said microfluidic structure is altered.

2. The device ofclaim 1 further comprising a second microfluidic structure on the opposite side of said first flexible sheet for transmitting pressure through air or fluid flow onto a specific location of said first flexible sheet such that a portion of said sheet moves in relationship to said microfluidic structure such that the cross-section of said microfluidic structure is altered at least in one dimension such that the fluid resistance in said microfluidic structure is altered.

3. A device for controlling flow in microfluidic devices, comprising:

a first substrate having at least one microfluidic structure manufactured therein;

a first flexible sheet placed on top of a at least a portion of said microfluidic structure; and

means for creating pressure onto multiple, individually addressable locations on said first flexible sheet such that one or more potions of said sheet move in relationship to said microfluidic structure such that the cross-section of said microfluidic structure is altered at least in one dimension in one or more locations such that the fluid resistance in said microfluidic structure is altered in one or more locations such that fluid flow through said microfluidic structure can be directed or altered.

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