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  
       [0001]     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  
       [0002]     1. Field of the Invention  
         [0003]     This invention relates generally to microscale devices for performing analytical testing and, in particular, to a valve interface for use in laminated microfluidic structures.  
         [0004]     2. Description of the Prior Art  
         [0005]     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.  
         [0006]     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.  
         [0007]     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.  
         [0008]     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.  
         [0009]     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.  
         [0010]     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.  
         [0011]     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.  
         [0012]     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.  
         [0013]     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.  
         [0014]     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.  
         [0015]     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.  
         [0016]     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  
       [0017]     It is therefore an object of the present invention to provide an efficient valve suitable for use in a microfluidic system.  
         [0018]     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.  
         [0019]     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.  
         [0020]     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  
       [0021]      FIG. 1  is a perspective view of a microfluidic valve according to the present invention;  
         [0022]      FIG. 2  is a fragmentary cross-sectional view of an alternative valve according to the present invention;  
         [0023]      FIG. 3  is a fragmentary cross-sectional view of the valve of  FIG. 2  shown in its activated position;  
         [0024]      FIG. 4  is a fragmentary top view, partly in phantom, of the valve of  FIG. 2 ;  
         [0025]      FIG. 5  is a fragmentary cross-sectional view of another alternative valve according to the present invention;  
         [0026]      FIG. 6  is a fragmentary cross-sectional view of the valve of  FIG. 5  shown in its activated position;  
         [0027]     and  FIG. 7  is a perspective view of an array which uses valves according to the present invention.  
     
    
     DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS  
       [0028]     A basic zero dead volume valve according to the present invention is shown in  FIG. 1 . Referring now to  FIG. 1 , a valve generally indicated at  10  consists of a membrane layer  12  which covers a flat surface  13  coupled to an input channel  14 , which is connected to a flow channel  16  and also an output channel  18  connected to a flow channel  20 . Above layer  12  is an air chamber  22  which is coupled to a pneumatic source  24  by a short air channel  26 . In operation, zero dead volume valve  10  works as follows: a liquid  30  enters channel  16  and travels into channel  14  where it contacts membrane layer  12 . Under atmospheric conditions within air chamber  22 , membrane lines flat against surface or seat  13 , causing liquid  30  to stop in channel  14 . However, if the fluid pressure within channel  14  exceeds the elastic force contained in membrane  13 , membrane  13  will bulge out into chamber  22 , allowing liquid  30  to pass under membrane  13  and flow out through channel  18  and into channel  20 , as shown by the arrows in  FIG. 1 . Valve  10  shown in  FIG. 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 within chamber  22 .  
         [0029]     When in operation within a microfluidic circuit, pneumatic pressure within channel  24  is used to open and close valve  10 . If it is desirable to keep valve  10  in its closed position, positive air pressure is applied through source  24  into channel  26 , when it fills air chamber  22 , which forces membrane  12  against seat  13 . It has been found that applying +1.0 psi air pressure within source  24  will adequately keep valve  10  closed. It is desirable to open valve  10 , a negative pressure of −55 mm Hg creates a vacuum within chamber  22  to completely lift membrane  12  away from seat  13  to allow liquid  30  to travel from channel  14  across surface  13  out of channel  18 . Pressure from source  24  can also be varied to vary the flow through valve  10 .  
         [0030]      FIGS. 2-4  show an alternate embodiment in which a valve  40  is constructed as a normally open valve. Referring now to  FIG. 2 , a latex rubber diaphragm membrane  50  is held between two spacing layers  54  of a laminated microfluidic structure. Valve  40  is fabricated from a series of laminar sheets  60  which are preferably MYLAR® or a similar plastic sheet. Channels are constructed within valve  40  by cutout spaces within spacing layers  54  between sheets  60 . In  FIG. 2  is in its relaxed state, which allows liquid to enter a flow inlet  62 , and pass through a channel  64  into a lower chamber  66  below membrane  50 . The liquid can flow out of valve  40  from chamber  66  through a channel  68  and out through a flow outlet  70 . Flow through valve  40  is controlled by pneumatic pressure which is supplied by a valve air supply channel  72  through a channel  74  into an upper chamber  76 .  
         [0031]     Operation of valve  40  is clearly shown in  FIG. 3 . Referring now to  FIG. 3 , sufficient air pressure is supplied via channel  72  through channel  74  and into upper chamber  76 . This pressure forces membrane  50  to flex downwardly into lower chamber  66 , blocking channels  64  and  68 , preventing fluid flow between inlet  62  and outlet  70 .  
         [0032]      FIGS. 5 and 6  show another embodiment of the valve of the present invention. Referring now to  FIG. 5 , which shows the normal “on” state of the valve, a valve  80  is constructed from a pair of laminar MYLAR® sheets  82  which are separated by a series of spacing layers  84 . Channels are formed in spacing layers  84  by cutout sections which form a flow structure. A flexible membrane  86  is held between two spacing layers  84  in its relaxed state. A fluid input channel  90  is connected to channel  92  and to an upper chamber  94 . A fluid output chamber  96  is also coupled to upper chamber  94 . A pneumatic supply channel  98  is connected to a lower chamber  100 . In its normal inactivated state, valve  80  is “on,” allowing liquid to flow from inlet  90  to outlet  96 . When it is desirable to turn valve  80  “off,” sufficient air pressure is supplied to supply channel  98 , filling lower chamber  100  with pressurized air and forcing membrane  86  upwardly into upper chamber  94 , sealing scaling channel  92  such that the flow passage from inlet  90  to outlet  96  is blocked, closing valve  80 , as can be seen in  FIG. 6 .  
         [0033]      FIG. 7  shows an array  110  in which a plurality of valves  80  can be constructed. Array  110  includes a plurality of input air ports  112  along with a plurality of input fluid ports  114 . Each of valves  80  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.  
         [0034]     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.