Microfluidic Sieve Valves

Abstract

Sieve valves for use in micorfluidic device are provided. The valves are useful for impeding the flow of particles, such as chromatography beads or cells, in a microfluidic channel while allowing liquid solution to pass through the valve. The valves find particular use in making microfluidic chromatography modules.

1 . A microfabricated sieve valve structure comprising an elastomeric membrane that separates a first channel lumen and a second channel lumen,
 wherein pressurizing the first channel over a wide range of pressures causes the membrane to be deflected into the second channel lumen and reduce the cross-sectional area of the second channel lumen by not more than 90% and not less than 50% of the cross-sectional area when the membrane is not deflected.   
     
     
         2 . The structure of  claim 1  wherein the cross-sectional profile of the second channel is rectangular. 
     
     
         3 . The structure of  claim 1  wherein pressurizing the first channel over a wide range of pressures causes the membrane to be deflected into the second channel lumen and reduce the cross-sectional area of the second channel lumen by not more than 90% and not less than 75% of the cross-sectional area when the membrane is not deflected. 
     
     
         4 . The structure of  claim 1  wherein the range of pressures is a range of at least 7 psi. 
     
     
         5 . The structure of  claim 3  wherein the range of pressures encompasses a range of 18-30 psi. 
     
     
         6 . The structure of  claim 1  wherein the sieve valve has a retention size of from 1 micron to 20 microns. 
     
     
         7 . A microfluidic device comprising two or more sieve valves. 
     
     
         8 . The device of  claim 7  wherein a chromatographic separation medium is disposed between two sieve valves thereby forming a separation column. 
     
     
         9 . The device of  claim 7  that comprises more than 20 separation columns. 
     
     
         10 . A microfluidic device comprising a microfluidic chromatography column, said column comprising a chromatographic separation medium disposed behind a sieve valve, and optionally disposed between two sieve valves. 
     
     
         11 . The device of  claim 10  wherein the chromatographic separation medium comprises a polymeric bead coupled to a ligand. 
     
     
         12 . The device of  claim 11  wherein the beads have been derivatized to bind a nucleic acid. 
     
     
         13 . The device of  claim 12  wherein the beads have been derivatized with oligo(dT). 
     
     
         14 . The device of  claim 10  wherein the beads have been derivatized with a protein, optionally an antibody. 
     
     
         15 . The device of  claim 7  that contains five or more sieve valves paired with conventional valves. 
     
     
         16 . A microfluidic device comprising two or more sieve valves paired with conventional valves. 
     
     
         17 . A method of making a microfluidic column in a microfluidic device, wherein the device comprises a flow channel and a sieve valve positioned to reduce the cross-sectional area of the lumen of the flow channel when closed, the method comprising
 providing a suspension of chromatography beads in the flow channel ante to the sieve valve, wherein the valve is closed and the beads are of a size that is retained by the closed sieve valve;   flowing the suspension through the flow channel, whereby the movement of the beads is impeded by the closed sieve valve and the solution in which the beads are suspended flows through the flow channel, thereby producing a column of beads in the flow channel.   
     
     
         18 . The method of  claim 17  wherein the device comprises two or more sieve valves each positioned to reduce the cross-sectional area of the lumen of the flow channel when closed, said method comprising:
 providing the suspension of chromatography beads ante to a second sieve valve, wherein said second sieve valve is open and is ante to the closed sieve valve, and wherein the beads are of a size that is retained by the second sieve valve;   flowing the suspension of chromatographic beads through the flow channel through and past the second sieve valve, wherein the flow of the beads is impeded by the closed sieve valve and the solution in which the beads are suspended flows through the flow channel, thereby producing a column of beads in the flow channel; and,   closing the second sieve valve, thereby trapping the beads betwixt the sieve valves.   
     
     
         19 . A method for trapping particles in a microfluidic flow channel of a microfluidic device, the method comprising:
 providing a suspension of the particles in a flow channel ante to a closed sieve valve, wherein the particles are of a size that is retained by the closed sieve valve;   flowing the suspension through the flow channel, whereby the movement of the particles is impeded by the closed sieve valve and the solution in which the particles are suspended flows through the flow channel, thereby trapping the particles in the flow channel.   
     
     
         20 . The method of  claim 19  wherein the particles are living cells.