Method and device for isolating cells from heterogeneous solution using microfluidic trapping vortices

Abstract

A method of isolating cells includes providing a microfluidic device having at least one microfluidic channel coupled to an inlet and an outlet, the at least one microfluidic channel comprises at least one expansion region disposed along the length thereof The at least one expansion region is an abrupt increase in a cross-sectional dimension of the at least one microfluidic channel configured to generate a vortex within the at least one expansion region in response to fluid flow. A solution containing a population of cells at least some of which have diameters ≧10 μm flows into the inlet. A portion of cells is trapped within vortex created within the at least one expansion region. The trapped cells may then released from the expansion region.

1 .- 71 . (canceled) 
     
     
         72 . A method, comprising:
 flowing a solution in a microfluidic channel at a first flow rate to capture one or more particles in a vortex generated in the microfluidic channel, the solution including the one or more particles, the microfluidic channel associated with an expansion region disposed along the length thereof, the expansion region including an abrupt increase in a cross-sectional dimension of the microfluidic channel followed by an abrupt decrease in the cross-sectional dimension of the microfluidic channel, the vortex being generated within the expansion region, the one or more particles having a diameter greater than or equal to 10 μm; and   changing the flow rate of solution from the first flow rate to a second flow rate to release the one or more particles from the expansion region, the second flow rate being less than the first flow rate.   
     
     
         73 . The method of  claim 72 , further comprising extracting the released one or more particles from an outlet of the microfluidic channel. 
     
     
         74 . The method of  claim 72 , the changing the flow rate including dissipating the vortex to permit the one or more particles to release from the expansion region into the microfluidic channel. 
     
     
         75 . The method of  claim 72 , wherein the second flow rate is substantially zero. 
     
     
         76 . The method of  claim 72 , wherein the expansion region is a first expansion region of a set of expansion regions of the microfluidic channel. 
     
     
         77 . The method of  claim 72 , the one or more particles including one or more cancer cells. 
     
     
         78 . The method of  claim 72 , wherein the solution comprises a bodily fluid. 
     
     
         79 . A system, comprising:
 a microfluidic channel, the microfluidic channel associated with an expansion region disposed along the length thereof, the expansion region including an abrupt increase in a cross-sectional dimension of the microfluidic channel followed by an abrupt decrease in the cross-sectional dimension of the microfluidic channel;   a pump fluidically coupled to the microfluidic channel, the pump configured to control a flow rate of a solution in the microfluidic channel; and   a processor operably coupled to the pump, the processor and the pump collectively configured to:   flow the solution in the microfluidic channel at a first flow rate to capture one or more particles in a vortex generated in the expansion region, the solution including the one or more particles, the one or more particles having a diameter greater than or equal to 10 μm; and   
       release the one or more particles from the expansion region by changing the flow rate of solution from the first flow rate to a second flow rate, the second flow rate being less than the first flow rate. 
     
     
         80 . The system of  claim 79 , wherein the pump comprises a pressurized source of gas configured to pump the solution in the microfluidic channel at controlled pressures to generate the first flow rate and the second flow rate. 
     
     
         81 . The system of  claim 79 , wherein the expansion region is a first expansion region of a set of expansion regions, the microfluidic channel associated with the set of expansion regions. 
     
     
         82 . The system of  claim 79 , further comprising a microfluidic substrate, wherein the microfluidic channel is a first microfluidic channel of a set of microfluidic channels, the microfluidic substrate including the set of microfluidic channels. 
     
     
         83 . The system of  claim 79 , the processor and the pump collectively further configured to extract the released one or more particles from an outlet of the microfluidic channel. 
     
     
         84 . The system of  claim 79 , the processor and the pump collectively further configured to change the flow rate by dissipating the vortex to permit the one or more particles to release from the expansion region into the microfluidic channel. 
     
     
         85 . The system of  claim 79 , a cross-section of the expansion region selected from the group consisting of: a rectangle, a square, a triangle, a polygonal, and a semi-circle. 
     
     
         86 . The system of  claim 79 , the expansion region including a leading wall extending at least 45° with respect to an axis of flow of the microfluidic channel. 
     
     
         87 . A method, comprising:
 flowing a solution in a microfluidic channel at a flow rate to capture one or more particles in a vortex generated in the microfluidic channel, the solution including the one or more particles, the microfluidic channel associated with an expansion region disposed along the length thereof, the expansion region including an abrupt increase in a cross-sectional dimension of the microfluidic channel followed by an abrupt decrease in the cross-sectional dimension of the microfluidic channel, the vortex being generated within the expansion region, the one or more particles having a diameter greater than or equal to 10 μm; and   dissipating the vortex to release, into the microfluidic channel, the one or more particles from the expansion region.   
     
     
         88 . The method of  claim 87 , wherein the solution is a first solution including the one or more particles and the flow rate is a first flow rate, the dissipating including flowing a second solution in the microfluidic channel at a second flow rate, the second flow rate being less than the first flow rate. 
     
     
         89 . The method of  claim 87 , further comprising extracting the released one or more particles from an outlet of the microfluidic channel. 
     
     
         90 . The method of  claim 87 , wherein the expansion region is a first expansion region of a set of expansion regions of the microfluidic channel. 
     
     
         91 . The method of  claim 87 , the one or more particles including one or more cancer cells. 
     
     
         92 . The method of  claim 87 , wherein the solution comprises a bodily fluid. 
     
     
         93 . A system, comprising:
 a microfluidic channel, the microfluidic channel associated with an expansion region disposed along the length thereof, the expansion region including an abrupt increase in a cross-sectional dimension of the microfluidic channel followed by an abrupt decrease in the cross-sectional dimension of the microfluidic channel;   a pump fluidically coupled to the microfluidic channel, the pump configured to control a flow rate of a solution in the microfluidic channel; and   a processor operably coupled to the pump, the processor and the pump collectively configured to:   flow the solution in the microfluidic channel at a first flow rate to capture one or more particles in a vortex generated in the expansion region, the solution including the one or more particles, the one or more particles having a diameter greater than or equal to 10 μm; and   dissipate the vortex to release, into the microfluidic channel, the one or more particles from the expansion region.   
     
     
         94 . The system of  claim 93 , wherein the expansion region is a first expansion region of a set of expansion regions, the microfluidic channel associated with the set of expansion regions. 
     
     
         95 . The system of  claim 93 , further including a microfluidic substrate, wherein the microfluidic channel is a first microfluidic channel of a set of microfluidic channels, the microfluidic substrate including the set of microfluidic channels. 
     
     
         96 . The system of  claim 93 , the processor and the pump collectively further configured to extract the released one or more particles from an outlet of the microfluidic channel. 
     
     
         97 . The system of  claim 93 , the microfluidic channel further including a first inlet and a second inlet, wherein the solution is a first solution including the one or more particles and the flow rate is a first flow rate, the processor and the pump collectively further configured to:
 flow the first solution in the microfluidic channel via the first inlet at a first flow rate to capture the one or more particles in the vortex; and   dissipate the vortex by flowing a second solution in the microfluidic channel via the second inlet at a second flow rate, the second flow rate being less than the first flow rate.   
     
     
         98 . The system of  claim 93 , the expansion region including a leading wall extending at least 45° with respect to an axis of flow of the microfluidic channel. 
     
     
         99 . The system of  claim 93 , wherein the second solution comprises a staining solution.