On-chip microfluidic processing of particles

Abstract

Described herein are microfluidic devices and methods that can greatly improve cell quality, streamline workflows, and lower costs. Applications include research and clinical diagnostics in cancer, infectious disease, and inflammatory disease, among other disease areas.

1 .- 201 . (canceled) 
     
     
         202 . A device comprising:
 (a) a channel extending from a plurality of inlets to a plurality of outlets, wherein the channel is bounded by a first wall and a second wall opposite from the first wall, and wherein the device is configured to flow a plurality of flow streams from the plurality of inlets to the plurality of outlets, wherein the plurality of flow streams flow parallel to each other; and   (b) an array of obstacles disposed within the channel configured to deflect particles in a sample comprising the particles toward the second wall when the particles are flowed from the inlets to the outlets;   wherein the array of obstacles comprises at least one separator wall oriented parallel to the flow of the plurality of flow streams and the first and second walls, wherein the at least one separator wall is configured to delay the flow of deflected particles,   wherein the delay serves to substantially increase an amount of time that deflected particles reside in a flow stream, and/or substantially reduce mixing between parallel flow streams, and   wherein the at least one separator wall extends into the interior of the array of obstacles for at least 2% of the length of the channel and at most 75% of the length of the channel.   
     
     
         203 . The device of  claim 202 , wherein the separator wall increases the amount of time a particle resides in a flow stream by at least 10%, and by no more than 100% compared to the time the particle would spend in the flow stream in the absence of the separator wall. 
     
     
         204 . The device of  claim 202 , wherein the separator wall increases the amount of time a particle resides in a flow stream by at least 15%, and by no more than 60% compared to the time the particle would spend in the flow stream in the absence of the separator wall. 
     
     
         205 . The device of  claim 202 , wherein the separator wall extends into the interior of the array of obstacles for at least 10% of the length of the channel and at most 50% the length of the channel. 
     
     
         206 . The device of  claim 202 , wherein the device is a microfluidic device and the particles are cells. 
     
     
         207 . The device of  claim 206 , wherein the particles are leukocytes or stem cells. 
     
     
         208 . The device of  claim 202 , wherein the separator wall extends into the array of obstacles for at least 20% of the length of the channel. 
     
     
         209 . The device of  claim 202 , wherein the separator wall is at least 10 mm in length. 
     
     
         210 . The device of  claim 202 , wherein the separator wall is at least 20 mm in length. 
     
     
         211 . The device of  claim 202 , wherein the array of obstacles comprises a series of separator walls wherein all separator walls in the series of separator walls extends from either an inlet or outlet portion of the channel, and wherein each of the separator walls in the series of separator walls extends further into the array of obstacles than the previous separator wall. 
     
     
         212 . The device of  claim 202 , wherein the array of obstacles comprises at least one pair of opposing separator walls, wherein the pair of separator walls comprises a first separator wall that extends from an inlet portion of the channel, and a second separator wall that extends from an outlet portion of the channel, wherein the first and second separator walls are configured to limit mixing between adjacent parallel flow streams, and wherein a gap exists between the pair of opposing separating walls, wherein the gap is configured to allow particles deflected through the adjacent parallel flow streams toward the second wall to pass between the pair of opposing separator walls and continue flowing through the array of obstacles. 
     
     
         213 . The device of  claim 212 , wherein each separator wall has a variable width along the length of the separator wall. 
     
     
         214 . The device of  claim 213 , wherein the array of obstacles is a deterministic lateral displacement array. 
     
     
         215 . The device of  claim 214 , wherein the obstacles are arranged in rows and columns, wherein the rows define an array direction that differs from the flow of the plurality of parallel flow streams by a tilt angle (c) that has a magnitude greater than zero and less than or equal to ⅓ radian, the obstacles in each respective column defining gaps between the obstacles through which the fluid flows generally transversely with respect to the columns, and wherein the obstacles are shaped such that surfaces of two obstacles defining a respective gap are asymmetrically oriented about a first plane that extends through the center of the respective gap and that is parallel to the flow of the plurality of parallel flow streams. 
     
     
         216 . The device of  claim 215 , wherein the columns have a periodicity that repeats and is equal to 1/ε, wherein ε is measured in radians.