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US 11,142,746 B2Granted
High efficiency microfluidic purification of stem cells to improve transplants
AssigneesUniversity of Maryland, Baltimore, The Trustees of Princeton University
InventorsCurt I. Civin, James C. Sturm, Robert H. Austin
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Abstract
Described herein is a novel, highly efficient system to remove erythrocytes and purify leukocytes would raise the quality of UCB and other transplant grafts, thereby significantly improving patient outcomes.
Claims23
A method for purifying leukocytes for therapeutic use from a sample comprising leukocytes and erythrocytes, the method comprising:
- (a) providing a sample comprising erythrocytes and leukocytes, wherein the sample volume is at least 100 ml and less than 300 mL;
- (b) separating said erythrocytes from said leukocytes by deterministic lateral displacement on a microfluidic device, wherein said microfluidic device comprises posts with one or more non-rounded vertices, wherein said posts are organized into an array of rows and columns such that adjacent posts form a gap through which fluid may pass and adjacent columns are offset from one another to form an array direction that differs from the flow direction of the device by a tilt angle (c) and wherein the array has a critical diameter such that, when said sample is flowed through the device, leukocytes travel in the array direction and erythrocytes travel in the direction of fluid flow;
- (c) collecting a product from said microfluidic device, wherein:
- i) the product comprises leukocytes;
- ii) relative to the sample applied to the device, the product is depleted in erythrocytes;
- and iii) the product comprises less than 10% erythrocytes;
- wherein the device is operated at a flow rate of at least 100 ml per hour and a linear flow rate of 5 mm/sec to 150 mm/sec, and wherein greater than 90% of the leukocytes collected in the product are viable.
4 more elements
A method for purifying leukocytes for therapeutic use from a sample comprising leukocytes and erythrocytes, the method comprising:
- (a) providing a sample comprising erythrocytes and leukocytes, wherein the sample volume is at least 100 ml;
- (b) separating said erythrocytes from said leukocytes by deterministic lateral displacement on a microfluidic device, wherein said microfluidic device comprises posts with one or more non-rounded vertices, wherein said posts are organized into an array of rows and columns such that adjacent posts form a gap through which fluid may pass and adjacent columns are offset from one another to form an array direction that differs from the flow direction of the device by a tilt angle (c) and wherein the array has a critical diameter such that, when said sample is flowed through the device, leukocytes travel in the array direction and erythrocytes travel in the direction of fluid flow;
- (c) collecting a product comprising leukocytes from said microfluidic device;
- wherein:
- i) relative to the sample applied to the device, the product is depleted in erythrocytes;
- ii) the product comprises less than 0.01 M/μl of erythrocytes;
- iii) the device is operated at a linear flow rate of 5 mm/sec to 150 mm/sec,
- iv) greater than 90% of the leukocytes collected in the product are viable.
5 more elements
Dependencies are inferred from the claim text.