Granted Patent
B2
US 12,436,081 · App. 17/168,081 · Granted Oct 7, 2025
Methods and devices for multi-step cell purification and concentration
Inventors:
Anthony Ward (Rancho Santa Fe, CA); Khushroo Gandhi (Palo Alto, CA); Alison Skelley (Riverside, CA); Curt Civin (Baltimore, MD); James C. Sturm (Princeton, NJ); Lee Aurich (Oakland, CA); Michael Grisham (Richmond, VA); Joseph D'Silva (Hillsboro, OR); Robert H. Austin (Princeton, NJ)
G01N15/1056B01L3/502715B01L3/502746B01L3/502753B01L3/502761B01L3/502776G01N15/1404G01N15/1459G01N15/1484G01N33/5091G01N33/574G01N33/6893B01L2200/0652B01L2300/0681B01L2300/0867B01L2400/043B01L2400/082B01L2400/086G01N2015/0065G01N2015/008G01N2015/1006G01N2015/1081G01N2015/142G01N2015/149
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Abstract
Described herein are microfluidic devices and methods that can separate and concentrate particles in a sample.
Claims (26)
1. A method for preparing an enriched cell population, the method comprising:
a) obtaining a blood-related sample;
b) passing the blood-related sample through a cell enrichment system comprising a microfluidic channel, the microfluidic channel comprising a first array of obstacles wherein said obstacles are configured to separate cells by deterministic lateral displacement (DLD) based on their sizes, such that a population of white blood cells or a population of stem cells flow in a first direction and platelets flow in a second direction different from the first direction to yield a population of enriched white blood cells or a population of enriched stem cells;
c) detecting, by a sensor of the cell enrichment system, that the population of enriched white blood cells or the population of enriched stem cells is in a sensing zone of the cell enrichment system, the sensing zone being coupled to a capture zone; and
d) capturing, at the capture zone of the cell enrichment system, the population of enriched white blood cells or the population of enriched stem cells, wherein the population of enriched white blood cells or the population of enriched stem cells is enriched with respect to the blood-related sample;
e) magnetically separating, by a magnetic separator of the cell enrichment system, the population of enriched white blood cells or the population of enriched stem cells to obtain a population of magnetically separated enriched white blood cells or a population of magnetically separated enriched stem cells; and
f) expanding the enriched white blood cells or the enriched stem cells, to obtain a population of expanded white blood cells or a population of expanded stem cells.
2. The method of claim 1 , wherein the obstacles in the microfluidic channel have a polygonal cross-section.
3. The method of claim 2 , wherein: a vertex of each of two adjacent obstacles points toward each other in a direction substantially perpendicular to a flow direction of the sample through the array of obstacles.
4. The method of claim 2 , wherein the first array of obstacles configured to separate cells by DLD comprises hexagon-shaped, diamond-shaped, tear drop shaped, or modified tear drop shaped obstacles.
5. The method of claim 1 , wherein the magnetic separator comprises one or more hard magnets, soft magnets, electromagnets, superconductor magnets, or combination thereof.
6. The method of claim 1 , wherein the method further comprises dispensing the magnetically separated enriched white blood cells or the population of magnetically separated enriched stem cells using a particle dispenser.
7. The method of claim 1 , wherein the population of white blood cells or the population of stem cells are magnetically labelled prior to passing through the microfluidic channel.
8. The method of claim 1 , wherein the population of white blood cells or the population of stem cells are not labelled magnetically until the population of white blood cells or the population of stem cells have passed thorough the microfluidic channel.
9. The method of claim 1 , wherein the enriched white blood cells or the enriched stem cells are magnetically labeled by magnetic beads.
10. The method of claim 1 , wherein the method separates the population of stem cells from platelets.
11. The method of claim 1 , wherein the method separates the population of white blood cells from platelets.
12. The method of claim 11 , wherein the population of white blood cells are a population of T cells.
13. The method of claim 12 , wherein the T cells are separated by negative selection.
14. The method of claim 9 , wherein the magnetic beads are conjugated to an antibody.
15. The method of claim 14 , wherein the antibody is an anti-CD45, an anti-CD66b, an anti-CD3, an anti-CD19, an anti-CD34, or an anti-CD41 antibody.
16. The method of claim 14 , wherein the antibody is not anti-CD3, anti-CD28, or anti-CD45.
17. The method of claim 1 , further comprising genetically modifying enriched white blood cells or enriched T-cells.
18. The method of claim 12 , further comprising genetically modifying the T cells.
19. The method of claim 1 , further comprising passing the expanded white blood cells or stem cells through a second microfluidic channel comprising a second array of obstacles wherein said second array of obstacles are configured to separate cells by deterministic lateral displacement (DLD) based on their sizes, such that unexpanded white blood cells or stem cells flow in a first direction and the expanded white blood cells or stem cells flow in a second direction different from the first direction to yield enriched expanded white blood cells or stem cells.
20. The method of claim 1 , wherein the population of enriched white blood cells or the population of enriched stem cells is enriched at least 4-fold with respect to the blood-related sample.
Assignments (8)
RELEASE OF SECURITY INTEREST
Recorded Jun 14, 2024
From: SILICON VALLEY BANK, A DIVISION OF FIRST-CITIZENS BANK & TRUST COMPANY
To: GPB SCIENTIFIC, INC.
Reel/Frame 067732/0146 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 14, 2024
From: CURATE (ABC), LLC
To: ZEON CORPORATION
Reel/Frame 067737/0769 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Jun 14, 2024
From: GPB SCIENTIFIC, INC. (D/B/A CURATE BIOSCIENCES)
To: CURATE (ABC), LLC
Reel/Frame 067737/0738 →
SECURITY INTEREST
Recorded Sep 28, 2023
From: GPB SCIENTIFIC, INC.
To: FIRST-CITIZENS BANK & TRUST COMPANY
Reel/Frame 065082/0354 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 12, 2021
From: WARD, ANTHONY; GANDHI, KHUSHROO; SKELLEY, ALISON; AURICH, LEE; GRISHAM, MICHAEL
To: GPB SCIENTIFIC, LLC
Reel/Frame 055889/0434 →
CONVERSION
Recorded Apr 12, 2021
From: GPB SCIENTIFIC, LLC
To: GPB SCIENTIFIC, INC.
Reel/Frame 055898/0061 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 12, 2021
From: CIVIN, CURT
To: UNIVERSITY OF MARYLAND, BALTIMORE
Reel/Frame 055898/0031 →
ASSIGNMENT OF ASSIGNOR'S INTEREST
Recorded Apr 12, 2021
From: STURM, JAMES C.; D'SILVA, JOSEPH; AUSTIN, ROBERT H.
To: THE TRUSTEES OF PRINCETON UNIVERSITY
Reel/Frame 055889/0522 →
Continuity (9)
Continuation In Part
PCTUS2016048455
· Aug 24, 2016
Provisional Application
62337619
· May 17, 2016
Provisional Application
62337273
· May 16, 2016
Provisional Application
62324293
· Apr 18, 2016
Provisional Application
62274031
· Dec 31, 2015
Provisional Application
62233915
· Sep 28, 2015
Provisional Application
62209246
· Aug 24, 2015
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WO WO2020014538
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