IP Library Granted Patent US 11,027,280
Granted Patent B2
US 11,027,280 · App. 16/112,259 · Granted Jun 8, 2021

Sorting particles in a microfluidic device

Inventors: Ravi Kapur (Sharon, MA); Kyle C. Smith (Cambridge, MA); Mehmet Toner (Charlestown, MA)
Assignee: The General Hospital Corporation
B01L3/502761A61K35/28B01L3/502715B01L3/502746B01L3/502753G01N1/4077G01N15/0255G01N15/0618G01N15/1484B01L3/502776B01L2200/0631B01L2200/0647B01L2200/0652B01L2200/0668B01L2200/0684B01L2200/12B01L2300/0681B01L2300/0877B01L2300/185B01L2400/043B01L2400/0409B01L2400/0415B01L2400/0436B01L2400/0457B01L2400/0487B01L2400/082G01N2001/4088G01N2015/0053G01N2015/0065G01N2015/0288G01N2015/149G01N2015/1486G01N2015/1493
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Quick Facts
Patent No.
US 11,027,280
App. No.
16/112,259
Granted
Jun 8, 2021
Kind
B2
Abstract

A microfluidic device includes a particle sorting region having a first, second and third microfluidic channels, a first array of islands separating the first microfluidic channel from the second microfluidic channel, and a second array of islands separating the first microfluidic channel from the third microfluidic channel, in which the island arrays and the microfluidic channels are arranged so that a first fluid is extracted from the first microfluidic channel into the second microfluidic channel and a second fluid is extracted from the third microfluidic channel into the first microfluidic channel, and so that particles are transferred from the first fluid sample into the second fluid sample within the first microfluidic channel.

Claims (25)

1. A method of producing a sample enriched in particles of a first type, the method comprising:

obtaining a fluid sample comprising particles of the first type;

altering a size of the particles of the first type in the fluid sample to provide particles of the first type having an increased effective size in the fluid sample; and

flowing the fluid sample containing the particles of the first type having the increased effective size into a region of a microfluidic device comprising a first microfluidic channel, a second microfluidic channel extending along the first microfluidic channel, and a first array of islands separating the first microfluidic channel from the second microfluidic channel,

wherein the first microfluidic channel, the second microfluidic channel, and the islands are arranged so that a ratio of a fluidic resistance of the first microfluidic channel to a fluidic resistance of the second microfluidic channel increases along a longitudinal direction of the first microfluidic channel such that a portion of the fluid sample flowing through the first microfluidic channel passes through one or more openings between adjacent islands into the second microfluidic channel, and

wherein, for a particular fluid velocity of the fluid sample within the first microfluidic channel, inertial lift forces cause the particles of the first type having the increased effective size to remain within the first microfluidic channel, thereby producing a sample enriched in particles of the first type.

2. The method of claim 1 , wherein altering the size of the particles of the first type comprises binding the particles of the first type to one or more other particles.

3. The method of claim 2 , wherein the one or more other particles comprise beads.

4. The method of claim 1 , wherein altering the size of the particles of the first type comprises binding the particles of the first type to one or more other particles of a second type that is different from the first type.

5. The method of claim 1 , wherein the particles of the first type are cells, and wherein altering the size of the particles of the first type comprises forming cell aggregations.

6. The method of claim 1 , wherein the particles of the first type are cells, and wherein altering the size of the particles of the first type comprises causing osmotic swelling of the cells.

7. The method of claim 1 , comprising focusing the particles of the first type having the increased effective size along one or more streamlines within the first microfluidic channel.

8. The method of claim 1 , wherein the fluid sample comprises particles of a second type, and a size of the particles of the second type is smaller than the effective size of the particles of the first type, and

wherein the inertial lift forces cause the particles of the second type to flow with the portion of the fluid sample passing through the one or more openings between adjacent islands into the second microfluidic channel.

9. The method of claim 8 , wherein a size of each of the particles of the first type and the particles of the second type is an average hydrodynamic particle size.

10. The method of claim 8 , wherein a size of each of the particles of the first type and the particles of the second type is an average diameter.

11. The method of claim 1 , wherein a size of the particles of the first type is an average hydrodynamic particle size.

12. The method of claim 1 , wherein a size of the particles of the first type is an average diameter.

13. The method of claim 1 , wherein the inertial lift forces shift the particles of the first type having the increased effective size across fluid streamlines within the first microfluidic channel.

14. The method of claim 1 , wherein the increase in the ratio of the fluidic resistance of the first microfluidic channel to the fluidic resistance of the second microfluidic channel is a result of an increase in a cross-sectional area of the second microfluidic channel along the longitudinal direction for a predefined section of the microfluidic device.

15. The method of claim 14 , wherein a cross-sectional area of the first microfluidic channel is substantially constant along the longitudinal direction for the predefined section of the microfluidic device.

16. The method of claim 1 , wherein the increase in the ratio of the fluidic resistance of the first microfluidic channel to the fluidic resistance of the second microfluidic channel is a result of a decrease in a cross-sectional area of the first microfluidic channel along the longitudinal direction for a predefined section of the microfluidic device.

17. The method of claim 16 , wherein a cross-sectional area of the second microfluidic channel is substantially constant along the longitudinal direction for the predefined section of the microfluidic device.

18. The method of claim 1 , wherein the first array of islands consists of a one-dimensional array of islands.

19. The method of claim 1 , wherein the first array of islands comprises a two-dimensional array of islands.

Assignments (3)
CONFIRMATORY LICENSE Recorded Oct 12, 2022
From: MASSACHUSETTS GENERAL HOSPITAL
To: NATIONAL INSTITUTES OF HEALTH (NIH), U.S. DEPT. OF HEALTH AND HUMAN SERVICES (DHHS), U.S. GOVERNMENT
Reel/Frame 061386/0854 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 19, 2019
From: KAPUR, RAVI; SMITH, KYLE C.; TONER, MEHMET
To: THE GENERAL HOSPITAL CORPORATION
Reel/Frame 048635/0087 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Nov 6, 2018
From: KAPUR, RAVI; SMITH, KYLE C.; TONER, MEHMET
To: THE GENERAL HOSPITAL CORPORATION
Reel/Frame 047422/0440 →
Continuity (5)
Continuation 15891579 · Feb 8, 2018
Division 14931223 · Nov 3, 2015
Provisional Application 62074213 · Nov 3, 2014
Provisional Application 62074315 · Nov 3, 2014
Related Publication 20180361383A1 · Dec 20, 2018
Cited By (2)
US 12,385,908 US 12,427,521