IP Library Granted Patent US 10,226,769
Granted Patent B2
US 10,226,769 · App. 15/785,191 · Granted Mar 12, 2019

Method and device for high-throughput solution exchange for cell and particle suspensions

Inventors: Dino Di Carlo (Los Angeles, CA); Daniel R. Gossett (Los Angeles, CA); Henry T. K. Tse (San Francisco, CA)
Assignee: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
B01L3/502776B01D12/00B01L3/502761B01L3/502746B01L2200/0652B01L2300/0816B01L2300/0864B01L2400/0487B01L2400/084G01N2015/149
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Quick Facts
Patent No.
US 10,226,769
App. No.
15/785,191
Granted
Mar 12, 2019
Kind
B2
Abstract

A method of exchanging fluids with suspended particles includes providing a microfluidic device with a first inlet channel operatively coupled to a source of particles and a second inlet channel operatively coupled to an exchange fluid. A transfer channel is connected at a proximal end to the first inlet channel and the second inlet channel. First and second outlet channels are connected to a distal end of the transfer channel. The source of particles is flowed at a first flow rate into the first inlet channel while the exchange fluid is flowed at a second flow rate into the second inlet channel wherein the ratio of the second flow rate to the first flow rate is at least 1.5. Particles are collected in one of the first and second outlet channels while fluid substantially free of particles is collected in the other of the first and second outlet channels.

Claims (25)

1. A method of migrating particles suspended in a fluid comprising:

providing a microfluidic device comprising a first inlet channel operatively coupled to a source of fluid containing particles suspended therein; a second inlet channel operatively coupled to a source of buffer solution; a transfer channel having a proximal end and a distal end, the proximal end of the transfer channel connected to the first inlet channel and the second inlet channel; and first and second outlet channels connected to a distal end of the transfer channel;

flowing the fluid containing the particles at a first flow rate into the first inlet channel;

flowing the buffer solution at a second flow rate into the second inlet channel wherein the ratio of the second flow rate to the first flow rate is at least 1.5, wherein the particles migrate toward an equilibrium position (X eq ) located within the transfer channel, the equilibrium position (X eq ) contained within the buffer solution, wherein inertial lift forces in the transfer channel direct the particles toward the equilibrium position (X eq );

collecting the particles that have migrated into the buffer solution in the first outlet channel.

2. The method of claim 1 , wherein the particles comprise cells.

3. The method of claim 1 , wherein the particles comprise red blood cells.

4. The method of claim 1 , wherein the particles comprise white blood cells.

5. The method of claim 1 , wherein the fluid containing the particles comprises blood.

6. The method of claim 1 , wherein the buffer solution occupies a larger volume of the transfer channel as compared to the fluid containing the particles.

7. The method of claim 1 , further comprising analyzing the particles collected in the first outlet channel with an analyzer selected from the group consisting of a flow cytometer, fluorescent-activated cell sorter (FACS), and imager.

8. The method of claim 1 , wherein the transfer channel comprises an aspect ratio (height/width) that is <1 and has a length of greater than 1 cm.

9. The method of claim 1 , further comprising collecting fluid substantially free of particles in the second outlet channel.

10. A method of migrating particles suspended in a fluid comprising:

providing a microfluidic device comprising a plurality of serially arranged stages, wherein at least two of the plurality of serially arranged stages comprise a transfer channel having an output coupled to an input of a transfer channel of a downstream stage;

flowing a fluid containing the particles suspended therein at a first flow rate into the plurality of serially arranged stages;

flowing a buffer solution at a second flow rate into the plurality of serially arranged stages, wherein the ratio of the second flow rate to the first flow rate is at least 1.5, wherein the particles migrate toward an equilibrium position (X eq ) located within respective transfer channels, the equilibrium position (X eq ) contained within the buffer solution, wherein inertial lift forces in the respective transfer channels direct the particles toward the equilibrium position (X eq );

collecting the particles that have migrated into the buffer solution in a first outlet channel in the microfluidic device; and

collecting fluid substantially free of the particles in a second outlet channel in the microfluidic device.

11. The method of claim 10 , wherein the particles comprise cells.

12. The method of claim 10 , wherein the particles comprise red blood cells.

13. The method of claim 10 , wherein the particles comprise white blood cells.

14. The method of claim 10 , wherein the fluid containing the particles comprises blood.

15. The method of claim 10 , wherein the buffer solution occupies a larger volume of the transfer channels as compared to the fluid containing the particles.

16. The method of claim 10 , further comprising analyzing the particles collected in the first outlet channel with an analyzer selected from the group consisting of a flow cytometer, fluorescent-activated cell sorter (FACS), and imager.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 17, 2022
From: DI CARLO, DINO; GOSSETT, DANIEL R.; TSE, HENRY TK
To: THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
Reel/Frame 059932/0301 →
Continuity (4)
Continuation 15346442 · Nov 8, 2016
Division 13884595
Provisional Application 61415067 · Nov 18, 2010
Related Publication 20180036732A1 · Feb 8, 2018