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

Patent metadata

Field	Value
Publication number	US-10967296-B2
Application number	US-201916676352-A
Country	US
Kind code	B2
Filing date	Nov 6, 2019
Priority date	Nov 18, 2010
Publication date	Apr 6, 2021
Grant date	Apr 6, 2021

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.

First claim

What is claimed is:

1. A method of transferring particles across fluid streamlines comprising:
providing a microfluidic device comprising a plurality of proximal channels and a plurality of distal channels connected to a transfer channel disposed between the plurality of proximal channels and the plurality of distal channels, wherein at least one of the proximal channels is operatively coupled to a source of fluid containing particles suspended therein, at least one of the proximal channels is operatively coupled to a source of exchange fluid;
flowing the fluid containing the particles in the at least one proximal channel operatively coupled to the source of fluid containing particles suspended therein;
flowing the exchange fluid into the at least one proximal channel operatively coupled to the source of exchange fluid, wherein a co-flow state of the fluid containing the particles suspended therein and the exchange fluid is maintained along substantially all of the transfer channel, wherein at least some of the particles of the fluid containing the particles suspended therein migrate in response to inertial lift forces toward an equilibrium position (X eq ) located within the transfer channel to become migrated particles;
transferring the migrated particles into at least one of the plurality of distal channels.

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 exchange fluid 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 transferred into one of the plurality of distal channels 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 directing fluid substantially free of particles into at least one of the plurality of distal channels.

10. A method of transferring particles across fluid streamlines comprising:
providing a microfluidic device comprising a plurality of solution exchange stages, wherein at least two of the plurality of solution exchange stages comprise a transfer channel having an output channel coupled to an input channel of a downstream transfer channel of a solution exchange downstream stage;
flowing a fluid containing the particles suspended therein into the plurality of solution exchange stages;
flowing an exchange fluid into the plurality of solution exchange stages, wherein the particles migrate toward an equilibrium position (X eq ) located within respective transfer channels and become migrated particles, wherein inertial lift forces in the respective transfer channels direct the particles toward the equilibrium position (X eq );
directing the migrated particles into one outlet channel in the microfluidic device; and
directing fluid substantially free of the migrated particles into one or more other outlet channels 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 exchange fluid occupies a larger volume of the transfer channels as compared to the fluid containing the particles.

16. The method of claim 10 , wherein a Particle Reynolds number for the migrated particles in the transfer channels is between about 0.25 and about 1.87.

Assignees

• Univ California

Inventors

• Di Carlo Dino
• Gossett Daniel R
• Tse Henry T K

Classifications

• B01L3/502761 Primary

  specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads or physically stretching molecules · CPC title

• B01L2400/0487

  fluid pressure, pneumatics · CPC title

• B01L3/502746

  characterised by the means for controlling flow resistance, e.g. flow controllers, baffles or throttle valves · CPC title

• B01L2200/0652

  Sorting or classification of particles or molecules · CPC title

• B01D12/00 Primary

  Displacing liquid, e.g. from wet solids or from dispersions of liquids or from solids in liquids, by means of another liquid · CPC title