Granted Patent B2

US 12,352,673 · App. 17/582,441 · Granted Jul 8, 2025

Inventors: Benjamin Miller (Cornelius, NC); Brian Hutchison (Medford, MA); Andrew Wilson (Arlington, MA); Jonathan William Larson (Chelsea, MA); Qun Zhong (Lexington, MA); Yevgeny Yurkovetsky (Winchester, MA); Darren Link (Lafayette, CA); Mark Weary (North Billerica, MA)

Assignee: Bio-Rad Laboratories, Inc.

G01N1/38B01F33/3021B01F35/2111B01F35/2202B01F35/2211B01L3/0241B01L3/502715B01L3/50273B01L3/502784F16K99/0001F17D3/01G01N27/44791B01L2200/061B01L2200/0673B01L2200/143B01L2300/0877B01L2400/0442B01L2400/0478F16K2099/0084G01N2021/0353G01N2021/1725Y10T137/2185Y10T137/2572Y10T137/7761Y10T137/8158Y10T137/8593Y10T436/118339

Abstract

Claims (20)

1. A feedback control system for microfluidic droplet manipulation, the system comprising:

at least one pump operable to pump a sample fluid from the pump through an inlet channel and into a junction with a main channel on a microfluidic device, thereby to cause the system to form microfluidic droplets of the sample fluid surrounded by a carrier fluid at the junction;

a flow rate sensor operable to measure a flow rate to the inlet channel; and

a feedback controller operable to receive a flow rate measurement from the flow rate sensor and adjust a flow rate of the at least one pump to cause the system to form the microfluidic droplets at a uniform size.

2. The system of claim 1 , wherein the at least one pump is a pressure-driven pump.

3. The system of claim 1 , wherein the flow rate is measured using heat transfer.

4. The system of claim 1 , wherein after the flow rate is adjusted, the droplets are formed with <1.5% polydispersity.

5. The system of claim 1 , wherein the feedback controller transmits automated instructions to the at least one pump to control the production of the microfluidic droplets.

6. The system of claim 1 , wherein the flow rate sensor is operable to measure flow rates between 10 to 10 4 μL/hour.

7. The system of claim 1 , wherein the at least one pump creates positive displacement pressure driven flow.

8. The system of claim 1 , wherein the feedback controller is operable to adjust pressure on the main channel and the inlet channel.

9. The system of claim 1 , wherein the sample fluid contains molecules or cells that are introduced into the droplets.

10. The system of claim 1 , wherein the sample fluid is pressurized.

11. The system of claim 1 , wherein feedback on the infusion rates of the carrier fluid and the sample fluid provides droplets that are uniform in size and generated at a fixed frequency over arbitrarily long periods of time.

12. The system of claim 1 , wherein the feedback controller controls a pressure difference between the carrier fluid in the main channel and the sample fluid at the inlet channel to regulate size and periodicity of the droplets.

13. The system of claim 1 , wherein the at least one pump comprises a pressure head.

14. The system of claim 1 , wherein the feedback controller controls droplet generation rate.

15. The system of claim 1 , wherein the feedback controller controls droplet properties including one or more of droplet volume, droplet generation rate, droplet release rate, and the total number of droplets generated.

16. The system of claim 1 , further comprising a second inlet channel to form a second species of aqueous droplet.

17. The system of claim 16 , wherein the system is operable to flow the droplets and the second species of aqueous droplet into a merge zone.

Assignments (2)

Continuity (8)

References Cited (400)