Microfluidic systems and methods for reducing the exchange of molecules between droplets

Patent metadata

Field	Value
Publication number	US-10837883-B2
Application number	US-201013518619-A
Country	US
Kind code	B2
Filing date	Dec 22, 2010
Priority date	Dec 23, 2009
Publication date	Nov 17, 2020
Grant date	Nov 17, 2020

Abstract

The present invention generally relates to systems and methods to create stable emulsions with low rates of exchange of molecules between microdroplets.

First claim

What is claimed is:

1. A method of stabilizing a plurality of microdroplets for introduction into a delay line, comprising the steps of:
(a) flowing in a main microfluidic channel a first emulsion comprising a plurality of microdroplets in an immiscible carrier fluid, wherein the plurality of microdroplets comprise a first microdroplet and a second microdroplet, and wherein the first microdroplet comprises a first biological or chemical material and the second microdroplet comprises a second biological or chemical material, and the carrier fluid comprises a surfactant at a first concentration within the carrier fluid;
(b) exchanging a portion of the immiscible carrier fluid by removing a portion of the carrier fluid from the main microfluidic channel via a first side microfluidic channel, and adding a second fluid into the main microfluidic channel via a second side microfluidic channel immediately downstream from the first side microfluidic channel to generate a second emulsion, wherein the second fluid is immiscible with the plurality of microdroplets and comprises a second concentration of the surfactant, thereby changing the first concentration to a second concentration, wherein the second concentration is lower than the first concentration; and
(c) introducing the second emulsion into a delay line.

2. The method of claim 1 , wherein the first biological or chemical material and/or the second biological or chemical material comprises a tissue, cell, particle, protein, antibody, amino acid, nucleotide, small molecule, pharmaceutical, and/or label.

3. The method of claim 1 , wherein the first concentration is sufficient to stabilize the microdroplets against coalescing with each other in the first carrier fluid.

4. The method of claim 3 , wherein the first concentration is determined, at least in part, based on stabilizing the microdroplets over a time frame determined by a reaction and/or detection of the one or more biological and/or chemical materials.

5. The method of claim 1 , wherein the second concentration is sufficient to reduce exchange of the first biological or chemical material from the first microdroplet to the second microdroplet, or of the second biological or chemical material from the second microdroplet to the first microdroplet.

6. The method of claim 5 , wherein the second concentration is determined, at least in part, based on stabilizing the microdroplets over a time frame determined by generation and/or use of the first microdroplet and the second microdroplet in one or more libraries.

7. The method of claim 5 , wherein the second fluid is substantially free of the first surfactant.

8. A method of adjusting a carrier fluid before introduction to a delay line in a microfluidic network, comprising the steps of:
(a) flowing a first emulsion comprising a plurality of microdroplets in an immiscible first carrier fluid in a main microfluidic channel, wherein the first carrier fluid comprises a first concentration of a surfactant;
(b) introducing a second carrier fluid to the main microfluidic channel via a first side microfluidic channel and removing a portion of the carrier fluid from the main microfluidic channel via a second side microfluidic channel immediately downstream from the first side microfluidic channel, thereby exchanging the portion of the first carrier fluid for the second carrier fluid to generate a second emulsion, wherein the second carrier fluid contains no surfactant or a second concentration of the surfactant that is lower than the first concentration; and
(c) introducing the second emulsion into a delay line.

9. The method of claim 8 , wherein step (b) is accomplished in a region of the main microfluidic channel comprising at least one obstacle.

10. The method of claim 8 , wherein step (b) is accomplished, at least in part, by shifting the microdroplets from the first carrier fluid into a stream of the second carrier fluid.

11. The method of claim 10 , wherein the shifting is accomplished by using one or more obstacles, changing channel depth, by dielectrophoresis, or by buoyancy.

12. The method of claim 1 , wherein the carrier fluid is a fluorinated oil.

13. The method of claim 1 , wherein the second fluid is the same as the carrier fluid.

14. The method of claim 8 , wherein step (b) is accomplished in a region of the main microfluidic channel comprising a filter.

15. The method of claim 1 , wherein the first microdroplet contains no more than one biological or chemical molecule and the second microdroplet contains no more than one biological or chemical molecule.

16. The method of claim 1 , wherein the first microdroplet contains no more than one biological or chemical molecule and the second microdroplet contains a plurality of biological or chemical molecules.

17. The method of claim 1 , wherein the first microdroplet contains a plurality of biological or chemical molecules and the second microdroplet contains a plurality of biological or chemical molecules.

18. The method of claim 1 , further comprising directing the microdroplets into a reservoir outside of the main microfluidic channel.

19. The method of claim 18 , wherein the reservoir contains a third carrier fluid, wherein the third carrier fluid contains no surfactant or a concentration of the surfactant that is lower than the first concentration.

20. The method of claim 19 , wherein the reservoir is attached to the top of the main microfluidic channel.

21. The method of claim 20 , further comprising adding the third carrier fluid from the bottom of the reservoir, thereby causing the microdroplets to rise out of the top of the reservoir.

22. The method of claim 1 , wherein the second concentration of the surfactant is zero.

Assignees

• Kleinschmidt Felix
• Griffiths Andrew David
• Caron Francois
• El Harrak Abdeslam
• Brouzes Eric
• Link Darren
• Bio Rad Laboratories
• Univ Of Strasbourg

Inventors

• Kleinschmidt Felix
• Griffiths Andrew David
• Caron François
• El Harrak Abdeslam
• Brouzes Eric
• Link Darren

Classifications

• G01N33/5302 Primary

  Apparatus specially adapted for immunological test procedures · CPC title

• C12M25/01

  Drops · CPC title

• B01L2400/0469

  Buoyancy · CPC title

• B01L2400/0424

  Dielectrophoretic forces · CPC title

• B01L3/502784

  specially adapted for droplet or plug flow, e.g. digital microfluidics · CPC title