Droplet creation techniques

• US 9,839,911 B2
• Filed: 05/08/2015
• Issued: 12/12/2017
• Est. Priority Date: 10/27/2009
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Weitz, David A., Abate, Adam R.
• Primary Examiner(s): Forman, Betty J
• Application Number:
  US14/707,771
• Publication Number:
  US 20150314292A1
• Time in Patent Office: 949 Days
• Field of Search: None
• CPC Class Codes: B01F 23/41 Emulsifying
• CPC Class Codes: B01F 33/3011 using a sheathing stream of a fluid surrounding a central stream of a different fluid, e.g. for reducing the cross-section of the central stream or to produce droplets from the central stream
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01L 2200/0636 Focussing flows, e.g. to laminate flows
• CPC Class Codes: B01L 2200/0652 Sorting or classification of particles or molecules
• CPC Class Codes: B01L 2300/0681 Filter
• CPC Class Codes: B01L 3/0241 Drop counters; Drop formers making arrays for combinatorial libraries B01J19/0046; automation of dispensing for analysis G01N35/10
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: Y10T 137/0318 Processes
• CPC Class Codes: Y10T 137/8593 Systems

Abstract

The present invention is generally related to systems and methods for producing droplets. The droplets may contain varying species, e.g., for use as a library. In some cases, at least one droplet is used to create a plurality of droplets, using techniques such as flow-focusing techniques. In one set of embodiments, a plurality of droplets, containing varying species, can be divided to form a collection of droplets containing the various species therein. A collection of droplets, according to certain embodiments, may contain various subpopulations of droplets that all contain the same species therein. Such a collection of droplets may be used as a library in some cases, or may be used for other purposes.

Claims

1. An article, comprising:

a first fluid containing a plurality of droplets, at least some of which have distinguishable compositions; and

a device comprising;

a microfluidic channel containing the first fluid flowing toward an intersection, a first channel portion upstream of the intersection, and a second channel portion downstream of the intersection;

two intersecting channels that intersect the microfluidic channel at the intersection, the intersecting channels containing a second fluid flowing toward the intersection; and

the second channel portion downstream of the intersection contains a plurality of divided droplets produced from a droplet upstream of the intersection,

wherein the device produces divided droplets in the microfluidic channel from the plurality of droplets contained within the first fluid upon intersection of the first fluid containing the plurality of droplets with the second fluid, the produced divided droplets having a distribution of diameters such that no more than about 5% of the divided droplets have a diameter greater than about 10% different than the average diameter of the divided droplets.

2. The article of claim 1, wherein the first fluid contains at least 5 distinguishable droplets.

3. The article of claim 1, wherein at least 10 divided droplets are produced from each droplet of the plurality of droplets contained within the first fluid.

4. The article of claim 1, wherein the intersection is an intersection of the two intersecting channels intersecting the microfluidic channel, each at an angle of about 90°

.

5. The article of claim 1, wherein in at least some droplets of the plurality of droplets contained within the first fluid, the distinguishable compositions comprise at least four distinguishable species, such that no more than about 5% of the droplets contains two or more of the at least four distinguishable species therein.

6. The article of claim 5, wherein the at least four distinguishable species comprise at least four distinguishable nucleic acids.

7. The article of claim 5, wherein the at least four distinguishable species comprise at least four distinguishable identification elements.

8. The article of claim 5, wherein the at least four distinguishable species comprise at least four distinguishable proteins.

9. The article of claim 5, wherein the plurality of droplets contained within the first fluid has an average diameter greater than about 500 microns and the divided droplets have an average diameter of less than about 500 microns.

10. The article of claim 5, wherein the average diameter of the divided droplets is less than about 1000 microns and wherein the divided droplets are substantially monodisperse.

11. The article of claim 1, wherein the first fluid and the plurality of droplets contained within the first fluid are substantially immiscible.

12. The article of claim 1, wherein the second fluid is substantially identical to the first fluid.

13. The article of claim 1, wherein the first fluid containing the plurality of droplets is an emulsion.

14. The article of claim 1, wherein the plurality of droplets contained within the first fluid has an average diameter of less than about 1 mm.

15. The article of claim 1, wherein the divided droplets have an average diameter of less than about 1 mm.

16. The article of claim 1, wherein at least 5 divided droplets are produced from each droplet of the plurality of droplets contained within the first fluid.