DROPLET CREATION TECHNIQUES

• US 20150314292A1
• Filed: 05/08/2015
• Published: 11/05/2015
• 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.
• Granted Patent: US 9,839,911 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• 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

1-17. -17. (canceled)

18. An article, comprising:

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

a flow-focusing device able to produce divided droplets using the plurality of droplets contained within the fluid, the produced divided droplets having a distribution of diameters such that no more than about 5% of the droplets have a diameter greater than about 10% of the average diameter of the droplets.

19. The article of claim 18, wherein the fluid contains at least 5 distinguishable droplets.

20. The article of claim 18, wherein at least 10 divided droplets are produced from each droplet.

21. The article of claim 18, wherein the flow-focusing device comprises a microfluidic channel.

22. The article of claim 18, wherein the flow-focusing device comprises an intersection in a microfluidic channel, the intersection comprising at least two intersecting channels intersecting the microfluidic channel.

23. The article of claim 22, wherein in the intersection is an intersection of two intersecting channels intersecting the microfluidic channel, each at an angle of about 90°

C.

24. The article of claim 18, wherein in at least some droplets, the distinguishable compositions comprises 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.

25. The article of claim 24, wherein the at least four distinguishable species comprises at least four distinguishable nucleic acids.

26. The article of claim 24, wherein the at least four distinguishable species comprises at least four distinguishable identification elements.

27. The article of claim 24, wherein the at least four distinguishable species comprises at least four distinguishable proteins.

28. The article of claim 24, wherein the plurality of droplets has an average diameter greater than about 500 microns and the divided droplets have an average diameter of less than about 500 microns.

29. The article of claim 24, wherein the average diameter of the divided droplets is less than about 1000 microns and wherein the divided droplets are substantially monodisperse.

30. The article of claim 18, wherein the fluid and the plurality of droplets are substantially immiscible.

31. The article of claim 30, wherein the flow-focusing device comprises a first microfluidic channel and a second microfluidic channel intersecting at an intersection, the first microfluidic channel containing the plurality of droplets contained within the fluid, and the second microfluidic channel containing a second fluid.

32. The article of claim 31, wherein the second fluid is substantially identical to the fluid.

33. The article of claim 31, wherein the flow-focusing device is able to produce divided droplets using the plurality of droplets at the intersection.

34. The article of claim 18, wherein the fluid is an emulsion.

35. The article of claim 18, wherein the plurality of droplets has an average diameter of less than about 1 mm.

36. The article of claim 18, wherein the divided droplets has an average diameter of less than about 1 mm.

37. The article of claim 18, wherein at least 5 divided droplets are produced from each droplet.