Method and apparatus for forming multiple emulsions

Patent metadata

Field	Value
Publication number	US-10316873-B2
Application number	US-201514681560-A
Country	US
Kind code	B2
Filing date	Apr 8, 2015
Priority date	Mar 4, 2005
Publication date	Jun 11, 2019
Grant date	Jun 11, 2019

Abstract

The present invention generally relates to multiple emulsions, and to methods and apparatuses for making multiple emulsions. A multiple emulsion generally describes larger droplets that contain one or more smaller droplets therein. The larger droplets may be suspended in a third fluid in some cases. These can be useful for encapsulating species such as pharmaceutical agents, cells, chemicals, or the like. In some cases, one or more of the droplets can change form, for instance, to become solidified to form a microcapsule, a liposome, a polymerosome, or a colloidosome. Multiple emulsions can be formed in one step in certain embodiments, with generally precise repeatability, and can be tailored to include one, two, three, or more inner droplets within a single outer droplet (which droplets may all be nested in some cases).

First claim

What is claimed is:

1. A method of making a droplet comprising:
forming a multiple emulsion droplet from a first fluid stream flowing in a first direction contained within a first microfluidic channel and a second fluid stream flowing substantially in the first direction contained within a second microfluidic channel, by simultaneously surrounding a portion of the first fluid stream with a portion of the second fluid stream, the portion of the first fluid stream in contact with the portion of the second fluid stream, while surrounding the portion of the second fluid stream with a third fluid upon contact with a third fluid stream flowing within the second microfluidic channel in a second direction that is substantially opposed to the first direction, and altering the direction of flow of the third fluid stream to flow substantially in the first direction upon contact of the third fluid stream with the second fluid stream, wherein the multiple emulsion droplet comprises a droplet of the first fluid, contained within a droplet of the second fluid, surrounded by the third fluid.

2. The method of claim 1 , wherein the first fluid is miscible in the third fluid.

3. The method of claim 1 , wherein the second fluid comprises a material selected from surfactants, prepolymers, polymers, lipids, copolymers and amphiphiles.

4. The method of claim 3 , wherein the copolymer is a diblock copolymer, a triblock copolymer and/or a random copolymer.

5. The method of claim 1 , wherein the first and second fluids form a polymerosome or a liposome.

6. The method of claim 1 , further comprising causing formation of a hardened shell in the droplet of the second fluid within the multiple emulsion droplet after formation of the multiple emulsion droplet.

7. The method of claim 1 , wherein the multiple emulsion droplet comprises a plurality of droplets of the first fluid inside the droplet of the second fluid.

8. A method comprising:
flowing a first fluid stream exiting a first microfluidic channel in a first direction;
flowing a second fluid stream contained within a second microfluidic channel in a direction substantially in the first direction, the second stream circumscribing the first stream upon exiting of the first fluid stream from the first microfluidic channel, the first microfluidic channel being disposed in the second microfluidic channel;
flowing a third fluid stream within the second microfluidic channel in a second direction that is substantially opposed to the first direction; and
altering the direction of flow of the third fluid stream to flow substantially in the first direction upon contact with the second fluid.

9. The method of claim 8 , wherein at least a portion of the third stream circumscribes a portion of the second stream.

10. The method of claim 8 , wherein the fluid of the first stream is miscible in the fluid of the third stream.

11. A method of packaging a species comprising:
suspending a species in a first fluid;
flowing the first fluid in a stream in a first direction;
surrounding a portion of the first fluid with a portion of a second fluid upon contact of the first fluid stream with a second fluid stream flowing substantially in the first direction, the second fluid being substantially immiscible with the first fluid;
introducing a third fluid stream flowing in a direction substantially opposed to the first direction; and
altering the direction of flow of the third fluid stream to flow substantially in the first direction upon contact of the third fluid stream with the second fluid stream, the third fluid stream surrounding the second fluid stream upon contact; and
forming multiple droplets of the first fluid wherein the droplets contain at least one of the species.

12. The method of claim 11 , wherein the species is selected from cells, drugs, nucleic acids, proteins, fragrances, nanoparticles and quantum dots.

13. The method of claim 11 , further comprising solidifying a portion of the second fluid surrounding the droplet.

14. The method of claim 11 , comprising solidifying at least a portion of the inner droplet.

15. A method for forming droplets, comprising:
flowing a first fluid in a first direction in a first microfluidic conduit having a first diameter;
flowing a second fluid in substantially the first direction in a second microfluidic conduit having an end defining an exit opening, wherein the second microfluidic conduit is disposed in the first microfluidic conduit;
expelling the second fluid, from the exit opening of the second conduit, into the first fluid in the first microfluidic conduit;
surrounding the first and second fluids with a third fluid upon contact with a third fluid stream flowing in a second direction that is substantially opposed to the first direction;
altering the direction of flow of the third fluid stream to flow substantially in the first direction upon contact with the first fluid;
advancing the second fluid, surrounded by the first fluid, into a restriction under conditions in which droplets of the second fluid in the first fluid are formed within the restriction; and
releasing the droplets of the second fluid carried in the first fluid from the restriction into a region of dimension larger than the restriction.

16. The method of claim 15 , wherein the second fluid surrounds a fourth fluid.

Assignees

• Weitz David A
• Link Darren Roy
• Utada Andrew S
• Harvard College

Inventors

• Weitz David A
• Link Darren Roy
• Utada Andrew S

Classifications

• B01F13/0059

  Operations & Transport · mapped topic

• A61K9/113

  Multiple emulsions, e.g. oil-in-water-in-oil {(A61K9/0026 takes precedence)} · CPC title

• Y10S516/924

  Significant dispersive or manipulative operation or step in making or stabilizing colloid system · CPC title

• B01F5/046

  Operations & Transport · mapped topic

• A61K9/1273 Primary

  Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances · CPC title