IP Library Granted Patent US 11,141,731
Granted Patent B2
US 11,141,731 · App. 16/285,984 · Granted Oct 12, 2021

Formation and control of fluidic species

Inventors: David A. Weitz (Bolton, MA); Darren Roy Link (Lexington, MA); Manuel Marquez-Sanchez (Lincolnshire, IL); Zhengdong Cheng (College Station, TX)
Assignee: President and Fellows of Harvard College
B01L3/502784B01F5/0682B01F13/0062B01F13/0071B01F13/0076B01J2/04B01L3/50273B01L3/502715B05B5/03B05B7/061B01F2215/0431B01L2200/0673B01L2300/0867B01L2400/02B01L2400/0415B01L2400/0424
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Quick Facts
Patent No.
US 11,141,731
App. No.
16/285,984
Granted
Oct 12, 2021
Kind
B2
Abstract

This invention generally relates to systems and methods for the formation and/or control of fluidic species, and articles produced by such systems and methods. In some cases, the invention involves unique fluid channels, systems, controls, and/or restrictions, and combinations thereof. In certain embodiments, the invention allows fluidic streams (which can be continuous or discontinuous, i.e., droplets) to be formed and/or combined, at a variety of scales, including microfluidic scales. In one set of embodiments, a fluidic stream may be produced from a channel, where a cross-sectional dimension of the fluidic stream is smaller than that of the channel, for example, through the use of structural elements, other fluids, and/or applied external fields, etc. In some cases, a Taylor cone may be produced. In another set of embodiments, a fluidic stream may be manipulated in some fashion, for example, to create tubes (which may be hollow or solid), droplets, nested tubes or droplets, arrays of tubes or droplets, meshes of tubes, etc. In some cases, droplets produced using certain embodiments of the invention may be charged or substantially charged, which may allow their further manipulation, for instance, using applied external fields. Non-limiting examples of such manipulations include producing charged droplets, coalescing droplets (especially at the microscale), synchronizing droplet formation, aligning molecules within the droplet, etc. In some cases, the droplets and/or the fluidic streams may include colloids, cells, therapeutic agents, and the like.

Claims (19)

1. A method for encapsulating a cell in a fluid droplet, the method comprising:

flowing a first fluid containing cells in a first channel wherein the first channel meets a second channel, a third channel, and an outlet channel at a junction;

flowing a second fluid in the second and third channels, immiscible with the first fluid, toward the junction with the first channel; and

generating droplets of the first fluid within the second fluid flowing away from the junction in the outlet channel wherein one or more of the cells are encapsulated in the droplets.

2. The method of claim 1 , wherein the first channel comprises a reduction in cross-sectional diameter after the junction with the second and third channels.

3. The method of claim 2 , wherein the reduction in cross-sectional diameter is at least 50%.

4. The method of claim 1 , wherein the first channel is substantially perpendicular to the second and third channels.

5. The method of claim 1 , wherein the first fluid is conductive and the second fluid is non-conductive.

6. The method of claim 5 , further comprising applying an electric field to the junction.

7. The method of claim 1 , wherein the droplets further comprise one or more reactants.

8. The method of claim 7 , wherein the one or more reactants are selected from the group consisting of an enzyme, a nucleic acid, an antibody, and a ligand.

9. The method of claim 7 , further comprising coalescing the cell-encapsulating droplets with one or more droplets containing the one or more reactants to form the droplets.

10. The method of claim 7 , wherein the first fluid further comprises the one or more reactants prior to encapsulation.

11. The method of claim 1 , wherein the first fluid is aqueous.

12. The method of claim 11 , wherein the second fluid is an oil.

13. The method of claim 1 , wherein the droplets flow away from the junction in the first microchannel.

14. The method of claim 1 , wherein the droplets are charged.

15. The method of claim 1 , wherein the first, second, and third channels are fabricated from silicon, glass, or polydimethylsiloxane.

16. The method of claim 1 , wherein at least a portion of the droplets is hardened.

Assignments (3)
CONFIRMATORY LICENSE Recorded May 13, 2020
From: HARVARD UNIVERSITY
To: NATIONAL SCIENCE FOUNDATION
Reel/Frame 052655/0177 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 4, 2019
From: CHENG, ZHENGDONG; LINK, DARREN R.; WEITZ, DAVID A.
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 050255/0941 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 4, 2019
From: MARQUEZ-SANCHEZ, MANUEL
To: PRESIDENT AND FELLOWS OF HARVARD COLLEGE
Reel/Frame 050255/0955 →
Continuity (5)
Continuation 14662668 · Mar 19, 2015
Continuation 11246911 · Oct 7, 2005
Continuation PCTUS2004010903 · Apr 9, 2004
Provisional Application 60461954 · Apr 10, 2003
Related Publication 20190184398A1 · Jun 20, 2019