Fluidic droplet coalescence

• US 20070195127A1
• Filed: 01/24/2007
• Published: 08/23/2007
• Est. Priority Date: 01/27/2006
• Status: Abandoned Application

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Link, Darren, Weitz, David, Ahn, Keunho, Agresti, Jeremy, Chong, Henry
• Application Number:
  US11/698,298
• Publication Number:
  US 20070195127A1
• Time in Patent Office: Days
• US Class Current: 347/55
• 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: B01F 33/3031 using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
• CPC Class Codes: B01J 19/0093 Microreactors, e.g. miniaturised or microfabricated reactors laboratory containers with capillary fluid transport in microfabricated channels or chambers B01L3/5027
• CPC Class Codes: B01J 2219/00272 Addition of reaction inhibitor
• CPC Class Codes: B01J 2219/00828 Silicon wafers or plates
• CPC Class Codes: B01J 2219/00833 Plastic
• CPC Class Codes: B01J 2219/00835 Comprising catalytically active material
• CPC Class Codes: B01J 2219/00853 Employing electrode arrangements
• CPC Class Codes: B01J 2219/00889 Mixing micromixers B01F33/30
• CPC Class Codes: B01J 2219/0093 Electric or magnetic energy
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• 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: G01N 15/1404 Handling flow, e.g. hydrodynamic focusing
• CPC Class Codes: G01N 2015/1006 for cytology

Abstract

The present invention generally relates to systems and methods for the control of fluidic species and, in particular, to the coalescence of fluidic droplets. In certain instances, the systems and methods are microfluidic. In one aspect, the invention relates to systems and methods for causing two or more fluidic droplets within a channel to coalescence. The fluidic droplets may be of unequal size in certain cases. In some embodiments, a first fluidic droplet may be caused to move at a first velocity, and a second fluidic droplet may be caused to move at a second velocity different from the first velocity, for instance, substantially greater than the first velocity. The droplets may then coalesce, for example, upon application of an electric field. In the absence of an electric field, in some cases, the droplets may be unable to coalesce. In some cases, two series of fluidic droplets may coalesce, one or both series being substantially uniform. For instance, one series of droplets may have 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. In certain cases, one or more series of droplets may each consist essentially of a substantially uniform number of entities of a species therein (i.e., molecules, cells, particles, etc.). The fluidic droplets may be coalesced to start a reaction, and/or to stop a reaction, in some cases. For instance, a reaction may be initiated when a species in a first droplet contacts a species in a second droplet after the droplets coalesce, or a first droplet may contain an ongoing reaction and a second droplet may contain a species that inhibits the reaction. Other embodiments of the invention are directed to kits or methods for promoting the coalescence of fluidic droplets.

Claims

1. A method, comprising:

providing a microfluidic system comprising a channel containing a first fluidic droplet and a second fluidic droplet;

causing the first droplet to move at a first velocity within the channel and the second droplet to move at a second velocity greater than the first velocity within the channel;

causing the second fluidic droplet to contact the first fluidic droplet such that the first fluidic droplet and the second fluidic droplet do not coalesce; and

applying an electric field to at least one of the first fluidic droplet and the second fluidic droplet such that the first droplet and the second droplet coalesce into one combined droplet.

2. The method of claim 1, wherein the second velocity is at least about 150% of the first velocity.

3. The method of claim 1, wherein the second velocity is at least about 200% of the first velocity.

4. The method of claim 1, wherein the second velocity is at least about 300% of the first velocity.

5. The method of claim 1, wherein the second velocity is at least about 500% of the first velocity.

6. The method of claim 1, wherein the volume of the first fluidic droplet is greater than the volume of the second fluidic droplet.

7. The method of claim 1, wherein the channel has an average cross-sectional dimension of less than about 5 mm.

8. The article of claim 1, wherein the first fluidic droplet has a cross-sectional dimension of less than about 100 microns.

9. The article of claim 1, wherein the first fluidic droplet has a cross-sectional dimension of less than about 30 microns.

10. The article of claim 1, wherein the first fluidic droplet has a cross-sectional dimension of less than about 10 microns.

15. The method of claim 1, wherein at least one of the first fluidic droplet and the second fluidic droplet comprises an enzyme.

16. The method of claim 1, wherein one of the first fluidic droplet and the second fluidic droplet comprises two reactants interacting in a chemical reaction;

and the other fluidic droplet comprises an inhibitor to the chemical reaction.

20. The method of claim 1, further comprising hardening at least a portion of the combined droplet.

38. The method of claim 1, wherein at least one of the first fluidic droplet and the second fluidic droplet comprises a nucleic acid.

11-14. -14. (canceled)

17-19. -19. (canceled)

21. A method, comprising:

providing a first fluidic stream of droplets, the droplets within the first fluidic stream having an average diameter of less than about 100 microns and 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;

providing a second fluidic stream of droplets, the droplets within the first fluidic stream having an average diameter of greater than about 125% of the average diameter of the droplets within the second fluidic stream; and

applying an electric field to at least one droplet of the first fluidic stream of droplets and at least one droplet of the second fluidic stream of droplets such that the at least one droplet of the first fluidic stream of droplets and the at least one droplet of the second fluidic stream of droplets coalesce into one combined droplet.

32. The method of claim 21, wherein at least one of the first fluidic droplet and the second fluidic droplet comprises an enzyme.

33. The method of claim 21, wherein one of the first fluidic droplet and the second fluidic droplet comprises two agents interacting in a chemical reaction;

and the other fluidic droplet comprises an inhibitor to the chemical reaction.

37. The method of claim 21, further comprising hardening at least a portion of the combined droplet.

22-23. -23. (canceled)

26-31. -31. (canceled)

34-36. -36. (canceled)