Electronic control of fluidic species
Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one aspect, the invention relates to systems and methods for making droplets of fluid surrounded by a liquid, using, for example, electric fields, mechanical alterations, the addition of an intervening fluid, etc. In some cases, the droplets may each have a substantially uniform number of entities therein. For example, 95% or more of the droplets may each contain the same number of entities of a particular species. In another aspect, the invention relates to systems and methods for dividing a fluidic droplet into two droplets, for example, through charge and/or dipole interactions with an electric field. The invention also relates to systems and methods for fusing droplets according to another aspect of the invention, for example, through charge and/or dipole interactions. In some cases, the fusion of the droplets may initiate or determine a reaction. In a related aspect of the invention, systems and methods for allowing fluid mixing within droplets to occur are also provided. In still another aspect, the invention relates to systems and methods for sorting droplets, e.g., by causing droplets to move to certain regions within a fluidic system. Examples include using electrical interactions (e.g., charges, dipoles, etc.) or mechanical systems (e.g., fluid displacement) to sort the droplets. In some cases, the fluidic droplets can be sorted at relatively high rates, e.g., at about 10 droplets per second or more. Another aspect of the invention provides the ability to determine droplets, or a component thereof, for example, using fluorescence and/or other optical techniques (e.g., microscopy), or electric sensing techniques such as dielectric sensing.
1. A method of sorting droplets in a microfluidic system, the method comprising:
providing a series of droplets of fluid surrounded by a liquid essentially immiscible with the fluid and flowing in a microfluidic channel;
selecting a first droplet from the series of droplets; and
separating the first droplet from the series of droplets using an applied electric field without substantially altering flow of the liquid containing the fluidic droplet.
2. The method of claim 1 , wherein one or more droplets in the series of droplets contain one or more cells.
3. The method of claim 1 , further comprising determining a characteristic in each of the series of cells.
4. The method of claim 3 , wherein the characteristic comprises fluorescence.
5. The method of claim 3 , wherein the first droplet is selected based on the presence or absence of the characteristic.
6. The method of claim 1 , further comprising sorting a plurality of droplets from the series of droplets by determining, for each of the plurality of droplets, presence of a contained specific chemical, biological, or biochemical species and directing the plurality of droplets into a one of a plurality of microfluidic channels based on the presence or absence of the contained specific chemical, biological, or biochemical species.
7. The method of claim 6 , comprising sorting the droplets at a rate of at least about 10 droplets/s.
8. The method of claim 6 , comprising sorting the droplets at a rate of at least about 100 droplets/s.
9. The method of claim 6 , comprising sorting the droplets at a rate of at least about 1000 droplets/s.
10. The method of claim 6 , comprising sorting the droplets at a rate of at least about 10,000 droplets/s.
11. The method of claim 6 , comprising sorting the droplets at a rate of at least about 100,000 droplets/s.
12. The method of claim 6 , further comprising collecting the sorted plurality of droplets in a collection region, wherein the plurality of droplets maintain their individual identities and do not fuse.
13. The method of claim 6 , further comprising coalescing two or more of the sorted plurality of droplets.
14. The method of claim 6 , further comprising using an applied electric field to coalesce the two or more of the sorted plurality of droplets.
15. The method of claim 6 , further comprising coalescing one or more of the sorted plurality of droplets with one or more additional droplets containing one or more additional reagents.
16. The method of claim 1 , further comprising causing mixing to occur within one or more of the series of droplets.
17. The method of claim 1 , wherein the microfluidic channel has a maximum cross-sectional dimension of less than about 500 micrometers.
18. A method of sorting droplets in a microfluidic system, the method comprising:
providing a series of droplets of fluid surrounded by a liquid essentially immiscible with the fluid and flowing in a microfluidic channel;
selecting a first droplet from the series of droplets; and
separating the first droplet from the series of droplets using an applied electric field to attract the first droplet without attracting the surrounding liquid.
19. The method of claim 18 , wherein one or more droplets in the series of droplets contain one or more cells.
20. The method of claim 18 , further comprising determining a characteristic in each of the series of cells, wherein the first droplet is selected based on the presence or absence of the characteristic.