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 producing droplet microreactors in a microfluidic system, comprising:
producing a series of droplets of fluid surrounded by a liquid and flowing in a microfluidic channel, the droplets containing at least one cell and one or more reagents for performing an assay on the cells; and
collecting the series of droplets in a collection region, without sorting the series of droplets, wherein the droplets maintain their individual identities and contact one another but do not fuse, due to the presence of a surfactant or due to the size or surface tension of the droplets.
2. The method of claim 1 , further comprising performing the assay on the at least one cell within the collected series of droplets using the one or more reagents.
3. The method of claim 1 , further comprising determining a characteristic of the at least one cell.
4. The method of claim 3 , wherein the characteristic comprises fluorescence.
5. The method of claim 2 , further comprising sorting the series of droplets collected in the collection region by selecting and separating a portion of droplets from the collected series of droplets.
6. The method of claim 5 , comprising sorting the droplets at a rate of at least about 10 droplets/s.
7. The method of claim 5 , comprising sorting the droplets at a rate of at least about 100 droplets/s.
8. The method of claim 5 , comprising sorting the droplets at a rate of at least about 1000 droplets/s.
9. The method of claim 5 , comprising sorting the droplets at a rate of at least about 10,000 droplets/s.
10. The method of claim 5 , comprising sorting the droplets at a rate of at least about 100,000 droplets/s.
11. The method of claim 5 , further comprising using an applied electric field to sort the series of collected droplets.
12. The method of claim 11 , further comprising inducing a dipole in the portion of the series of droplets.
13. The method of claim 11 , further comprising creating an electric charge on the portion of the series of droplets.
14. The method of claim 1 , further comprising coalescing two or more of the series of droplets.
15. The method of claim 14 , further comprising using an applied electric field to coalesce the two or more of the series of droplets.
16. The method of claim 1 , further comprising coalescing one or more of the series of droplets with one or more additional droplets containing one or more additional reagents.
17. The method of claim 1 , further comprising causing mixing to occur within one or more of the series of droplets.
18. The method of claim 1 , wherein the microfluidic channel has a maximum cross-sectional dimension of less than about 500 micrometers.