Methods of introducing a fluid into droplets
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 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. 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 introducing a fluid into a droplet, comprising:
flowing a plurality of liquid droplets through a first microchannel in a carrier liquid, wherein each of the plurality of liquid droplets comprises a first liquid that is immiscible with the carrier liquid;
flowing a single phase liquid stream in a second microchannel, wherein the second microchannel intersects the first microchannel at an opening into the first microchannel;
directly injecting a portion of the single phase liquid stream that is flowing in the second microchannel into each of the plurality of liquid droplets as each of the plurality of liquid droplets in the first microchannel comes into contact with the opening of the second microchannel, thereby introducing a portion of the single phase liquid stream into each of the plurality of liquid droplets to form mixed liquid droplets; and
collecting at least a portion of the mixed liquid droplets in a collection region operably associated with the first microchannel and downstream from the intersection of the first and second microchannels, wherein the mixed liquid droplets contact each other but do not fuse with each other.
2. The method of claim 1 , wherein the first liquid and the single phase liquid stream comprise hydrophilic liquids.
3. The method of claim 2 , wherein the first liquid and the single phase liquid stream comprise aqueous solutions.
4. The method of claim 1 , wherein the carrier liquid comprises a hydrophobic liquid.
5. The method of claim 1 , wherein the first liquid and the single phase liquid stream comprise a reactant selected from the group consisting of a chemical reagent, a biological entity, and a biochemical entity.
6. The method of claim 5 , wherein the first liquid and the single phase liquid stream comprise a reactant selected from the group consisting of a chemical reagent, a biological entity, and a biochemical entity,
wherein the reactant in the single phase liquid is different than the reactant in the first liquid.
7. The method of claim 1 , wherein the first microchannel has a maximum cross-sectional dimension of less than about 500 micrometers.
8. The method of claim 1 , further comprising mixing, in at least a portion of the mixed liquid droplets, the portion of the single phase liquid stream with the first liquid.
9. The method of claim 1 , further comprising:
detecting electromagnetic radiation arising from the mixed liquid droplets after the directly injecting step using a sensor.
10. The method of claim 9 , further comprising:
performing an operation on the mixed liquid droplets in response to the detected electromagnetic radiation.
11. The method of claim 1 , wherein the directly injecting is carried out under an electric field.