MICROFLUIDIC SYSTEMS AND METHODS FOR REDUCING THE EXCHANGE OF MOLECULES BETWEEN DROPLETS
The present invention generally relates to systems and methods to create stable emulsions with low rates of exchange of molecules between microdroplets.
1 . A method comprising the steps of:
(a) providing within a carrier fluid a plurality of microdroplets comprising a first microdroplet comprising a first biological or chemical material and a second microdroplet comprising a second biological or chemical material, wherein the carrier fluid is immiscible with the first microdroplet and second microdroplet and comprises a first oil and a first surfactant at a first concentration within the first oil;
(b) changing the carrier fluid, in the presence of the plurality of microdroplets, by changing (i) some or all of the first oil for a second oil, (ii) some or all of the first surfactant for a second surfactant, (iii) the first concentration to a second concentration, or any combination of (i), (ii) and/or (iii).
2 . The method of claim 1 , further comprising the step (c) of providing a microfluidic device and wherein step (a) further comprises providing the plurality of microdroplets and the carrier fluid in the microfluidic device and/or step (b) further comprises changing the carrier fluid within the microfluidic device.
3 . The method of claim 1 , wherein the first biological or chemical material and/or the second biological or chemical material comprises a tissue, cell, particle, protein, antibody, amino acid, nucleotide, small molecule, pharmaceutical, and/or label.
4 . The method of claim 1 , wherein the first concentration is sufficient to stabilize the microdroplets against coalescing with each other in the first carrier fluid.
5 . The method of claim 4 , wherein the first concentration is determined, at least in part, based on stabilizing the microdroplets over a time frame determined by a reaction and/or detection of the one or more biological and/or chemical materials.
6 . The method of claim 1 , wherein the second concentration is sufficient to reduce exchange of the first biological or chemical material from the first microdroplet to the second microdroplet, or of the second biological or chemical material from the second microdroplet to the first microdroplet.
7 . The method of claim 6 , wherein the second concentration is determined, at least in part, based on stabilizing the microdroplets over a time frame determined by generation and/or use of the first microdroplet and the second microdroplet in one or more libraries.
8 . The method of claim 6 , wherein the changing of step (b) comprises changing the first concentration to the second concentration at least in part by providing the second oil substantially free of the first surfactant.
9 . A method comprising the steps of:
(a) generating a plurality of aqueous microdroplets in a continuous phase in a microfluidic device, wherein the first continuous phase comprises a high concentration of a surfactant; and
(b) exchanging the first continuous phase containing the high concentration of surfactant for a second continuous phase containing no surfactant or a reduced concentration of surfactant.
10 . The method of claim 9 , wherein step (b) is accomplished in the microfluidic device.
11 . The method of claim 9 , wherein step (b) is accomplished, at least in part, by shifting the microdroplets from the first continuous phase into a stream of the second continuous phase.
12 . The method of claim 10 , wherein the shifting is accomplished by using obstacles, changing channel depth, by dielectrophoresis, or by buoyancy.