Creating and harvesting surface-bound emulsion
Provided is an emulsion comprising: (a) droplets that contain a single polymeric compound or a pre-defined mixture thereof, and (b) an immiscible liquid, wherein: (i) each of the droplets comprises multiple molecules of the compound(s) contained therein; and the droplets do not contain monomeric precursors for the polymeric compound. A method for making the emulsion is also provided.
1. A method of making an emulsion, comprising:
(a) obtaining an array of polymeric compounds on the surface of a substrate, wherein the polymeric compounds are bound to the substrate via a cleavable linker and wherein the areas that contain said polymeric compounds on the surface of the substrate are hydrophilic relative to the remainder of the surface of the substrate;
(b) selectively hydrating the areas that contain said polymeric compounds by flooding the substrate with an aqueous reagent and then removing the aqueous reagent from the substrate to leave discrete droplets of the aqueous reagent on the areas that contain said polymeric compounds, wherein each droplet contains a single polymeric compound or a pre-defined combination of polymeric compounds that are adjacent to one another on the substrate;
(c) releasing the polymeric compounds from the surface of the substrate by cleaving the cleavable linker, either before, during or after the hydrating step (b);
(d) collecting the droplets in an immiscible liquid, thereby producing an emulsion containing discrete droplets, each of which containing, in the solution phase, a single polymeric compound or a combination of polymeric compounds that are adjacent to one another on the substrate.
2. The method of claim 1 , wherein the polymeric compounds are synthetically made oligonucleotides, peptides or organic molecules that have been made by combinatorial chemistry.
3. The method of claim 2 , wherein step (a) comprises synthesizing the polymeric compounds in situ on the surface of the substrate.
4. The method of claim 1 , wherein the polymeric compounds are at a density of at least 1000 molecules per μm 2 .
5. The method of claim 1 , wherein the areas are in the range of 1 μm 2 to 1 mm 2 .
6. The method of claim 1 , wherein the areas are separated from one another by a distance of at least 1 μm.
7. The method of claim 1 , wherein the releasing step (c) is done before the selectively hydrating step (b).
8. The method of claim 7 , wherein the releasing step (c) is done by:
exposing said array to ammonia gas, thereby cleaving an ammonia-sensitive linkage that attaches the polymeric compounds to the substrate; or
exposing said array to a light, thereby cleaving a photocleavable linkage that attaches the polymeric compounds to the substrate.
9. The method of claim 1 , wherein the releasing step (c) is done during or after the selectively hydrating step (b).
10. The method of claim 9 , wherein the releasing step (c) is done by printing a solution that contains a cleavage agent onto the areas that contain said compounds, thereby cleaving a cleavage agent-sensitive linkage that attaches the polymeric compounds to the substrate.
11. The method of claim 9 , wherein releasing step (c) is done by exposing the array to a light, wherein the light cleaves a photocleavable linkage that attaches the polymeric compounds to the substrate.
12. A method of making an emulsion, comprising:
(a) obtaining an array of polymeric compounds on the surface of a substrate, wherein the polymeric compounds are bound to the substrate via a cleavable linker and wherein the areas that contain said polymeric compounds on the surface of the substrate are hydrophilic relative to the remainder of the surface of the substrate;
(b) selectively hydrating the areas that contain said polymeric compounds by flooding the substrate with an aqueous reagent and then removing the aqueous reagent from the substrate to leave discrete droplets of the aqueous reagent on the areas that contain said polymeric compounds, wherein each droplet contains a single polymeric compound or a pre-defined combination of polymeric compounds that are adjacent to one another on the substrate;
(c) releasing the polymeric compounds from the surface of the substrate by cleaving the cleavable linker, during or after the hydrating step (b);
wherein the releasing step (c) is done by immersing the array in an immiscible agent that contains a cleavage agent, thereby cleaving a cleavage agent-sensitive linkage that attaches the polymeric compounds to the substrate.