Low volume hybridization
The present document relates to a system and method of commingling a low volume of a target solution with an array. For example, a quantity of the target solution and a quantity of an immiscible liquid may be introduced into a cavity having an array on an interior surface. The quantities of target solution and immiscible liquid do not fill the volume. Therefore, a gas is contained within the volume. The cavity is then agitated.
1. A method of commingling a target solution dissolved in an aqueous phase with an array, the method comprising:
introducing a quantity of the target solution dissolved in an aqueous phase and a quantity of an immiscible liquid into a cavity having an array on an interior surface, so that the quantities of target solution and immiscible liquid do not fill the volume, and so that a gas is contained within the volume; and
agitating the cavity to form liquid bubbles of the immiscible liquid in said aqueous phase.
2. The method of claim 1 , wherein the aqueous phase and immiscible liquid exhibit substantially different surface tensions.
3. The method of claim 1 , wherein the aqueous phase includes a blocking reagent or a hybridization buffer.
4. The method of claim 1 , wherein the aqueous phase fills one-fourth of the cavity or less.
5. The method of claim 1 , wherein, together, the quantity of immiscible liquid and aqueous phase fill at least one-half of the cavity.
6. The method of claim 1 , wherein the gas fills one-half of the cavity or less.
7. The method of claim 1 , wherein the immiscible liquid is nonflammable.
8. The method of claim 1 , wherein the immiscible liquid comprises a fluorocarbon liquid.
9. The method of claim 1 , wherein the immiscible liquid comprises a perfluorocarbon liquid.
10. The method of claim 1 , wherein the immiscible liquid comprises a hydrofluoropolyether liquid.
11. The method of claim 1 , wherein the immiscible liquid comprises a perfluoropolyether liquid.
12. The method of claim 1 , wherein the immiscible liquid comprises a hydrofluoroether liquid.
13. The method of claim 1 , wherein the immiscible liquid comprises a perfluoroalkylamine liquid.
14. The method of claim 1 , wherein the immiscible liquid comprises a mixture of a hydrofluoropolyether liquid and a perfluoroalkylamine liquid.
15. The method of claim 1 , wherein the agitation of the cavity comprises rotating the cavity at a frequency chosen so that the immiscible liquid forms a plurality of liquid bubbles.
16. The method of claim 15 , wherein the cavity is rotated at a frequency chosen so that a portion of the plurality of bubbles exhibits free motion about the cavity.
17. The method of claim 15 , wherein the cavity is rotated at a frequency chosen so that the immiscible liquid forms between 10 and 1,000 bubbles within the cavity.
18. The method of claim 15 , wherein the cavity is approximately 600 microliters.
19. The method of claim 15 , wherein the cavity is rotated at a frequency chosen so that a single air bubble is exhibited in the cavity.
20. The method of claim 1 , further comprising the act of heating the cavity.
21. The method of claim 1 , wherein said agitating moves said liquid bubbles of the immiscible liquid in said aqueous phase.
22. The method of claim 1 , wherein said array is a two-dimensional, addressable array.