Bubble formation techniques using physical or chemical features to retain a gas bubble within a droplet actuator

• US 8,877,512 B2
• Filed: 01/25/2010
• Issued: 11/04/2014
• Est. Priority Date: 01/23/2009
• Status: Expired due to Fees

• Current Assignee: Advanced Liquid Logic, Inc. (Illumina Incorporated)
• Original Assignee: Advanced Liquid Logic, Inc. (Illumina Incorporated)
• Inventors: Srinivasan, Vijay, Pollack, Michael G., Sudarsan, Arjun, Hua, Zhishan
• Primary Examiner(s): Soderquist, Arlen
• Application Number:
  US12/692,954
• Publication Number:
  US 20100190263A1
• Time in Patent Office: 1,744 Days
• Field of Search: 436/174
• US Class Current: 436/174
• CPC Class Codes: B01F 33/3031 using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
• CPC Class Codes: B01F 33/30351 using hydrophilic/hydrophobic surfaces
• CPC Class Codes: B01F 33/30352 using roughness of the surfaces
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2300/0867 Multiple inlets and one sample wells, e.g. mixing, dilution
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• CPC Class Codes: B01L 2400/0406 capillary forces
• CPC Class Codes: B01L 2400/0427 Electrowetting
• CPC Class Codes: B01L 2400/0688 surface tension valves, capillary stop, capillary break
• CPC Class Codes: B01L 3/502723 characterised by venting arrangements
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502792 for moving individual droplets on a plate, e.g. by locally altering surface tension
• CPC Class Codes: C07K 1/26 Electrophoresis
• CPC Class Codes: G01N 2001/2244 Exhaled gas, e.g. alcohol detecting
• CPC Class Codes: G01N 2035/1034 Transferring microquantities of liquid
• CPC Class Codes: Y10T 436/25 including sample preparation

Abstract

The present invention is directed to a droplet actuator and methods of making and using the droplet actuator including one or more substrates configured to form a droplet operations gap and including a physical or chemical feature that may be provided at a predetermined locus within or exposed to the droplet operations gap and configured to retain a bubble in position within the droplet operations gap.

Claims

1. A method of forming a bubble in a droplet actuator, the method comprising:

(a) providing a droplet actuator comprising;

(i) one or more substrates configured to form a droplet operations gap, the one or more substrates comprising electrodes arranged for conducting droplet operations in the droplet operations gap; and

(ii) a physical or chemical feature provided at a predetermined locus within or exposed to the droplet operations gap and configured to retain a bubble in position within the droplet operations gap; and

(b) dispensing an oil filler fluid, which fluid is sufficiently immiscible with a droplet phase to render the droplet phase subject to electrode-mediated droplet operations, into the droplet operations gap at a rate and volume sufficient to fill the fluid reservoir and to form a gaseous bubble at the physical or chemical feature, wherein the gaseous bubble is at least partially surrounded by the oil filler fluid.

2. The method of claim 1 wherein the droplet actuator further comprises more than one of the physical or chemical features.

3. The method of claim 2 wherein the droplet actuator further comprises an array of the chemical or physical features and an array of bubbles formed in the droplet operations gap and surrounded by an oil filler fluid.

4. The method of claim 3 wherein the droplet actuator further comprises an array of dried reagent, each dried reagent situated within a gaseous bubble in the array of bubbles.

5. The method of claim 1 wherein the physical feature comprises a recessed region of a surface of the one or more substrates facing the droplet operations gap.

6. The method of claim 1 wherein the physical feature comprises recessed regions of opposing surfaces of the one or more substrates facing the droplet operations gap.

7. The method of claim 1 wherein the physical feature comprises a chemically treated region of a surface of the one or more substrates facing the droplet operations gap.

8. The method of claim 1 wherein the physical feature comprises a hydrophilic or lipophobic region of a surface of the one or more substrates facing the droplet operations gap.

9. The method of claim 1 wherein the bubble spans the gap between opposing surfaces of the one or more substrates facing the droplet operations gap.

10. The method of claim 1 wherein the bubble comprises a gaseous bubble substantially surrounded by the oil filler fluid within the droplet operations gap.

11. The method of claim 1 wherein the oil filler fluid comprises low viscosity oil.

12. The method of claim 1 wherein the oil filler fluid comprises low viscosity oil doped with a surfactant.

13. The method of claim 1 wherein:

(a) the one or more substrates comprise a top substrate and a bottom substrate; and

(b) the bottom substrate is separated from the top substrate by a gap defined by a spacer to form the droplet operations gap.

14. The method of claim 13 wherein the physical feature comprises a recessed region of a surface of the one or more substrates facing the droplet operations gap.

15. The method of claim 14 wherein the recessed region is on the top substrate facing the bottom substrate, and the bottom substrate further comprises a recessed region opposite to the recessed region of the top substrate.

16. The method of claim 15 wherein the top substrate recessed region and bottom substrate recessed region are of sufficient depth to form a bubble as filler fluid is flowed into the gap, and for retaining a bubble in position in the gap.

17. The method of claim 14 wherein the recessed region is formed by a technique comprising patterning, embossing and/or etching.

18. The method of claim 14 wherein the recessed region is provided only in the top substrate.

19. The method of claim 14 wherein the recessed region is provided only in the bottom substrate.

20. The method of claim 1 wherein the droplet actuator further comprises a fluid reservoir formed in the droplet operations gap and comprising the bubble, the fluid reservoir comprising fluid barriers which at least partially surround the bubble.

21. The method of claim 1 wherein the droplet actuator further comprises a path of electrodes arranged for transporting a droplet situated in the droplet operations gap into the reservoir.

22. The method of claim 1 wherein the bubble is arranged to restrain movement of a droplet in the filler fluid.

23. The method of claim 1 wherein the droplet actuator comprises a fluid path arranged for flowing fluid from a source which is external to the droplet operations gap into the bubble.

24. The method of claim 1 wherein the droplet actuator further comprises a dried reagent situated within the gaseous bubble.

25. The method of claim 1 wherein the bubble comprises a preselected gas composition.

26. The method of claim 1 wherein the bubble comprises a preselected gas composition that is not air.

27. The method of claim 1 wherein the bubble consists substantially of a single gas.

28. The method of claim 1 wherein the bubble is formed under pressure.

29. The method of claim 1 wherein the droplet actuator further comprises a temperature control element arranged to control temperature of the bubble.

30. The method of claim 1 wherein the droplet actuator further comprises one or more physical barriers arranged to restrain movement of the bubble.

31. A method of providing a droplet actuator comprising a bubble in a droplet operations gap thereof, the method comprising:

(a) forming a gaseous bubble in a droplet operations gap of a droplet actuator, comprising electrodes arranged for conducting droplet operations in the droplet operations gap; and

a physical or chemical feature provided at a predetermined locus within or exposed to the droplet operations gap and configured to retain a bubble in position within the droplet operations gap;

wherein the bubble is;

(i) at least partially surrounded by an oil filler fluid, which fluid is sufficiently immiscible with a droplet phase to render the droplet phase subject to electrode-mediated droplet operations; and

(ii) optionally, partially surrounded by one or more droplet actuator surfaces; and

(b) forming an aqueous droplet in the filler fluid, wherein the droplet is substantially immiscible with and surrounded by the filler fluid.

32. The method of claim 31 further comprising transporting, by droplet operations mediated by the electrodes, the droplet from the oil filler fluid into the bubble.

33. The method of claim 32 further comprising subjecting the droplet to one or more droplet operations within the bubble.

34. The method of claim 32 further comprising evaporating the droplet within the bubble.

35. The method of claim 32 further comprising evaporating a portion of the droplet to concentrate one or more components in the droplet.

36. The method of claim 31 further comprising providing a dried reagent in the bubble.

37. The method of claim 36 further comprising transporting a droplet from the filler fluid into the bubble to reconstitute the dried reagent.

38. The method of claim 37 wherein transporting the droplet from the filler fluid into the bubble is mediated by the electrodes.

39. The method of claim 31 wherein forming a gaseous bubble in a droplet operations gap of a droplet actuator comprises flowing the oil filler fluid into the droplet operations gap at a rate and volume sufficient to cause formation of a bubble in the droplet operations gap at the predetermined locus.

40. The method of claim 31 wherein the bubble comprises a preselected gas composition.

41. The method of claim 31 wherein the bubble consists substantially of a single gas.

42. The method of claim 31 wherein the bubble is formed under pressure.

43. The method of claim 31 wherein the droplet actuator comprises one or more physical barriers in the reservoir for supporting and retaining the bubble in the reservoir.

44. The method of claim 31 further comprising flowing the bubble out of the droplet operations gap.

45. The method of claim 31 further comprising flowing the bubble into a different region of the droplet operations gap.

46. The method of claim 31 further comprising using the bubble to prevent movement of the droplet.