Surface Assisted Fluid Loading and Droplet Dispensing

• US 20090304944A1
• Filed: 01/22/2008
• Published: 12/10/2009
• Est. Priority Date: 01/22/2007
• Status: Active Grant

• Current Assignee: Advanced Liquid Logic, Inc. (Illumina Incorporated)
• Original Assignee: Advanced Liquid Logic, Inc. (Illumina Incorporated)
• Inventors: Pamula, Vamsee K., Sudarsan, Arjun, Srinivasan, Vijay, Pollack, Michael G.
• Granted Patent: US 8,685,344 B2
• Time in Patent Office: Days
• US Class Current: 427/458
• CPC Class Codes: B01F 33/3021 the components to be mixed being combined in a single independent droplet, e.g. these droplets being divided by a non-miscible fluid or consisting of independent droplets
• CPC Class Codes: B01F 33/3031 using electro-hydrodynamic [EHD] or electro-kinetic [EKI] phenomena to mix or move the fluids
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• CPC Class Codes: B01L 2300/165 Specific details about hydrophobic, oleophobic surfaces
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0427 Electrowetting
• CPC Class Codes: B01L 3/0241 Drop counters; Drop formers making arrays for combinatorial libraries B01J19/0046; automation of dispensing for analysis G01N35/10
• CPC Class Codes: B01L 3/502792 for moving individual droplets on a plate, e.g. by locally altering surface tension

Abstract

The present invention relates to surface assisted fluid loading and droplet dispensing on a droplet micro actuator. A droplet actuator is provided and includes one or more electrodes configured for conducting one or more droplet operations on a droplet operations surface of the substrate. The droplet actuator further includes a wettable surface defining a path from a fluid reservoir into a locus which is sufficiently near to one or more of the electrodes that activation of the one or more electrodes results in a droplet operation. Methods and systems are also provided.

Claims

1. A droplet actuator comprising a first substrate and a second substrate, wherein:

(a) the first substrate comprises one or more electrodes configured for conducting one or more droplet operations; and

(b) the second substrate is arranged in relation to the first substrate and spaced from the surface of the first substrate by a distance to define a space between the first substrate and second substrate, wherein the distance is sufficient to contain a droplet disposed in the space;

(c) the first or second substrate comprises a wettable surface defining a path from a position accessible to an exterior locus of the droplet actuator into an internal locus of the droplet actuator sufficient to;

(i) cause a fluid from the external locus to flow from the external locus to the internal locus, or

(ii) permit fluid to be forced into the internal locus by a force sufficient to traverse the wettable surface without extending sufficiently beyond the internal locus;

(d) the internal locus is in sufficient proximity to one or more of the electrodes such that activation of the one or more electrodes results in a droplet operation.

2. The droplet actuator of claim 1 wherein the wettable surface is selected so that the fluid has a contact angle with the wettable surface which is less than about 90 degrees.

3. The droplet actuator of claim 1 wherein the wettable surface is selected so that the fluid has a contact angle with the wettable surface which is less than about 50 degrees.

4. The droplet actuator of claim 1 wherein the wettable surface is selected so that the fluid has a contact angle with the wettable surface which is less than about 10 degrees.

5. The droplet actuator of claim 1 wherein the wettable surface is selected so that the fluid has a contact angle with the wettable surface which is approximately 0 degrees.

6. The droplet actuator of claim 1 wherein the wettable surface is uncoated glass surrounded by teflon or cytop coated glass.

7. The droplet actuator of claim 1 comprising the fluid on the wettable path, wherein the fluid is at least partially surrounded by a filler fluid.

8. The droplet actuator of claim 7 wherein the fluid comprises beads.

9. The droplet actuator of claim 7 wherein the fluid comprises biological cells.

10. A method of loading a droplet actuator with a fluid, the method comprising providing a droplet actuator of claim 1, flowing the fluid along the wettable path, and into proximity with one or more of the electrodes.

11. The method of claim 10 further comprising activating one or more of the electrodes to extend the fluid further into the droplet actuator.

12. A droplet actuator comprising a substrate comprising:

(a) one or more electrodes configured for conducting one or more droplet operations on a droplet operations surface of the substrate; and

(b) a wettable surface defining a path from a fluid reservoir into a locus which is sufficiently near to one or more of the electrodes that activation of the one or more electrodes results in a droplet operation.

13. The droplet actuator of claim 12 comprising the fluid on the wettable path, 5 wherein the fluid is at least partially surrounded by a filler fluid.

14. The droplet actuator of claim 13 wherein the fluid comprises beads.

15. The droplet actuator of claim 13 wherein the fluid comprises biological cells.

16. A droplet actuator comprising a substrate comprising:

(a) one or more electrodes configured for conducting one or more droplet operations on a droplet operations surface of the substrate; and

(b) a wettable surface defining a path from a first portion of the substrate into a locus which is sufficiently near to one or more of the electrodes that activation of the one or more electrodes results in a droplet operation.

17. The droplet actuator of claim 16 comprising the fluid on the wettable path, wherein the fluid is at least partially surrounded by a filler fluid.

18. The droplet actuator of claim 17 wherein the fluid comprises beads.

19. The droplet actuator of claim 17 wherein the fluid comprises biological cells.

20. A droplet actuator comprising:

(a) a base substrate and a top plate separated to form a gap, wherein the base substrate comprises;

(i) a hydrophobic surface facing the gap; and

(ii) electrodes arranged to conduct droplet operations in the gap;

(b) a reservoir in the gap or in fluid communication with the gap;

(c) a wettable path;

(i) provided on one or more droplet actuator surfaces; and

(ii) arranged to conduct a fluid from the reservoir to an electrode for conducting one or more droplet operations.

21. The droplet actuator of claim 20 wherein the wettable path is selected to provide a contact angle between an aqueous droplet and a surface of the path, which angle is less than about 90 degrees.

22. The droplet actuator of claim 20 wherein the wettable path is selected to provide a contact angle between an aqueous droplet and a surface of the path, which angle is less than about 50 degrees.

23. The droplet actuator of claim 20 wherein the wettable path is selected to provide a contact angle between an aqueous droplet and a surface of the path, which angle is less than about 30 degrees.

24. The droplet actuator of claim 20 wherein the wettable path is provided on a surface of the top plate facing the gap and extends from the reservoir to a position which overlaps a base substrate electrode.

25. The droplet actuator of claim 20 wherein the wettable path is arranged to conduct fluid from the reservoir to two or more electrodes for conducting droplet operations sufficient to provide multiple droplets in the gap.

26. The droplet actuator of claim 20 wherein the wettable path is arranged at least in part on a surface of the top plate facing the gap.

27. The droplet actuator of claim 20 wherein the wettable path is arranged at least in part on a surface of the bottom plate facing the gap.

28. The droplet actuator of claim 20 wherein the wettable path is arranged at least in part on a surface between the top and bottom substrates.

29. The droplet actuator of claim 20 comprising the fluid on the wettable path, wherein the fluid is at least partially surrounded by a filler fluid.

30. The droplet actuator of claim 29 wherein the fluid comprises beads.

31. The droplet actuator of claim 29 wherein the fluid comprises biological cells.

32. A droplet actuator comprising:

(a) a base substrate and a top plate separated to form a gap, wherein;

(i) the base substrate comprises;

(1) a hydrophobic surface facing the gap; and

(2) electrodes arranged to conduct droplet operations in the gap; and

(ii) an opening provides a fluid path from an exterior of the droplet actuator into the gap, wherein the opening is provided;

(1) in the top plate; and

/or

(2) in the base substrate; and

/or

(3) between the top plate and base substrate; and

(b) a wettable path;

(i) provided on one or more droplet actuator surfaces; and

(ii) arranged to conduct fluid from the opening to an electrode for conducting one or more droplet operations.

33. The droplet actuator of claim 32 wherein the opening is in the top plate and the droplet actuator further comprises a reservoir on the top plate in fluid communication with the opening.

34. The droplet actuator of claim 32 wherein the wettable path is provided on a surface of the top plate facing the gap and extends from the opening to a position which overlaps a base substrate electrode.

35. The droplet actuator of claim 32 wherein the wettable path is arranged to conduct fluid from the opening to two or more electrodes for conducting droplet operations sufficient to provide multiple droplets in the gap.

36. The droplet actuator of claim 32 comprising the fluid on the wettable path, wherein the fluid is at least partially surrounded by a filler fluid.

37. The droplet actuator of claim 36 wherein the fluid comprises beads.

38. The droplet actuator of claim 36 wherein the fluid comprises biological cells.

39. A system comprising the droplet actuator of claim 33 comprising means for monitoring and controlling fluid volume in the reservoir and thereby facilitating production of droplet volumes that are more precise than droplet volumes using the droplet actuator in the absence of such sensing and monitoring.

40. A method of dispensing a droplet from a droplet source, the method comprising:

(a) flowing fluid from the droplet source;

(i) along a wettable path provided on a surface of a droplet actuator; and

(ii) into proximity with a first electrode;

(b) activating the first electrode alone or in combination with one or more additional electrodes to extend fluid into the gap to provide a droplet in the gap.

41. The method of claim 40 further comprising deactivating an intermediate electrode among the first electrode and one or more additional electrodes to provide the droplet in the gap.

42. The method of claim 41 wherein:

(a) the activating step comprises activating;

(i) the first electrode; and

(ii) a second electrode adjacent to the first electrode; and

(b) the deactivating step comprises deactivating the first electrode.

43. The method of claim 41 wherein:

(a) the activating step comprises activating;

(i) the first electrode;

(ii) a second electrode adjacent to the first electrode; and

(iii) a third electrode adjacent to the second electrode; and

(b) the deactivating step comprises deactivating the second electrode.

44. The method of claim 41 further comprising:

(a) transporting droplets produced in the deactivating step to a reservoir in the gap; and

(b) dispensing a droplet from the second reservoir;

(c) transporting a droplet produced in the deactivating step to the reservoir to substantially replace the dispensed droplet;

(d) repeating step (b).

45. The method of claim 40 wherein the fluid comprises beads.

46. The method of claim 40 wherein the fluid comprises biological cells.