Fluid delivery system and method

• US 8,030,057 B2
• Filed: 01/26/2005
• Issued: 10/04/2011
• Est. Priority Date: 01/26/2004
• Status: Active Grant

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Linder, Vincent, Whitesides, George M., Sia, Samuel K.
• Primary Examiner(s): YANG, NELSON C
• Application Number:
  US10/587,156
• Publication Number:
  US 20080038839A1
• Time in Patent Office: 2,442 Days
• Field of Search: None
• US Class Current: 435/286.4
• CPC Class Codes: B01L 2200/0673 Handling of plugs of fluid surrounded by immiscible fluid
• CPC Class Codes: B01L 2200/16 Reagents, handling or storing thereof
• CPC Class Codes: B01L 2300/0816 Cards, e.g. flat sample carriers usually with flow in two horizontal directions
• CPC Class Codes: B01L 2300/0877 Flow chambers
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/0293 for liquids
• CPC Class Codes: B01L 3/50273 characterised by the means or forces applied to move the fluids micropumps F04B19/006, of the membrane type F04B43/043
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: B01L 3/502784 specially adapted for droplet or plug flow, e.g. digital microfluidics automatic analysis using a stream of discrete samples in a tube system G01N35/08
• CPC Class Codes: G01N 21/11 Filling or emptying of cuvettes
• CPC Class Codes: G01N 33/54366 Apparatus specially adapted for solid-phase testing
• CPC Class Codes: G01N 33/54386 Analytical elements
• CPC Class Codes: G01N 33/54388 based on lateral flow
• CPC Class Codes: G01N 33/553 Metal or metal coated
• CPC Class Codes: G01N 35/08 using a stream of discrete samples flowing along a tube system, e.g. flow injection analysis
• CPC Class Codes: G01N 35/1002 Reagent dispensers
• CPC Class Codes: Y10T 436/25 including sample preparation

Abstract

Method and device for storing and/or delivering fluids, wherein at least a first and a second fluid, such as chemical or biochemical reagents or rinse solutions, are maintained separately from each other in a common vessel and transferred in series from the vessel to a reaction site to carry out a predetermined chemical or biochemical reaction. Separation may be achieved by interposing a third fluid, e.g., a gaseous fluid plug, between the first and second fluids.

Claims

1. A method comprising:

providing a first and a second fluid maintained separately from each other by a third fluid in a common, sealed vessel, wherein the third fluid is adjacent to and substantially immiscible with the first and second fluids, and wherein the first, second and third fluids are stored within the common, sealed vessel for at least one day;

unsealing the vessel;

transferring the first, third, and second fluids in series from the vessel to a reaction site to carry out a predetermined chemical or biochemical reaction; and

avoiding substantial contact between the first and second fluids, at least until after the fluids have been applied to the reaction site.

2. The method of claim 1 further comprising connecting the vessel to a device comprising the reaction site.

3. The method of claim 1 wherein the vessel and reaction site are on a common platform.

4. The method of claim 1 wherein the vessel and reaction site are integrally connected during storage of the first, second and third fluids in the vessel.

5. The method of claim 1 wherein the vessel comprises a tube.

6. The method of claim 1 further comprising applying a pressure differential across the reaction site.

7. The method of claim 6 wherein the pressure differential is provided by suction on a downstream side of the reaction site.

8. The method of claim 6 wherein the pressure differential is provided by a pump on an upstream side of the reaction site.

9. The method of claim 1 wherein the first and second fluids are transferred in series to the reaction site without actuating a valve.

10. The method of claim 1 wherein the first and second fluids are transferred in series to the reaction site without actuation of any device that controls the rate, the order, or timing of introduction of either of the first and second fluids, relative to each other, to the reaction site.

11. The method of claim 2 wherein the device is a microfluidic device.

12. The method of claim 1 wherein at least one of an antibody or an antigen is associated with the reaction site.

13. The method of claim 1 wherein the third fluid is a gas or a gaseous mixture.

14. The method of claim 1 wherein the second fluid is a rinse solution.

15. The method of claim 2 further comprising disposing a sample in the device prior to applying the first and second fluids to the reaction site.

16. The method of claim 1 wherein the vessel contains a fourth fluid, the method further comprising combining the fourth fluid and the second fluid while transferring the first, third, and second fluids from the vessel to the reaction site.

17. The method of claim 1 wherein the vessel has a length to inner diameter ratio of at least 10:

1.

18. The method of claim 1 wherein the vessel has an inner diameter of less than 1 millimeter.

19. The method of claim 1 wherein the vessel has an inner diameter of less than 500 microns.

20. The method of claim 1 wherein one of the fluids comprises a gold conjugated antibody.

21. The method of claim 1 wherein one of the fluids comprises a metal precursor.

22. The method of claim 21 further comprising electrolessly depositing metal at the reaction site to produce an opaque material.

23. The method of claim 22 further comprising determining light absorbance or transmission through the opaque material.

26. The method of claim 3 wherein the vessel and reaction site are formed on a microfluidic chip.

27. The method of claim 1 wherein the vessel comprises at least first and second branches that are in fluid communication with each other and with the remaining interior of the vessel.

28. The method of claim 27 wherein the first branch contains a fourth fluid and the second branch contains a fifth fluid, the fourth and fifth fluids adapted and arranged to react with one another to form a sixth fluid.

29. The method of claim 1, further comprising passing a sample across the reaction site prior to initiation of the transferring step.

30. The method of claim 2, further comprising introducing a sample into the device from a vessel different from the vessel containing the first, third and second fluids.

24. A method comprising:

providing a reaction site;

providing a first and a second fluid statically maintained separately from each other by a third fluid adjacent to and substantially immiscible with the first and second fluids in a common, sealed vessel for greater than one minute, wherein the vessel and the reaction site are formed in a microfluidic chip;

unsealing the vessel;

applying in series the first, third, and second fluids to the reaction site; and

avoiding substantial contact between the first and second fluids, at least until after the fluids have been applied to the reaction site.

25. The method of claim 24 wherein the first and second fluids are statically maintained for greater than one day.

32. The method of claim 24, comprising applying a pressure differential across the reaction site, wherein the pressure differential is provided by suction on a downstream side of the reaction site.

33. The method of claim 24 wherein at least one of an antibody or an antigen is associated with the reaction site.

34. The method of claim 24 wherein the third fluid is a gas or a gaseous mixture.

35. The method of claim 24 wherein the second fluid is a rinse solution.

36. The method of claim 24 further comprising disposing a sample in the microfluidic chip prior to applying the first and second fluids to the reaction site.

37. The method of claim 24 wherein the vessel contains a fourth fluid, the method further comprising combining the fourth fluid and the second fluid while transferring the first, third, and second fluids from the vessel to the reaction site.

38. The method of claim 24 wherein the vessel has a length to inner diameter ratio of at least 10:

1.

39. The method of claim 24 wherein the vessel comprises at least first and second branches that are in fluid communication with each other and with the remaining interior of the vessel.

40. The method of claim 39 wherein the first branch contains a fourth fluid and the second branch contains a fifth fluid, the fourth and fifth fluids adapted and arranged to react with one another to form a sixth fluid.

41. The method of claim 24 wherein the vessel has an inner diameter of less than 1 millimeter.

42. The method of claim 24 wherein the vessel has an inner diameter of less than 500 microns.

31. A method comprising:

providing a reaction site;

providing a first and a second fluid statically maintained separately from each other by a third fluid adjacent to and substantially immiscible with the first and second fluids in a common, sealed vessel for greater than one minute, wherein the vessel and the reaction site are integrally connected to one another;

unsealing the vessel;

applying in series the first, third, and second fluids to the reaction site; and

avoiding substantial contact between the first and second fluids, at least until after the fluids have been applied to the reaction site.

43. The method of claim 31, comprising applying a pressure differential across the reaction site, wherein the pressure differential is provided by suction on a downstream side of the reaction site.

44. The method of claim 31 wherein at least one of an antibody or an antigen is associated with the reaction site.

45. The method of claim 31 wherein the third fluid is a gas or a gaseous mixture.

46. The method of claim 31 wherein the second fluid is a rinse solution.

47. The method of claim 31 wherein the vessel and the reaction site are a part of a device, the method comprising disposing a sample in the device prior to applying the first and second fluids to the reaction site.

48. The method of claim 31 wherein the vessel contains a fourth fluid, the method further comprising combining the fourth fluid and the second fluid while transferring the first, third, and second fluids from the vessel to the reaction site.

49. The method of claim 31 wherein the vessel has a length to inner diameter ratio of at least 10:

1.

50. The method of claim 31 wherein the vessel comprises at least first and second branches that are in fluid communication with each other and with the remaining interior of the vessel.

51. The method of claim 50 wherein the first branch contains a fourth fluid and the second branch contains a fifth fluid, the fourth and fifth fluids adapted and arranged to react with one another to form a sixth fluid.

52. The method of claim 31 wherein the vessel has an inner diameter of less than 1 millimeter.

53. The method of claim 31 wherein the vessel has an inner diameter of less than 500 microns.

54. The method of claim 31 wherein the first and second fluids are statically maintained for greater than one day.