Biochips including ion transport detecting structures and methods of use

• US 20050266478A1
• Filed: 06/15/2005
• Published: 12/01/2005
• Est. Priority Date: 01/24/2002
• Status: Active Grant

• Current Assignee: AVIVA Biosciences Corporation
• Original Assignee: AVIVA Biosciences Corporation
• Inventors: Wang, Xiaobo, Wu, Lei, Xu, Jia, Guia, Antonio, Huang, Mingxian, Rothwarf, David
• Granted Patent: US 7,723,029 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01L 2200/027 for microfluidic devices
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0627 Sensor or part of a sensor is integrated
• CPC Class Codes: B01L 2300/0645 Electrodes
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 2300/089 Virtual walls for guiding liquids
• CPC Class Codes: B01L 2400/0415 electrical forces, e.g. electrokinetic
• CPC Class Codes: B01L 2400/0418 electro-osmotic flow [EOF]
• CPC Class Codes: B01L 2400/0421 electrophoretic flow
• CPC Class Codes: B01L 2400/043 magnetic forces
• CPC Class Codes: B01L 2400/0436 acoustic forces, e.g. surface acoustic waves [SAW]
• CPC Class Codes: B01L 2400/0457 passive flow or gravitation
• CPC Class Codes: B01L 2400/049 vacuum
• 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 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/502792 for moving individual droplets on a plate, e.g. by locally altering surface tension
• CPC Class Codes: B01L 3/5088 confining liquids at a location by surface tension, e.g. virtual wells on plates, wires B01L3/50857 takes precedence
• CPC Class Codes: G01N 33/48728 Investigating individual cells, e.g. by patch clamp, voltage clamp investigating individual particles in general G01N15/10

Abstract

The present invention recognizes that the determination of an ion transport function or property using direct detection methods, such as patch-clamps, whole cell recording or single channel recording, are preferable to methods that utilize indirect detection methods, such as FRET based detection system. The present invention provides biochips and methods of use that allow for the direct analysis of ion transport functions or properties using microfabricated structures that can allow for automated detection of one or more ion transport functions or properties. These biochips and methods of use thereof are particularly appropriate for automating the detection of ion transport functions or properties, particularly for screening purposes.

Claims

1. A biochip, comprising:

an array of capillaries, wherein one or more members of said array of capillaries are capable of engaging a particle with a high resistance electrical seal.

2. The biochip of claim 1, wherein members of said array of capillaries further comprise recording electrodes.

3. A device for detecting ion transport activity of one or more particles, comprising:

an array of fluidic compartments separated by a biochip of claim 2 and connected by the array of capillaries on the biochip of claim 2, wherein each fluidic compartment of said array of fluidic compartments comprises at least one fluidic inlet.

4. A method of detecting ion transport activity of one or more particles, comprising:

a) contacting a sample comprising at least one particle with the device of claim 1

b) positioning said at least one particle at or near at least one capillary of said array of capillaries; and

c) measuring ion transport activity of said at least one particle using said at least one capillary.

5. The method of claim 4, wherein said at least one particle is at least one cell.

31. The method of claim 1, further comprising contacting said ion transport measuring means with an environment having decreased oxygen or carbon dioxide relative to the ambient environment.

32. The method of claim 31, wherein said environment is water or a salt solution.

33. An ion transport measuring means modified by the method of claim 1.

60. A method of measuring ion transport activity of a particle, comprising:

a) contacting a sample comprising at least one particle with the ion transport measuring means of claim 1;

b) engaging said at least one particle at said at least one ion transport measuring means; and

c) measuring ion transport activity of said at least one particle.

62. A method of storing an ion transport measuring means capable of forming a high resistance electrical seal with a particle or membrane, comprising:

a) providing the ion transport measuring means of claim 1;

and

b) storing said ion transport measuring means in an environment having decreased oxygen or carbon dioxide relative to the ambient environment;

wherein the capability of said ion transport measuring means to form a high resistance electrical seal between with a particle or membrane is maintained.

63. The method of claim 62, wherein said environment having decreased oxygen or carbon dioxide is deionized water or a salt solution.

64. A method of shipping or transporting an ion transport measuring means capable of forming a high resistance electrical seal with a particle or membrane, comprising:

providing the ion transport measuring means of claim 1;

shipping or transporting said ion transport measuring means in an environment with decreased oxygen or carbon dioxide relative to the ambient environment;

wherein the capability of said ion transport measuring means to form a high resistance electrical seal between with a particle or membrane is maintained.

65. The method of claim 64, wherein said environment having decreased oxygen or carbon dioxide is deionized water or a salt solution.

6. A method of modifying an ion transport measuring means to enhance the electrical seal of the ion transport measuring means with one or more particles or membranes, comprising:

a) providing an ion transport measuring means;

b) modifying at least a portion of said ion transport measuring means to have appropriate electric charge, hydrophilicity or hydrophobicity, texture, or composition to enhance sealing between said ion transport measuring means and said one or more membranes or particles.

7. The method of claim 6, wherein said one or more ion transport measuring means comprises one or more holes, apertures, or capillaries.

8. The method of claim 6, wherein said ion transport measuring means comprises glass, silicon, silicon dioxide, quartz, one or more plastics, one or more polymers, one or more ceramics, or polydimethylsiloxane (PDMS), or a combination thereof.

9. The method of claim 8, wherein said modifying comprises treatment with a salt solution.

10. The method of claim 8, wherein said modifying comprises treatment with oxygen plasma, treatment with reactive compounds, radiation, baking, fire polishing, flame annealing, laser polishing, or combinations thereof.

11. The method of claim 10, wherein said modifying comprises baking, fire polishing, or laser polishing.

12. The method of claim 11, wherein said modifying comprises laser polishing.

13. The method of claim 8, wherein said modifying comprises treatment with acid, treatment with base, or both.

14. The method of claim 13, wherein said modifying comprises treatment with base.

15. The method of claim 14, wherein said base is selected from group consisting of NaOH, KOH, LiOH, CsOH, NaOH, Ba(OH)₂, Ca(OH)₂, and NH₄(OH).

16. The method of claim 14, wherein the base is of concentration is about 0.1 M or greater.

17. The method of claim 14, further comprising contacting said ion transport measuring means with a salt solution.

18. The method of claim 14, further comprising treating said ion transport measuring means with oxygen plasma, reactive compounds, radiation, or baking, fire polishing, flame annealing, or laser polishing said ion transport measuring means.

19. The method of claim 18, wherein said further comprising comprises baking, fire polishing, or laser polishing said ion transport measuring means.

20. The method of claim 19, wherein said further comprising comprises laser polishing said ion transport measuring means.

21. The method of claim 14, further comprising treating said ion transport measuring means with acid.

22. The method of claim 21, further comprising baking, fire polishing, or laser polishing said ion transport measuring means.

23. The method of claim 21, further comprising laser polishing said ion transport measuring means.

24. The method of claim 13, wherein said modifying comprises treatment with acid.

25. The method of claim 24, wherein said acid is selected from the group consisting of HCl, HF, HBr, HCOOH, HClO₃, H₂SO₄, NaHSO₄, H₂SO₄, or HNO₃.

26. The method of claim 24, wherein said acid is of a solution having a concentration of greater than about 1M.

27. The method of claim 24, further comprising contacting said ion transport measuring means with a salt solution.

28. The method of claim 24, further comprising treating said ion transport measuring means with oxygen plasma, reactive compounds, radiation, or baking, fire polishing, flame annealing, or laser polishing said ion transport measuring means.

29. The method of claim 24, wherein said further comprising comprises baking, fire polishing, or laser polishing said ion transport measuring means.

30. The method of claim 29, wherein said further comprising comprises laser polishing said ion transport measuring means.

34. An ion transport measuring means modified by the method of claim 14.

35. An ion transport measuring means modified by the method of claim 23.

36. A biochip, comprising:

one or more holes that extends through said biochip,

wherein when said biochip is in contact with a measurement solution said holes have negatively charged surfaces and are capable of engaging particles or membranes with high resistance electric seals.

37. The biochip of claim 36, wherein said surfaces of said one or more holes possess surface charge density approximately that or substantially equivalent to that of a capillary that has an electro-osmotic mobility between about 10⁻

6 cm²/(V sec) and about 10<sup>−

4</sup> cm²/(V sec) in an aqueous solution that has an ionic concentration equivalent to that of a one in ten dilution of PBS in water, and a pH between about 7 and about 8.

38. The biochip of claim 36, wherein said surfaces of said one or more holes possess surface charge density approximately that or substantially equivalent to that of a capillary that has an electro-osmotic mobility between about 10⁻

4 cm²/(V sec) and about 3×

10<sup>−

4</sup> cm²/(V sec) in an aqueous solution that has an ionic concentration equivalent to that of a one in ten dilution of PBS in water, and a pH between about 7 and about 8.

39. The biochip of claim 36, wherein said surfaces of said one or more holes possess surface charge density approximately that or substantially equivalent to that of a capillary that has an electroosmotic mobility between about 3×

10<sup>−

4</sup> cm²/(V sec) and about 6×

10<sup>−

4</sup> cm²/(V sec) in an aqueous solution that has an ionic concentration equivalent to that of a one in ten dilution of PBS in water, and a pH between about 7 and about 8.

40. The biochip of claim 36, wherein said surfaces of said one or more holes possess surface charge density approximately that or substantially equivalent to that of a capillary that has an electroosmotic mobility higher than 6×

10<sup>−

4</sup> cm²/(V sec) in an aqueous solution that has an ionic concentration equivalent to that of a one in ten dilution of PBS in water, and a pH between about 7 and about 8.

41. The biochip of claim 36, wherein said biochip comprises one or more materials selected from the group consisting of glass, quartz, silicon dioxide, silicon, plastics, polymers, polydimethylsiloxane (PDMS), oxygen plasma treated PDMS, and combinations thereof.

42. The biochip of claim 41, wherein the surface of said biochip comprises at least one SiOM group, where M is H or a metal, or at least one ionized SiOM group (SiO⁻

).

43. The biochip of claim 42, wherein the surface density of said SiOM groups and ionized SOM groups is more than about 1%

44. The biochip of claim 41, wherein said biochip comprises a polymer that comprises at least one negatively charged chemical group.

45. The biochip of claim 44, wherein said biochip is coated with a polymer material that comprises at least one negatively charged chemical group.

46. The biochip of claim 41, wherein the surface of said biochip comprises at least one chemical group selected from sulfate, phosphate, and carboxyl groups.

47. The biochip of claim 36, wherein said one or more holes is fabricated using laser ablation, laser drilling, or both.

48. The biochip of claim 36, wherein said biochip has been treated with oxygen plasma, reactive compounds, or radiation, or has been baked, fire polished, flame annealed, or laser polished.

49. The biochip of claim 48, wherein the front side surface of said biochip surrounding said at least one hole has been polished using a laser.

50. The biochip of claim 48, wherein said biochip has been baked.

51. The biochip of claim 36, wherein said one or more holes of said biochip have been treated with acid, treated with base, or treated with acid and with base.

52. The method of claim 51, wherein said one or more holes of said biochip have been treated with base.

53. The method of claim 52, wherein said base is selected from group consisting of NaOH, KOH, LiOH, CsOH, NaOH, Ba(OH)₂, Ca(OH)₂, and NH₄(OH).

54. The method of claim 52, wherein the base is a solution of a concentration of about 0.1 M or greater.

55. The biochip of claim 52, wherein said biochip has been further treated with acid.

56. The method of claim 55, wherein said acid is selected from the group consisting of HCl, HF, HBr, HCOOH, HClO₃, H₂SO₄, NaHSO₄, H₂SO₄, or HNO₃.

57. The method of claim 55, wherein said acid is of a solution having a concentration of greater than about 1M.

58. The biochip of claim 36, wherein said one or more holes is an array of holes.

59. The biochip of claim 58, wherein the size of said holes is between 0.5 micron and 5 microns.

61. A method of measuring ion transport activity of a particle, comprising:

a) contacting a sample comprising at least one particle with the biochip of claim 36;

b) engaging said at least one particle at said one or more holes; and

c) measuring ion transport activity of said at least one particle.