REUSABLE DETECTION SURFACES AND METHODS OF USING SAME

• US 20090068759A1
• Filed: 09/05/2008
• Published: 03/12/2009
• Est. Priority Date: 09/06/2007
• Status: Active Grant

• Current Assignee: ProterixBio, Inc.
• Original Assignee: BioScale, Inc.
• Inventors: Madison, Lara Louise, Arenas, Jamie E., Choi, Hyun-Goo, Dickerson, William Matthew, Hembree, Sarah Beth, Miller, Michael F., Masters, Brett P., Wang, Wayne U.
• Granted Patent: US 8,354,280 B2
• Time in Patent Office: Days
• US Class Current: 436/518
• CPC Class Codes: B01L 13/02 for receptacle or instruments
• CPC Class Codes: B01L 9/52 Supports specially adapted for flat sample carriers, e.g. for plates, slides, chips
• CPC Class Codes: G01N 2291/014 Resonance or resonant frequency
• CPC Class Codes: G01N 2291/0255 (Bio)chemical reactions, e.g. on biosensors
• CPC Class Codes: G01N 2291/0256 Adsorption, desorption, surface mass change, e.g. on biosensors
• CPC Class Codes: G01N 2291/02809 Concentration of a compound, e.g. measured by a surface mass change
• CPC Class Codes: G01N 2291/02836 Flow rate, liquid level
• CPC Class Codes: G01N 2291/0427 Flexural waves, plate waves, e.g. Lamb waves, tuning fork, cantilever
• CPC Class Codes: G01N 29/022 Fluid sensors based on microsensors, e.g. quartz crystal-microbalance [QCM], surface acoustic wave [SAW] devices, tuning forks, cantilevers, flexural plate wave [FPW] devices microdevices per se B81B
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings

Abstract

The technology provided herein generally relates to reusable detection surfaces and methods for reusing a detection surface after using the detection surface in an assay for an analyte.

Claims

1. A method of reusing a detection surface wherein the detection surface comprises an acoustic device having a vibrating membrane and a first capture agent, wherein the first capture agent is capable of binding an analyte, and wherein the first capture agent is linked to the detection surface such that an analyte bound to the first capture agent can be removed such that the first capture agent remains linked to the detection surface, the method comprising

a) using the detection surface to detect one or more analytes,

a) exposing the detection surface to at least one solution;

b) generating one or more flow transients over the detection surface in succession;

c) optionally exposing the detection surface to a chemical wash, and

d) reusing the detection surface to detect one or more analytes.

2. The method of claim 1, wherein the at least one solution comprises a salt solution.

3. The method of claim 2, wherein the salt solution comprises phosphate buffered saline.

4. The method of claim 1, wherein the chemical wash is acidic.

5. The method of claim 4, wherein the chemical wash comprises phosphoric acid.

6. The method of claim 1, wherein the detection surface is exposed to the chemical wash.

7. The method of claim 1, wherein a flow transient is generated comprising restricting flow of a solution upstream of the detection surface while pumping flow of solution downstream of the detection surface and then removing the restriction after a first period of time.

8. The method of claim 1, wherein the first capture agent has a lower binding affinity for the analyte than an affinity of the capture agent for the analyte.

9. The method of claim 1, wherein the first capture agent is an antibody or antigen binding portion thereof.

10. A method of reusing a detection surface wherein the detection surface comprises an acoustic device having a vibrating membrane and a first capture agent, wherein the first capture agent is capable of binding an analyte, and wherein the first capture agent is linked to the detection surface such that an analyte bound to the first capture agent can be removed such that the first capture agent remains linked to the detection surface, the method comprising instructing a user to after using the detection surface to detect one or more analytes,

a) expose the detection surface to at least one solution;

b) generate one or more flow transients over the detection surface in succession;

c) optionally expose the detection surface to a chemical wash, and

d) reuse the detection surface to detect one or more analytes.

11. A method for detecting one or more analytes in a sample comprising,

a) introducing a sample and a plurality of magnetic particles into a fluid chamber, the fluid chamber comprising a detection surface, wherein the detection surface comprises an acoustic device having a vibrating membrane and a first capture agent, wherein the first capture agent is capable of binding an analyte, and wherein the first capture agent is linked to the detection surface such that an analyte bound to the first capture agent can be removed such that the first capture agent remains linked to the detection surface, and wherein the magnetic particles are coated with a second capture agent capable of binding an analyte;

b) monitoring a first signal output by the detection surface;

c) generating one or more flow transients over the detection surface in succession;

d) optionally exposing the detection surface to a chemical wash; and

e) conducting a further round of detection comprising repeating steps a) and b) at least one time.

12. The method of claim 11, wherein the signal output of a first step b) is suitable to detect a first concentration of a first analyte and the signal output of a second step b) is suitable to detect a second concentration of a second analyte concentration and wherein the second concentration of the second analyte is at least 50% of the first concentration of the first analyte.

13. The method of claim 11, wherein the detection surface is exposed to the chemical wash.

14. The method of claim 13, wherein the chemical wash is acidic.

15. The method of claim 14, wherein the chemical wash comprises phosphoric acid.

16. The method of claim 11, wherein steps a)-b) are repeated at least one time.

17. The method of claim 11, wherein the first capture agent has a lower binding affinity for the analyte than the second capture agent.

18. The method of claim 11, wherein steps a)-d) are repeated at least twelve times.

19. The method of claim 11, wherein the flow transient is generated comprising restricting flow of a solution upstream of the detection surface while pumping flow of solution downstream of the detection surface and then removing the restriction after a first period of time.

20. The method of claim 11, wherein the affinity of the second capture agent for the analyte is greater than 2×

10⁹ M<sup>−

1</sup>.

21. The method of claim 11, wherein the affinity of the second capture agent for the analyte is greater than about 2 times the affinity of the first capture agent for the analyte.

22. The method of claim 11, wherein the sample comprises an unknown quantity of one or more analytes.

23. The method of claim 11, wherein the sample comprises a known quantity of one or more analytes.

24. The method of claim 11, wherein the second capture agent is an antibody or antigen binding fragment thereof.

25. A kit for detecting an analyte, comprising:

a cartridge comprising a fluid chamber, the fluid chamber comprising a detection surface, wherein the detection surface comprises an acoustic device having a vibrating membrane and a first capture agent, wherein the first capture agent is capable of binding a analyte, and wherein the first capture agent is linked to the detection surface such that a analyte bound to the first capture agent can be removed such that the first capture agent remains linked to the detection surface; and

reagents for detecting the analyte, comprising a plurality of magnetic particles coated with a second capture agent, wherein the second capture agent is capable of binding the analyte, and wherein the second capture agent has a higher binding affinity for the analyte than the first capture agent.

26. The kit of claim 25, wherein the affinity of the second capture agent for the analyte is greater than 2×

10⁹ M<sup>−

1</sup>.

27. The kit of claim 25, wherein the affinity of the second capture agent for the analyte is greater than about 2 times the affinity of the first capture agent.

28. The kit of claim 25, wherein the second capture agent is a first member of a binding pair.

29. The kit of claim 25 wherein the first member of the binding pair is capable of binding biotin, and wherein the reagents for detecting the analyte comprise an antibody or antigen binding fragment, wherein the antibody or antigen binding fragment is capable of binding the analyte and wherein the antibody or antigen binding fragment is coupled to biotin.

30. A method of reusing a detection surface wherein the detection surface comprises an acoustic device having a vibrating membrane and a first capture agent, wherein the first capture agent is capable of binding a non-analyte tag molecule, and wherein the first capture agent is linked to the detection surface such that a tag molecule bound to the first capture agent can be removed such that the first capture agent remains linked to the detection surface, the method comprising

a) using the detection surface to detect one or more analytes,

b) exposing the detection surface to at least one solution;

c) optionally generating one or more flow transients over the detection surface in succession, and

d) reusing the detection surface to detect one or more analytes.

31. The method of claim 30, wherein the at least one solution comprises a salt solution.

32. The method of claim 31, wherein the salt solution comprises phosphate buffered saline.

33. The method of claim 30, wherein the at least one solution is a chemical wash.

35. The method of claim 33, wherein the chemical wash is acidic.

36. The method of claim 35, wherein the chemical wash comprises phosphoric acid.

37. The method of claim 30, wherein one or more flow transients are generated.

39. The method of claim 37, wherein a flow transient is generated comprising restricting flow of a solution upstream of the detection surface while pumping flow of solution downstream of the detection surface and then removing the restriction after a first period of time.

40. The method of claim 30, wherein the tag molecule is a hapten.

41. The method of claim 40, wherein the hapten is fluorescein.

42. The method of claim 30, wherein the first capture agent has a lower binding affinity for the non-analyte tag molecule than the second capture agent has for the analyte.

43. A method of reusing a detection surface wherein the detection surface comprises an acoustic device having a vibrating membrane and a first capture agent, wherein the first capture agent is capable of binding a first non-analyte tag molecule, and wherein the first capture agent is linked to the detection surface such that a tag molecule bound to the first capture agent can be removed such that the first capture agent remains linked to the detection surface, the method comprising instructing a user to after using the detection surface to detect one or more analytes,

a) expose the detection surface to at least one solution;

b) optionally generate one or more flow transients over the detection surface in succession, and

c) reuse the detection surface to detect one or more analytes.

44. A method for detecting one or more analytes in a sample comprising,

a) introducing a sample and a plurality of magnetic particles into a fluid chamber, wherein the detection surface comprises an acoustic device having a vibrating membrane and a first capture agent, wherein the first capture agent is capable of binding a first non-analyte tag molecule, and wherein the first capture agent is linked to the detection surface such that a tag molecule bound to the first capture agent can be removed such that the first capture agent remains linked to the detection surface, and wherein the magnetic particles are coated with a second capture agent capable of binding an analyte, the method comprising;

b) monitoring a first signal output by the detection surface;

c) exposing the detection surface to at least one solution;

d) optionally generating one or more flow transients over the detection surface in succession; and

e) repeating steps a) and b) at least one time.

45. The method of claim 44, wherein the signal output of the first step b) is suitable to detect a first concentration of a first analyte and the signal output of the second step b) is suitable to detect a second concentration of a second analyte concentration and wherein the second concentration of the second analyte is at least 50% of the first concentration of the first analyte.

46. The method of claim 44, wherein steps a)-b) are repeated at least one time.

47. The method of claim 44, wherein the signal output of the first step b) is suitable to detect a first concentration of a first analyte and the signal output of a last repeat of step b) is suitable to detect a last concentration of a last analyte and wherein the last concentration of the last analyte is at least 50% of the first concentration of the first analyte.

48. The method of claim 44, wherein steps a)-c) are repeated at least twelve times.

49. The method of claim 44, wherein the flow transient is generated.

50. The method of claim 49, wherein the flow transient is generated comprising restricting flow of a solution upstream of the detection surface while pumping flow of the solution downstream of the detection surface and then removing the restriction after a first period of time.

51. The method of claim 44, wherein the solution comprises a salt solution.

52. The method of claim 51, wherein the solution comprises phosphate buffered saline.

53. The method of claim 44, wherein the at least one solution is a chemical wash.

54. The method of claim 53, wherein the chemical wash is acidic.

55. The method of claim 54, wherein the chemical wash comprises phosphoric acid.

56. The method of claim 44, wherein the first capture agent has a lower binding affinity for the non-analyte tag molecule than the second capture agent has for the analyte.

57. A reusable cartridge, comprising

a fluid chamber having at least one detection surface wherein the detection surface comprises an acoustic device having a vibrating membrane and a first capture agent, wherein the first capture agent is capable of binding a first non-analyte tag molecule, and wherein the first capture agent is linked to the detection surface such that a tag molecule bound to the first capture agent can be removed such that the first capture agent remains linked to the detection surface.

58. The cartridge of claim 57, wherein the detection surface is coated with a self-assembling matrix (SAM) and wherein the first capture agent is linked to the SAM.

59. The cartridge of claim 57, wherein the detection surface is coated with a carboxymethyl dextran (CMD) layer and wherein the first capture agent is linked to the CMD layer.

60. The cartridge of claim 57, wherein the tag molecule is a hapten.

61. The cartridge of claim 60, wherein the hapten is fluorescein.

62. The cartridge of claim 57, wherein the first capture agent is linked to the detection surface such that a tag molecule bound to the first capture agent can be removed such that at least 98% of the first capture agent remains linked to the detection surface.

63. A kit for detecting an analyte, comprising:

a fluid chamber having at least one detection surface wherein the detection surface comprises an acoustic device having a vibrating membrane and a first capture agent, wherein the first capture agent is capable of binding a non-analyte tag molecule, and wherein the first capture agent is linked to the detection surface such that a tag molecule bound to the first capture agent can be removed such that the first capture agent remains linked to the detection surface, and

reagents for detecting the analyte comprising either a detection antibody or antigen binding portion thereof, wherein the detection antibody or antigen binding portion is capable of binding the analyte and wherein the detection antibody or antigen binding portion is coupled to the first tag molecule, or a plurality of magnetic particles coated with a second capture agent.

64. The kit of claim 63, wherein the reagents for detecting the analyte comprise both the detection antibody or antigen binding portion thereof, wherein the detection antibody or antigen binding portion thereof is capable of binding the analyte and wherein the detection antibody or antigen binding portion thereof is coupled to the first tag molecule, and a plurality of magnetic particles coated with a second capture agent.

65. The kit of claim 63, wherein the kit comprises a plurality of beads coated with a second capture agent and wherein the second capture agent is a first member of a binding pair.

66. The kit of claim 65, wherein the first member of the binding pair is capable of binding biotin, and wherein the reagents for detecting the analyte comprise a second antibody or antigen binding portion thereof, wherein the second antibody or antigen binding portion thereof is capable of binding the analyte and wherein the second antibody or antigen binding portion thereof is coupled to biotin.

67. The kit of claim 63, wherein the kit comprises a plurality of magnetic particles coated with a second capture agent and wherein the second capture agent is capable of binding the analyte.

68. The kit of claim 67, wherein the second capture agent is an antibody or antigen binding portion thereof.