Target analyte detection using asymmetrical self-assembled monolayers

• US 20020121314A1
• Filed: 05/01/2001
• Published: 09/05/2002
• Est. Priority Date: 05/01/2000
• Status: Active Grant

• Current Assignee: Roche Molecular Systems (Roche Holding AG)
• Original Assignee: Clinical Micro Sensors Incorporated
• Inventors: Tao, Chunlin, Yu, Changjun
• Granted Patent: US 6,753,143 B2
• Time in Patent Office: Days
• US Class Current: 148/251
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: B82Y 40/00 Manufacture or treatment of nanostructures
• CPC Class Codes: B82Y 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: G01N 2610/00 Assays involving self-assembled monolayers [SAMs]
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: G01N 33/553 Metal or metal coated

Abstract

The present invention relates to the use asymmetric monolayer forming species and electroconduit forming species to detect target analytes.

Claims

1. A composition comprising a metallic surface and an asymmetric monolayer forming species having the formula:

2. A composition according to claim 1 wherein A is sulfur.

3. A composition according to claim 1 wherein said metallic surface is gold.

4. A composition according to claim 1 wherein said MFS is an insulator.

5. A composition according to claim 4 wherein said insulator comprises an alkyl group from about 7 to 20 carbons.

6. A composition according to claim 5 wherein said alkyl group comprises a heteroalkyl.

7. A composition according to claim 5 wherein said alkyl group comprises a substituted alkyl.

8. A composition according to claim 1 wherein said AG comprises an alkyl group from about 1 to 6 carbons.

9. A composition according to claim 1 or 8 wherein said AG is branched, having the formula:

10. A composition according to claim 9 wherein said AG is attached to said attachment linker via a (CH₂)_n group, wherein n is an integer from 0 to 4.

11. A composition according to claim 9 wherein said AG is attached directly to said attachment linker.

13. A method according to claim 12 further comprising contacting said metallic surface with a biological species having the formula:

A-MFS-capture binding ligand

wherein

A is an attachment linker; and

MFS is a monolayer forming species.

14. A method according to claim 13 wherein said capture binding ligand is a nucleic acid.

15. A method according to claim 13 wherein said capture binding ligand is a n protein.

16. A method according to claim 12 wherein A is sulfur.

17. A method according to claim 12 wherein said metallic surface is gold.

18. A method according to claim 12 wherein said MFS is an insulator.

19. A method according to claim 18 wherein said insulator comprises an alkyl group from about 7 to 20 carbons.

20. A method according to claim 19 wherein said alkyl group comprises a heteroalkyl.

21. A method according to claim 19 wherein said alkyl group comprises a substituted alkyl.

22. A method according to claim 12 wherein said AG comprises an alkyl group from about 1 to 6 carbons.

23. A method according to claim 12 or 22 wherein said AG is branched, having the formula:

24. A method according to claim 23 wherein said AG is attached to said attachment linker via a (CH₂)_n group, wherein n is an integer from 0 to 4.

25. A method according to claim 23 wherein said AG is attached directly to said attachment linker.

27. A method according to claim 26 wherein said recruitment linker is directly attached to said target analyte.

28. A method according to claim 26 wherein said recruitment linker is indirectly attached to said target analyte.

29. A method according to claim 26 wherein said ETM is a transition metal complex.

30. A method according to claim 26 wherein said ETM is metallocene.

31. A method according to claim 26 wherein said ETM is ferrocene.

32. A method according to claim 26 wherein said ETM is an organic electron transfer moiety.

33. A method according to claim 26 wherein said capture binding ligand is a nucleic acid.

34. A method according to claim 26 wherein said capture binding ligand is a protein.

35. A method according to claim 26 wherein A is sulfur.

36. A method according to claim 26 wherein said metallic surface is gold.

37. A method according to claim 26 wherein said MFS is an insulator.

38. A method according to claim 37 wherein said insulator comprises an alkyl group from about 7 to 20 carbons.

39. A method according to claim 38 wherein said alkyl group comprises a heteroalkyl.

40. A method according to claim 38 wherein said alkyl group comprises a substituted alkyl.

41. A method according to claim 26 wherein said AG comprises an alkyl group from about 1 to 6 carbons.

42. A method according to claim 26 wherein said AG is branched, having the formula:

43. A method according to claim 26 wherein said AG is attached to said attachment linker via a (CH₂)n group, wherein n is an integer from 0 to 4.

44. A method according to claim 26 wherein said AG is attached directly to said attachment linker.

12. A method of modifying a metallic surface comprising contacting the metallic surface with an asymmetric monolayer forming species having the formula:

26. A method of detecting a target analyte in a sample comprising:

a) binding said target analyte to a metallic surface comprising

i) an asymmetric monolayer forming species having the formula;

ii) a species having the formula A-MFS-capture binding ligand; and

wherein

A is an attachment linker moiety;

MFS is a monolayer forming species; and

AG is an electroconduit forming species; and

b) binding a solution binding ligand to said target analyte, wherein said solution binding ligand comprises a first portion that will bind to said target analyte and a recruitment linker comprising a first portion comprising at least one ETM; and

c) detecting the presence of said ETM as an indication of the presence of the target analyte.