Electrodes linked via conductive oligomers to nucleic acids

• US 6,977,151 B2
• Filed: 02/20/2002
• Issued: 12/20/2005
• Est. Priority Date: 11/05/1996
• Status: Expired due to Fees

• Current Assignee: Roche Molecular Systems (Roche Holding AG)
• Original Assignee: Clinical Micro Sensors Inc. (Roche Holding AG)
• Inventors: Kayyem, Jon Faiz, O'Connor, Stephen D., Meade, Thomas J., Yu, Changjun, Gozin, Michael
• Primary Examiner(s): WHISENANT, ETHAN C
• Application Number:
  US10/081,936
• Publication Number:
  US 20030003473A1
• Time in Patent Office: 1,399 Days
• Field of Search: 435/6, 435/287.2, 536/23.1, 536/24.3
• US Class Current: 435/6.11
• CPC Class Codes: C07H 21/00 Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors

Abstract

The invention relates to nucleic acids covalently coupled to electrodes via conductive oligomers. More particularly, the invention is directed to the site-selective modification of nucleic acids with electron transfer moieties and electrodes to produce a new class of biomaterials, and to methods of making and using them.

Claims

1. A composition comprising:

a) an electrode comprising a self-assembled monolayer comprising nucleic acid probes attached to said electrode with a spacer; and

b) a hybridization indicator.

2. A composition according to claim 1 wherein said hybridization indicator is an intercalator.

3. A composition according to claim 1 wherein said hybridization indicator is methylene blue.

4. A composition according to claim 1 further comprising a target nucleic acid hybridized to said probe to form a hybridization complex, wherein said hybridization indicator is associated with said hybridization complex.

5. A composition according to claim 1 further comprising a co-reductant.

6. A composition according to claim 1 wherein said nucleic acid probe is a single stranded nucleic acid.

7. A composition according to claim 1 wherein said nucleic acid probe comprises a double stranded portion.

8. A composition according to claim 1 further comprising a soluble electron source.

9. A composition according to claim 8 where said soluble electron source comprises ferricyanide.

10. A composition according to claim 1 wherein said spacer is a conductive oligomer.

11. A composition according to claim 1 wherein said spacer is an insulator.

12. A composition according to claim 11 wherein said insulator comprises (CH₂)₆.

13. A composition according to claim 1 wherein said self-assembled monolayer further comprises passivation agents.

14. A composition according to claim 13 wherein said passivation agents are insulators.

15. A composition comprising:

a) a hybridization indicator; and

b) an array of electrodes, each comprising

i) a self-assembled monolayer;

ii) a nucleic acid probe attached to said electrode with a spacer.

16. A composition according to claim 15 wherein said hybridization indicator is an intercalator.

17. A composition according to claim 15 wherein said hybridization indicator is methylene blue.

18. A composition according to claim 15 further comprising a target nucleic acid hybridized to said probe to form a hybridization complex, wherein said hybridization indicator is associated with said hybridization complex.

19. A composition according to claim 15 further comprising a co-reductant.

20. A composition according to claim 15 wherein said nucleic acid probe is a single stranded nucleic acid.

21. A composition according to claim 15 wherein said nucleic acid probe comprises a double stranded portion.

22. A composition according to claim 15 further comprising a soluble electron source.

23. A composition according to claim 22 where said soluble electron source comprises ferricyanide.

24. A composition according to claim 15 wherein said spacer is a conductive oligomer.

25. A composition according to claim 15 wherein said spacer is an insulator.

26. A composition according to claim 25 wherein said insulator comprises (CH₂)₆.

27. A composition according to claim 15 wherein said self-assembled monolayer further comprises passivation agents.

28. A composition according to claim 27 wherein said passivation agents are insulators.

29. A composition comprising:

a) an array of electrodes, each comprising a self-assembled monolayer comprising nucleic acid probes attached to said electrode with a spacer, wherein said spacer comprises an insulator; and

b) a hybridization indicator.