Compositions for the electronic detection of analytes utilizing monolayers

• US 7,393,645 B2
• Filed: 08/19/2005
• Issued: 07/01/2008
• 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.
• Primary Examiner(s): WHISENANT, ETHAN C
• Application Number:
  US11/208,384
• Publication Number:
  US 20070207465A1
• Time in Patent Office: 1,047 Days
• Field of Search: 435/6, 536/23.1, 536/24.3
• US Class Current: 435/6.11
• CPC Class Codes: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: C12Q 2563/113 the label being electroactive, e.g. redox labels
• CPC Class Codes: C12Q 2565/519 characterised by the capture moiety being a single stranded oligonucleotide
• CPC Class Codes: G01N 2610/00 Assays involving self-assembled monolayers [SAMs]
• CPC Class Codes: G01N 33/54353 with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393

Abstract

The present invention relates to the use of self-assembled monolayers with mixtures of conductive oligomers and insulators to detect target analytes.

Claims

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

a) contacting said sample with an electrode comprising;

i) a monolayer comprising insulators; and

ii) a capture binding ligand wherein said capture binding ligand is covalently attached to said electrode via an attachment linker, under conditions wherein said target analyte binds to said capture binding ligand;

b) binding a target analyte binding ligand to said target analyte, wherein said target analyte binding ligand comprises at least one non-electrochemiluminescent electron transfer moiety (ETM) covalently attached to said target analyte binding ligand; and

c) detecting the presence of said target analyte.

2. A method according to claim 1 wherein said attachment linker is selected from the group consisting of conductive oligomers and insulators.

3. A method according to claim 1 wherein said capture binding ligand is a nucleic acid.

4. A method according to claim 1 wherein said capture binding ligand is a protein.

5. A method according to claim 1 wherein said target analyte is a protein.

6. A method according to claim 1 wherein said target analyte is a peptide.

7. A method according to claim 1 wherein said target analyte is a nucleic acid.

8. A method according to claim 1 wherein said ETM is a metallocene.

9. A method according to claim 8 wherein said metallocene is ferrocene.

10. A method according to claim 1 wherein said insulators are alkyl chains.

18. A method according to claim 1 wherein said monolayer further comprises conductive oligomers.

20. A method according to claim 2 wherein said attachment linker is a conductive oligomer.

21. A method according to claim 2 wherein said attachment linker is an insulator.

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

a) contacting said sample with an electrode comprising;

i) a monolayer comprising insulators; and

ii) a capture binding ligand wherein said capture binding ligand is covalently attached to said electrode via an attachment linker, under conditions wherein said target analyte binds to said capture binding ligand;

b) binding a target analyte binging ligand to said target analyte, wherein said target analyte binding ligand comprises;

i) nucleic acid;

ii) at least one non-electrochemiluminescent electron transfer moiety (ETM) covalently attached to said target analyte binding ligand; and

c) detecting the presence of said target analyte.

12. A method according to claim 11 wherein said attachment linker is selected from the group consisting of conductive oligomers and insulators.

13. A method according to claim 11 wherein said capture binding ligand is a nucleic acid.

14. A method according to claim 11 wherein said capture binding ligand is a protein.

15. A method according to claim 11 wherein said ETM is a metallocene.

16. A method according to claim 15 wherein said metallocene is ferrocene.

17. A method according to claim 11 wherein said insulators are alkyl chains.

19. A method according to claim 11 wherein said monolayer further comprises conductive oligomers.

22. A method according to claim 2 or 12 wherein said attachment linker is a conductive oligomer.

23. A method according to claim 2 or 12 wherein said attachment liker is an insulator.

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

a) contacting said sample with an electrode comprising;

i) a monolayer comprising insulators; and

ii) a capture binding ligand wherein said capture binding ligand is covalently attached to said electrode via an attachment linker, under conditions wherein said target analyte binds to said capture binding ligand;

b) binding a target analyte binding ligand to said target analyte, wherein said target analyte binding ligand comprising at least one electron transfer moiety (ETM) covalently attached to said target analyte binding ligand; and

c) detecting the presence of said target analyte electronically.