Electrodes linked via conductive oligomers to nucleic acids

• US 7,125,668 B2
• Filed: 09/05/2002
• Issued: 10/24/2006
• Est. Priority Date: 11/05/1996
• Status: Expired due to Fees

• Current Assignee: Roche Molecular Systems Inc (Roche Holding AG)
• Original Assignee: Clinical Micro Sensors Inc. (Roche Holding AG)
• Inventors: Gozin, Michael, Kayyem, Jon Faiz, O'Connor, Stephen D., Yu, Changjun
• Primary Examiner(s): Riley, Jezia
• Application Number:
  US10/236,481
• Publication Number:
  US 20030150723A1
• Time in Patent Office: 1,510 Days
• Field of Search: 435/6, 436/501, 422/68.1
• 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 method of detecting a mismatch in a target sequence, comprising

a) hybridizing a probe nucleic acid to said target sequence to form a hybridization complex comprising said mismatch, wherein said probe nucleic acid is covalently attached to a first electron transfer moiety comprising an electrode, wherein said hybridization complex comprises a second electron transfer moiety, and wherein said electrode further comprises a monolayer;

and

b) detecting electron transfer between said electrode and said second electron transfer moiety as an indicator of the presence or absence of said mismatch.

3. A method according to claim 1 or 2, wherein said monolayer comprises insulators.

4. A method according to claim 1 or 2, wherein said monolayer comprises conductive oligomers.

5. A method according to claim 3, wherein said insulator is an alkyl group.

6. A method according to claim 5, wherein said alkyl group is linear.

7. A method according to claim 5, wherein said alkyl group is branched.

8. A method according to claim 5, wherein said insulator comprises ethylene glycol.

9. A method according to claim 1 or 2, wherein said second electron transfer moiety is a transition metal complex.

10. A method according to claim 1 or 2, wherein said second electron transfer moiety is covalently attached to said target sequence.

11. A method according to claim 1 or 2, wherein said second electron transfer moiety is a ferrocene.

12. A method according to claim 1 or 2, wherein said electrode is gold.

13. A method according to claim 1 or 2, wherein said electrode is indium tin oxide.

14. A method according to claim 1 or 2 wherein said second electron transfer moiety is an intercalator.

15. A method according to claim 1 or 2 wherein said electron transfer is detected using AC impedance.

2. A method of detecting a mismatch in a target sequence, comprising:

a) adding a target nucleic acid to an array of a plurality of different probe nucleic acids to form a hybridization complex comprising said target sequence, wherein each said probe nucleic acid is covalently attached to one of a plurality of electrodes, wherein said hybridization complex comprises an electron transfer moiety, and wherein said electrodes further comprise a monolayer; and

b) detecting electron transfer between said one of said plurality of electrodes and said second electron transfer moiety as an indicator of the presence or absence of said mismatch.