Detection of analytes using reorganization energy

• US 7,582,419 B2
• Filed: 10/30/2007
• Issued: 09/01/2009
• Est. Priority Date: 06/12/1997
• Status: Expired due to Fees

• Current Assignee: Osmetech Technology Inc. (Roche Holding AG)
• Original Assignee: Osmetech Technology Inc. (Roche Holding AG)
• Inventors: Meade, Thomas J.
• Primary Examiner(s): Monshipouri; Maryam
• Application Number:
  US11/978,930
• Publication Number:
  US 20080179196A1
• Time in Patent Office: 672 Days
• Field of Search: 205/793.5, 205/777.5, 205/778, 435 5- 7, 435/7.8, 435/7.9, 435/7.91
• US Class Current: 435/5
• 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 5/00 Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: G01N 33/542 with steric inhibition or signal modification, e.g. fluorescent quenching
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

The invention relates to novel methods and compositions for the detection of analytes using the nuclear reorganization energy, λ, of an electron transfer process.

Claims

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

a) adding a target analyte to an electrode comprising

i) a transition metal complex having water in its first or second coordination sphere comprising a metal selected from the group consisting of manganese, technetium, rhenium, iron, ruthenium, osmium, cobalt, rhodium, iridium, nickel, palladium, platinum, copper, silver and gold, wherein said transition metal complex has a first E⁰;

and

ii) a binding ligand which is sterically close to the transition metal complex, that will bind said target analyte;

such that upon binding of said target analyte to said binding ligand, water is excluded from the first or second coordination sphere of said metal complex resulting in a second E⁰; and

b) measuring electron transfer of said transition metal complex at said second E⁰.

2. The method according to claim 1, further comprises measuring electron transfer of said transition metal complex at said first E⁰.

3. The method according to claim 2, further comprises comparing electron transfer of said transition metal complex at said first E⁰ and at said second E⁰.

4. The method according to claim 1, wherein said measuring comprises applying at least a first input signal to said redox active molecule and receiving an output signal.

5. The method according to claim 4,wherein said first input signal comprises at least an AC component.

6. The method according to claim 4, wherein said input signal comprises at least a DC component.

7. The method according to claim 1, wherein said electrode comprises gold.

8. The method according to claim 1 wherein said electrode further comprises a self-assembled monolayer.

9. The method according to claim 8, wherein said self-assembled monolayer comprises conductive oligomers.

10. The method according to claim 8, wherein said self-assembled monolayer comprises insulators.

11. The method according to claim 1, wherein said transition metal complex has at least one coordination site occupied by a polar coordination group.

12. The method according to claim 1, wherein said transition metal complex two coordination sites occupied by polar coordination groups.

13. The method according to claim 1, wherein said binding ligand is covalently attached to said redox active molecule.

14. The method according to claim 1, wherein said binding ligand is covalently attached to said electrode.

15. The method according to claim 1, wherein transition metal complex is covalently attached to said electrode.

16. The method according to claim 14, wherein said covalent attachment is via a spacer.

17. The method according to claim 15, wherein said covalent attachment is via a spacer.

18. The method according to claim 16 or 17, wherein said spacer is a conductive oligomer.

19. The method according to claim 16 or 17, wherein said spacer is an insulator.

20. The method according to claim 1, wherein said metal is iron.

21. The method according to claim 1, wherein said metal is ruthenium.

22. The method according to claim 1, wherein said metal is osmium.

23. The method according to claim 1, wherein said binding ligand is a protein.

24. The method according to claim 23, wherein said protein is a peptide.

25. The method according to claim 1, wherein said analyte is an enzyme and said binding ligand is a substrate of said enzyme.

26. The method according to claim 1, wherein said transition metal complex comprises at least one cyano group.

27. The method according to claim 1, wherein at least one of said transition metal complex and said binding ligand is covalently attached to said electrode via a sulfur atom.

28. The method according to claim 1, wherein at least one of said transition metal complex and said binding ligand is covalently attached to said electrode via two or more sulfur atoms.