Electronic methods for the detection of analytes

• US 7,759,073 B2
• Filed: 02/05/2009
• Issued: 07/20/2010
• 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: Kayyem, Jon Faiz, O'Connor, Stephen D., Meade, Thomas J.
• Primary Examiner(s): Cook; Lisa V
• Application Number:
  US12/366,471
• Publication Number:
  US 20090242430A1
• Time in Patent Office: 530 Days
• Field of Search: None
• US Class Current: 435/7.1
• 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: G01N 2458/30 Electrochemically active labels
• CPC Class Codes: G01N 27/3277 being a redox reaction, e.g. detection by cyclic voltammetry voltammetry per se G01N27/42, G01N27/48
• CPC Class Codes: G01N 2800/04 Endocrine or metabolic disorders
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: G01N 33/58 involving labelled substances G01N33/53 takes precedence
• CPC Class Codes: G01N 33/84 involving inorganic compounds or pH

Abstract

The present invention is directed to the detection of target analytes using electronic techniques, particularly AC techniques.

Claims

1. A method of detecting a target analyte comprising:

a) contacting a sample comprising said target analyte with an electrode comprising a passivation agent monolayer comprising;

i) a covalently attached first passivation species;

ii) a covalently attached second passivation species comprising a self-associated binding ligand, whereby upon binding of said target analyte with said binding ligand, said binding ligand is released from self-association;

iii) a redox active molecule; and

b) detecting a change in a redox property of the redox active molecule as a result of the association of the target analyte with the binding ligand.

2. The method of claim 1, wherein when said binding ligand is self-associated, said redox active molecule is in closer proximity to said electrode than when said binding ligand is not self-associated.

3. The method of claim 2, wherein said binding ligand is released from self-association upon binding of said target analyte.

4. The method of claim 1, wherein said binding ligand is selected from the group consisting of a nucleic acid and a protein.

5. The method of claim 1, wherein said binding ligand is a nucleic acid.

6. The method of claim 5, wherein said target analyte is a nucleic acid.

7. The method of claim 1, wherein said redox active molecule is a transition metal complex.

8. The method of claim 7, wherein said transition metal complex comprises a metal selected from the group consisting of cadmium, copper, cobalt, palladium, zinc, iron, ruthenium, rhodium, osmium, rhenium, platinium, scandium, titanium, vanadium, chromium, manganese, nickel, molybdenum, technetium, tungsten, and iridium.

9. The method of claim 8, wherein metal is iron.

10. The method of claim 7, wherein said transition metal complex is ferrocene.

11. The method of claim 1, wherein said electrode is selected from the group consisting of gold, platinum, palladium, silicon, and aluminum.

12. The method of claim 11, wherein said electrode is gold.

13. The method of claim 1, wherein said detecting is by a method selected from the group consisting of amperommetry, voltammetry, capacitance and impedence.

14. An apparatus comprising:

a) a test chamber comprising an array of measuring electrodes, wherein a first and second of said measuring electrodes comprise a passivation agent monolayer comprising;

i) a covalently attached first passivation species;

ii) a covalently attached second passivation species comprising a self-associated binding ligand,

wherein the binding ligand on said first electrode and the binding ligand on said second electrode are different; and

b) a voltage source electrically connected to said test chamber.

15. The apparatus of claim 14, further comprising an electronic detector.