Biologic electrode array with integrated optical detector

• US 20020131899A1
• Filed: 05/07/2002
• Published: 09/19/2002
• Est. Priority Date: 07/09/1996
• Status: Active Grant

• Current Assignee: Gamida for Life B.V.
• Original Assignee: Nanogen, Inc.
• Inventors: Kovacs, Gregory T.A.
• Granted Patent: US 7,045,097 B2
• Time in Patent Office: Days
• US Class Current: 422/82.01
• CPC Class Codes: B01J 19/0046 Sequential or parallel reactions, e.g. for the synthesis of polypeptides or polynucleotides; Apparatus and devices for combinatorial chemistry or for making molecular arrays synthesis methods per se C40B50/00
• CPC Class Codes: B01J 2219/00527 Sheets
• CPC Class Codes: B01J 2219/00585 Parallel processes
• CPC Class Codes: B01J 2219/00596 Solid-phase processes
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: G01N 27/27 Association of two or more measuring systems or cells, each measuring a different parameter, where the measurement results may be either used independently, the systems or cells being physically associated, or combined to produce a value for a further parameter
• CPC Class Codes: G01N 27/3276 being a hybridisation with immobilised receptors using a FET type sensor G01N27/4145; concerning the hybridisation C12Q1/68
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: Y10T 436/142222 Hetero-O [e.g., ascorbic acid, etc.]
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]
• CPC Class Codes: Y10T 436/144444 Glucose
• CPC Class Codes: Y10T 436/17 Nitrogen containing
• CPC Class Codes: Y10T 436/170769 N-Nitroso containing [e.g., nitrosamine, etc.]
• CPC Class Codes: Y10T 436/171538 : Urea or blood urea nitrogen
• CPC Class Codes: Y10T 436/173845 : Amine and quaternary ammonium
• CPC Class Codes: Y10T 436/20 : Oxygen containing
• CPC Class Codes: Y10T 436/200833 : Carbonyl, ether, aldehyde or ketone containing
• CPC Class Codes: Y10T 436/203332 : Hydroxyl containing

Abstract

A biologic electrode array is formed on a semiconductor substrate. A matrix of electrode sites is disposed on the semiconductor substrate. A matrix of optical detectors is disposed beneath the electrode sites in the semiconductor substrate, wherein each electrode site is associated with a corresponding optical detector. The optical detectors are coupled to detection circuitry formed on the semiconductor substrate. The electrode sites may include slitted electrodes, punctuated electrodes, or optically transparent electrodes.

Claims

1. A site for use in a biologic electrode array, the biologic electrode array being formed on an integrated circuit chip, comprising:

an optical detector coupled to detection circuitry, the optical detector and the detective circuitry formed on the integrated circuit chip;

an electrode disposed on the integrated circuit chip above the optical detector;

a coupling layer disposed over at least a portion of a surface of the electrode; and

one or more biomolecules bound to the coupling layer.

2. A site according to claim 1, wherein the electrode is slitted.

3. A site according to claim 1, wherein the electrode is punctuated.

4. A site according to claim 1, wherein the electrode is optically transparent.

5. A site according to claim 4, wherein the electrode comprises indium tin oxide.

6. A site according to claim 1, wherein the optical detector is a photodiode.

7. A site according to claim 1, wherein the optical detector is a charge-coupled device.

8. A site according to claim 1, wherein the biomolecules are nucleic acids.

9. A site according to claim 1, further comprising a source of light disposed above the biologic electrode array.

10. A biologic electrode array comprising:

a semiconductor substrate;

a matrix of electrode sites disposed on the semiconductor substrate; and

a matrix of optical detectors disposed beneath the electrode sites in the semiconductor substrate, wherein each electrode site is associated with a corresponding optical detector, the optical detectors coupled to detection circuitry formed on the semiconductor substrate.

11. An array according to claim 10, further comprising a coupling layer disposed on top of at least a portion of the electrode sites.

12. An array according to claim 11, further comprising one or more biomolecules bound to the coupling layer of at least one electrode site.

13. An array according to claim 12, wherein the biomolecules are nucleic acids.

14. An array according to claim 10, wherein the electrode sites comprise slitted electrodes.

15. An array according to claim 10, wherein the electrode sites comprise punctuated electrodes.

16. An array according to claim 10, wherein the electrode sites comprise optically transparent electrodes.

17. An array according to claim 10, wherein the electrodes comprise indium tin oxide.

18. An array according to claim 10, wherein the optical detectors are photodiodes.

19. An array according to claim 10, wherein the optical detectors are charge-coupled devices.

20. An array according to claim 10, further comprising a plurality of row and column lines for addressing individual electrode sites within the matrix.

21. An array according to claim 10, wherein at least a portion of the array is formed using CMOS fabrication techniques.