Biologic electrode array with integrated optical detector

• US 7,045,097 B2
• Filed: 05/07/2002
• Issued: 05/16/2006
• Est. Priority Date: 07/09/1996
• Status: Expired due to Fees

• Current Assignee: Gamida for Life B.V.
• Original Assignee: Nanogen, Inc.
• Inventors: Kovacs, Gregory T. A.
• Primary Examiner(s): Soderquist, Arlen
• Application Number:
  US10/143,036
• Publication Number:
  US 20020131899A1
• Time in Patent Office: 1,470 Days
• Field of Search: 436/73, 436/79, 436 86- 90, 436 93- 95, 436106-113, 436127-132, 436149-151, 436164-165, 436/172, 436/501, 436/503, 436/509, 436512-513, 436/518, 436/527, 204412-413, 204/435, 422/68.1, 422 8201- 8203, 422/82.05, 422/82.08
• US Class Current: 422/82.08
• 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, the biologic electrode array including a coupling layer, 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 between the optical detector and the coupling layer, the electrode covering at least a portion of the optical detector;

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

one or more biomolecules bound to the coupling layer;

at least one switch coupled to the electrode;

a voltage line that is selectively connected to the electrode via the switch;

a voltage source coupled to the voltage line;

a local addressable memory associated with each electrode of the array, the memory controlling the level of electrical stimulus applied to the associated electrode; and

wherein the electrode is selected from the group consisting of a slitted electrode, a punctuated electrode, and an optically transparent electrode.

2. A site according to claim 1, wherein the electrode comprises indium tin oxide.

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

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

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

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

7. A biologic electrode array comprising:

a semiconductor substrate;

a coupling layer;

a matrix of optical detectors;

a matrix of electrode sites disposed between the coupling layer and the matrix of optical detectors, the matrix of optical detectors disposed beneath and at least partially covered by 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;

at least one switch coupled to at least one of the electrode sites within the matrix;

a voltage line that is selectively connected to the at least one electrode via the switch;

a voltage source coupled to the voltage line;

a local addressable memory associated with each electrode of the array, the memory controlling the level of electrical stimulus applied to the associated electrode; and

wherein the electrode site is selected from the group consisting of a slitted electrode, a punctuated electrode, and an optically transparent electrode.

8. An array according to claim 7, further comprising one or more biomolecules bound to the coupling layer of at least one electrode site.

9. An array according to claim 8, wherein the biomolecules are nucleic acids.

10. An array according to claim 7, wherein the electrodes comprise indium tin oxide.

11. An array according to claim 7, wherein the optical detectors are photodiodes.

12. An array according to claim 7, wherein the optical detectors are charge-coupled devices.

13. An array according to claim 7, further comprising a plurality of row and column lines for addressing individual electrode sites within the matrix.

14. An array according to claim 7, wherein at least a portion of the array is formed using CMOS fabrication techniques.