Biological identification system with integrated sensor chip

• US 8,062,491 B1
• Filed: 06/20/2008
• Issued: 11/22/2011
• Est. Priority Date: 05/03/2000
• Status: Expired due to Fees

• Current Assignee: Secretary of The Navy United States Government As Represented By The
• Original Assignee: The United States of America As Represented By The Secretary of Agriculture
• Inventors: Gau, Jen-Jr
• Primary Examiner(s): Noguerola, Alex
• Application Number:
  US12/154,017
• Time in Patent Office: 1,250 Days
• Field of Search: 20440301-40315, 205/777.5, 205/778, 205/792
• US Class Current: 204/403.08
• CPC Class Codes: B01J 2219/00317 Microwell devices, i.e. having large numbers of wells
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• 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 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00619 using hydrophilic or hydrophobic regions
• CPC Class Codes: B01J 2219/00621 by physical means, e.g. trenches, raised areas
• CPC Class Codes: B01J 2219/0063 Other, e.g. van der Waals forces, hydrogen bonding
• 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 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: B01L 3/5088 confining liquids at a location by surface tension, e.g. virtual wells on plates, wires B01L3/50857 takes precedence
• CPC Class Codes: B81C 2201/0133 Wet etching
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12Q 1/68 : involving nucleic acids
• CPC Class Codes: C12Q 1/6876 : Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
• CPC Class Codes: C12Q 2600/156 : Polymorphic or mutational markers
• CPC Class Codes: C40B 40/06 : Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 : Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: C40B 60/14 : for creating libraries
• CPC Class Codes: G01N 27/3277 : being a redox reaction, e.g. detection by cyclic voltammetry voltammetry per se G01N27/42, G01N27/48

Abstract

A microelectromechanical systems (MEMS) and integrated circuit (IC) based biosensor capable of sensing or detecting various ionic molecules and macromelecules (DNA, RNA or protein). The MEMS based biosensor utilizes a hybridization and enzyme amplification scheme and an electrochemical detection scheme for sensitivity improvement and system miniaturization. The biosensor or biosensors are incorporated on a single substrate. Preferably, the biosensor system includes at least two electrodes. The electrodes includes a working electrode, a reference electrode and a counter (auxiliary) electrode. The biosensor or biosensors also provide an apparatus and method for confinement of reagent and/or solution in the biosensor or biosensors using surface tension at small scale. The confinement system provides controlled contacts between the reagent(s) and/or solution(s) with the components (i.e., electrodes) of the biosensor or biosensors using controllable surface properties and surface tension forces. The confinement system allows for incorporation of the biosensor or biosensors into a portable or handheld device and is immune to shaking and/or flipping. The invention also provides for a biosensor and/or sensors that are integrated with integrated circuit (IC) technologies. Preferably, the entire sensor system or systems are fabricated on a single IC substrate or chip and no external component and/or instrument is required for a complete detection system or systems. Preferably, the sensor system or systems are fabricated using the IC process and on a silicon substrate.

Claims

1. A device for detecting the presence or measuring the quantity of a target analyte in a sample, comprising:

an electrochemical sensor including electrodes on a substrate, the electrodes including a working electrode, a reference electrode, and a counter electrode,

the reference electrode consisting of a single layer of an electrically conductive material, and

a self-assembly monolayer, the self-assembly monolayer being bonded directly to the layer of electrically conductive material.

2. The device of claim 1, wherein the self-assembly monolayer includes biotinylated thiol molecules.

3. The device of claim 2, wherein the biotinylated thiol molecules include a sulfur bonded directly to the layer of electrically conductive material.

4. The device of claim 1, wherein the self-assembly monolayer is bonded directly to the working electrode and the counter electrode.

5. The device of claim 1, wherein the substrate is selected from the group consisting of silicon, gallium arsenide, plastic and glass.

6. The device of claim 1, wherein the working electrode, the reference electrode, and the counter electrode each include a layer of gold.

7. The device of claim 1, wherein the electrodes occupy an area of 160 μ

m² to 25 mm² on the substrate.

8. The device of claim 1, wherein the reference electrode is arranged about the perimeter of the working electrode such that a portion of the working electrode is positioned between different regions of the reference electrode.

9. The device of claim 1, wherein the counter electrode is arranged about the perimeter of the working electrode such that a portion of the working electrode is positioned between different regions of the reference electrode.

10. The device of claim 1, wherein at least one of the electrodes is positioned in a well that extends into the substrate.

11. The device of claim 1, wherein the working electrode is positioned in the well.

12. The device of claim 1, wherein the electrodes are each in contact with the substrate.

13. The device of claim 1, further comprising electrically conductive materials positioned on the substrate and contacts pads positioned on the substrate, each of the electrically conductive materials extending from one of the electrodes to different one of the contact pads.

14. The device of claim 13, wherein each of the electrodes, each of the contact pads, and each of the electrically conductive materials are positioned on a side of the substrate.

15. The device of claim 1, wherein each of the electrodes is constructed of the same material.

16. The device of claim 1, wherein the reference electrode and the counter electrode each have a shape that is different from a shape of the working electrode.

17. The device of claim 1, wherein the reference electrode, the working electrode and the counter electrode each consist of a single layer of an electrically conducting material.