Capacity affinity sensor

• US 6,436,699 B1
• Filed: 06/15/2000
• Issued: 08/20/2002
• Est. Priority Date: 09/15/1997
• Status: Expired due to Fees

• Current Assignee: AB Sangtec Medical
• Original Assignee: AB Sangtec Medical
• Inventors: Johansson, Gillis, Berggren, Christine
• Primary Examiner(s): Whisenant, Ethan C.
• Assistant Examiner(s): LU, FRANK WEI MIN
• Application Number:
  US09/508,782
• Time in Patent Office: 796 Days
• Field of Search: 435/6, 435/7.1, 435/7.94, 435/91.1, 435/183, 435/283.1, 435/285.2, 435/287.1, 435/287.2, 436/94, 436/501, 536/23.1, 536/23.2, 536/24.3, 530/300, 530/350, 530/387.1, 424/130.1, 424/178.1, 424/184.1, 424/94.1, 424/198.1
• US Class Current: 435/287.2
• 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: C12Q 1/6825 Nucleic acid detection involving sensors
• CPC Class Codes: G01N 2610/00 Assays involving self-assembled monolayers [SAMs]
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

This invention describes a capacity affinity sensor based on self-assembled monolayers on an electrode with immobilized recognition elements available to analyte in the surrounding solution. Additional insulation is provided by auxiliary self-assembled molecules. The sensor has exceptional sensitivity and wide operating range due to these parts of the invention. It is versatile because different kinds of recognition elements can be immobilized directly on the surface of the measuring electrode. The electrode then becomes selective to those molecules in the solution, the analytes, that show affinity to the recognition element on the surface. Compared to capacitive sensors described before those described here shows at least a 1000-fold better sensitivity because of the properties of the layer binding the recognition element.

Claims

1. A capacity affinity sensor for determining the presence of and/or the quantity of a compound of interest in a liquid sample, comprising:

a noble metal surface; and

a first immobilized and electrically insulating layer having a first measurable capacitance, wherein the first immobilized and electrically insulating layer comprises a first self-assembled monolayer-forming compound having coupled thereto an affinity compound, and a second self-assembled monolayer-forming compound, the noble metal surface being at least 99% covered with the first immobilized and electrically insulating layer;

wherein the affinity compound, upon contact with the liquid sample, is capable of specifically binding the compound of interest so as to form a second immobilized and electrically insulating layer having a second measurable capacitance.

2. The capacity affinity sensor of claim 1 wherein the noble metal is gold, silver, copper, platinum or palladium.

3. The capacity affinity sensor of claim 1 wherein the noble metal surface is provided by a piece of the noble metal.

4. The capacity affinity sensor of claim 3 wherein the piece of a noble metal is in the shape of a rod.

5. The capacity affinity sensor of claim 1 wherein the noble metal surface is provided as a layer of the noble metal coating a piece of an electrically insulating material.

6. The capacity affinity sensor of claim 5 wherein the electrically insulating material is glass or quartz.

7. The capacity affinity sensor of claim 1 wherein the first self-assembled monolayer-forming compound is D/L-thioctic acid, activated with 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide.

8. The capacity affinity sensor of claim 1 wherein the second self-assembled monolayer-forming compound is a thiol comprising 3-25 carbon atoms in a straight saturated chain.

9. The capacity affinity sensor of claim 8 wherein the thiol is 1-dodecanethiol.

10. The capacity affinity sensor of claim 1 wherein the affinity compound is an antibody, a monoclonal antibody, an antibody fragment or a F(ab′

)₂ fragment.

11. The capacity affinity sensor of claim 1 wherein the affinity compound is a nucleic acid.

12. The capacity affinity sensor of claim 1 wherein the affinity compound is a single-stranded DNA compound.

13. The capacity affinity sensor of claim 1 wherein the sensor is adapted to determine the presence of human chorionic gonadotripin hormone (HCG), interleukin-2, human serum albumin, atrazine, or a DNA sequence.

14. A method for qualitatively or quantitatively determining the presence of a compound of interest in a liquid sample, comprising the steps of:

(a) contacting the sensor of claim 1 with a reference liquid not containing the compound of interest and determining the capacitance of the sensor;

(b) contacting the sensor with a sample suspected of containing the compound of interest so as to bind the compound of interest and determining the capacitance of the sensor having the compound of interest bound thereto; and

(c) calculating the difference between the capacitance measured in step (a) and the capacitance measured in step (b) and optionally calculating the amount of the compound of interest by using prerecorded calibration data.

15. The method of claim 14 wherein the compound of interest is human chorionic gonadotropin hormone (HCG), interleukin-2, human serum albumin, atrazine, or a DNA sequence.

16. A capacity affinity sensor for determining the presence of and/or the quantity of a compound of interest in a liquid sample, comprising:

a noble metal surface; and

a first immobilized and electrically insulating layer having a first measurable capacitance, wherein the first immobilized and electrically insulating layer comprises a first self-assembled monolayer-forming compound and a second self-assembled monolayer-forming compound, the noble metal surface being at least 99% covered with the first immobilized and electrically insulating layer;

wherein upon contact with the liquid sample, the first self-assembled monolayer-forming compound is capable of specifically binding the compound of interest so as to form a second immobilized and electrically insulating layer having a second measurable capacitance.

17. A method for qualitatively or quantitatively determining the presence of a compound of interest in a liquid sample, comprising the steps of:

(a) contacting the sensor of claim 16 with a reference liquid not containing the compound of interest and determining the capacitance of the sensor;

(b) contacting the sensor with a sample suspected of containing the compound of interest so as to bind the compound of interest and determining the capacitance of the sensor having the compound of interest bound thereto; and

(c) calculating the difference between the capacitance measured in step (a) and the capacitance measured in step (b) and optionally calculating the amount of the compound of interest by using prerecorded calibration data.

18. The method according to claim 17 wherein the compound of interest is human chorionic gonadotropin hormone (HCG), interleukin-2, human serum albumin, atrazine, or a DNA sequence.