Bio-assay device and test system for detecting molecular binding events

• US 6,368,795 B1
• Filed: 02/01/1999
• Issued: 04/09/2002
• Est. Priority Date: 02/02/1998
• Status: Expired due to Term

• Current Assignee: DH Technologies Development Pte. Ltd. (Danaher Corporation)
• Original Assignee: Signature BioScience, Inc.
• Inventors: Hefti, John
• Primary Examiner(s): Chin, Christopher L.
• Application Number:
  US09/243,194
• Time in Patent Office: 1,163 Days
• Field of Search: 435/4, 435/6, 435/7.1, 435/7.92, 435/287.1, 435/287.2, 436/517, 436/518, 436/149, 436/150, 436/151, 436/805, 436/806, 436/524, 436/525, 422/82.01, 422/82.02, 204/400, 204/403
• US Class Current: 435/6.11
• 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 1/001 Enzyme electrodes
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: G11C 13/0014 comprising cells based on organic memory material
• CPC Class Codes: Y10S 436/806 Electrical property or magnetic property

Abstract

Systems and methods for detecting molecular binding events and other environmental effects using the unique dielectric properties of the bound molecular structure or structures are presented. A molecular binding layer is coupled along the surface of a signal path. A test signal is propagated along the signal path, whereby the test signal couples to the molecular binding layer, and in response, exhibits a signal response.

Claims

1. A bio-assay device configured to detect a molecular binding event formed between a ligand and an antiligand, the bio-assay device comprising:

(i) a signal path operable to support the propagation of a test signal at one or more frequencies from 10 MHz to 1000 GHz, said signal path comprising;

an electrically conductive transmission line;

a ground element; and

a dielectric layer interposed between said electrically conductive transmission line and said ground element; and

(ii) a molecular binding layer electromagnetically coupled to said signal path, said molecular binding layer comprising said antiligand operable to bind said ligand,

wherein said molecular binding layer is located between at least a portion of said electrically conductive transmission line and at least a portion of said ground element.

2. The bio-assay device of claim 1, further comprising:

an input port coupled to said signal path, said input port comprising;

a first signal conductor coupled to said transmission line; and

a first ground conductor coupled to said ground element; and

an output port coupled to said signal path, said output port comprising;

a second output signal conductor coupled to said transmission line; and

a second ground conductor coupled to said ground element.

3. The bio-assay device of claim 1, wherein said molecular binding layer is formed along at least a portion of said electrically conductive transmission line.

4. The bio-assay device of claim 1, wherein said molecular binding layer is formed along at least a portion of said ground element.

5. The bio-assay device of claim 1, wherein said transmission line is physically separated from said ligand.

6. The bio-assay device of claim 1, wherein said test signal comprises a signal at one or more frequencies from 45 MHz to 20 GHz.

7. The bio-assay device of claim 1, wherein said electrically conductive transmission line comprises a derivatized surface and said antiligand is attached to said derivatized surface.

8. A bio-assay test system configured to detect the presence or absence of a molecular binding event formed between a ligand and an antiligand, the system comprising:

(i) a signal source operable to provide a test signal at one or more frequencies from 10 MHz to 1000 GHz;

(ii) a bio-assay device, comprising;

(a) a signal path operable to support the propagation of said test signal, said signal path comprising;

an electrically conductive transmission line;

a ground element; and

a dielectric layer interposed between said electrically conductive transmission line and said ground element; and

(b) a molecular binding layer electromagnetically coupled to said signal path, said molecular binding layer comprising said antiligand operable to bind to said ligand, wherein said molecular binding layer is located between at least a portion of said electrically conductive transmission line and at least a portion of said ground element; and

(iii) a signal detector coupled to said bio-assay device,

wherein said test signal couples to said molecular binding layer, thereby producing said modulated signal, said modulated signal being recoverable by said signal detector, wherein said modulated signal exhibits a response indicating the presence or absence of a molecular binding event formed between said ligand and said antiligand.

9. The bio-assay test system of claim 8, wherein said signal response comprises an S-parameter transmission loss S₂₁ response.

10. The bio-assay test system of claim 8, wherein said signal response comprises an S-parameter return loss S₁₁ response.

11. The bio-assay test system of claim 8, wherein said signal source and said signal detector are included within a vector network analyzer.

12. The bio-assay test system of claim 8, wherein said signal source and said signal detector are included within a scalar network analyzer.

13. The bio-assay test system of claim 8, wherein said signal source and said signal detector are included within a time domain reflectometer.