Electronic-property probing of biological molecules at surfaces

• US 6,306,584 B1
• Filed: 04/10/1997
• Issued: 10/23/2001
• Est. Priority Date: 01/21/1997
• Status: Expired due to Term

• Current Assignee: Harvard University
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Bamdad, Cynthia C.
• Primary Examiner(s): Houtteman, Scott W.
• Application Number:
  US08/843,623
• Time in Patent Office: 1,657 Days
• Field of Search: 435/6, 435/7.6, 435/7.1, 435/7.7, 536/24.3, 536/26.6
• US Class Current: 435/6.12
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• 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: C12Q 2565/607 being a sensor, e.g. electrode
• CPC Class Codes: G01N 2610/00 Assays involving self-assembled monolayers [SAMs]

Abstract

A technique for immobilizing biological molecules, in particular nucleic acid strands, is described. Biological molecules immobilized at surfaces can be used in electron-transfer detection techniques in which a binding partner of a biological molecule is brought into proximity of the surface-immobilized biological molecule, an electrical potential created between the two biologically-binding species, and electron transfer through the species determined. Another technique involves immobilizing a bioligical molecule such as a protein, DNA, etc. at a surface via a self-assembled monolayer, affecting the biological molecule via, for example, biological binding, inducing a change in conformation via a prion, etc., and detecting an electronic property change in the molecule via a change in inpedence associated with an electronic circuit addressed by the biological molecule. These technique facilitates combinatorial array detection articles.

Claims

1. A method for detecting the formation of a biological binding complex between a first biological species and a second biological species comprising:

a) providing said first biological species immobilized on a first metal surface of an article via a self-assembled monolayer;

b) providing said second biological species immobilized on a second metal surface of an article via a self-assembled monolayer, wherein said first and second surfaces are different;

c) detecting electron transfer associated with the passing of an electron from the first surface to the second surface as a result of the formation of said binding complex.

2. A method according to claim 1 wherein said first and said second biological species comprise a biological binding pair.

3. A method according to claim 2 wherein said first and said second biological species are nucleic acids.

4. A method according to claim 3 wherein said first biological species is a first nucleic acid strand and said second biological species is a second nucleic acid strand complementary to said first nucleic acid.

5. A method according to claim 1 wherein said monolayer on said first surface comprises a second self-assembled monolayer forming species.

6. A method according to claim 1 wherein said monolayer on said second surface comprises a second self-assembled monolayer forming species.

7. A method according to claim 1 wherein said first and said second surfaces are electrodes.

8. A method according to claim 7 wherein said electrodes are gold.

9. A method according to claim 1 wherein said self-assembled monolayer-forming species comprise thiols.

10. A method according to claim 1 wherein said first surface is a first article and said second surface is on a second article.

11. A method according to claim 1 wherein said first and said second surfaces are on the same article.

12. A method according to claim 11 wherein said article comprises a plurality of surface, each with a different biological species.