Molecular recognition at surfaces derivatized with self-assembled monolayers

• US 6,322,979 B1
• Filed: 04/21/1999
• Issued: 11/27/2001
• Est. Priority Date: 09/26/1994
• Status: Expired due to Term

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Whitesides, George M., Bamdad, Cynthia C., Sigal, George B., Strominger, Jack L.
• Primary Examiner(s): HOUTTEMAN, SCOTT W
• Application Number:
  US09/296,078
• Time in Patent Office: 951 Days
• Field of Search: 435/6, 536/24.3
• US Class Current: 435/6.12
• 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: B82Y 40/00 Manufacture or treatment of nanostructures
• CPC Class Codes: C07H 21/04 with deoxyribosyl as saccharide radical
• CPC Class Codes: C12Q 1/6837 using probe arrays or probe chips C12Q1/6874 takes precedence
• CPC Class Codes: G01N 2610/00 Assays involving self-assembled monolayers [SAMs]
• CPC Class Codes: G01N 33/54353 with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/553 Metal or metal coated

Abstract

An article suitable for use as a biosensor includes a molecule of a formula X—R—Ch adhered to a surface of the article as part of a self-assembled monolayer. X is a functionality that adheres to the surface, R is a spacer moiety, and Ch is a chelating agent. A metal ion can be coordinated by the chelating agent, and a polyamino acid-tagged biological binding partner of a target biological molecule coordinated to the metal ion. A method of the invention involves bringing the article into contact with a medium containing or suspected of containing the target biological molecule and allowing the biological molecule to biologically bind to the binding partner. The article is useful particularly as a surface plasmon resonance chip.

Claims

1. A method for capturing a biological binding partner of a nucleic acid strand in a sample, said method comprising:

a) providing a surface comprising;

i) a first species having a formula X—

R—

NA, wherein X represents a functional group that adheres to said surface, R represents a spacer moiety that promotes formation of a self-assembled monolayer of a plurality of said species, and NA represents a nucleic acid strand; and

ii) a second species that will form a mixed self-assembled monolayer with said first species; and

b) contacting said surface with a medium containing a biological molecule and allowing the molecule to bind to the nucleic acid strand.

2. A method according to claim 1 further comprising determining the biological molecule.

3. A method according to claim 2 wherein said determining is done via spectroscopy.

4. A method according to claim 1 wherein said nucleic acid strand is a single-stranded nucleic acid.

5. A method according to claim 4 wherein said biological molecule is a second nucleic acid strand that is a binding partner of NA.

6. A method according to claim 1 wherein said nucleic acid strand is a double-stranded nucleic acid.

7. A method according to claim 1 wherein said second species has the formula X—

R.

8. A method according to claim 1 wherein said second species has the formula X—

R—

O—

(—

CH₂—

CH₂—

O)_n—

H, wherein n is from 1 to 10.

9. A method according to claim 1 wherein X is a sulfur containing functional group.

10. A method according to claim 1 wherein R is a hydrocarbon chain optionally interrupted by at least one hetero group.

11. A method according to claim 7 wherein R has the formula —

(CH₂)_n—

, wherein n is from about 8 to about 24.

12. A method according to claim 1 wherein said surface comprises gold.

13. A method according to claim 1 wherein said species has the formula X—

R—

NA—

NAB, wherein NAB represents a biological binding partner of NA.

14. A method according to claim 1 wherein said second species has a formula X—

R—

NSBi, wherein NSBi is a non-specific binding inhibitor.