Polymer-coated optical structures and methods of making and using the same

• US 4,992,385 A
• Filed: 07/22/1987
• Issued: 02/12/1991
• Est. Priority Date: 07/24/1986
• Status: Expired due to Term

• Current Assignee: Applied Research Systems ARS Holding NV (Merck & Co., Inc.)
• Original Assignee: Ares-Serono Research & Development Limited Partnership
• Inventors: Godfrey, Robin E.
• Primary Examiner(s): Hill, Jr., Robert J.
• Application Number:
  US07/076,519
• Time in Patent Office: 1,301 Days
• Field of Search: 436/805, 436/525, 436/164, 436/807, 436/528, 250/461.1, 250/461.2, 422/55-57, 422/58, 422/69, 422/82.11, 350/96.19, 264/212, 264/298, 427/169, 427/430.1, 427/162, 427/409, 427/410, 427/435
• US Class Current: 436/525
• CPC Class Codes: G01N 33/54373 involving physiochemical end-point determination, e.g. wave-guides, FETS, gratings
• CPC Class Codes: G01N 33/544 the carrier being organic
• CPC Class Codes: G01N 33/553 Metal or metal coated
• CPC Class Codes: Y10S 436/805 Optical property

Abstract

A method of treating the surface of an optical structure which comprises forming on the surface a thin layer of organic polymer using a solvent casting technique. Preferably the process includes the subsequent treatment of the polymer layer with a solution of a specific ligand.

Complex formation between the bound ligand and its specific binding partner present in a sample to be analyzed alters the optical properties of the diffraction grating surface and the change can form the basis of an assay method.

Claims

1. A method of applying a uniform, thin polymer film to the surface of a metallised diffraction grating which comprises the steps of:

(i) inserting the metallised diffraction grating into a bath containing a casting liquid,

(ii) forming a thin film of a desired polymer over the surface of the casting liquid, and

(iii) either raising the diffraction grating through the casting liquid to engage the film of polymer on the surface of the liquid or allowing the casting liquid to drain out of the bath so that the polymer film on the surface of the liquid drops as the liquid level drops until it engages and spreads over the surface of the diffraction grating, in either case the diffraction grating being located at a small angle to the horizontal to facilitate draining of the casting liquid from the surface of the diffraction grating.

2. The method of claim 1 wherein the thin polymer film is 5 to 100 nm thick.

3. The method of claim 2 wherein the casting solution is water and the polymer is cellulose nitrate.

4. The method of claim 3 wherein the thin film of polymer is formed by dropping a solution of cellulose nitrate in amyl acetate onto the water surface.

5. The method of claim 4 additionally comprising adsorbing on or binding to the thin polymer film either directly or indirectly, a specific binding partner for a ligand which is desired to be assayed.

6. A method of preparing an optical structure useful for the detection of a ligand in a spectrophotometric assay technique, said optical structure having a surface relief profile or being capable of supporting surface plasmon resonance, which method comprises applying to the entire surface of the optical structure a uniform, thin layer of an organic polymer by means of a solvent casting technique and adsorbing on or binding to the thin layer of organic polymer, either directly or indirectly, a specific binding partner for the ligand.

7. The method of claim 6 wherein the optical structure is a metallized diffraction grating.

8. The method of claim 7 wherein the thin layer of organic polymer is 5 to 100 nm thick.

9. The method of claim 8 wherein the metallized diffraction grating is adapted to support surface plasmon resonance of a ligand/specific binding partner complex formed thereon.

10. The method of claim 9 wherein the thin layer of organic polymer is activated prior to contact with the specific binding partner to facilitate binding thereof.

11. The method of claim 10 wherein the specific binding partner is applied to at least one discrete region of the thin layer of organic polymer to form at least one test region and a non-binding protein is applied to at least one other discrete region of the thin layer of organic polymer to form at least one reference region.

12. The method of claim 11 wherein the metallized diffraction grating has a surface comprising a thin film of silver less than 500 nm thick.

13. The method of claim 12 wherein the specific binding partner is an antigen or antibody.

14. The method of claim 13 wherein the organic polymer is cellulose nitrate.

15. An optical biosensor useful for the detection of a ligand in a spectrophotometric assay technique which comprises an optical structure having a surface relief profile coated over its entire surface with a uniform, thin layer of an organic polymer of 5 to 100 nm thick to which is bound or adsorbed, directly or indirectly, a specific binding partner for the ligand.

16. The optical biosensor of claim 16 wherein the optical structure is a metallized diffraction grating.

17. The optical biosensor of claim 16 wherein the metallized diffraction grating has a surface comprising a thin film of silver less than 500 nm thick.

18. In a method of detecting a ligand in a sample utilizing a spectrophotometric assay technique which comprises contacting the sample with an optical biosensor and measuring the change in optical characteristics of the optical biosensor caused by formation of a ligand/specific binding partner complex thereon, the improvement wherein the optical biosensor comprises an optical structure having a surface relief profile coated over its entire surface with a uniform, thin layer of an organic polymer of 5 to 100 nm thick to which is bound or adsorbed, directly or indirectly, the specific binding partner for the ligand.

19. The method of claim 18 wherein the optical structure is a metallized diffraction grating.

20. The method of claim 19 wherein the metallized diffraction grating has a surface comprising a thin film of silver less than 50 nm thick.