Articles having bioactive surfaces and solvent-free methods of preparation thereof

• US 20050255327A1
• Filed: 05/16/2005
• Published: 11/17/2005
• Est. Priority Date: 05/14/2004
• Status: Active Grant

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Montgomery, David, Jacobson, Ross W., Chaney, Bryce
• Granted Patent: US 7,815,922 B2
• Time in Patent Office: Days
• US Class Current: 428/448
• CPC Class Codes: A61L 2300/00 Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 31/10 Macromolecular materials
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: A61L 33/0088 by grafting of a monomer onto the substrate
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: G01N 33/54353 with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393

Abstract

Methods for preparing articles having a bioactive surface comprising treating a substrate to form free reactive groups, depositing a monomer onto the treated substrate, and covalently immobilizing a biologically functional molecule onto the deposited monomer. Additional embodiments include methods for the deposition of the monomer onto the treated substrate in a solvent-free environment. Further embodiments include articles having surfaces prepared using the methods described herein. Additional embodiments include articles prepared using the methods described herein.

Claims

1. An article comprising a bioactive surface, said article comprising:

a) a substrate;

b) an aminopropyltrimethoxysilane (APTMS) layer on said substrate, wherein said layer is of substantially uniform thickness and is substantially defect free; and

c) a biologically functional molecule covalently attached to said APTMS.

2. The article of claim 1, wherein said substrate is glass, metal, plastic, hydrogel or ceramic.

3. The article of claim 1, wherein said biologically functional molecule is selected from the group consisting of monosaccharides, disaccharides, polysaccharides, amino acids, oligopeptides, polypeptides, proteins, proteoglycans, glycoprotein, nucleic acids, oligonucleotides, polynucleotides, lipids, fatty acids, natural polymers, synthetic polymers, small molecular weight compounds and combinations thereof.

4. The article of claim 1, wherein said biologically functional molecule is selected from the group consisting of alginate, hyaluronic acid, polyethylene glycol, hydroxyethyl methacrylate, polylactide, polyglycolic acid and co-polymers thereof.

5. The article of claim 4, wherein said biologically functional molecule is hyaluronic acid.

6. The article of claim 1, said biologically functional molecule imparts a three-dimensional structure on said bioactive surface.

7. The article of claim 1, wherein said substrate is a plastic comprised of at least one compound selected from the group consisting of polypropylene, polycarbonate, polystyrene, polyurethane, polyester, polyacrylamide, cyclic olefinic copolymer, polymethylpentene, and polyethylene.

8. The article of claim 1, wherein said substrate further comprises a hydroxyl-rich polymer layer comprising free reactive groups, wherein said APTMS layer is deposited on said hydroxyl-rich polymer layer.

9. The article of claim 8, wherein said hydroxyl-rich polymer layer is hydroxyethyl methacrylate (polyHEMA).

10. The article of claim 1, wherein said article is an optical fiber.

11. The optical fiber of claim 10, wherein said optical fiber has a proximal end and a distal end, and wherein said APTMS layer is present on at least a portion of said fiber distal end.

12. The optical fiber of claim 11, wherein said biologically functional molecule comprises a polymer matrix covalently attached to the optical fiber distal end, wherein said polymer matrix is configured to receive a sensing element for sensing a target analyte in a sample.

13. The optical fiber of claim 12, wherein said polymer matrix is selected from the group consisting of hyaluronic acid (HA), alginate (AA), polyethylene glycol (PEG), hydroxyethyl methacrylate, polylactide, polyglycolic acid, methacrylate, acrylate, methacrylate-hydroxyethyl methacrylate, acrylate-hydroxyethyl methacrylate, and acrylate-methacrylate-hydroxyethyl methacrylate.

14. A biosensor comprising the optical fiber of claim 12 and a sensing element entrapped in or attached to the polymer matrix.

15. The biosensor of claim 14, wherein said sensing element comprises at least one luminescent labeled periplasmic binding protein.

16. The article of claim 1, wherein said article is a plastic or glass tissue culture vessel.

17. The article of claim 1, wherein said article is a stent.

18. A method of making the article of claim 1, comprising:

a) treating said substrate to form free reactive groups on the surface of said substrate;

b) depositing said APTMS layer onto said treated substrate in a solvent-free environment; and

c) covalently attaching a biologically functional molecule onto said APTMS-deposited layer to provide the bioactive surface of said article.

19. The method of claim 18, wherein said treating said substrate comprises exposing said substrate to water or oxygen plasma.

20. The method of claim 18, wherein said free reactive groups are hydroxyl groups.

21. The method of claim 18, wherein depositing APTMS layer onto said treated substrate in a solvent-free environment is performed by vapor deposition.

22. The method of claim 21, wherein said vapor deposition is chemical vapor deposition or physical vapor deposition or a combination of chemical and physical vapor deposition.

23. The method of claim 21, wherein said vapor deposition comprises a plasma.

24. The method of claim 18, wherein said treating said substrate comprises coating said substrate with a hydroxyl-rich polymer layer, said hydroxyl-rich polymer layer comprises free reactive groups, wherein said APTMS is deposited on said hydroxyl-rich polymer layer.

25. An article comprising a bioactive surface, said article comprising:

a) a non-metallic substrate;

b) a layer comprising a monomer that has been deposited on said substrate in a solvent-free environment, wherein said layer is of substantially uniform thickness and is substantially defect free; and

c) a biologically functional molecule covalently attached to said monomer.

26. The article of claim 25, wherein said monomer comprises a chemical group selected from the group consisting of amine, chloro, sulfhydryl, bromo, sulfhydryl, epoxide, glycidyl, cyano, acrylate, and vinyl, wherein said biologically functional molecule is covalently attached to said chemical group.

27. The article of claim 26, wherein said chemical group is an amine.

28. The article of claim 27, wherein said monomer is a silane.

29. The article of claim 28, wherein said silane is aminopropyltrimethoxysilane (APTMS), aminopropyltriethoxysilane, or 3-aminopropyltriethoxy silane (APTES).

30. An article comprising a bioactive surface, said article comprising:

a) a substrate;

b) a layer comprising a hydroxyl-rich polymer and a monomer that has been deposited on said substrate in a solvent-free environment;

c) a biologically functional molecule covalently attached to said layer.