Methods for functionalizing and coating substrates and devices made according to the methods

• US 5,830,539 A
• Filed: 11/17/1995
• Issued: 11/03/1998
• Est. Priority Date: 11/17/1995
• Status: Expired due to Fees

• Current Assignee: Advanced Microbotics Corporation
• Original Assignee: University of Oregon
• Inventors: Wybourne, Martin N., Yan, Mingdi, Karapetrov, Goran, Sevrain, Christopher J-P, Keana, John F. W.
• Primary Examiner(s): DUDASH, DIANA L
• Application Number:
  US08/565,199
• Time in Patent Office: 1,082 Days
• Field of Search: 435/176, 435/177, 427/512, 427/387, 427/2.13, 427/2.24, 427/551, 427/552, 427/596, 427/388.1, 427/337, 427/338
• US Class Current: 427/551
• CPC Class Codes: A61L 27/28 Materials for coating prostheses
• CPC Class Codes: A61L 33/0076 Chemical modification of the substrate
• CPC Class Codes: B01J 2219/00497 Features relating to the solid phase supports
• CPC Class Codes: B01J 2219/00605 the compounds being directly bound or immobilised to solid supports
• CPC Class Codes: B01J 2219/0061 The surface being organic
• CPC Class Codes: B01J 2219/00612 the surface being inorganic
• CPC Class Codes: B01J 2219/00617 by chemical means
• CPC Class Codes: B01J 2219/00626 Covalent
• CPC Class Codes: B01J 2219/00637 by coating it with another layer
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B05D 1/185 applying monomolecular layers B05D1/204 takes precedence
• 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

Abstract

Methods for coating substrates are described. The methods comprise coating at least a portion of a substrate with particular coating materials. The coating materials can be crosslinked and coated onto a substrate. Alternatively, the coating materials may be covalently bonded to the substrates. The coating materials might themselves functionalize the substrate, or provide a biocompatible coating on the substrate. The coating materials might also include electrophilic or nucleophilic groups that allow for the subsequent reaction of the coating materials with additional reagents. The present invention also provides coated workpieces, particularly medical workpieces having a surface for contacting tissue or blood. These workpieces comprise a first layer and a second layer. The first layer comprises a molecular tether covalently bonded to the surface. The second layer is bonded to the article by the first layer and comprises a bioactive agent selected from the group consisting of biocompatible polymers, antibiotics, antimicrobials and anticoagulants.

Claims

1. A method for coating a substrate, comprising:

providing a substrate; and

coating at least a portion of the substrate with a monolayer of a coating material to provide a substrate coated with a monolayer of the coating material wherein, prior to the coating, the coating material satisfies the formula

space="preserve" listing-type="equation">Y--R--Si(OR'"'"').sub.n X.sub.3-n

wherein n is 0-3, R is an aromatic group or an alkyl chain having 1-20 carbon atoms, R'"'"' is an alkyl chain having 1-10 carbon atoms, X is a halogen, Y is selected from the group consisting of H, --OH, --NH₂ and --SH, so that if Y is H the method further comprises bringing the coated substrate into reactive proximity with a perhalophenyl azide (PHPA), and exposing the substrate and the PHPA to a reaction energy source to couple the PHPA to the substrate, and if Y is selected from the group consisting of OH, --SH and --NH₂ the method further comprises reacting the coated substrate with a PHPA to produce a substrate having a PHPA attached thereto.

2. The method according to claim 1 wherein the step of exposing comprises exposing only preselected portions of the substrate to the reaction energy source.

3. The method according to claim 1 wherein the PHPA is an N-hydroxysuccinimide active ester-functionalized perfluorophenyl azide (NHS-PFPA).

4. The method according to claim 3 and further comprising reacting the NHS-PFPA with a nucleophile to couple the nucleophile to the substrate.

5. The method according to claim 4 wherein the nucleophile is selected from the group consisting of peptides, nucleotides, cells and antibodies.

6. The method according to claim 1 and further comprising:

bringing the substrate with attached PHPA into reactive proximity with a material having chemical moieties each capable of undergoing an insertion and/or addition reaction with a nitrene; and

exposing the substrate to a reaction energy source to form nitrenes that undergo insertion and/or addition reactions with the chemical moieties capable of undergoing insertion and/or addition reactions with nitrenes.

7. The method according to claim 6 wherein the step of exposing comprises exposing only preselected portions of the substrate to the reaction energy source.

8. The method according to claim 6 wherein the material having chemical moieties each capable of undergoing an insertion and/or addition reaction with a nitrene is a polymeric material.

9. The method according to claim 8 wherein the polymeric material is a biocompatible polymer.

10. A method for coating a substrate, comprising coating at least a portion of the substrate with a monolayer of a material that, prior to the coating, satisfies the formula

View Dependent Claims (11, 12, 13, 14, 15, 16)

11. The method according to claim 10 wherein the PHPA is an NHS-PFPA.

12. The method according to claim 11 and further comprising reacting a nucleophile with the NHS-PFPA to attach the nucleophile to the substrate.

13. The method according to claim 12 wherein the nucleophile is selected from the group consisting of a peptide, a nucleotide, cells and antibodies.

14. The method according to claim 10 wherein the material having chemical moieties each capable of undergoing an insertion and/or addition reaction with a nitrene is a polymeric material.

15. The method according to claim 14 wherein the polymeric material is a biocompatible material.

16. The method according to claim 15 wherein the substrate is an implantable medical device or comes into contact with blood or tissue.

17. A method for coating a material, comprising:

providing a metal or metal alloy workpiece comprising surface molecules capable of reacting with Si atoms without the addition of a free-radical generator;

exposing at least a portion of the surface molecules to a monolayer of a coating material that, prior to the exposing step, satisfies the formula

space="preserve" listing-type="equation">Y--R--Si--(OR'"'"').sub.n (X).sub.3-n

wherein n is 0-3, R is selected from the group consisting of aromatic organic compounds and alkyl chains having from about 1-20 carbon atoms, R'"'"' is a carbon chain having from about 1 to about 10 carbon atoms, X is a halogen and Y is selected from the group consisting of H, --OH, --SH and NH₂ ; and

bringing the substrate and the coating material into reactive proximity to form a substrate having a coating material covalently attached thereto.

18. The method according to claim 17 wherein Y is --OH, --SH or NH₂, and further comprising:

providing an electrophile capable of reacting with Y; and

bringing the substrate and electrophile into reactive proximity to covalently bond the electrophile to the substrate.

19. The method according to claim 18 wherein the electrophile is an electrophilic PHPA.

20. The method according to claim 19 wherein the electrophilic PHPA is an NHS-PFPA.

21. The method according to claim 17 and further comprising:

providing a nucleophilic coating material; and

bringing the substrate and nucleophilic coating material into reactive proximity to covalently bond the nucleophilic coating material to the substrate.

22. The method according to claim 21 wherein the nucleophilic coating material is selected from the group consisting of peptides, nucleotides, cells and antibodies.

23. The method according to claim 17 wherein Y is H, and further comprising:

providing a reagent comprising molecules each including a nitrenogenic group;

bringing the substrate with its coating material into reactive proximity with the reagent; and

while the substrate with its coating material and the reagent are in reactive proximity, exposing the reagent to a reaction energy source to convert the nitrenogenic groups to nitrenes that undergo insertion and/or addition reactions with the coating material.

24. The method according to claim 23 wherein the reagent is a functionalized PHPA.

25. The method according to claim 24 wherein the functionalized PHPA is an electrophilic PHPA.

26. The method according to claim 25 wherein the electrophilic PHPA is an NHS-PFPA.

27. A method for coating a metal or alloy substrate, comprising coating at least a portion of a metal or alloy substrate with a monolayer of a coating material that, prior to the coating, satisfies a first formula

View Dependent Claims (28, 29, 30, 31, 32)

28. The method according to claim 27 wherein the coating material is a carboxylic acid or an anhydride and the substrate is an aluminum substrate.

29. The method according to claim 27 wherein the coating material is applied only to preselected portions of the substrate.

30. The method according to claim 29 wherein the preselected portions are arrays.

31. The method according to claim 27 wherein Y is --OH, --SH --NH₂ and further comprising reacting the coated substrate with a PHPA to produce a substrate having an PHPA attached thereto.

32. The method according to claim 27 wherein Y is H, and further comprising:

providing a reagent comprising molecules each including a nitrenogenic group;

bringing the substrate with its coating material into reactive proximity with the reagent; and

while the substrate with its coating material and the reagent are in reactive proximity, exposing the reagent to a reaction energy source to convert the nitrenogenic groups to nitrenes that undergo insertion and/or addition reactions with the coating material.