Method of biomolecule attachment to hydrophobic surfaces

• US 5,258,041 A
• Filed: 03/19/1991
• Issued: 11/02/1993
• Est. Priority Date: 09/29/1982
• Status: Expired due to Term

• Current Assignee: Surmodics Incorporated
• Original Assignee: Bio-Tree Systems, Inc.
• Inventors: Guire, Patrick, Dunkirk, Shawn G.
• Primary Examiner(s): PREBILIC, PAUL B
• Application Number:
  US07/671,621
• Time in Patent Office: 959 Days
• Field of Search: 427/2, 435/181, 436/501, 604/266, 623/1, 623/2, 623/11, 623/66, 623/901
• US Class Current: 435/181
• CPC Class Codes: A61F 2/0077 Special surfaces of prostheses, e.g. for improving ingrowth A61F2/30767 takes precedence
• CPC Class Codes: A61K 47/68 the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/36 containing ingredients of undetermined constitution or reaction products thereof , e.g. transplant tissue, natural bone, extracellular matrix isolated natural compounds, e.g. collagen A61L27/24
• CPC Class Codes: A61L 33/0011 Anticoagulant, e.g. heparin, platelet aggregation inhibitor, fibrinolytic agent, other than enzymes, attached to the substrate
• CPC Class Codes: A61L 33/0029 using an intermediate layer of polymer
• CPC Class Codes: C12N 11/06 attached to the carrier via a bridging agent
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 2533/54 Collagen; Gelatin
• CPC Class Codes: C12N 2533/70 Polysaccharides
• CPC Class Codes: C12N 2533/78 Cellulose
• CPC Class Codes: C12N 2533/80 Hyaluronan
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: G01N 33/531 Production of immunochemical test materials
• CPC Class Codes: G01N 33/543 with an insoluble carrier for immobilising immunochemicals
• CPC Class Codes: Y10S 623/901 Method of manufacturing prosthetic device
• CPC Class Codes: Y10S 623/92 Method or apparatus for preparing or treating prosthetic

Abstract

A method for attaching a biomolecule to a support having a hydrophobic surface, involving the use of a long chain chemical spacer having a hydrophobic guiding group capable of becoming embedded in the surface, and the biomolecule being covalently bound to the spacer at its opposite end.

Claims

1. A method for attaching a biomolecule to a support having a hydrophobic surface, comprising:

attaching, to the hydrophobic surface of the support, a spacer comprising a hydrophilic chemical chain carrying a relatively hydrophobic guiding group capable of becoming embedded in the hydrophobic surface, and covalently bonding a biomolecule to the spacer,

wherein the spacer includes, along its length, a stopping group that is relatively hydrophilic to the guiding group and to the hydrophobic surface of the support, the stopping group being positioned between the bulk of the hydrophilic chain and the hydrophobic guiding group, and

wherein the guiding group is an omega aminoundecanoic acid, an epsilon amino caproic acid, a gamma aminobutyric acid, or a beta-alanine.

2. A method for attaching a biomolecule to a support having a hydrophobic surface, comprising:

(1) attaching, to the hydrophobic surface of the support a spacer comprising a hydrophilic chemical chain carrying a relatively hydrophobic guiding group capable of becoming embedded in the hydrophobic surface, and a stopping group, along the length of the spacer, the stopping group being relatively hydrophilic to the guiding group and to the hydrophobic surface of the support, the stopping group being positioned between the bulk of the hydrophilic chain and the hydrophobic guiding group, and

(2) covalently bonding a biomolecule to the spacer, wherein the guiding group is derived from an aminoalkyl carboxylic acid.

3. A method according to claim 2 wherein the aminoalkyl carboxylic acid is selected from the group consisting of omega aminoundecanoic acid, epsilon amino caproic acid, gamma aminobutyric acid, and beta-alanine.

4. A method according to claim 2 wherein the spacer further comprises a latent reactive group adjacent the guiding group in such a manner that the guiding group is positioned between the latent reactive group and the remainder of the spacer.

5. A method according to claim 2 wherein the spacer provides a chemical backbone extended chain length of not less than about 25 Angstroms between the guiding group and the biomolecule.

6. A method according to claim 2 wherein the stopping group and the spacer are both provided by the same molecule.

7. A method according to claim 6 wherein the same molecule is albumin.

8. A method for attaching a biomolecule to a support having a hydrophobic surface, comprising:

(1) covalently bonding a biomolecule to a spacer, the spacer comprising a hydrophilic chemical chain carrying a relatively hydrophobic guiding group capable of becoming embedded in the hydrophobic surface, and a stopping group, along the length of the spacer, the stopping group being relatively hydrophilic to the guiding group and to the hydrophobic surface of the support, the stopping group being positioned between the bulk of the hydrophilic chain and the hydrophobic guiding group, and

(2) attaching the spacer to the hydrophobic surface of the support, wherein the guiding group is derived from an aminoalkyl carboxylic acid.

9. A method according to claim 8 wherein the aminoalkyl carboxylic acid is selected from the group consisting of omega aminoundecanoic acid, epsilon amino caproic acid, gamma aminobutyric acid, and beta-alanine.

10. A method according to claim 8 wherein the spacer further comprises a latent reactive group adjacent the guiding group in such a manner that the guiding group is positioned between the latent reactive group and the remainder of the spacer.

11. A method according to claim 8 wherein the spacer provides a chemical backbone extended chain length of not less than about 25 Angstroms between the guiding group and the biomolecule.

12. A method according to claim 8 wherein the stopping group and the spacer are both provided by the same molecule.

13. A method according to claim 12 wherein the same molecule is albumin.

14. A method according to claim 8 wherein the spacer is covalently attached to the surface.

15. A method according to claim 14 wherein the spacer is covalently attached to the surface via a latent reactive group adjacent the guiding group.