Biomolecule attachment to hydrophobic surfaces

• US 5,217,492 A
• Filed: 04/03/1991
• Issued: 06/08/1993
• 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:
  US07/681,478
• Time in Patent Office: 797 Days
• Field of Search: 427/2, 435/181, 436/501, 623/1, 623/2, 623/11, 623/66, 623/901, 604/266
• US Class Current: 600/36
• 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 2300/252 Polypeptides, proteins, e.g. glycoproteins, lipoproteins, cytokines
• CPC Class Codes: A61L 2300/254 Enzymes, proenzymes
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/418 Agents promoting blood coagulation, blood-clotting agents, embolising agents
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 27/34 Macromolecular materials
• CPC Class Codes: A61L 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• 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: 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 623/924 Material characteristic

Abstract

A long chain chemical spacer useful for attaching a biomolecule to a support having a hydrophobic surface, the spacer having a hydrophobic guiding group capable of becoming embedded in the surface, and optionally including a stopping group and/or an attached biomolecule.

Claims

1. A spacer for attaching a biomolecule to a support having a hydrophobic surface, the spacer comprising a hydrophilic chemical chain carrying a relatively hydrophobic guiding group capable of becoming embedded in the hydrophobic surface, the spacer being capable of covalently bonding to a biomolecule,

the spacer further comprising 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,

wherein the guiding group is derived from an aminoalkyl carboxylic acid.

2. A spacer according to claim 1 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.

9. A spacer according to claim 1 or 3 further comprising a latent reactive group adjacent the guiding group, the latent reactive group being capable of covalently attaching the spacer to the surface.

10. A spacer according to claim 9 wherein;

the latent reactive group is selected from the group consisting of aryl, alkyl, and acyl azides, oxazidines, isocyanates, alkyl and 2-ketodiazo derivatives and diazirines, aromatic ketones, and aromatic diazonium derivatives;

the guiding group is selected from the group consisting of omega aminoundecanoic acid, epsilon amino caproic acid, gamma aminobutyric acid, and beta-alanine;

the stopping group is selected from the group consisting of albumin, monosaccharides, polysaccharides, cysteic acid, gluconic acid, and taurine; and

the spacer chain is selected from the group consisting of chains having repeating ethoxy or isopropoxy groups.

11. A spacer according to claim 10 wherein;

the latent reactive group is benzoyl benzoic acid;

the guiding group is omega aminoundecanoic acid;

the stopping group is cysteic acid; and

the spacer chain is polyethylene glycol.

3. A spacer and biomolecule combination for attaching the biomolecule to a support having a hydrophobic surface, the spacer comprising a hydrophilic chemical chain carrying a relatively hydrophobic guiding group capable of becoming embedded in the hydrophobic surface, the spacer having the biomolecule covalently bound thereto,

the spacer further comprising 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,

wherein the guiding group is derived from an aminoalkyl carboxylic acid.

4. A spacer according to claim 3 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.

5. A spacer according to claim 3 wherein the stopping group and the spacer are both provided by the same molecule.

6. A spacer according to claim 5 wherein the same molecule is albumin.

7. A combination of spacer and support having a hydrophobic surface, for attaching a biomolecule to the support surface, the spacer comprising a hydrophilic chemical chain carrying a relatively hydrophobic guiding group, the group being embedded in the hydrophobic surface of the support, the spacer being capable of covalently bonding to a biomolecule,

the spacer further comprising 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,

wherein the guiding group is derived from an aminoalkyl carboxylic acid.

8. A combination of spacer, biomolecule, and support having a hydrophobic surface, comprising a spacer covalently bound to the biomolecule, thereby attaching the biomolecule to the support surface, the spacer comprising a hydrophilic chemical chain carrying a relatively hydrophobic guiding group, the group being embedded in the hydrophobic surface of the support,

the spacer further comprising 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,

wherein the guiding group is derived from an aminoalkyl carboxylic acid.