Methods of surface modification to enhance cell adhesion

• US 20050059140A1
• Filed: 09/12/2003
• Published: 03/17/2005
• Est. Priority Date: 09/12/2003
• Status: Abandoned Application

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Liebmann-Vinson, Andrea, Chaney, Bryce N.
• Application Number:
  US10/660,759
• Publication Number:
  US 20050059140A1
• Time in Patent Office: Days
• US Class Current: 506/32
• CPC Class Codes: B82Y 15/00 Nanotechnology for interacting, sensing or actuating, e.g. quantum dots as markers in protein assays or molecular motors
• CPC Class Codes: B82Y 30/00 Nanotechnology for materials or surface science, e.g. nanocomposites
• CPC Class Codes: C12N 11/06 attached to the carrier via a bridging agent
• CPC Class Codes: C12N 11/16 Enzymes or microbial cells immobilised on or in a biological cell
• CPC Class Codes: C12N 2533/30 Synthetic polymers thermoreactive polymers, e.g. PNIPAm, C12N2539/10
• CPC Class Codes: C12N 2533/52 Fibronectin; Laminin
• CPC Class Codes: C12N 5/0068 General culture methods using substrates for specific animal cell type C12N5/06
• CPC Class Codes: G01N 2610/00 Assays involving self-assembled monolayers [SAMs]
• CPC Class Codes: G01N 33/54353 with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393
• CPC Class Codes: G01N 33/54393 Improving reaction conditions or stability, e.g. by coating or irradiation of surface, by reduction of non-specific binding, by promotion of specific binding

Abstract

The current invention relates to methods of producing a surface with enhanced cell-adhesive properties comprising treating a pre-formed surface such that at least one intermediate reactive group is exposed on the surface. The exposed intermediate reactive group is then reacted to create a self-assembled monolayer, comprising at least one reactive group. The self-assembled monolayer is created non-mechanically. The reactive group is then coupled to at least one cell-adhesive molecule. The current invention also relates to cell culture devices comprising at least one oxygen-sensing compound and a cell-adhesive molecule.

Claims

1. A method of producing a surface with enhanced cell-adhesive properties, comprising

a) treating a pre-formed surface to expose at least one intermediate reactive group on said pre-formed surface;

b) reacting said at least one intermediate reactive group to form a non-mechanical self-assembled monolayer comprising at least one reactive group; and

c) coupling at least one cell-adhesive molecule to said at least one reactive group to produce a surface with enhanced cell-adhesive properties.

2. The method of claim 1, wherein said at least one reactive group is present on said non-mechanical self-assembled monolayer immediately after said reacting said at least one intermediate reactive group.

3. The method of claim 1, wherein said at least one reactive group is not present on said non-mechanical self-assembled monolayer immediately after said reacting said at least one intermediate reactive group, and wherein a terminal group on said non-mechanical self-assembled monolayer is converted to said reactive group.

4. The method of claim 1, wherein said intermediate reactive group is a hydroxyl group.

5. The method of claim 1, wherein said pre-formed surface comprises polymer matrix.

6. The method of claim 5, wherein said polymer matrix comprises silicone.

7. The method of claim 6 wherein said silicone is polydimethyl siloxane (PDMS).

8. The method of claim 1, wherein said pre-formed surface comprises at least one oxygen-sensing compound.

9. The method of claim 8, wherein said oxygen-sensing compound is luminescent.

10. The method of claim 1, wherein said at least one reactive group comprises a reactive group selected from the group consisting of a carboxyl group, a hydroxyl group, an amide, an amino, an acyl group, an ester, an epoxy, a silane, a silanol, an aldehyde, and a sulfhydryl group.

11. The method of claim 1, wherein said reacting said at least one intermediate reactive comprises using a reactive solution.

12. The method of claim 11, wherein said reactive solution comprises a silane.

13. The method of claim 12, wherein said silane is trichlorosilane.

14. The method of claim 1, wherein said at least one cell-adhesive molecule is selected from the group consisting of a protein, a protein fragment, a polypeptide, an oligopeptide, an amino acid, a proteoglycan, a glycoprotein, a lipoprotein, a carbohydrate, a disaccharide, a polysaccharide, a nucleic acid, an oligonucleotide, a polynucleotide, a synthetic polymer, a natural polymer and combinations thereof.

15. The method of claim 14, wherein said at least one cell-adhesive molecule is selected from the group consisting of an extracellular matrix molecule, a growth factor and an antibody.

16. The method of claim 1, wherein said coupling comprises a carbodiimide.

17. The method of claim 16, wherein said carbodiimide is selected from the group consisting of ethyldimethylaminopropyl-carbodiimide, 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide and dicyclohexyl carbodiimide.

18. The method of claim 16, wherein said coupling further comprises a stabilizing agent.

19. The method of claim 18, wherein said stabilizing agent is selected from the group consisting of N-hydroxysulfosuccinimide (sulfo-NHS), hydroxysulfosuccinimide and hydroxybenzotriazolohydrate.

20. A device comprising a surface, said surface comprising

a) a polymeric matrix;

b) at least one oxygen-sensing compound; and

c) at least one cell-adhesive molecule coupled to a non-mechanical self-assembled monolayer via at least one reactive group, said non-mechanical self-assembled monolayer comprising said reactive group.