CELL CULTURE ARTICLE AND METHODS THEREOF

• US 20100285453A1
• Filed: 11/18/2008
• Published: 11/11/2010
• Est. Priority Date: 10/10/2007
• Status: Active Grant

• Current Assignee: Corning Incorporated
• Original Assignee: Corning Incorporated
• Inventors: Goodrich, Terry T.
• Granted Patent: US 8,105,822 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: G01N 33/545 Synthetic resin
• CPC Class Codes: G01N 33/551 the carrier being inorganic

Abstract

A biosensor or cell culture article including: a substrate having a bio-compatible layer. The bio-compatible layer can be obtained from surface oxidation of a substrate coating comprising the reaction product of a suitable oxidizable polymer and modifier compound, such as a triamine, attached to the oxidizable polymer. Methods for making the biosensor or cell culture article and methods for performing an assay of a ligand with the biosensor article are also disclosed.

Claims

1. A biosensor article comprising:

a substrate;

a bio-compatible layer directly or indirectly attached to the substrate; and

a second tie-layer attached to the bio-compatible layer,

the surface of the article, comprising at least the bio-compatible layer and the second tie-layer, having been oxidized prior to biosensing.

2. The article of claim 1, wherein the second tie-layer comprises a polyether triamine.

3. The article of claim 2, wherein the molecular weight of the polyether triamine is from about 200 to about 1,000.

4. The article of claim 2, wherein the molecular weight of the polyether triamine is from about 300 to about 500.

5. The article of claim 1, wherein the surface of the substrate comprises a metal oxide or a mixed metal oxide.

6. The article of claim 1, wherein the bio-compatible layer comprises at least one oxidizable polymer comprising a copolymer comprising at least one of:

poly(styrene-co-maleic anhydride), poly(styrene-maleic acid), poly(vinyl acetate-maleic anhydride), poly(maleic anhydride-alt-methyl vinyl ether), poly(triethyleneglycol methylvinyl ether-co-maleic anhydride), or a combination thereof, and the substrate comprises a surface of a metal oxide, a mixed metal oxide, SiO₂, cyclic olefin copolymer, or a combination thereof.

7. The article of claim 1, wherein the bio-compatible layer is directly attached to the substrate surface.

8. The article of claim 1, wherein the bio-compatible layer comprises the product of the second tie-layer and a polymer selected from a poly(styrene-co-maleic anhydride), poly(styrene-maleic acid), or a combination thereof, is directly attached to the substrate surface comprised of a metal oxide, a mixed metal oxide, cyclic olefin copolymer, or a combination thereof.

9. The article of claim 1, further comprising a first tie-layer attached to at least the substrate.

10. The article of claim 1, wherein the surface of the substrate comprises a cyclic olefin copolymer.

11. The article of claim 1, wherein the second tie-layer comprises a polyether diamine.

12. A method for preparing the biosensor article of claim 1, the method comprising:

providing a substrate having a polymer attached to the surface of the substrate and a second tie-layer attached to the polymer, the polymer comprising at least one oxidizable monomer, and

oxidizing the surface of the combined polymer and second tie-layer to form a bio-compatible surface on the substrate.

13. The method of claim 12, wherein oxidizing comprises contacting the surface with UV-ozone, a plasma, or both to produce the bio-compatible surface.

14. The method of claim 13, further comprising associating a bio-material with resulting bio-compatible surface.

15. The method of claim 12, wherein the polymer comprises an oxidizable a copolymer comprising at least one of:

poly(styrene-co-maleic anhydride), poly(styrene-maleic acid), poly(vinyl acetate-maleic anhydride), poly(maleic anhydride-alt-methyl vinyl ether), poly(triethyleneglycol methylvinyl ether-co-maleic anhydride), or a combination thereof, the second tie-layer comprises a polyether triamine having a molecular weight of from about 200 to about 1,000, and the substrate comprises a surface of a metal oxide, a mixed metal oxide, SiO₂, cyclic olefin copolymer, or a combination thereof

16. The method of claim 12, wherein the polymer oxidation product comprises a poly(styrene-maleic acid), the second tie-layer comprises a polyether triamine having a molecular weight of from about 200 to about 1,000, and the substrate comprises a surface of a metal oxide, a mixed metal oxide, cyclic olefin copolymer, or a combination thereof.

17. A method for performing an assay of a ligand, the method comprising:

contacting the ligand with a biosensor article of claim 1 having a bio-material associated with the bio-compatible layer, and if the ligand binds to the bio-material, then;

detecting the ligand-induced response of the bio-material with the biosensor.

18. The method of claim 17, wherein the ligand comprises a stimulus, a therapeutic candidate compound, a therapeutic candidate, a prophylactic candidate, a prophylactic agent, a chemical compound, a biological molecule, a peptide, a protein, a biological sample, a small molecule drug candidate having a molecular weight of less than about 500 Daltons, a biologic drug molecule candidate, a small molecule-biologic conjugate, a pathogen, or combinations thereof, and the bio-material comprises a natural or synthetic oligonucleotide, a natural or synthetic nucleotide/nucleoside, a nucleic acid (DNA or RNA), a natural peptide, a natural or synthetic peptide optionally comprising one or more modified or blocked amino acids, an antibody, a hapten, a biological ligand, a protein membrane, a lipid membrane, a protein, a small molecule, a cell, or a combination thereof, or a conjugate thereof.

19. The method of claim 17, wherein the biosensor comprises at least one of a surface plasmon resonance biosensor, a waveguide resonant grating biosensor, an impedance biosensor, a mass spectrometry biosensor, or a combination thereof.

20. The method of claim 17, wherein the biomaterial comprises a live-cell.

23. A biosensor article or cell culture article by the method of claim 12.

21. A cell culture article comprising:

a substrate;

a bio-compatible layer directly or indirectly attached to the substrate; and

a second tie-layer attached to the bio-compatible layer,

the surface of the article, comprising at least the bio-compatible layer and the second tie-layer, having been oxidized prior to cell culture.

22. The article of claim 21, wherein the second tie-layer comprises a polyether triamine, a polyether diamine, or a combination thereof.