Polymer brushes for immobilizing molecules to a surface and having water-soluble or water-dispersible segments therein and probes bonded thereto

• US 20050158879A1
• Filed: 12/15/2004
• Published: 07/21/2005
• Est. Priority Date: 07/02/1999
• Status: Abandoned Application

• Current Assignee: Freeslate Inc. (Unchained Labs Inc.)
• Original Assignee: Symyx Technologies Incorporated (Dassault Systemes SA)
• Inventors: Jandeleit, Bernd, Charmot, Dominique, Klaerner, Gerrit, Mansky, Paul, Mazzola, Laura T., Benoit, Didier, Nielsen, Ralph B.
• Application Number:
  US11/012,416
• Publication Number:
  US 20050158879A1
• Time in Patent Office: Days
• US Class Current: 436/532
• CPC Class Codes: C08F 220/54 Amides , e.g. N,N-dimethylacrylamide or N-isopropylacrylamide
• CPC Class Codes: C08F 4/00 Polymerisation catalysts
• CPC Class Codes: G01N 27/44747 Composition of gel or of carrier mixture
• CPC Class Codes: G01N 33/54353 with ligand attached to the carrier via a chemical coupling agent coatings G01N33/54393
• CPC Class Codes: Y10T 428/8305 Miscellaneous [e.g., treated surfaces, etc.]
• CPC Class Codes: Y10T 436/10 Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing

Abstract

Sensors for determining the presence and concentration of bio-molecules in a biological sample are provided in the form of polymer brushes, which comprise a substrate having a surface that is modified with a water-dispersible or water-soluble polymer segment having functional groups that bind probes. The method of synthesis of such sensors preferably includes use of controlled free radical polymerization techniques, and in particular the use of an iniferter initiator, which allows for controlled architecture polymers to modify the surface of the substrate. In this manner functional groups in the polymer chain are removed from the surface, which allows for solution chemistry to be more realistically reproduced with the benefits of a solid bound probe.

Claims

1. A polymer brush comprising:

(a) a substrate having a surface, and

(b) a layer on the substrate surface comprising polymer chains having two termini and an intermediate portion between the termini, one terminus being free and the other terminus being bound to the substrate surface, the intermediate portion being a copolymer and having a weight average molecular weight of at least about 1,000, and being substantially free of crosslinks to the intermediate portion of other polymer chains, the polymer chains having a density of from about 1 picomole per square centimeter to about 100 picomoles per square centimeter of substrate surface area.

2. The polymer brush of claim 1 further comprising functional sites on the intermediate portions of the polymer chains and a probe attached to the functional sites for binding a molecule, the functional sites having a density of at least about 20 picomoles per square centimeter of substrate surface area.

3. The polymer brush of claim 1 wherein said polymer chains are non-linear polymers selected from the group consisting of branched polymers, star polymers, and combinations thereof.

4. The polymer brush of claim 1 wherein said polymer chains are terpolymers.

5. The polymer brush of claim 1 wherein said density of said polymer chains is from about 10 picomoles per square centimeter to about 45 picomoles per square centimeter of substrate surface area.

6. The polymer brush of claim 1 wherein said polymer chains are random copolymers.

7. The polymer brush of claim 1 wherein said polymer chains are block copolymers.

8. The polymer brush of claim 1 wherein said polymer chains comprise units having the formula:

9. The polymer brush of claim 1 wherein said polymer chains form a layer on said surface having a dry thickness ranging from about 10 angstroms to about 2000 angstroms.

10. The polymer brush of claim 1 further comprising spacer molecules bound to said surface so that the ratio of polymer chains to the sum of polymer chains and spacer molecules is less than 1.

11. The polymer brush of claim 10 wherein said spacer molecules bound to said surface are characterized by the formula:

12. The polymer brush of claim 1 wherein the intermediate portions are water-dispersible or water-soluble.

13. A polymer brush comprising:

(a) a substrate having a surface, and

(b) a layer on the substrate surface comprising polymer chains having two termini and an intermediate portion between the termini, one terminus being free and the other terminus being bound to the substrate surface, the intermediate portion being a copolymer and having a weight average molecular weight of at least about 1,000,

wherein an average number of polymer chain attachment points per unit area of substrate surface, denoted by n, is greater than n_c/25, where n_c is the number of attachment points per unit area at which the average distance between attachment points is twice the radius of gyration of the polymer chains under the condition of the assay.

14. The polymer brush of claim 13 wherein n is greater than n_c/4.

15. The polymer brush of claim 13 wherein n is greater than n_c.

16. The polymer brush of claim 13 wherein the polymer chains have a weight average molecular weight of at least 100,000 and n is greater than n_c/4.

17. The polymer brush of claim 13 wherein said polymer chains are non-linear polymers selected from the group consisting of branched polymers, star polymers, and combinations thereof.

18. The polymer brush of claim 13 wherein said polymer chains are terpolymers.

19. The polymer brush of claim 13 wherein said polymer chains comprise units having the formula:

20. The polymer brush of claim 13 wherein said polymer chains form a layer on said surface having a dry thickness ranging from about 20 angstroms to about 2000 angstroms.

21. The polymer brush of claim 13 further comprising spacer molecules bound to said surface so that the ratio of polymer chains to the sum of polymer chains and spacer molecules is less than 1.

22. The polymer brush of claim 21 wherein said spacer molecules bound to said surface are characterized by the formula: