Permeation layer attachment chemistry and method

• US 20050158451A1
• Filed: 12/23/2004
• Published: 07/21/2005
• Est. Priority Date: 12/15/1999
• Status: Abandoned Application

• Current Assignee: Nanogen, Inc.
• Original Assignee: Nanogen, Inc.
• Inventors: Onofrey, Thomas J., Krotz, Jain, Winger, Theodore M., Dan, Smolko, John, Havens R.
• Application Number:
  US11/022,200
• Publication Number:
  US 20050158451A1
• Time in Patent Office: Days
• US Class Current: 427/2.110
• CPC Class Codes: B01J 2219/00653 the compounds being bound to electrodes embedded in or on the solid supports
• CPC Class Codes: B01J 2219/00659 Two-dimensional arrays
• CPC Class Codes: B01J 2219/00722 Nucleotides
• CPC Class Codes: B01J 2219/00725 Peptides
• CPC Class Codes: C40B 40/06 Libraries containing nucleotides or polynucleotides, or derivatives thereof
• CPC Class Codes: C40B 40/10 Libraries containing peptides or polypeptides, or derivatives thereof
• CPC Class Codes: G01N 27/40 Semi-permeable membranes or partitions
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

Electronically addressable microchips having covalently bound permeation layers and methods of making such covalently bonded permeation layers to microchips are provided. The covalent bonding is derived from combining the use of electrodes with silane derivatives. Such chemistry provides the ability to apply an electronic bias to the electrodes of the microchip while preventing permeation layer delaminating from the electrode surface. Methods for covalently attaching the permeation layer to the microchips are also described.

Claims

1. A method of covalently attaching a permeation layer having reactive moieties to an electrode of an electronically addressable microchip comprising:

contacting the surface of the electrode with a linker molecule by vapor deposition wherein the linker molecule comprises a first reactive moiety that is capable of reacting with the electrode surface to form a covalent bond with the electrode, and a second reactive moiety that is capable of reacting with monomers to form the permeation layer;

reacting the first moiety of the linker molecule with the electrode surface to form a covalent bond between the linker molecule and the electrode surface;

synthesizing the permeation layer by reacting the linker molecule with monomers under conditions where polymerization is conducted between the monomers and the second reactive moiety of the linker;

wherein the resulting covalent attachment between the electrode and the linker and the permeation layer material is stable at a current density of at least 0.10 nA/μ

m².

2. The method of claim 1, wherein the electrode is a metal/silicide electrode selected from the group consisting of platinum silicide, tungsten silicide, titanium silicide, and gold silicide.

3. The method of claim 1, wherein the electrode is a metal/metal electrode selected from the group consisting of platinum/titanium and gold /titanium.

4. The method of claim 1, wherein the electrode is an organic electrode selected from the group consisting of poly(phenylene vinylene), polythiophene, and polyaniline.

5. The method of claim 1, wherein the linker has the formula

6. The method of claim 5, wherein the linker is selected from the group consisting of

H₂NCH₂CH₂CH₂Si(OCH₃)_3,
H₂NCH₂CH₂NHCH₂CH₂CH₂Si(OCH₃)_3,
H₂NCH₂CH₂CH₂CH₂CH₂CH₂NHCH₂CH₂CH₂Si(OCH₃)_3,
CH₂═

C(CH₃)COOCH₂CH₂CH₂Si(OCH₃)_3, and
CH₂═

CHCONHCH₂CH₂CH₂Si(OC₂Hs)₃.

7. The method of claim 6, wherein the linker is H₂NCH₂CH₂CH₂Si(OCH₃)₃.

8. The method of claim 6, wherein the linker is H₂NCH₂CH₂NHCH₂CH₂CH₂Si(OCH₃)₃.

9. The method of claim 6, wherein the linker is CH₂═

C(CH₃)COOCH₂CH₂CH₂Si(OCH₃)₃.

10. The method of claim 5, wherein the linker is an acrylate linker selected from the group consisting of

CH₂═

CHCOOCH₂CH₂CH₂Si(OCH₃)_3,
CH₂═

CHCOOCH₂CH₂CH₂SiCl_3,
CH₂═

CHCOOCH₂CH₂CH₂Si(CH₃)(OCH₃)_2,
CH₂═

CHCOOCH₂CH₂CH₂Si(CH₃)₂(OCH₃),
CH₂═

CHCOOCH₂CH₂CH₂Si(CH₃)Cl_2, and
CH₂═

CHCOOCH₂CH(OH)CH₂NHCH₂CH₂CH₂Si(OC2H₅)_3.

11. The method of claim 5, wherein the linker is a methacrylate linker selected from the group consisting of

CH₂═

C(CH₃)COOCH₂CH₂CH₂Si(OCH₃)₃,
CH₂═

C(CH₃)COOCH₂CH₂CH₂SiCl_3,
CH₂═

C(CH₃)COOCH₂CH₂CH₂Si(CH₃)(OCH₃)_2,
CH₂═

C(CH₃)COOCH₂CH₂CH₂Si(CH₃)₂(OCH₃),
CH₂═

C(CH₃)COOCH₂CH₂CH₂Si(CH₃)Cl_2, and
CH₂═

C(CH₃)COOCH₂CH(OH)CH₂NHCH₂CH₂CH₂Si(OC₂H₅)_3.

12. The method of claim 5, wherein the linker is an acrylamide linker selected from the group consisting of

CH₂═

CHCONHCH₂CH₂CH₂Si(OC₂H₅)_3,
CH₂═

CHCONHCH₂CH₂CH₂SiCl_3,
CH₂═

CHCONHCH₂CH₂CH₂Si(CH₃)(OCH₃)_2,
CH₂═

CHCONHCH₂CH₂CH₂Si(CH₃)₂(OCH₃),
CH₂═

CHCONRCH₂CH₂CH₂Si(CH₃)C1_2,
CH₂═

CHCONHCH₂CH(OH)CH₂NHCH₂CH₂CH₂Si(OC₂H₅)₃, and
CH₂═

CHCONHCH₂CH₂CONHCH₂CH₂CONHCH₂CH₂CH₂Si(OC₂H₅)_3.

13. The method of claim 5, wherein the linker is a methacrylamide linker selected from the group consisting of

CH₂═

C(CH₃)CONHCH₂CH₂CH₂Si(OCH₃)₃,
CH₂═

C(CH₃)CONHCH₂CH₂CH₂SiCl_3,
CH₂═

C(CH₃)CONHCH₂CH₂CH₂Si(CH₃)(OCH₃)_2,
CH₂═

C(CH₃)CONHCH₂CH₂CH₂Si(CH₃)₂(OCH₃),
CH₂═

C(CH₃)CONHCH₂CH₂CH₂Si(CH₃)Cl_2, and
CH₂═

C(CH₃)CONHCH₂CH(OH)CH₂NHCH₂CH₂CH₂Si(OC₂H₅)_3.

14. The method of claim 5, wherein the linker is an allyl derivative linker selected from the group consisting of

CH₂═

CHCH₂NHCH₂CH₂CH₂Si(OCH₃)_3,
CH₂═

CHCH₂SiH(OCH₃)_2,
CH₂═

CHCH₂Si(CH₃)₂Cl,
CH₂═

CHCH₂SiHCl_2, and
CH₂═

CHCH₂Si(OCH₃)_3.

15. The method of claim 5, wherein the linker is an amino derivative linker selected from the group consisting of

H₂NCH₂CH₂NHCH₂CH₂CH₂Si(OCH₃)_3,
H₂NCH₂CH₂CH₂CH₂CH₂CH₂NHCH₂CH₂CH₂Si(OCH₃)₃,
H₂NCH₂CH₂CH₂Si(OCH₃)₃, and
H₂NCH₂CH₂CH₂Si(OC₂H₅)_3.

16. The method of claim 5, wherein the linker is an epoxy derivative linker selected from the group consisting of

17. The method according to claim 1, wherein the permeation layer is a hydrogel comprising a material selected from the group consisting of agarose, glyoxylagarose, acrylamide, methacrylamide, polyacrylamide, and other synthetic polymers.

18. The method of claim 17, wherein the hydrogel comprises glyoxylagarose.

19. The method of claim 17, wherein the hydrogel comprises polyacrylamide.

20. The method of claim 1, wherein the step of reacting the linker molecule with monomers is a Schiff base reduction or polymerization.

21. The method of claim 1, wherein the second reactive moiety of the linker comprises an amine group.

22. The method of claim 1, wherein steps (b) and (c) occur at different times.

23. The method of claim 1, wherein the step of reacting the first moiety of the linker molecule with the electrode surface comprises heat curing of the linker molecule and the electrode surface.

24. The method of claim 1, wherein the resulting covalent attachment between the electrode and the linker and the permeation layer material is stable at a current density of at least 0.14 nA/μ

m².

25. The method of claim 1, wherein the resulting covalent attachment between the electrode and the linker and the permeation layer material is stable at a current density of at least 0.2 nA/μ

m².

26. The method of claim 1, wherein the resulting covalent attachment between the electrode and the linker and the permeation layer material is stable at a current density of at least 0.4 nA/μ

m².

27. The method of claim 1, wherein the step of reacting the linker molecule with monomers is a free radical polymerization reaction.

28. The method of claim 1, wherein the polymerization is conducted in a solution phase reaction.

29. The method of claim 1, wherein the polymerization is conducted between the monomers, and between the monomers and the second reactive moiety of the linker.