Mesoporous permeation layers for use on active electronic matrix devices

• US 20050164283A1
• Filed: 03/16/2005
• Published: 07/28/2005
• Est. Priority Date: 12/10/2001
• Status: Active Grant

• Current Assignee: Ador Diagnostics S.R.L.
• Original Assignee: Nanogen, Inc.
• Inventors: Havens, John R., Wang, Daguang, Onofrey, Thomas J., Smolko, Daniel D., Krotz, Jainamma, Reese, Howard R., Winger, Theodore M.
• Granted Patent: US 7,270,850 B2
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01D 2323/18 Pore-control agents or pore formers
• CPC Class Codes: B01D 2323/34 Use of radiation
• CPC Class Codes: B01D 2323/42 Details of membrane preparation apparatus
• CPC Class Codes: B01D 67/003 by selective elimination of components, e.g. by leaching
• CPC Class Codes: B01D 69/125 In situ manufacturing by polymerisation, polycondensation, cross-linking or chemical reaction
• CPC Class Codes: C09D 123/26 modified by chemical after-treatment
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: C12Q 1/003 Functionalisation
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: G01N 33/545 Synthetic resin

Abstract

The present invention provides improved synthetic polymer hydrogel permeation layers for use on active electronic matrix devices for biological assays. The present invention includes methods for forming a permeation layer on an array of microelectrodes including the steps of attaching a linker to the surface of the array by treating the surface with a linker by vapor deposition and providing a polymerization solution that includes at least one monomer having a polymerizable moiety, a modified streptavidin, a surfactant or porogen, and a cross-linking agent. The surface of the array is then contacted with the polymerization solution and the polymerization solution is then polymerized on the surface of the array to form a permeation layer that is attached o the surface of the array through the linker.

Claims

1. A method for forming a permeation layer on an array of microelectrodes comprising the steps of:

attaching a linker to a surface of the array of microelectrodes by treating the surface with a linker by vapor deposition;

providing a polymerization solution comprising;

at least one monomer having a polymerizable moiety;

a modified streptavidin;

a surfactant or porogen;

and a cross-linking agent;

contacting the surface of the array with the polymerization solution;

polymerizing the polymerization solution on the surface of the array to form a permeation layer, wherein the permeation layer is attached to the surface of the array through the linker.

2. The method of claim 1, wherein the streptavidin is modified with an acryloyl functional group.

3. The method of claim 2, wherein the modified streptavidin is formed by reacting streptavidin with N-acryloxysuccinimide.

4. The method of claim 1, wherein the streptavidin is modified with PEG-ester linked acrylate moieties.

5. The method of claim 1, wherein the polymerization solution is placed in a mold cavity.

6. The method of claim 5, wherein the mold cavity comprises a bottom and at least one side and wherein the array and mold cavity form a closed volume for the polymerization mixture that is in contact with at least one microelectrode in the array of microelectrodes.

7. The method of claim 1, wherein the porogen is a templating porogen.

8. The method of claim 7, wherein the templating porogen is a Brij surfactant.

9. The method of claim 1, wherein the templating porogen is a micelle-forming surfactant.

10. The method of claim 1, further comprising the step of removing the porogen or surfactant with a solvent.

11. The method of claim 1, wherein the polymerizable moiety is selected from the group consisting of alkenyl, vinyl, allyl, homoallyl, alkynyl, epoxide, cyclic anhydride, ester, ether, and alkylene moieties.

12. The method of claim 1, wherein the at least one monomer having a polymerizable moiety is an acryloyl or acrylamido monomer.

13. The method of claim 12, wherein the acrylamido monomer is selected from the group consisting of acrylamides, N-substituted acrylamides;

N-substituted methacrylamides, and methacrylamide.

14. The method of claim 12, wherein the acrylamido monomer is methacrylamide.

15. The method of claim 1, wherein the cross-linker is metheylene bisacylamide.

16. The method of claim 1, wherein the polymerization solution further comprises a free radical initiator.

17. The method of claim 16, wherein the free radical initiator is a photoinitiator, and wherein the polymerization step comprises irradiating the polymerization solution with radiation at a wavelength appropriate to activate the photoinitiator.

18. The method of claim 1, wherein the permeation layer is approximately 1 nanometer to 100 microns thick.

19. The method of claim 1, wherein the array of microelectrodes comprises electrodes made from a material selected from the group consisting of platinum silicide, tungsten silicide, titanium silicide, and gold silicide.

20. The method of claim 1, wherein the array of microelectrodes comprises electrodes made from a material selected from the group consisting of aluminum, copper, carbon, iron, silver, gold, palladium, platinum, titanium, tungsten, polysilicon, and indium tin oxide.

21. The method of claim 1, wherein the array of microelectrodes comprise platinum electrodes.

22. The method of claim 1, further comprising the step of treating the array with an argon plasma before attaching the linker.

23. The method of claim 1, further comprising insulating material that overlays the array of microelectrodes, and wherein the insulating material has been removed to expose at least one microelectrode in the array of microelectrodes.

24. The method of claim 23, wherein the insulating material has been removed to expose all of the microelectrodes in the array of microelectrodes.

25. The method of claim 23, wherein the insulating material is silicon dioxide.

26. The method of claim 1, wherein the linker is covalently attached to the surface.

27. The method of claim 1, wherein the linker has a acryloyl moiety.

28. The method of claim 27, wherein the linker is 3-methacryloxy-propyl-trimethoxysilane.

29. The method of claim 1, wherein the linker is selected from the group consisting of acrylates, methacrylates, acrylamides, methacrylamides, allyl derivatives, amino derivatives, and epoxy derivatives.

30. The method of claim 1, wherein the linker is selected from the group consisting of APS, AEAPS, AHAPS, MOTS, and AMPTS.