Printable hydrogels for biosensors

• US 20100166607A1
• Filed: 05/20/2005
• Published: 07/01/2010
• Est. Priority Date: 05/20/2004
• Status: Active Grant

• Current Assignee: Sanofi S.A. (Sanofi )
• Original Assignee: Sanofi S.A. (Sanofi )
• Inventors: Bartetzko, Norbert
• Granted Patent: US 8,828,203 B2
• Time in Patent Office: Days
• US Class Current: 422/68.100
• CPC Class Codes: C08F 10/02 Ethene
• CPC Class Codes: C08F 6/006 Removal of residual monomers by chemical reaction, e.g. scavenging
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: C12Q 1/004 mediator-assisted
• CPC Class Codes: G01N 27/327 Biochemical electrodes , e.g. electrical or mechanical details for in vitro measurements
• CPC Class Codes: G01N 27/3272 Test elements therefor, i.e. disposable laminated substrates with electrodes, reagent and channels optical biosensors G01N33/52
• CPC Class Codes: G01N 33/5438 Electrodes

Abstract

Methods and apparatus are provided for manufacturing an analyte detecting device. In one embodiment, the method comprises providing a substrate, applying a plurality of layer of materials on said substrate; applying a layer containing at least one mediator; and screen printing a hydrogel on the layer.

Claims

1. A method of manufacturing an analyte detecting device, said method comprising:

providing a substrate;

applying a plurality of layers of materials on said substrate, wherein said layers form an electrode device; and

screen printing a hydrogel on said layers.

2. The method of claim 1 further comprising applying a plurality of layers of materials to form a sample capture device.

3. The method of claim 1 wherein said hydrogel includes a zwitterionic compound.

4. The method of claim 1 wherein said hydrogel includes a zwitterionic compound selected from one of the following:

CHAPS or its derivatives.

5. The method of claim 1 wherein said hydrogel further comprises applying a layer containing at least one mediator, said hydrogel being formed in contact with the mediator.

6. A method manufacturing an analyte detecting device, said method comprising:

providing a substrate;

coating analyte detecting member surfaces/electrodes on said substrate with a cross-linkable hydrophilic polymer dispersion containing at least one of the following;

a hydrophilic monomer mixture, a low molecular weight cross-linker and/or a hydrophilic high molecular weight polymer and preferably with an initiator.

10. A compound described in claim 6 wherein compound is configured to achieve highly cross-linked hydrogel to allow the permeation of low molecular weight analytes to the entrapped enzyme.

11. The hydrophilic high molecular weight compound as described in claim 6 is homo- or copolymer based on monomers such as but not limited to, N-vinyl pyrrolidone, ethylene oxide, acrylic or methacrylic acid and salts, esters and amides thereof, vinyl alcohol and derivatives thereof and glucose and the derivatives thereof.

12. The hydrophilic high molecular weight compound as described in claim 6 wherein macromolecular compound can be partially vinyl functionalized and will be entrapped in or covalently bond to the formed poly vinyl matrix by thermal- or UV-induced radical polymerization.

13. The compound as described in claim 6 wherein the macromer is a di- or polyvinylfunctional macromolecular substance based on di- or polyhydroxy-functionized polymers such as but not limited to, polyvinyl alcohol and derivatives thereof, poly ethylene glycol, polyalkylene oxide, polysaccharides or hydroxy terminated polyurethane'"'"'s which are as well rheological additive as well as macromolecular cross-linker.

14. The hydrophilic monomer mixture as described in claim 6 further comprising water-soluble vinyl monomers selected from one of the following:

acrylic and methacrylic acid and salts, amides and esters thereof, N-vinyl pyrrolidone and other water-soluble vinyl monomers.

15. The compound as described in as described in claim 6 wherein the low molecular weight cross-linkers are di- or polyesters, -ethers or -amides of acrylic or methacrylic acid and other radically polymerisable vinyl compounds.

16. The compound as described in claim 6 wherein the concentration as well as the molecular weight of the cross-linker as described in claim 17 as well as the degree of vinyl fictionalizations of the macromer as decried in claim 14 determines the porosity of the gel, which allows entrapment or permeation of the biological active species.

17. The compound as described in claim 6 contains a thermal or photochemical initiator selected from one of the following:

(functionalized) alkylphenones or redox initiators, preferably UV-cleavable initiators.

18. The compound as described in claim 6 contains at least one surfactant, which enhances the wettability of the analyte solution on the surface as well as the swelling of the hydrogel coating in contact with the analyte solution.

19. The compound as described in claim 17 wherein the surfactants are non-ionic surfactants such as but not limited to, alkylphenol polyglycol ethers, sorbitan esters, (ethoxylated) alkin dolls (partially) fluorinated nonionic surfactants, anionic surfactants, alkylsulfonates, alkylbenzenesulfonates or (partially) fluorinated surfactants, or zwitter-ionic surfactants, zwitter-ionic cholic acid derivatives or betain sulfates.

20. The compound as described in claim 17 wherein the surfactant (mixture) increases the wettability of the polymer dispersion applied on the more hydrophobic substrate surface by means of (screen-) printing.

21. The compound as described in claim 6 wherein the polymer dispersion can contain further additives enabling the printability such as but not limited to, defoamers, retarders, pigments, dyes or further rheological additives.

7. A compound for use on an analyte detecting device, said compound comprising:

a cross-linkable hydrophilic polymer dispersion containing a hydrophilic monomer mixture, a low molecular weight cross-linker and a hydrophilic high molecular weight polymer and preferably with an initiator.

8. The compound described in claim 7 wherein the low molecular weight cross-linker and the high molecular weight polymer may be replaced or used in combination with one of the following:

a hydrophilic, (partially) vinyl functionalized high molecular weight polymer, a so-called macromer.

9. The compound described in claim 7 wherein said compound is configured to allow rapid wicking of the analyte solution as well as rapid swelling of the resulting hydrogel membrane to allow a fast diffusion of the analyte to the enzyme.

22. A method of manufacturing an analyte detecting device, said method comprising:

stencil or screen-printing a hydrophilic coating that contains at least one of the following;

a hydrophilic polymerbinder, a surface-active compound, and a solvent.

23. A method of manufacturing an analyte detecting device, said method comprising:

stencil or screen-printing a hydrophilic coating that contains at least a hydrophilic polymerbinder, surface-active compound, defoamer and a solvent.

24. A method of manufacturing an analyte detecting device, said method comprising:

stencil or screen-printing a hydrophilic coating that contains at least one of the following;

a hydrophilic polymerbinder, surface-active compound, defoamer, retarder and a solvent.

25. A device comprising:

a substrate;

at least one electrically conductive lead line formed on the substrate;

an insulating layer;

a least one working electrode and at least one counterelectrode each formed to contact at least one electrically conductive lead line, wherein an upper portion of the working electrode has a width greater than a lower portion of the electrode;

a hydrogel layer formed over the electrode; and

a sample capture structure coupled and positioned to deliver fluid to the hydrogel layer.

26. The device of claim 25 wherein the lower portion is at least 25% narrower than the upper portion of the electrode.

27. The device of claim 25 wherein the lower portion is at least 50% narrower than the upper portion of the electrode.

28. The device of claim 25 wherein the lower portion is at least 75% narrower than the upper portion of the electrode.

29. The device of claim 25 wherein the counter electrode also has an upper portion wider than a lower portion.

30. The device of claim 25 wherein said hydrogel includes a zwitterionic compound.

31. The device of claim 25 wherein said hydrogel includes a zwitterionic compound selected from one of the following:

CHAPS or its derivatives.

32. The device of claim 25 further comprising a surfactant.

33. The device of claim 25 further comprising a mediator.

34. The device of claim 25 wherein said hydrogel comprises a cross-linkable hydrophilic polymer dispersion containing at least one of the following:

a hydrophilic monomer mixture, a low molecular weight cross-linker and/or a hydrophilic high molecular weight polymer and preferably with an initiator.