Adjustment of sensor sensitivity by controlling copolymer film thickness through a controlled drying step

• US 9,763,605 B2
• Filed: 11/27/2013
• Issued: 09/19/2017
• Est. Priority Date: 11/27/2013
• Status: Active Grant

• Current Assignee: Google LLC (Alphabet Inc.)
• Original Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Inventors: Liu, Zenghe, Yao, Huanfen
• Primary Examiner(s): Kaur, Gurpreet
• Application Number:
  US14/092,655
• Publication Number:
  US 20150148647A1
• Time in Patent Office: 1,392 Days
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/6821 Eye
• CPC Class Codes: C12Q 1/001 Enzyme electrodes
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: C12Q 1/005 involving specific analytes or enzymes including groups of enzymes, e.g. oxydases; C12Q1/004 takes precedence
• CPC Class Codes: G01N 27/3271 Amperometric enzyme electrodes for analytes in body fluids, e.g. glucose in blood amperometry per se G01N27/49; aspects concerning the enzyme reagent C12Q1/001
• CPC Class Codes: G02C 7/04 Contact lenses for the eyes disinfection or sterilisation of contact lenses A61L12/00

Abstract

An analyte sensor and a method for making the analyte sensor are disclosed. In one aspect, the analyte sensor includes a crosslinked, hydrophilic copolymer in contact with a surface of an electrode, and an analyte sensing component embedded within the crosslinked, hydrophilic copolymer. The method of making the analyte sensor includes depositing a precursor mixture containing monomers and an analyte sensing component onto an electrode, exposing the deposited precursor mixture to a controlled environment for a specified period of time, and photopolymerizing the deposited exposed precursor mixture into a copolymer layer in contact with a surface of the electrode. Exposing the deposited precursor mixture to a controlled environment can increase the sensitivity of the sensor by reducing the thickness of the copolymer layer and/or by causing the analyte sensitive component within the copolymer layer to have a non-uniform concentration within the layer.

Claims

1. A method, comprising:

depositing a mixture on a surface of an electrode, wherein the mixture comprises an analyte sensing component, an initiator, a first methacrylate monomer having a first hydrophilic side chain, a dimethacrylate monomer, and a second methacrylate monomer having a second hydrophilic side chain, wherein the initiator is sensitive to light;

exposing the deposited mixture to a controlled environment for a specified period of time; and

photopolymerizing the exposed deposited mixture to form a copolymer layer disposed on the surface of the electrode, whereby the analyte sensing component has a non-uniform concentration in the formed copolymer layer such that the concentration is higher proximate the surface of the electrode, wherein photopolymerizing comprises exposing the exposed deposited mixture to light.

2. The method of claim 1, wherein the controlled environment is an open-air environment.

3. The method of claim 1, wherein the controlled environment has at least one of a controlled pressure, a controlled humidity, or a controlled temperature.

4. The method of claim 1, wherein the specified period of time is between 0 minutes and 60 minutes.

5. The method of claim 4, wherein the specified period of time is 5 minutes.

6. The method of claim 1, wherein the specified period of time is specified based on a desired analyte sensor thickness.

7. The method of claim 1, wherein the specified period of time is specified based on a desired concentration profile of the analyte sensing component within the copolymer layer disposed on the surface of the electrode.

8. The method of claim 1, wherein the specified period of time is specified based on a desired analyte sensor sensitivity.

9. The method of claim 1, wherein depositing the mixture on a surface of an electrode comprises depositing a specified volume of the mixture, wherein the specified volume of the mixture is based on an area of the surface of the electrode.

10. The method of claim 9, wherein the specified volume of the mixture based on the area of the surface of the electrode is between 50 nL and 150 nL of mixture per square millimeter of electrode surface.

11. The method of claim 10, wherein the specified volume of the mixture based on the area of the surface of the electrode is 100 nL of mixture per square millimeter of electrode surface.

12. The method of claim 1, wherein the first methacrylate monomer has the structure of formula (I):

13. The method of claim 1, wherein the second methacrylate monomer has the structure of formula (II):

14. The method of claim 1, wherein the dimethacrylate monomer has a structure of formula (III):

15. The method of claim 1, wherein the analyte sensing component is glucose oxidase.

16. The method of claim 1, wherein the light is ultraviolet light.

17. The method of claim 1, wherein the initiator is 2,2-dimethoxy-2-phenylacetophenone.

18. An analyte sensor comprising:

an electrode;

a layer on a surface of the electrode, wherein the layer comprises;

a crosslinked, hydrophilic copolymer; and

an analyte sensing component embedded within the crosslinked, hydrophilic copolymer, wherein the analyte sensing component has a non-uniform concentration in the layer, such that the concentration is higher proximate the surface of the electrode, wherein the crosslinked, hydrophilic copolymer comprises backbone chains comprising;

first methacrylate-derived units, each having a first hydrophilic side chain;

second methacrylate-derived units, each having a second hydrophilic side chain, wherein the first and second side chains are the same or different;

third methacrylate-derived units; and

hydrophilic crosslinks between third methacrylate-derived units in different backbone chains.

19. The sensor according to claim 18, wherein the analyte sensing component comprises glucose oxidase.

20. The sensor according to claim 18, wherein the layer has a thickness of less than 20 μ

m.

21. The sensor according to claim 18, wherein the first methacrylate-derived units have the structure of formula (IV):

22. The sensor according to claim 18, wherein the first methacrylate-derived units have the structure:

23. The sensor according to claim 18, wherein the second methacrylate-derived units have the structure of formula:

(V);

24. The sensor according to claim 18, wherein the hydrophilic crosslinks have the structure of formula (VI):

25. The sensor according to claim 18, wherein

the first methacrylate-derived units are derived from 2-hydroxyethylmethacrylate;

the second methacrylate-derived units have the structure of formula (VII);