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

Patent metadata

Field	Value
Publication number	US-9763605-B2
Application number	US-201314092655-A
Country	US
Kind code	B2
Filing date	Nov 27, 2013
Priority date	Nov 27, 2013
Publication date	Sep 19, 2017
Grant date	Sep 19, 2017

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.

First claim

What is claimed is:

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):

wherein
X is —O—, —NR′— or —S—;
y is 0-10; and
R 1 is hydrogen, —C 1 -C 12 alkyl, —C 1 -C 12 alkyl-OH, —SiR′ 3 , —C 1 -C 12 alkyl-C(O)OR′, wherein R′ is —C 1 -C 12 alkyl.

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

wherein
Y is —O—, —NR′— or —S—;
R 2 is hydrogen, —C 1 -C 12 alkyl, —SiR′ 3 , —C(O)—C 1 -C 12 alkyl, —C 1 -C 12 alkyl-C(O)OR′, where
R′ is hydrogen or —C 1 -C 12 alkyl; and
z is an average value of from about 2 to about 250.

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

wherein w is an average value of from about 2 to about 250.

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 μm.

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

wherein
X is —O—, —NR′— or —S—;
y is 0-10; and
R 1 is hydrogen, —C 1 -C 12 alkyl, —SiR′ 3 , —C 1 -C 12 alkyl-C(O)OR′, wherein R′ is —C 1 -C 12 alkyl.

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):

wherein
Y is —O—, —NR′— or —S—;
R 2 is hydrogen, —C 1 -C 12 alkyl, —SiR′ 3 , —C(O)—C 1 -C 12 alkyl, —C 1 -C 12 alkyl-C(O)OR′, where R′ is hydrogen or —C 1 -C 12 alkyl; and

z is an average value of from 2 to about 250.

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

wherein w is an average value of from about 2 to about 250.

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):

wherein
Y is —O—, —NR′— or —S—;
R 2 is hydrogen, —C 1 -C 12 alkyl, —SiR′ 3 , —C 1 -C 12 alkyl-C(O)OR′,

where R′ is hydrogen or —C 1 -C 12 alkyl; and
z is an average value of from about 10 to about 15;
the hydrophilic crosslinks have the structure of formula (VIII):

wherein w is 2; and
the analyte sensing component comprises glucose oxidase.

Assignees

• Verily Life Sciences Llc

Inventors

• Liu Zenghe
• Yao Huanfen

Classifications

• A61B5/6821

  Eye · CPC title

• G02C7/04

  Contact lenses for the eyes (disinfection or sterilisation of contact lenses A61L12/00) · CPC title

• A61B5/14532 Primary

  for measuring glucose, e.g. by tissue impedance measurement · CPC title

• A61B5/1486

  using enzyme electrodes, e.g. with immobilised oxidase · CPC title

• C12Q1/002

  Electrode membranes · CPC title