Metal-enzyme sandwich layers

Patent metadata

Field	Value
Publication number	US-11109784-B2
Application number	US-201816191357-A
Country	US
Kind code	B2
Filing date	Nov 14, 2018
Priority date	Apr 9, 2018
Publication date	Sep 7, 2021
Grant date	Sep 7, 2021

Abstract

Measurement of target analytes is carried out with an enzyme-based sensor. The enzyme hydrogel is protected by a porous layer of a metallic material. The size of the pores is small enough to prevent degradation of the enzyme layer caused by the immune system of an organism, but large enough to allow transfer of molecules that participate in the electrochemical reaction allowing the enzyme to detect the target analytes.

First claim

What is claimed is:

1. A sensing device comprising:
a working electrode on a substrate;
wherein:
the working electrode comprises:
a metallic layer contacting the substrate;
an enzyme layer on the metallic layer; and
a metallic porous layer on the enzyme layer,

the metallic layer, the enzyme layer, and the metallic porous layer are configured to detect a target analyte through an electrochemical reaction, and
the metallic porous layer is electrically connected to the metallic layer.

2. The sensing device of claim 1 , wherein the metallic layer comprises an array of pillars.

3. The sensing device of claim 2 , wherein the enzyme layer is deposited between the pillars.

4. The sensing device of claim 1 , wherein the metallic porous layer comprises an array of pores having a diameter between 2 nm and 2 micrometers.

5. The sensing device of claim 4 , wherein the array of pores has a total area between 0.001% and 50% of a total area of the metallic porous layer.

6. The sensing device of claim 5 , wherein the metallic porous layer is made of a material selected from the group consisting of: Pt, Au, W, Ti, Pd, Ir, Si, TiO 2 , WO 3 , SnO 2 , graphene, and InO 2 .

7. The sensing device of claim 6 , wherein the enzyme layer comprises an oxidase enzyme and a hydrogel.

8. The sensing device of claim 7 , wherein the enzyme layer comprises an oxidase enzyme selected from the group consisting of: glucose oxidase, lactate oxidase, xanthine oxidase, cholesterol oxidase, sarcosine oxidase, cortisol oxidase, urate oxidase, alcohol oxidase, glutathione oxidase, and nicotine oxidase.

9. The sensing device of claim 8 , wherein the sensing device is configured to be implanted internally to an organism, or configured to be attached externally to skin of the organism.

10. The sensing device of claim 7 , wherein the enzyme layer further comprises glutaraldehyde.

11. The sensing device of claim 4 , wherein the array of pores has a total area between 0.1% and 10% of a total area of the metallic porous layer.

12. The sensing device of claim 4 , wherein the metallic porous layer comprises an array of pores having a diameter between 2 nm and 200 nm.

13. The sensing device of claim 12 , wherein the metallic porous layer comprises an array of pores having a diameter between 2 nm and 20 nm.

14. The sensing device of claim 1 , wherein the metallic layer has a thickness between 1 nm and 1 mm.

15. The sensing device of claim 14 , wherein the metallic porous layer has a thickness between 1 nm and 10 micrometers.

16. The sensing device of claim 15 , wherein the enzyme layer has a thickness less than 10 micrometers.

17. The sensing device of claim 16 , wherein the enzyme layer has a thickness less than 1 micrometer.

18. The sensing device of claim 15 , wherein the enzyme layer has a thickness less than 400 nm.

19. The sensing device of claim 1 , further comprising:
a counter electrode on the substrate; and
a reference electrode on the substrate,
wherein:
the counter electrode comprises:
a metallic layer contacting the substrate;
an enzyme layer on the metallic layer of the counter electrode; and
a metallic porous layer on the enzyme layer of the counter electrode, and

the reference electrode comprises:
a metallic layer contacting the substrate;
an enzyme layer on the metallic layer of the reference electrode; and
a metallic porous layer on the enzyme layer of the reference electrode.

20. The sensing device of claim 19 , wherein the working electrode, the counter electrode, and the reference electrode have concentric square shapes.

21. The sensing device of claim 1 , wherein the target analyte is glucose, and the enzyme layer comprises glucose oxidase.

22. The sensing device of claim 1 , wherein:
the enzyme layer comprises a plurality of holes, and
the holes are filled with the metallic porous layer, thereby forming the electrical connection between the metallic porous layer and the metallic layer.

23. The sensing device of claim 1 , wherein:
the enzyme layer is laterally smaller than the metallic layer, and
the metallic porous layer surrounds lateral sides of the enzyme layer, thereby forming the electrical connection between the metallic porous layer and the metallic layer.

24. The sensing device of claim 1 , wherein:
the metallic layer comprises pillars, and
spaces between the pillars are filled with the enzyme layer, thereby forming the electrical connection between the metallic porous layer and top surfaces of the pillars of the metallic layer.

25. An array of sensing devices according to claim 1 , wherein a spacing between the sensing devices of the array of sensing devices is configured to avoid crosstalk due to leakage of intermediate reporting molecules.

26. The array of claim 25 , wherein the spacing is between 10 nm and 250 nm.

Assignees

• California Inst Of Techn

Inventors

• Adalian Dvin
• Chen Samson
• Jilani Muhammad M
• Scherer Axel
• Madero Xiomara Linnette
• Smith Richard

Classifications

• A61B5/14865 Primary

  invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors · CPC title

• A61B5/14532

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

• A61B5/14546

  for measuring analytes not otherwise provided for, e.g. ions, cytochromes · CPC title

• A61B5/1473

  invasive, e.g. introduced into the body by a catheter · CPC title