ENHANCED INTERFERENCE MEMBRANE FOR A WORKING ELECTRODE OF A CONTINUOUS BIOLOGICAL SENSOR

• US 20190310219A1
• Filed: 04/05/2019
• Published: 10/10/2019
• Est. Priority Date: 04/06/2018
• Status: Abandoned Application

• Current Assignee: Allez Health Incorporated
• Original Assignee: Zense-Life, Inc.
• Inventors: Boock, Robert James
• Application Number:
  US16/375,875
• Publication Number:
  US 20190310219A1
• Time in Patent Office: Days
• CPC Class Codes: A61B 2562/125 characterised by the manufacture of electrodes
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: C12N 9/0006 acting on CH-OH groups as donors (1.1)
• CPC Class Codes: C12Q 1/002 Electrode membranes
• CPC Class Codes: C12Q 1/006 for glucose
• CPC Class Codes: C12Y 101/01027 L-Lactate dehydrogenase (1.1.1.27)
• CPC Class Codes: C12Y 101/0103 3-Hydroxybutyrate dehydrogenase (1.1.1.30)
• CPC Class Codes: C12Y 101/03004 Glucose oxidase (1.1.3.4)
• CPC Class Codes: C25D 7/0607 Wires
• CPC Class Codes: C25D 9/02 with organic materials
• 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: G01N 27/3275 Sensing specific biomolecules, e.g. nucleic acid strands, based on an electrode surface reaction
• CPC Class Codes: H01M 2004/024 Insertable electrodes
• CPC Class Codes: H01M 4/02 Electrodes composed of, or comprising, active material
• CPC Class Codes: H01M 4/0402 Methods of deposition of the material
• CPC Class Codes: H01M 4/0419 involving spraying
• CPC Class Codes: H01M 4/045 Electrochemical coating; Electrochemical impregnation
• CPC Class Codes: H01M 4/1395 of electrodes based on metals, Si or alloys
• CPC Class Codes: H01M 4/1399 of electrodes based on electro-active polymers
• CPC Class Codes: H01M 4/96 : Carbon-based electrodes
• CPC Class Codes: Y02E 60/10 : Energy storage using batteries
• CPC Class Codes: Y02E 60/50 : Fuel cells

Abstract

Briefly, a sensor for a continuous biological monitor is provided that has a working electrode with a new interfere layer that is (1) non-electron conducting, (2) ion passing, and (3) permselective for molecular weight. The new interference layer is made by mixing a monomer and a mildly basic buffer, and then electropolymerizing the monomer and the buffer into a polymer. The polymer is deposited onto a working electrode for a continuous metabolic monitor, for example, using an electro depositing process in the form of cyclic voltammety (CV). The interference layer is permselectable for molecule size by adjusting the pH of the basic buffer.

Claims

1. A subcutaneous sensor for use with a continuous metabolic monitor for a patient, comprising:

a working electrode further comprising;

a conductive substrate;

an enzyme membrane comprising an enzyme selected for a target metabolic function;

an interference membrane between the conductive substrate and the enzyme membrane, the interference membrane being conformally deposited on the substrate surface; and

a glucose limiting layer applied over the enzyme layer that limits the number of glucose molecules from a patient'"'"'s blood or ISF that are transferred to the enzyme layer;

a reference electrode; and

wherein the interference membrane is constructed to be (1) non-electron conducting, (2) ion permeable, and (3) permselective for molecular weight.

2. The sensor according to claim 1, wherein the enzyme layer further comprises GOx, and the continuous metabolic monitor is a continuous glucose monitor.

3. The sensor according to claim 1, wherein the interference membrane comprises PoAP.

4. The sensor according to claim 1, wherein the conductive substrate is platinum, a platinum coated substrate, or a conductive carbon coating on a plastic substrate.

5. The sensor according to claim 1, wherein the reference electrode is coated with a non-electron conducting and ion limiting insulation layer.

6. A method of making a subcutaneous sensor for use with a continuous metabolic monitor, comprising:

providing a reference electrode;

providing a conductive substrate;

making an interference membrane compound, further comprising;

mixing a monomer and a mildly basic buffer; and

electropolymerizing the monomer and the buffer into a polymer;

conformally applying the polymer onto the conductive substrate to form a continuous interference membrane;

applying an enzyme membrane over the interference membrane, the enzyme membrane having an enzyme selected according to the metabolic function to be monitored;

applying a glucose limiting membrane over the enzyme membrane; and

wherein the interference membrane (1) passes molecules to the substrate surface to generate free electrons for conducting on the conductive substrate to the continuous metabolic monitor; and

(2) restricts the passage of molecules larger than a cutoff molecular weight.

7. The method according to claim 6, wherein the buffer has a pH of between 7.4 and 10, the pH of the buffer selected to define the cutoff molecular weight for molecules that can pass through the interference membrane.

8. The method according to claim 6, wherein the buffer comprises Phosphate Buffered Saline (PBS) and the pH of the buffer is adjusted using sodium hydroxide.

9. The method according to claim 6, wherein the monomer comprises 2-Aminophenol and the polymer comprises Poly-Ortho-Aminophenol (PoAP).

10. The method according to claim 6, wherein the monomer comprises 2-Aminophenol, 3-Aminophelol, 4-Aminophelol, Aniline, Napthol, Phenolenediamine, or blends thereof.

11. The method according to claim 6, wherein the polymer is deposited using an electro depositing process in the form of cyclic voltammety (CV).

12. The method according to claim 6, wherein the reference electrode is coated with a non-electron conducting and ion permeable insulation layer.

13. The method according to claim 6, further including the step of removing oxides from the conducting substrate surface prior to applying the interference membrane.

14. The method according to claim 6, wherein the enzyme is GOx, lactate dehydrogenase or hydroxybutyrate dehydrogenase.

15. A method of making an interference layer for a working electrode for a continuous metabolic monitor, comprising:

mixing a monomer and a mildly basic buffer; and

electropolymerizing the monomer and the buffer into a polymer;

applying the polymer to the working electrode; and

curing the polymer.

16. The method according to claim 15, wherein the buffer has a pH of between 7.4 and 10, the pH of the buffer selected to define the cutoff molecular weight for molecules that can pass through the interference membrane.

17. The method according to claim 15, wherein the buffer comprises Phosphate Buffered Saline (PBS) and the pH of the buffer is adjusted using sodium hydroxide.

18. The method according to claim 15, wherein the monomer comprises 2-Aminophenol and the polymer comprises Poly-Ortho-Aminophenol (PoAP).

19. The method according to claim 15, wherein the monomer comprises 2-Aminophenol, 3-Aminophelol, 4-Aminophelol, Aniline, Napthol, Phenolenediamine, or blends thereof.

20. The method according to claim 15, wherein the polymer is deposited using an electro depositing process in the form of cyclic voltammety (CV).