Identification of degradative species

Patent metadata

Field	Value
Publication number	US-12000784-B2
Application number	US-202017097678-A
Country	US
Kind code	B2
Filing date	Nov 13, 2020
Priority date	Nov 13, 2019
Publication date	Jun 4, 2024
Grant date	Jun 4, 2024

Abstract

A sensor (e.g., an optical sensor) that may be implanted within a living animal (e.g., a human) and may be used to measure an analyte (e.g., glucose or oxygen) in a medium (e.g., interstitial fluid, blood, or intraperitoneal fluid) within the animal. The sensor may include a sensor substrate, electrode or housing, an analyte indicator covering at least a portion of the sensor, and one or more probes that identify degradative species in an environment of the sensor.

First claim

What is claimed is:

1. A sensor for measurement of an analyte in a medium within a living animal, the sensor comprising:
an analyte indicator; and
one or more degradative species probes having absorption and/or emission profiles that are selective for a specific degradative species, wherein the one or more degradative species probes comprise:
(a) a degradative species probe of Formula I:

(b) a degradative species probe of Formula II:

(c) a degradative species probe of Formula IV:

(d) the degradative species probe of the Formula I and the degradative species probe of the Formula II;
(e) the degradative species probe of the Formula II and the degradative species probe of the Formula IV;
(f) the degradative species probe of the Formula I and the degradative species probe of the Formula IV; or
(g) the degradative species probe of the Formula I, the degradative species probe of the Formula II, and the degradative species probe of the Formula IV,
wherein each R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 is independently selected from the group consisting of H, C1-C20 alkyl, C1-C20 alkoxy, carboxy, aryl, heteroaryl, polycyclic, alkoxy, halide, SH, aryloxy, alkylthio, amino, substituted amino, alkoxycarbonyl, alkanoylamido, aroylamido, heterocyclocarbonylamido, heteroaroylamido, alkanoyl(alkylsubstituted) amido, aroyl(alkylsubstituted)amido, heteroaroyl(alkylsubstituted)amido, and heterocyclocarbonyl(alkyl substituted)amido.

2. The sensor of claim 1 , further comprising a sensor housing, wherein the analyte indicator covers at least a portion of the sensor housing.

3. The sensor of claim 1 , further comprising a sensor substrate or sensor electrode, wherein the analyte indicator covers at least a portion of the sensor substrate or sensor electrode.

4. The sensor of claim 1 , wherein the sensor is implantable within a living animal.

5. The sensor of claim 1 , wherein the one or more degradative species probes are co-monomers with the analyte indicator.

6. The sensor of claim 1 , wherein the one or more degradative species probes are co-monomers with the analyte indicator in a hydrogel.

7. The sensor of claim 2 , wherein the one or more degradative species probes are entrapped in a hydrogel covering at least a portion of the sensor housing.

8. The sensor of claim 1 , wherein the one or more degradative species probes bind to the degradative species.

9. The sensor of claim 1 , wherein the one or more degradative species probes reduce chemical degradation and/or oxidation of the analyte indicator.

10. The sensor of claim 1 , wherein the one or more degradative species probes sequester the degradative species so as to reduce, and/or prevent degradation of the analyte indicator by the degradative species.

11. The sensor of claim 1 , wherein the analyte indicator comprises a polymer comprising co-monomers of four monomers according to Formula IX: A_B_C_D [Formula IX],
wherein A is an analyte indicator monomer, B is a methacrylate monomer, C is a polyethylene glycol monomer, and D is the one or more degradative species probes, wherein A is 0.01 to 10% by weight, B is 1 to 99% by weight, C is 1 to 99% by weight, and D is 0.01 to 99% by weight of the total polymer.

12. The sensor of claim 1 , wherein the one or more degradative species probes are provided at a molar ratio of 0.1 to 100 to analyte indicator monomer.

13. The sensor of claim 1 , wherein the sensor comprises a mixture of two or more of the degradative species probes.

14. A method of fabricating a sensor for measurement of an analyte in a medium within a living animal, the method comprising:
applying an analyte indicator to a sensor such that the applied analyte indicator covers at least a portion of the sensor, wherein the analyte indicator comprises one or more degradative species probes, wherein the degradative species probes have absorption and/or emission profiles that are selective for a specific degradative species, wherein the one or more degradative species probes comprise:
(a) a degradative species probe of Formula I:

(b) a degradative species probe of Formula II:

(c) a degradative species probe of Formula IV:

(d) the degradative species probe of the Formula I and the degradative species probe of the Formula II;
(e) the degradative species probe of the Formula II and the degradative species probe of the Formula IV;
(f) the degradative species probe of the Formula I and the degradative species probe of the Formula IV; or
(g) the degradative species probe of the Formula I, the degradative species probe of the Formula II, and the degradative species probe of the Formula IV,
wherein each R1, R2, R3, R4, R5, R6, R7, R8, R9, and R10 is independently selected from the group consisting of H, C1-C20 alkyl, C1-C20 alkoxy, carboxy, aryl, heteroaryl, polycyclic, alkoxy, halide, SH, aryloxy, alkylthio, amino, substituted amino, alkoxycarbonyl, alkanoylamido, aroylamido, heterocyclocarbonylamido, heteroaroylamido, alkanoyl(alkylsubstituted) amido, aroyl(alkylsubstituted)amido, heteroaroyl(alkylsubstituted)amido, and heterocyclocarbonyl(alkyl substituted)amido.

15. The method of claim 14 , wherein the one or more degradative species probes are co-monomers with the analyte indicator.

16. The method of claim 14 , wherein the one or more degradative species probes are co-monomers with the analyte indicator in a hydrogel.

17. The method of claim 14 , further comprising a sensor housing, wherein the one or more degradative species probes are entrapped in a hydrogel covering at least a portion of the sensor housing.

18. The method of claim 14 , wherein the one or more degradative species probes reduce chemical degradation and/or oxidation of the analyte indicator.

19. The method of claim 14 , wherein the one or more degradative species probes interact or react with a degradative species, wherein the degradative species is hydrogen peroxide, a reactive oxygen species, a reactive nitrogen species, an enzyme, a free radical or a metal ion.

20. The method of claim 14 , wherein the one or more degradative species probes bind to the degradative species.

21. The method of claim 14 , wherein the one or more degradative species probes sequester the degradative species so as to reduce, and/or prevent degradation of the analyte indicator by the degradative species.

22. The method of claim 14 , wherein the analyte indicator comprises a polymer comprising co-monomers of four monomers according to Formula IX: A-B-C-D [Formula IX], wherein A is an analyte indicator monomer, B is a methacrylate monomer, C is a polyethylene glycol monomer, and D is the one or more degradative species probes, wherein A is 0.01 to 10% by weight, B is 1 to 99% by weight, C is 1 to 99% by weight, and D is 0.01 to 99% by weight of the total poly

Assignees

• Senseonics Inc

Inventors

• Velvadapu Venkata
• Mortellaro Mark

Classifications

• G01N21/6428 Primary

  Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" (in vivo A61B5/00; immunoassay G01N33/53) · CPC title

• A61B5/14532

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

• A61B5/14865

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

• G01N33/521

  Single-layer analytical elements · CPC title

• G01N33/66

  involving blood sugars, e.g. galactose · CPC title