Detecting and correcting for changes to an analyte indicator

Patent metadata

Field	Value
Publication number	US-11517230-B2
Application number	US-202017092830-A
Country	US
Kind code	B2
Filing date	Nov 9, 2020
Priority date	Apr 19, 2017
Publication date	Dec 6, 2022
Grant date	Dec 6, 2022

Abstract

A sensor, system, and method for detecting and correcting for changes to an analyte indicator of an analyte sensor. The analyte indicator may be configured to exhibit a first detectable property that varies in accordance with an analyte concentration and an extent to which the analyte indicator has degraded. The analyte sensor may also include a degradation indicator configured to exhibit a second detectable property that varies in accordance with an extent to which the degradation indicator has degraded. The analyte sensor may generate (i) an analyte measurement based on the first detectable property exhibited by the analyte indicator and (ii) a degradation measurement based on the second detectable property exhibited by the degradation indicator. The analyte sensor may be part of a system that also includes a transceiver. The transceiver may use the analyte and degradation measurements to calculate an analyte level.

First claim

What is claimed is:

1. An analyte sensor for measurement of an analyte in a medium within a living animal, the analyte sensor comprising:
an analyte indicator configured to exhibit a first detectable property that varies in accordance with (i) an amount or concentration of the analyte in the medium and (ii) an extent to which the analyte indicator has degraded; and
a degradation indicator configured to exhibit a second detectable property that varies in accordance with an extent to which the degradation indicator has degraded, wherein the extent to which the degradation indicator has degraded corresponds to the extent to which the analyte indicator has degraded;
wherein the degradation indicator is a compound of formula I:

wherein A, B, C, A′, B′, C′, W, X, Y, and Z represent —CH, and the hydrogen of —CH may optionally and independently be substituted with an alkyl group;
wherein R 1 and R 2 are independently selected from one or more vinyl groups, alkyl vinyl groups, acrylamide groups, methacrylamide groups, or other polymerizable groups.

2. The analyte sensor of claim 1 , wherein the extent to which the degradation indicator has degraded is proportional to the extent to which the analyte indicator has degraded.

3. The analyte sensor of claim 1 , wherein degradation to the analyte indicator comprises reactive oxidation species (ROS)-induced oxidation, and degradation to the degradation indicator comprises ROS-induced oxidation.

4. The analyte sensor of claim 1 , wherein the analyte indicator is a phenylboronic-based analyte indicator.

5. The analyte sensor of claim 1 , wherein the degradation indicator is a phenylboronic-based degradation indicator.

6. The analyte sensor of claim 1 , further comprising an indicator element comprising the analyte indicator and the degradation indicator.

7. The analyte sensor of claim 6 , wherein the analyte indicator comprises analyte indicator molecules distributed throughout the indicator element, and the degradation indicator comprises degradation indicator molecules distributed throughout the indicator element.

8. The analyte sensor of claim 7 , wherein a ratio of the analyte indicator molecules to the degradation indicator molecules is 1:1, 2:1, 1:2, 3:1, 5:1, or 10:1.

9. The analyte sensor of claim 1 , wherein the degradation indicator comprises a fluorescent probe compound having a wavelength of excitation between about 450 nm and about 550 nm.

10. The analyte sensor of claim 9 , wherein the fluorescent probe compound has a Stokes shift between about 500 nm and about 650 nm.

11. The analyte sensor of claim 10 , wherein the fluorescent probe compound has a half-life of between 50 days and 150 days.

12. The analyte sensor of claim 1 , wherein the second detectable property does not vary in accordance with the amount or concentration of the analyte in the medium.

13. An analyte sensor for measurement of an analyte in a medium within a living animal, the analyte sensor comprising:
an analyte indicator configured to exhibit a first detectable property that varies in accordance with (i) an amount or concentration of the analyte in the medium and (ii) an extent to which the analyte indicator has degraded; and
a degradation indicator configured to exhibit a second detectable property that varies in accordance with an extent to which the degradation indicator has degraded, wherein the extent to which the degradation indicator has degraded corresponds to the extent to which the analyte indicator has degraded;
wherein the degradation indicator comprises a molecule selected from the group consisting of:

14. The analyte sensor of claim 13 , wherein the degradation indicator comprises the following molecule:

15. A method comprising:
using an analyte indicator of an analyte sensor to generate an analyte measurement indicative of an amount or concentration of an analyte in a medium;
using a degradation indicator of the analyte sensor to generate a degradation measurement indicative of an extent to which the degradation indicator has degraded;
calculating an extent to which the analyte indicator of the analyte sensor has degraded based at least on the degradation measurement;
adjusting a conversion function based on the calculated extent to which the analyte indicator has degraded; and
calculating an analyte level using the adjusted conversion function and the analyte measurement;
wherein the degradation indicator is a compound of formula I:

wherein A, B, C, A′, B′, C′, W, X, Y, and Z represent —CH, and the hydrogen of —CH may optionally and independently be substituted with an alkyl group;
wherein R 1 and R 2 are independently selected from one or more vinyl groups, alkyl vinyl groups, acrylamide groups, methacrylamide groups, or other polymerizable groups.

16. A method comprising:
using an analyte indicator of an analyte sensor to generate an analyte measurement indicative of an amount or concentration of an analyte in a medium;
using a degradation indicator of the analyte sensor to generate a degradation measurement indicative of an extent to which the degradation indicator has degraded;
calculating an extent to which the analyte indicator of the analyte sensor has degraded based at least on the degradation measurement;
adjusting a conversion function based on the calculated extent to which the analyte indicator has degraded; and
calculating an analyte level using the adjusted conversion function and the analyte measurement;
wherein the degradation indicator comprises a molecule selected from the group consisting of:

17. The method of claim 16 , wherein the degradation indicator comprises the following molecule:

18. An analyte monitoring system comprising:
an analyte indicator configured to exhibit a first detectable property that varies in accordance with (i) an amount or concentration of an analyte in a medium and (ii) an extent to which the analyte indicator has degraded;
a degradation indicator configured to exhibit a second detectable property that varies in accordance with an extent to which the degradation indicator has degraded;
sensor elements configured to generate (i) an analyte measurement based on the first detectable property exhibited by the analyte indicator and (ii) a degradation measurement based on the second detectable property exhibited by the degradation indicator; and
a controller configured to:
(i) calculate an extent to which the analyte indicator of the analyte sensor has degraded based at least on the degradation measurement;
(ii) adjust a conversion function based on the calculated extent to which the analyte indicator has degraded;
(iii) calculate an analyte level using the adjusted conversion function and the analyte measurement;

wherein the degradation indicator is a compound of formula I:

wherein A, B, C, A′, B′, C

Assignees

• Senseonics Inc

Inventors

• Dehennis Andrew
• Mortellaro Mark
• Chavan Abhi
• Velvadapu Venkata
• Huffstetler Philip
• Kim Tina Hyunjung
• Masciotti James

Classifications

• A61B5/1473

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

• A61B5/14556

  by fluorescence (A61B5/14555 takes precedence) · CPC title

• A61B5/1459

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

• A61B2560/0219

  of externally powered implanted units · CPC title

• A61B2560/0266

  for monitoring or limiting apparatus function · CPC title