Methods to improve oxygen delivery to implantable sensors

Patent metadata

Field	Value
Publication number	US-11718865-B2
Application number	US-201916523882-A
Country	US
Kind code	B2
Filing date	Jul 26, 2019
Priority date	Jul 26, 2019
Publication date	Aug 8, 2023
Grant date	Aug 8, 2023

Abstract

Embodiments of the invention provide multilayer analyte sensors having elements and/or architectures that function to improve oxygen delivery to sensor enzymes in manner that enhances sensor function, as well as methods for making and using such sensors. Typical embodiments of the invention include glucose sensors used in the management of diabetes.

First claim

The invention claimed is:

1. An electrochemical analyte sensor comprising:
a base layer;
a working electrode disposed on the base layer; and
a multilayer analyte sensor stack disposed upon the working electrode comprising:
(a) an analyte sensing layer disposed directly on the working electrode, wherein the analyte sensing layer detectably alters the electrical current at the working electrode in the presence of an analyte;
(b) an analyte modulating layer disposed over the analyte sensing layer, wherein the analyte modulating layer facilitates the diffusion of O 2 from an external environment to the analyte sensing layer; and

one or more channels disposed in the electrochemical analyte sensor architecture that operably couple the analyte sensing layer to an external environment, wherein the plurality of channels facilitate the diffusion of O 2 from the external environment to the analyte sensing layer, and
a first silicone bridge having a first portion in operable contact with air in an ex vivo environment and a second portion in operable contact with at least one channel, the channel comprising a via, wherein:
the first silicone bridge facilitates the diffusion of O 2 from the air and to the analyte sensing layer; and
the first silicone bridge comprises a portion in contact with interstitial fluid.

2. The electrochemical analyte sensor of claim 1 , further comprising an oxygen diffusion composition disposed within the plurality of channels, wherein the oxygen diffusion composition is selected to facilitate the diffusion of O 2 therethrough.

3. The electrochemical analyte sensor of claim 2 , wherein:
a same composition is used to form the analyte modulating layer and the oxygen diffusion composition; and/or
at least one channel forms an O 2 conduit from an external environment on a first side of a sensor, through the base layer and the electrode, and to the analyte sensing layer.

4. The electrochemical analyte sensor of claim 1 , wherein the external environment comprises interstitial fluid.

5. The electrochemical analyte sensor of claim 1 , further comprising a second silicone bridge having a first portion in operable contact with air in an ex vivo environment and a second portion in operable contact with at least one channel, wherein said second silicone bridge facilitates the diffusion of O 2 from the air and to the analyte sensing layer.

6. The electrochemical analyte sensor of claim 1 , further comprising an oxygen generating electrode, wherein the oxygen generating electrode is disposed in the sensor such that oxygen generated by the electrode is in operable contact with the analyte sensing layer.

7. The electrochemical analyte sensor of claim 6 , wherein the oxygen generating electrode is in operable contact with one or more channels that operably couple the analyte sensing layer to the oxygen generating electrode.

8. The electrochemical analyte sensor of claim 6 , wherein the oxygen generating electrode further functions as a counter electrode in the electrochemical analyte sensor.

9. The electrochemical analyte sensor of claim 1 , wherein the electrochemical analyte sensor further comprises at least one of:
a layer comprising high density amine layer comprise poly-l-lysine polymers having molecular weights between 30 KDa and 300 KDa;
a layer comprising an albumin;
a layer comprising a siloxane adhesion promo ting agent; or
a layer comprising glutaraldehyde.

10. The method of claim 9 , wherein the electrochemical analyte sensor is formed to further comprise at least one of:
a layer comprising high density amine layer comprise poly-l-lysine polymers having molecular weights between 30 KDa and 300 KDa;
a layer comprising an albumin;
a layer comprising a siloxane adhesion promoting agent; or
a layer comprising glutaraldehyde.

11. The electrochemical analyte sensor of claim 1 , wherein the base layer has a first side and a second side and the working electrode is disposed on the first side of the base layer and the first silicone bridge is disposed on the second side of the base layer.

12. The electrochemical analyte sensor of claim 11 , wherein a second silicone bridge is disposed on the first side of the base layer.

13. The electrochemical analyte sensor of claim 12 , wherein the second silicone bridge is in direct contact with the analyte sensing layer.

14. The electrochemical analyte sensor of claim 13 , wherein base layer comprises one or more air conduits disposed therethrough and connecting the first silicone bridge with the second silicone bridge.

15. A method of making an electrochemical analyte sensor comprising:
providing a base layer;
forming a conductive layer over the base layer, wherein the conductive layer includes a working electrode;
forming an analyte sensing layer over the conductive layer, wherein the analyte sensing layer includes a composition that can alter the electrical current at the working electrode in the conductive layer in the presence of an analyte;
forming an analyte modulating layer over the analyte sensing layer; and
forming one or more channels within the electrochemical analyte sensor in regions of the electrochemical analyte sensor so as to operably couple the analyte sensing layer to an external environment, wherein the one or more channels facilitate the diffusion of O 2 from the external environment to the analyte sensing layer, wherein the one or more channels comprise one or more vias;
forming a first silicone bridge in a configuration such that when the electrochemical analyte sensor is disposed in vivo, a first portion is in operable contact with air in an ex vivo environment and a second portion is in operable contact with at least one channel formed in the base layer, wherein:
the first silicone bridge facilitates the diffusion of O 2 from the air and to the analyte sensing layer; and
the first silicone bridge comprises a portion in contact with interstitial fluid when the electrochemical analyte sensor is disposed in vivo, so that the electrochemical analyte sensor is made.

16. The method of claim 15 , further comprising disposing an oxygen diffusion composition disposed within the one or more channels, wherein the oxygen diffusion composition is selected to facilitate the diffusion of O 2 therethrough.

17. The method of claim 15 , further comprising disposing an oxygen generating electrode in the electrochemical analyte sensor, wherein the oxygen generating electrode is disposed in the electrochemical analyte sensor such that oxygen generated by the electrode is in operable contact with the analyte sensing layer.

18. The method of claim 17 , wherein the oxygen generating electrode is disposed in the electrochemical analyte sensor so as to be in operable contact with one or more channels that operably couple the analyte sensing layer to the oxygen generating electrode.

19. The method of claim 17 , wherein the oxygen generating electrode is disposed in the electrochemical analyte sensor so as to function as a counter electrode in the electrochemical analyte sensor.

20. A method of sensing an analyte within the body of a mammal, the method comprising:
implanting an electrochemical analyte sensor of claim 1 in to the mammal;
sensing an alteration in current at the working electrode in the presence of the analyte; and
correlating the alteration in current with the presence of the analyte, so that the analyte is sensed.

Assignees

• Medtronic Minimed Inc

Inventors

• Pesantez Daniel E
• Rao Ashwin K
• Garai Ellis
• Kong Rui
• Miller Michael E

Classifications

• C12Q1/006 Primary

  for glucose · CPC title

• A61B5/14532 Primary

  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

• G01N27/3271

  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 title

• A61B2562/04

  Arrangements of multiple sensors of the same type · CPC title