Method and system for measuring pyruvate

• US 9,095,312 B2
• Filed: 10/17/2013
• Issued: 08/04/2015
• Est. Priority Date: 10/17/2013
• Status: Active Grant

• Current Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Original Assignee: Google Inc. (Alphabet Inc.)
• Inventors: Yao, Huanfen, Liu, Zenghe
• Primary Examiner(s): Natnithithadha, Navin
• Assistant Examiner(s): MESSERSMITH, ERIC J
• Application Number:
  US14/056,837
• Publication Number:
  US 20150112173A1
• Time in Patent Office: 656 Days
• Field of Search: 600/345, 600/347, 600/365, 20440301-40315
• US Class Current: 1/1
• CPC Class Codes: A61B 5/0004 characterised by the type of physiological signal transmitted
• CPC Class Codes: A61B 5/14507 specially adapted for measuring characteristics of body fluids other than blood devices for taking samples of body liquids A61B10/0045
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1477 non-invasive
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/6803 Head-worn items, e.g. helmets, masks, headphones or goggles
• CPC Class Codes: A61B 5/6821 Eye
• CPC Class Codes: A61B 5/742 using visual displays A61B5/339 takes precedence

Abstract

A body-mountable pyruvate sensing device includes an electrochemical sensor embedded in a polymeric material configured for mounting to a surface of an eye. The electrochemical sensor includes a working electrode, a reference electrode, and a reagent localized near the working electrode that selectively reacts with pyruvate. Application of a voltage between the working electrode and the reference electrode causes a current related to a concentration of pyruvate in a fluid to which the electrochemical sensor is exposed; the current is measured by the body-mountable device and wirelessly communicated.

Claims

1. A body-mountable device comprising:

a shaped polymeric material having a channel formed therein;

a substrate at least partially embedded within the shaped polymeric material;

an antenna disposed on the substrate;

an electrochemical sensor disposed on the substrate and comprising;

a working electrode;

a reagent that selectively reacts with pyruvate, wherein the reagent is localized within a layer of polymer disposed in the channel proximate to the working electrode, and wherein the polymer comprises 2-hydroxyethyl methacrylate units; and

a reference electrode; and

a controller electrically connected to the electrochemical sensor and the antenna, wherein the controller is configured to;

(i) apply a voltage between the working electrode and the reference electrode sufficient to generate an amperometric current through the working electrode related to the concentration of pyruvate in a fluid to which the body-mountable device is exposed;

(ii) measure the amperometric current; and

(iii) use the antenna to indicate the measured amperometric current.

2. The body-mountable device according to claim 1, wherein the fluid is a tear fluid of an eye, and wherein the shaped polymeric material has a concave surface and a convex surface, wherein the concave surface is configured to be removably mounted over a corneal surface and the convex surface is configured to be compatible with eyelid motion when the concave surface is so mounted.

3. The body-mountable device according to claim 1, wherein the reagent comprises pyruvate oxidase, flavin adenine dinucleotide, and thiamine pyrophosphate.

4. The body-mountable device according to claim 1, wherein the working electrode includes a plurality of extensions extending from a base, and wherein each of the plurality of extensions includes a first side edge and a second side edge that are at least partially adjacent to respective sections of the reference electrode.

5. The body-mountable device according to claim 4, wherein the plurality of extensions of the working electrode and the respective sections of the reference electrode are interdigitated with one another.

6. The body-mountable device according to claim 1, wherein the reference electrode has an area at least five times the area of the working electrode.

7. The body-mountable device according to claim 1, wherein the working electrode and the reference electrode each comprise platinum.

8. The body-mountable device according to claim 7, wherein the voltage applied to the working electrode relative to the reference electrode is between +400 mV and +500 mV.

9. The body-mountable device according to claim 1, wherein the antenna is configured to receive radio frequency energy to power the body-mountable device.

10. The body-mountable device according to claim 1, wherein using the antenna to indicate the measured amperometric current comprises sending a radio frequency signal.

11. The body-mountable device according to claim 1, wherein using the antenna to indicate the measured amperometric current comprises reflecting a radio frequency signal.

12. A method comprising:

exposing a working electrode and a reference electrode to a fluid via a channel, wherein the working electrode and reference electrode are disposed in a body-mountable device, wherein the working electrode is selectively sensitive to pyruvate, wherein the working electrode being selectively sensitive to pyruvate comprises a reagent that selectively interacts with pyruvate being localized within a layer of polymer disposed in the channel proximate to the working electrode, wherein the polymer comprises 2-hydroxyethyl methacrylate units, wherein the body-mountable device additionally includes an antenna and measurement electronics, and wherein the working electrode, reference electrode, antenna, and measurement electronics are disposed on a substrate that is at least partially embedded in a shaped polymeric material;

applying a voltage between the working electrode and the reference electrode sufficient to generate an amperometric current through the working electrode related to the concentration of pyruvate in the fluid to which the body-mountable device is exposed;

measuring the amperometric current through the working electrode; and

wirelessly indicating the measured current using the antenna.

13. The method of claim 12, wherein the fluid is a tear fluid of an eye, and wherein the shaped polymeric material has a concave surface and a convex surface, wherein the concave surface is configured to be removably mounted over a corneal surface of the eye and the convex surface is configured to be compatible with eyelid motion when the concave surface is so mounted.

14. The method of claim 12, wherein the voltage applied between the working electrode and the reference electrode is between +400 mV and +500 mV.

15. The method of claim 12, wherein applying the voltage, measuring the amperometric current, and wirelessly indicating the measured current using the antenna are performed in response to an interrogating radio frequency signal received by the antenna.

16. The method of claim 15, where the interrogating radio frequency signal is used to power the body-mountable device.

17. The method of claim 15, wherein wirelessly indicating the measured current comprises reflecting a version of the interrogating radio frequency signal.

18. A system comprising:

an antenna configured to wirelessly communicate with a body-mountable device, wherein the body-mountable device is configured to measure a current related to the concentration of pyruvate in a fluid to which a working electrode and a reference electrode of the body-mountable device are exposed via a channel, wherein the working electrode is selectively sensitive to pyruvate, wherein the working electrode being selectively sensitive to pyruvate comprises a reagent that selectively interacts with pyruvate being localized within a layer of polymer disposed in the channel proximate to the working electrode, and wherein the polymer comprises 2-hydroxyethyl methacrylate units;

a processor; and

a non-transitory computer readable medium containing instructions that, when executed by the processor, cause the system perform functions comprising;

(i) using the radio frequency antenna to interrogate the body-mountable device by transmitting a radio frequency signal, (ii) receiving from the body-mountable device a radio-frequency signal indicating a measured current, (iii) determining a pyruvate concentration in the fluid based on the indicated measured current.

19. The system of claim 18, wherein the transmitted radio frequency signal is sufficient to power the body-mountable device.

20. The system of claim 18, further comprising:

a display;

and wherein the functions further comprise (iv) indicating the determined pyruvate concentration on the display.

21. The system of claim 18, further comprising a communication interface, wherein the communication interface is configured to transmit the indicated measured current and/or determined pyruvate concentration to another device.

22. A method comprising:

interrogating a body-mountable device, the body-mountable device including an antenna, measurement electronics, and an electrochemical sensor with a working electrode and a reference electrode, wherein a reagent that selectively reacts with pyruvate is localized within a layer of polymer disposed in a channel proximate to the working electrode, wherein the polymer comprises 2-hydroxyethyl methacrylate units, and wherein the antenna, measurement electronics, and the electrochemical sensor are disposed on a substrate that is at least partially embedded in a shaped polymeric material, by transmitting radio frequency radiation sufficient to power the electrochemical sensor and measurement electronics to create a voltage difference between the working electrode and the reference electrode and to measure a current related to pyruvate;

receiving, from the body-mountable device, a radio frequency signal indicating the measured current; and

determining a concentration of pyruvate based on the measured current indicated by the radio frequency signal.

23. The method of claim 22, wherein receiving a radio frequency signal comprises receiving a reflected version of the transmitted radio frequency radiation.

24. The method of claim 22, further comprising:

displaying an indication of the determined concentration of pyruvate.

25. The method of claim 22, further comprising:

determining the concentration of pyruvate at multiple points in time.

26. A method comprising:

forming a substrate;

disposing components on the substrate, wherein the components include an electrochemical sensor having at least a working electrode and a reference electrode, measurement electronics, and a radio frequency antenna;

at least partially embedding the substrate and components disposed thereon in a shaped polymeric material, wherein the shaped polymeric material has a channel formed therein; and

localizing a reagent that reacts selectively with pyruvate proximate to the working electrode by forming a layer of polymer in the channel proximate to the working electrode, wherein the reagent that reacts selectively with pyruvate is localized within the formed layer of polymer, and wherein the polymer comprises 2-hydroxyethyl methacrylate units.

27. The method of claim 26, wherein the shaped polymeric material has a concave surface and a convex surface, wherein the concave surface is configured to be removably mounted over a corneal surface of the eye and the convex surface is configured to be compatible with eyelid motion when the concave surface is so mounted.

28. The method of claim 26, wherein at least partially embedding the substrate and components disposed thereon in a shaped polymeric material comprises covering the substrate and components disposed thereon with the polymeric material except for the working electrode and reference electrode of the electrochemical sensor.

29. The method of claim 26, wherein the reagent that reacts selectively with pyruvate comprises pyruvate oxidase, flavin adenine dinucleotide, and thiamine pyrophosphate.