Fluorescence-based sensor with multiple indicator grafts

• US 10,080,514 B2
• Filed: 11/14/2014
• Issued: 09/25/2018
• Est. Priority Date: 11/15/2013
• Status: Active Grant

• Current Assignee: Senseonics, Incorporated (Senseonics Holdings, Inc.)
• Original Assignee: Senseonics, Incorporated (Senseonics Holdings, Inc.)
• Inventors: Emken, Jeremy, Huffstetler, Philip, Whitehurst, Todd
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Fardanesh, Marjan
• Application Number:
  US14/541,987
• Publication Number:
  US 20150141777A1
• Time in Patent Office: 1,411 Days
• Field of Search: None
• CPC Class Codes: A61B 2560/0219 of externally powered implanted units
• CPC Class Codes: A61B 2560/0247 for compensation or correction of the measured physiological value
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/1451 for interstitial fluid
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14556 by fluorescence A61B5/14555 takes precedence
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• CPC Class Codes: A61B 5/14735 comprising an immobilised reagent
• CPC Class Codes: A61B 5/6861 Capsules, e.g. for swallowing or implanting
• CPC Class Codes: G01N 2021/6421 Measuring at two or more wavelengths
• CPC Class Codes: G01N 2021/6441 with two or more labels
• CPC Class Codes: G01N 21/27 using photo-electric detection G01N21/31 takes precedence; circuits for computing concentration logarithmic circuits G06G7/24; photometric circuits in general G01J
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters

Abstract

A system including a sensor and a transceiver and configured to determine a concentration of an analyte in a medium of a living animal. The sensor may include first and second signal photodetectors and first and second reference photodetectors, which may each be covered by an associate filter. The first photodetector may receive light emitted from first and second grafts, respectively. The grafts may receive excitation light from one or more light sources. The transceiver may receive signals from the photodetectors of the sensor and may determine the analyte concentration based on the received signals.

Claims

1. A system for determining a concentration of an analyte in a medium of a living animal, the system comprising:

an optical sensor, the sensor including;

a sensor housing;

a first graft covering at least a first portion of the sensor housing;

first indicator molecules embedded in the first graft and having a first optical characteristic responsive to the concentration of the analyte;

a second graft covering at least a second portion of the sensor housing;

second indicator molecules embedded in the second graft and having a second optical characteristic responsive to the concentration of the analyte;

a substrate;

a first light source fabricated in or mounted on the substrate and configured to emit first excitation light to the first indicator molecules in the first graft;

a first signal photodetector fabricated in or mounted on the substrate and configured to receive first emission light emitted by the first indicator molecules and output a signal indicative thereof;

a first reference photodetector fabricated in or mounted on the substrate and configured to receive first reference light and output a signal indicative thereof;

a second light source fabricated in or mounted on the substrate and configured to emit second excitation light to the second indicator molecules in the second graft;

a second signal photodetector fabricated in or mounted on the substrate and configured to receive second emission light emitted by the second indicator molecules and output a signal indicative thereof; and

a second reference photodetector fabricated in or mounted on the substrate and configured to receive second reference light and output a signal indicative thereof; and

a transceiver configured to;

receive the signals indicative of the first signal light, the first reference light, the second signal light, and the second reference light;

determine whether the first graft is damaged or degraded using one or more of the received signals; and

if the first graft is determined to be damaged or degraded, calculate a concentration of the analyte in the medium of the living animal based on the received signals indicative of the second signal light and the second reference light but not the received signals indicative of the first signal light and the first reference light.

2. The system of claim 1, wherein the sensor further comprises a temperature sensor configured to output a temperature signal indicative of the temperature of the sensor, and the transceiver is further configured to receive the temperature signal and use the received temperature signal in the calculation of the analyte concentration.

3. The system of claim 1, wherein the sensor further comprises first and second temperature sensors configured to output first and second temperature signals, respectively, and the transceiver is further configured to receive the first and second temperature signals and use the received first and second temperature signals in the calculation of the analyte concentration.

4. The system of claim 1, wherein the transceiver is further configured to:

determine whether the second graft is damaged or degraded using one or more of the received signals; and

if the second graft is determined to be damaged or degraded, calculate a concentration of the analyte in the medium based on the received signals indicative of the first signal light and the first reference light but not the received signals indicative of the second signal light and the second reference light.

5. The system of claim 1, wherein:

the sensor housing has a first side and a second side opposite the first side;

the first portion is a portion of the first side of the sensor housing;

the second portion is a portion of the second side of the sensor housing;

the substrate has a first side and a second side opposite the first side of the substrate;

the first light source is fabricated in or mounted on the first side of the substrate;

the first signal photodetector is fabricated in or mounted on the first side of the substrate;

the first reference photodetector is fabricated in or mounted on the first side of the substrate;

the second light source is fabricated in or mounted on the second side of the substrate;

the second signal photodetector is fabricated in or mounted on the second side of the substrate; and

the second reference photodetector is fabricated in or mounted on the second side of the substrate.

6. The system of claim 1, wherein:

the sensor housing has a first side and a second side opposite the first side;

the second portion is a portion of the second side of the sensor housing;

the substrate has a first side and a second side opposite the first side of the substrate; and

the first light source, the first signal photodetector, the first reference photodetector, the second light source, the second signal photodetector, and the second reference photodetector are fabricated in or mounted on the first side of the substrate.

7. The system of claim 1, wherein the optical sensor is for implantation with the living animal.

8. The system of claim 1, wherein the wavelength of the first excitation light emitted by the first light source is different than the wavelength of the second excitation light emitted by the second light source.

9. The system of claim 1, wherein the transceiver comprises an inductive element.

10. The system of claim 1, wherein the first reference light is the first excitation light emitted by the first light source, and the second reference light is the second excitation light emitted by the second light source.

11. The system of claim 1, wherein the sensor further comprises:

a first signal filter configured to pass only a first narrow band of wavelengths including the wavelength of the first emission light emitted by the first indicator molecules, wherein the first signal filter covers a light receiving surface of the first signal photodetector;

a first reference filter configured to pass only a second narrow band of wavelengths including the wavelength of the first reference light, wherein the first reference filter covers a light receiving surface of the first reference photodetector;

a second signal filter configured to pass only a third narrow band of wavelengths including the wavelength of the second emission light emitted by the second indicator molecules, wherein the second signal filter covers a light receiving surface of the second signal photodetector; and

a second reference filter configured to pass only a fourth narrow band of wavelengths including the wavelength of the second reference light, wherein the second reference filter covers a light receiving surface of the second reference photodetector.

12. The system of claim 11, wherein the first reference light is the first excitation light emitted by the first light source, and the second reference light is the second excitation light emitted by the second light source.

13. The system of claim 11, wherein the wavelength of the first emission light emitted by the first indicator molecules is different than the wavelength of the second emission light emitted by the second indicator molecules.

14. The system of claim 1, wherein the first indicator molecules are different than the second indicator molecules, and the wavelength of the first emission light emitted by the first indicator molecules is different than the wavelength of the second emission light emitted by the second indicator molecules.

15. The system of claim 1, wherein the first indicator molecules are identical to the second indicator molecules, and the wavelength of the first emission light emitted by the first indicator molecules is the same as the wavelength of the second emission light emitted by the second indicator molecules.

16. The sensor system of claim 1, wherein the sensor further comprises an inductive element configured to convey signals generated by the first signal photodetector, the first reference photodetector, the second signal photodetector, and the second reference photodetector.

17. The system of claim 1, wherein the analyte is glucose.

18. The system of claim 1, wherein the analyte is oxygen.

19. The system of claim 1, wherein the animal is a human.

20. The system of claim 1, wherein the medium is interstitial fluid.

21. The system of claim 1, wherein the medium is blood.

22. The system of claim 1, wherein the medium is intraperitoneal fluid.

23. The system of claim 1, wherein the sensor further comprises:

a third signal photodetector fabricated in or mounted on the substrate and configured to receive third emission light; and

a third reference photodetector fabricated in or mounted on the substrate and configured to receive third reference light.

24. The system of claim 23, wherein the sensor further comprises third indicator molecules embedded in the first graft and having a third optical characteristic responsive to the concentration of the analyte, and the third emission light is emitted by third indicator molecules embedded in the first graft.

25. The system of claim 23, wherein the sensor further comprises:

a third graft covering at least a third portion of the sensor housing; and

third indicator molecules embedded in the third graft and having a third optical characteristic responsive to the concentration of the analyte;

wherein the third emission light is emitted by the third indicator molecules.

26. The system of claim 23, wherein the third reference light is the same as the first reference light.

27. The system of claim 23, wherein the sensor further comprises:

a third signal filter configured to pass only a fifth narrow band of wavelengths including the wavelength of the third emission light, wherein the third signal filter covers a light receiving surface of the third signal photodetector; and

a third reference filter configured to pass only a sixth narrow band of wavelengths including the wavelength of the third reference light, wherein the third reference filter covers a light receiving surface of the third reference photodetector.

28. The system of claim 23, wherein the sensor further comprises:

a fourth signal photodetector fabricated in or mounted on the substrate and configured to receive fourth emission light; and

a fourth reference photodetector fabricated in or mounted on the substrate and configured to receive fourth reference light.

29. A method for determining a concentration of an analyte in a medium of a living animal, the method comprising:

using a first signal photodetector to receive first emission light emitted by first indicator molecules of a first graft covering at least a first portion of a sensor housing of an optical sensor, wherein the first indicator molecules have a first optical characteristic responsive to the concentration of the analyte in the medium;

using the first signal photodetector to output a signal indicative of an amount of the first emission light received by the first signal photodetector;

using a first reference photodetector to receive first reference light and output a signal indicative of an amount of the first reference light received by the first reference photodetector;

using a second signal photodetector to receive second emission light emitted by second indicator molecules of a second graft covering at least a second portion of the sensor housing of the optical sensor, wherein the second indicator molecules have a second optical characteristic responsive to the concentration of the analyte in the medium;

using the second signal photodetector to output a signal indicative of an amount of the second emission light received by the second signal photodetector;

using a second reference photodetector to receive second reference light and output a signal indicative of an amount of the second reference light received by the second reference photodetector;

determining that the first graft is damaged or degraded using one or more of the received signals; and

if the first graft is determined to be damaged or degraded, calculating a concentration of the analyte in the medium of the living animal based on the signals indicative of the second signal light and the second reference light but not the received signals indicative of the first signal light and the first reference light.

30. A transceiver for determining a concentration of an analyte in a medium of a living animal, the transceiver comprising:

an inductive element configured to receive measurement information from an optical sensor including a sensor housing, a first graft covering at least a first portion of the sensor housing, and a second graft covering at least a second portion of the sensor housing, wherein the first graft includes first indicator molecules having a first optical characteristic responsive to the concentration of the analyte, and the second graft includes second indicator molecules having a second optical characteristic responsive to the concentration of the analyte; and

circuitry configured to;

determine whether the first graft is damaged or degraded using the received measurement information; and

if the first graft is determined to be damaged or degraded, calculate a concentration of the analyte in the medium of the living animal using a signal indicative of the second optical characteristic of the second indicator molecules of the second graft but not a signal indicative of the first optical characteristic of the first indicator molecules of the first graft.

31. The transceiver of claim 30, wherein the circuitry is further configured to:

determine whether the second graft is damaged or degraded using the received measurement information; and

if the second graft is determined to be damaged or degraded, calculate a concentration of the analyte in the medium of the living animal using a signal indicative of the first optical characteristic of the first indicator molecules of the first graft but not a signal indicative of the second optical characteristic of the second indicator molecules of the second graft.

32. The transceiver of claim 31, wherein the circuitry is further configured to, if neither the first graft nor the second graft is determined to be damaged or degraded, calculate a concentration of the analyte in the medium of the living animal using a signal indicative of the first optical characteristic of the first indicator molecules of the first graft but not a signal indicative of the second optical characteristic of the second indicator molecules of the second graft.

33. The transceiver of claim 30, wherein the transceiver is configured to calculate the concentration of the analyte in the medium of the living animal using the signal indicative of the second optical characteristic of the second indicator molecules of the second graft and a signal indicative of an amount of reference light received by a reference photodetector of the optical sensor.

34. A method for determining a concentration of an analyte in a medium of a living animal, the method comprising:

using an inductive element of a transceiver to receive measurement information from an optical sensor including a sensor housing, a first graft covering at least a first portion of the sensor housing, and a second graft covering at least a second portion of the sensor housing, wherein the first graft includes first indicator molecules having a first optical characteristic responsive to the concentration of the analyte, and the second graft includes second indicator molecules having a second optical characteristic responsive to the concentration of the analyte;

using the transceiver to determine that the first graft is damaged or degraded based on the received measurement information; and

if the first graft is determined to be damaged or degraded, using the transceiver to calculate a concentration of the analyte in the medium of the living animal based on a signal indicative of the second optical characteristic of the second indicator molecules of the second graft but not based on a signal indicative of the first optical characteristic of the first indicator molecules of the first graft.

35. The method of claim 34, wherein the concentration of the analyte in the medium of the living animal is calculated based on the signal indicative of the second optical characteristic of the second indicator molecules of the second graft and a signal indicative of an amount of reference light received by a reference photodetector of the optical sensor.