Purification of glucose concentration signal in an implantable fluorescence based glucose sensor

• US 9,414,775 B2
• Filed: 07/09/2013
• Issued: 08/16/2016
• Est. Priority Date: 03/29/2012
• Status: Active Grant

• Current Assignee: Senseonics, Incorporated (Senseonics Holdings, Inc.)
• Original Assignee: Senseonics, Incorporated (Senseonics Holdings, Inc.)
• Inventors: Colvin, Arthur E. Jr., Wang, Xiaolin, Mdingi, Colleen, DeHennis, Andrew
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Fardanesh, Marjan
• Application Number:
  US13/937,871
• Publication Number:
  US 20140018644A1
• Time in Patent Office: 1,134 Days
• Field of Search: 600310-344
• US Class Current: 1/1
• 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 5/7203 for noise prevention, reduction or removal

Abstract

Methods, sensors, and systems for determining a concentration of glucose in a medium of a living animal are disclosed. Determining the glucose concentration may involve emitting excitation light from a light source to indicator molecules, generating a raw signal indicative of the amount of light received by a photodetector, purifying and normalizing the raw signal, and converting the normalized signal to a glucose concentration. The purification may involve removing noise (e.g., offset and/or distortion) from the raw signal. The purification and normalization may involve tracking the cumulative emission time that the light source has emitted the excitation light and tracking the implant time that has elapsed since the optical sensor was implanted. The purification and normalization may involve measuring the temperature of the sensor. The purification, normalization, and conversion may involve using parameters determined during manufacturing, in vitro testing, and/or in vivo testing.

Claims

1. A method of determining a concentration of glucose in a medium of a living animal using an optical sensor implanted in the living animal and a sensor reader external to the living animal, the method comprising:

emitting, using a light source of the optical sensor, excitation light to indicator molecules of the optical sensor, the indicator molecules having an optical characteristic responsive to the concentration of glucose;

generating, using a photodetector of the optical sensor, a raw signal indicative of the amount of light received by the photodetector, wherein the light received by the photodetector includes glucose-modulated light emitted by the indicator molecules and at least one of excitation light emitted by the light source and non-glucose modulated light emitted by the indicator molecules;

conveying, using an inductive element of the optical sensor, the raw signal;

receiving, using an inductive element of the sensor reader, the conveyed raw signal;

tracking, using circuitry of the sensor reader, the cumulative emission time that the light source has emitted the excitation light;

tracking, using circuitry of the sensor reader, the implant time that has elapsed since the optical sensor was implanted in the living animal;

adjusting, using circuitry of the sensor reader, the received raw signal to compensate for offset and distortion based on the tracked cumulative emission time and the tracked implant time; and

converting, using circuitry of the sensor reader, the adjusted signal into a measurement of glucose concentration in the medium of the living animal.

2. The method of claim 1, further comprising:

measuring, using a temperature sensor of the optical sensor, a temperature of the optical sensor;

conveying, using the inductive element of the optical sensor, the measured temperature of the optical sensor;

receiving, using the inductive element of the sensor reader, the conveyed temperature of the optical sensor;

correcting, using circuitry of the sensor reader, the received raw signal indicative of the amount of light received by the photodetector to compensate for temperature sensitivity of the light source based on the received temperature.

3. The method of claim 1, wherein the non-glucose modulated light emitted by the indicator molecules comprises light emitted by distortion producing indicator molecule subspecies.

4. The method of claim 3, wherein the distortion producing indicator molecule subspecies include oxidated species, and adjusting the received raw signal comprises:

calculating the light emitted by the oxidated species based on the tracked cumulative emission time and the tracked implant time; and

subtracting the calculated light emitted by the oxidated species from the received raw signal.

5. The method of claim 4, wherein the distortion producing indicator molecule subspecies include photo-activated oxidated species, and adjusting the received raw signal comprises:

calculating the light emitted by the photo-activated oxidated species based on the tracked cumulative emission time and the tracked implant time; and

subtracting the calculated light emitted by the photo-activated oxidated species from the received raw signal.

6. The method of claim 3, wherein the distortion producing indicator molecule subspecies include then tal degradation product species, and adjusting the received raw signal comprises:

calculating the light emitted by the thermal degradation product species based on the tracked cumulative emission time and the tracked implant time; and

subtracting the calculated light emitted by the thermal degradation product species from the received raw signal.

7. The method of claim 1, wherein the offset is hardware based, and adjusting the received raw signal comprises:

calculating the offset based on the tracked cumulative emission time; and

subtracting the calculated offset from the received raw signal.

8. The method of claim 1, wherein the adjusted signal is directly proportional to glucose concentration in the medium.

9. The method of claim 1, wherein the glucose-modulated light is emitted by active indicator species of the indicator molecules.

10. The method of claim 9, wherein adjusting the received raw signal comprises normalizing the received raw signal to a normalized raw signal that would be equal to one at zero glucose concentration.

11. The method of claim 10, wherein normalizing comprises:

calculating the amount of light emitted by the active indicator species at zero glucose concentration based on the tracked cumulative emission time and the tracked implant time; and

dividing the received raw signal by the calculated amount of light emitted by the active indicator species at zero glucose concentration.

12. The method of claim 10, further comprising:

measuring, using a temperature sensor of the optical sensor, a temperature of the optical sensor;

conveying, using the inductive element of the optical sensor, the measured temperature of the optical sensor; and

receiving, using the inductive element of the sensor reader, the conveyed temperature of the optical sensor;

wherein calculating the amount of light emitted by the active indicator species at zero glucose concentration is based on the received temperature, the tracked cumulative emission time, and the tracked implant time.

13. The method of claim 1, wherein the non-glucose modulated light is emitted by oxidated species, photo-activated oxidated species, and/or photo-activated oxidated species of the indicator molecules.

14. A system for determining a concentration of glucose in a medium of a living animal, the system comprising:

(1) an optical sensor configured to be implanted in the living animal, wherein the optical sensor includes;

(a) indicator molecules having an optical characteristic responsive to the concentration of glucose;

(b) a light source configured to emit excitation light to the indicator molecules;

(c) a photodetector configured to generate a raw signal indicative of the amount of light received by the photodetector, wherein the light received by the photodetector includes glucose-modulated light emitted by the indicator molecules and at least one of excitation light emitted by the light source and non-glucose modulated light emitted by the indicator molecules; and

(d) an inductive element configured to convey the raw signal; and

(2) an external sensor reader, the sensor reader including;

(a) an inductive element configured to receive the conveyed raw signal; and

(b) circuitry configured to;

(i) track the cumulative emission time that the light source has emitted the excitation light;

(ii) track the implant time that has elapsed since the optical sensor was implanted in the living animal;

(iii) adjust the received raw signal to compensate for offset and distortion based on the tracked cumulative emission time and the tracked implant time; and

(iv) convert the adjusted signal into a measurement of glucose concentration in the medium of the living animal.

15. The system of claim 14, wherein the optical sensor further comprises a temperature sensor configured to measure a temperature of the optical sensor;

wherein the inductive element of the optical sensor is configured to convey the measured temperature of the optical sensor, the inductive element of the sensor reader is configured to receive the conveyed temperature, and the circuitry of the sensor reader is further configured to correct the received raw signal to compensate for temperature sensitivity of the light source based on the received temperature.

16. The system of claim 14, wherein the circuitry is further configured to normalize the received raw signal to a normalized raw signal that would be equal to one at zero glucose concentration.

17. The system of claim 14, wherein the optical sensor includes (e) circuitry configured to convert the raw signal into a digital raw signal, and the conveyed raw signal is the digital raw signal.

18. A method of determining a concentration of glucose in a medium of a living animal using an optical sensor implanted in the living animal and a sensor reader external to the living animal, the method comprising:

emitting, using a light source of the optical sensor, excitation light to indicator molecules of the optical sensor, the indicator molecules having an optical characteristic responsive to the concentration of glucose;

generating, using a photodetector of the optical sensor, a raw signal indicative of the amount of light received by the photodetector, wherein the light received by the photodetector includes glucose-modulated light emitted by the indicator molecules and at least one of excitation light emitted by the light source and non-glucose modulated light emitted by the indicator molecules;

measuring, using a temperature sensor of the optical sensor, a temperature of the optical sensor;

conveying, using an inductive element of the optical sensor, the raw signal and the measured temperature;

receiving, using an inductive element of the sensor reader, the conveyed raw signal and the conveyed temperature;

tracking the cumulative emission time that the light source has emitted the excitation light;

tracking the implant time that has elapsed since the optical sensor was implanted in the living animal;

temperature correcting, using circuitry of the sensor reader, the received raw signal to compensate for temperature sensitivity of the light source based on the received temperature;

offset adjusting, using the circuitry of the sensor reader, the temperature corrected raw signal to compensate for offset based on the tracked cumulative emission time;

distortion adjusting, using the circuitry of the sensor reader, the offset adjusted raw signal to compensate for distortion based on the tracked cumulative emission time and the tracked implant time;

normalizing, using the circuitry of the sensor reader, the distortion adjusted raw signal to a normalized raw signal that would be equal to one at zero glucose concentration based on the measured temperature, the tracked cumulative emission time, and the tracked implant time; and

converting, using the circuitry of the sensor reader, the normalized raw signal into a measurement of glucose concentration in the medium of the living animal.

19. A method of determining a concentration of glucose in a medium of a living animal using an optical sensor implanted in the living animal and a sensor reader external to the living animal, the method comprising:

emitting, using a light source of the optical sensor, excitation light to indicator molecules of the optical sensor, the indicator molecules having an optical characteristic responsive to the concentration of glucose;

generating, using a photodetector of the optical sensor, a raw signal indicative of the amount of light received by the photodetector, wherein the light received by the photodetector includes glucose-modulated light emitted by the indicator molecules and at least one of excitation light emitted by the light source and non-glucose modulated light emitted by the indicator molecules;

tracking the cumulative emission time that the light source has emitted the excitation light;

tracking the implant time that has elapsed since the optical sensor was implanted in the living animal;

adjusting the raw signal to compensate for offset and distortion based on the tracked cumulative emission time and the tracked implant time; and

converting the adjusted signal into a measurement of glucose concentration in the medium of the living animal.

20. The method of claim 19, further comprising:

measuring, using a temperature sensor of the optical sensor, a temperature of the optical sensor; and

correcting the raw signal to compensate for temperature sensitivity of the light source based on the received temperature.

21. The method of claim 19, wherein the non-glucose modulated light emitted by the indicator molecules comprises light emitted by distortion producing indicator molecule subspecies.

22. The method of claim 21, wherein the distortion producing indicator molecule subspecies include oxidated species, and adjusting the raw signal comprises:

calculating the light emitted by the oxidated species based on the tracked cumulative emission time and the tracked implant time; and

subtracting the calculated light emitted by the oxidated species from the raw signal.

23. The method of claim 22, wherein the distortion producing indicator molecule subspecies include photo-activated oxidated species, and adjusting the raw signal comprises:

calculating the light emitted by the photo-activated oxidated species based on the tracked cumulative emission time and the tracked implant time; and

subtracting the calculated light emitted by the photo-activated oxidated species from the raw signal.

24. The method of claim 21, wherein the distortion producing indicator molecule subspecies include thermal degradation product species, and adjusting the raw signal comprises:

calculating the light emitted by the thermal degradation product species based on the tracked cumulative emission time and the tracked implant time; and

subtracting the calculated light emitted by the thermal degradation product species from the raw signal.

25. The method of claim 19, wherein the offset is hardware based, and adjusting the raw signal comprises:

calculating the offset based on the tracked cumulative emission time; and

subtracting the calculated offset from the raw signal.

26. The method of claim 19, wherein the adjusted signal is directly proportional to glucose concentration in the medium.

27. The method of claim 19, wherein the glucose-modulated light is emitted by active indicator species of the indicator molecules.

28. The method of claim 27, wherein adjusting the raw signal comprises normalizing the signal to a normalized raw signal that would be equal to one at zero glucose concentration.

29. The method of claim 28, wherein normalizing comprises:

calculating the amount of light emitted by the active indicator species at zero glucose concentration based on the tracked cumulative emission time and the tracked implant time; and

dividing the raw signal by the calculated amount of light emitted by the active indicator species at zero glucose concentration.

30. The method of claim 28, further comprising measuring, using a temperature sensor of the optical sensor, a temperature of the optical sensor;

wherein calculating the amount of light emitted by the active indicator species at zero glucose concentration is based on the received temperature, the tracked cumulative emission time, and the tracked implant time.

31. The method of claim 19, wherein the non-glucose modulated light is emitted by oxidated species, photo-activated oxidated species, and/or photo-activated oxidated species of the indicator molecules.

32. A method of determining a concentration of glucose in a medium of a living animal using an optical sensor implanted in the living animal and a sensor reader external to the living animal, the method comprising:

emitting, using a light source of the optical sensor, excitation light to indicator molecules of the optical sensor, the indicator molecules having an optical characteristic responsive to the concentration of glucose;

generating, using a photodetector of the optical sensor, a raw signal indicative of the amount of light received by the photodetector, wherein the light received by the photodetector includes glucose-modulated light emitted by the indicator molecules and at least one of excitation light emitted by the light source and non-glucose modulated light emitted by the indicator molecules;

measuring, using a temperature sensor of the optical sensor, a temperature of the optical sensor;

tracking the cumulative emission time that the light source has emitted the excitation light;

tracking the implant time that has elapsed since the optical sensor was implanted in the living animal;

temperature correcting the raw signal to compensate for temperature sensitivity of the light source based on the measured temperature;

offset adjusting the temperature corrected raw signal to compensate for offset based on the tracked cumulative emission time;

distortion adjusting the offset adjusted raw signal to compensate for distortion based on the tracked cumulative emission time and the tracked implant time;

normalizing the distortion adjusted raw signal to a normalized raw signal that would be equal to one at zero glucose concentration based on the measured temperature, the tracked cumulative emission time, and the tracked implant time; and

converting the normalized raw signal into a measurement of glucose concentration in the medium of the living animal.