PURIFICATION OF GLUCOSE CONCENTRATION SIGNAL IN AN IMPLANTABLE FLUORESCENCE BASED GLUCOSE SENSOR

• US 20130331667A1
• Filed: 03/29/2013
• Published: 12/12/2013
• 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., DeHennis, Andrew, Wang, Xiaolin, Mdingi, Colleen
• Granted Patent: US 9,345,426 B2
• Time in Patent Office: Days
• US Class Current: 600/316
• 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, 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, using circuitry of the optical sensor, the cumulative emission time that the light source has emitted the excitation light;

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

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

converting, using circuitry of the optical sensor, the adjusted signal into a measurement of glucose concentration in the medium of the living animal; and

conveying, using an inductive element of the optical sensor, the measurement of glucose concentration.

2. The method of claim 1, further comprising:

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

correcting, using circuitry of the optical sensor, the raw signal to compensate for temperature sensitivity of the light source based on the measured 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 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.

5. The method of claim 4, 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.

6. The method of claim 3, 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.

7. The method of claim 1, 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.

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 raw signal comprises normalizing the 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 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;

wherein calculating the amount of light emitted by the active indicator species at zero glucose concentration is based on the measured 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. An optical sensor for determining a concentration of glucose in a medium of a living animal, the sensor comprising:

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

a light source configured to emit excitation light to the indicator molecules;

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;

circuitry configured to;

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

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

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

convert the adjusted signal into a measurement of glucose concentration in the medium of the living animal; and

an inductive element configured to convey the measurement of glucose concentration.

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

wherein the circuitry is further configured to correct the raw signal to compensate for temperature sensitivity of the light source based on the measured temperature.

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

17. A method of determining a concentration of glucose in a medium of a living animal using an optical sensor implanted in 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, using circuitry of the optical sensor, the raw signal to compensate for temperature sensitivity of the light source based on the measured temperature;

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

distortion adjusting, using the circuitry of the optical sensor, 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 optical sensor, 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;

converting, using the circuitry of the optical sensor, the normalized raw signal into a measurement of glucose concentration in the medium of the living animal; and

conveying, using an inductive element of the optical sensor, the measurement of glucose concentration.

18. A method of configuring an optical sensor to determine a concentration of glucose in blood of a living animal when implanted in the living animal, the method comprising:

operating the optical sensor at a first temperature;

while the optical sensor is being operated at the first temperature, measuring three different known glucose concentrations;

operating the optical sensor at a second temperature different than the first temperature;

while the optical sensor is being operated at the second temperature, measuring the three different known glucose concentrations;

based on the measurements of the three different known glucose concentrations at the first and second temperatures, determining;

(i) the amount of light emitted by a light source of the optical sensor, reflected by a graft of the optical sensor containing indicator molecules, and received by a photodetector of the optical sensor,

(ii) the amount of light emitted by the light source of the optical sensor and received by the photodetector of the optical sensor without encountering the graft,

(iii) the temperature sensitivity of the light source,

(iv) a dissociation constant for converting a normalized signal indicative of glucose modulated fluorescence to a glucose concentration, and

(v) a normalized signal indicative of glucose modulated fluorescence at infinite glucose concentration; and

configuring an optical sensor with the determined values such that the optical sensor is configured to;

(i) determine a hardware based offset based on (a) the determined amount of light emitted by the light source, reflected by the graft, and received by the photodetector;

(b) the determined amount of light emitted by the light source and received by the photodetector without encountering the graft; and

(c) a tracked cumulative emission time that the light source has emitted the excitation light;

(ii) temperature correct a raw signal based on the determined temperature sensitivity of the light source and a measured temperature; and

(iii) convert a normalized signal indicative of glucose modulated fluorescence to a glucose concentration based on (a) the determined dissociation constant and (b) the determined normalized signal indicative of glucose modulated fluorescence at infinite glucose concentration.