METHOD AND DEVICE FOR CORRECTING OPTICAL SIGNALS

• US 20140275869A1
• Filed: 03/06/2014
• Published: 09/18/2014
• Est. Priority Date: 03/14/2013
• Status: Active Grant

• Current Assignee: Profusa, Inc.
• Original Assignee: Profusa, Inc.
• Inventors: McMillan, William, Wisniewski, Natalie, Kintz, Gregory J.
• Granted Patent: US 10,045,722 B2
• Time in Patent Office: Days
• US Class Current: 600/310
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• 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

An optical device is used to monitor an implant embedded in the tissue of a mammal (e.g., under the skin). The implant receives excitation light from the optical device and emits light that is detected by the optical device, including an analyte-dependent optical signal. Scatter and absorption properties of tissue change over time due to changes in hydration, blood perfusion and oxygenation. The optical device has an arrangement of light sources, filters and detectors to transmit excitation light within excitation wavelength ranges and to measure emitted light within detection wavelengths. Changes in scattering and absorption of light in the tissue, such as diffuse reflectance, are monitored. The light sources, filters and detectors may also be used to monitor autofluorescence in the tissue to correct autofluorescence background.

Claims

1. A method for correcting at least one analyte-dependent optical signal emitted from an implant embedded in tissue of a mammalian body, the implant being capable of emitting, in response to excitation light within an excitation wavelength range, the analyte-dependent optical signal within an emission wavelength range, the method comprising:

a) transmitting first excitation light within the excitation wavelength range through the tissue to the implant;

b) measuring, in response to the first excitation light, a first optical signal emitted from the tissue within the emission wavelength range;

c) transmitting second excitation light into the tissue, wherein the second excitation light is substantially within the emission wavelength range of the analyte-dependent optical signal;

d) measuring, in response to the second excitation light, a second optical signal emitted from the tissue within the emission wavelength range; and

e) calculating at least one corrected signal value in dependence upon the measured signals.

2. The method of claim 1, wherein the second optical signal travels a light path that extends to a depth in the tissue that is substantially equal to the depth at which the implant is embedded.

3. The method of claim 2, wherein the depths are in the range of 1 to 5 mm under a surface of skin.

4. The method of claim 1, wherein the second optical signal travels a light path that extends to a depth in the tissue that is greater than the depth at which the implant is embedded.

5. The method of claim 1, further comprising the steps of:

transmitting third excitation light into the tissue, wherein the third excitation light is within the excitation wavelength range; and

measuring, in response to the third excitation light, a third optical signal emitted from the tissue in the emission wavelength range, wherein the third optical signal travels a light path that is spaced laterally from the implant a sufficient distance to avoid significant contribution from implant reporters, and wherein the corrected signal value is calculated in further dependence upon the measured third optical signal.

6. The method of claim 1, wherein the implant is embedded in subcutaneous tissue, and wherein the second optical signal travels a light path that extends to a depth in the tissue that is greater than or equal to 2 mm under a surface of skin.

7. The method of claim 1, further comprising the steps of transmitting third excitation light into the tissue and measuring a third optical signal emitted from the tissue, wherein the implant is embedded at a first depth in the tissue, the second optical signal travels a light path that extends to a second depth in the tissue, the third optical signal travels another light path that extends to a third depth in the tissue, the third depth differs from the first and second depths, and the corrected signal value is calculated in further dependence upon the third optical signal.

8. The method of claim 1, wherein the implant is embedded at a first depth in the tissue, the second optical signal travels a light path that extends to a second depth in the tissue, and the second depth is determined by transmitting excitation light within a second excitation wavelength range through the tissue to the implant, measuring at least one analyte-independent optical signal emitted from the tissue, and determining the second depth in dependence upon the analyte-independent optical signal.

9. The method of claim 1, wherein the step of calculating at least one corrected signal value includes the steps of measuring at least one analyte-independent optical signal emitted from the implant and assigning a quantity or weight to the measurement of the second optical signal in dependence upon the measurement of the analyte-independent signal.

10. The method of claim 1, further comprising the steps of:

transmitting third excitation light within a second excitation wavelength range through the tissue to the implant;

measuring, in response to the third excitation light, a third optical signal emitted from the tissue within a second emission wavelength range;

transmitting fourth excitation light into the tissue, wherein the fourth excitation light is within the second emission wavelength range; and

measuring, in response to the fourth excitation light, a fourth optical signal emitted from the tissue, wherein the corrected signal value is calculated in further dependence upon the measured third and fourth optical signals.

11. The method of claim 1, further comprising the steps of transmitting third excitation light into the tissue and measuring a third optical signal emitted from the tissue, wherein the third excitation light is within the excitation wavelength range, and wherein the corrected signal value is calculated in further dependence upon the third optical signal.

12. An optical detection device for monitoring an implant embedded in tissue of a mammalian body, the implant being capable of emitting, in response to excitation light within an excitation wavelength range, at least one analyte-dependent optical signal within an emission wavelength range, the device comprising:

a) a first light source arranged to transmit first excitation light within the excitation wavelength range through the tissue to the implant;

b) a second light source arranged to transmit second excitation light into the tissue, wherein the second excitation light is substantially within the emission wavelength range; and

c) at least one detector arranged to measure, in response to the first excitation light, a first optical signal emitted from the tissue in the emission wavelength range and arranged to measure, in response to the second excitation light, a second optical signal emitted from the tissue in the emission wavelength range.

13. The device of claim 12, further comprising at least one processor arranged to receive data to representative of the measured optical signals, wherein the processor is programmed to calculate at least one quantity or concentration of analyte according to the measured optical signals.

14. The device of claim 12, wherein the second light source and at least one detector are arranged such that the second optical signal travels a light path that extends to a depth in the tissue that is substantially equal to the depth at which the implant is embedded.

15. The device of claim 12, wherein the second light source and at least one detector are arranged such that the second optical signal travels a light path that extends to a depth in the tissue that is greater than the depth at which the implant is embedded.

16. The device of claim 15, wherein the depths in the tissue are in a range of 1 to 5 mm under a surface of skin.

17. The device of claim 12, further comprising:

a third light source arranged to transmit third excitation light within the excitation wavelength range into the tissue; and

at least a second detector arranged to measure, in response to the third excitation light, a third optical signal emitted from the tissue within the emission wavelength range, wherein the third light source and at least second detector are arranged such that the third excitation light and the light emitted in response to the third excitation light form a light path that is spaced laterally from the implant a sufficient distance to avoid significant contribution from implant reporters.

18. The device of claim 12, wherein the implant is embedded in subcutaneous tissue, and the second light source and at least one detector are arranged such that the second optical signal travels a light path that extends to a depth in the tissue greater than or equal to 3 mm under a surface of skin.

19. The device of claim 12, further comprising:

a third light source arranged to transmit third excitation light into the tissue; and

at least a second detector arranged to measure, in response to the third excitation light, a third optical signal emitted from the tissue, wherein the implant is embedded at a first depth in the tissue, the light sources and detectors are arranged such that the second optical signal travels a light path that extends to a second depth in the tissue, the third optical signal travels another light path that extends to a third depth in the tissue, and the third depth differs from the first and second depths.

20. The device of claim 13, wherein the implant is embedded at a first depth in the tissue, the second light source and at least one detector are arranged such that the second optical signal travels a light path that extends to a second depth in the tissue, and the processor is further programmed to determine the second depth in dependence upon a measurement of at least one analyte-independent signal emitted from the implant.

21. The device of claim 13, wherein the processor is further programmed to determine the corrected signal value by assigning a quantity or weight to the measurement of the second optical signal in dependence upon a measurement of at least one analyte-independent signal emitted from the implant.

22. The device of claim 12, wherein the implant is further capable of emitting, in response to excitation light within a second excitation wavelength range, at least one analyte-independent optical signal within a second emission wavelength range, and the device further comprises:

a third light source arranged to transmit third excitation light in the second excitation wavelength range through the tissue to the implant, wherein the at least one detector is arranged with the third light source to measure, in response to the third excitation light, a third optical signal emitted from the tissue in the second emission wavelength range; and

to a fourth light source arranged to transmit fourth excitation light into the tissue, wherein the fourth excitation light is substantially within the second emission wavelength range, and wherein the at least one detector is arranged with the fourth light source to measure, in response to the fourth excitation light, a fourth optical signal emitted from the tissue.

23. The device of claim 13, wherein the at least one detector is further arranged to measure, in response to third excitation light transmitted into the tissue, a third optical signal emitted from the tissue within the excitation wavelength range, and wherein the processor is further programmed to calculate the quantity or concentration of analyte in dependence upon the third optical signal.

24. The device of claim 12, wherein the light sources and at least one detector are arranged in a sensor patch adapted to be placed on a surface of skin.

25. A method for correcting at least one analyte-dependent optical signal emitted from an implant embedded in tissue of a mammalian body, the implant being capable of emitting, in response to excitation light within an excitation wavelength range, the analyte-dependent optical signal within an emission wavelength range, the method comprising:

a) transmitting first excitation light within the excitation wavelength range through the tissue to the implant;

b) measuring, in response to the first excitation light, a first optical signal emitted from the tissue within the emission wavelength range;

c) transmitting second excitation light within the excitation wavelength range into the tissue;

d) measuring, in response to the second excitation light, a second optical signal emitted from the tissue within the emission wavelength range, wherein the second excitation light and light emitted in response to the second excitation light form a light path that is spaced laterally from the implant a sufficient distance to avoid significant contribution from implant reporters; and

e) determining at least one corrected signal value in dependence upon the measured optical signals.

26. The method of claim 25, wherein the implant is embedded in subcutaneous tissue, and the light path extends to a depth in the tissue that is substantially equal to the depth at which the implant is embedded.

27. The method of claim 25, wherein the implant is embedded at a first depth in the tissue, the light path extends to a second depth in the tissue, and the method further comprises the steps of transmitting third excitation light into the tissue and measuring a third optical signal emitted from the tissue, wherein the third optical signal travels another light path that extends to a third depth in the tissue that differs from the first and second depths, and wherein the corrected signal value is calculated in further dependence upon the third optical signal.

28. The method of claim 25, further comprising the steps of:

transmitting third excitation light within a second excitation wavelength range through the tissue to the implant;

measuring, in response to the third excitation light, a third optical signal emitted from the tissue within a second emission wavelength range;

transmitting fourth excitation light into the tissue, wherein the fourth excitation light is within the second emission wavelength range; and

measuring, in response to the fourth excitation light, a fourth optical signal emitted from the tissue, wherein the corrected signal value is calculated in further dependence upon the measured third and fourth optical signals.

29. The method of claim 25, wherein the lateral spacing of the light path from the implant is greater than or equal to 1 cm.

30. The method of claim 25, further comprising the steps of:

transmitting third excitation light into the tissue; and

measuring, in response to the third excitation light, a third optical signal emitted from the tissue, wherein the third excitation light and the light emitted in response to the third excitation light form a second light path that is spaced laterally from the implant a sufficient distance to avoid significant contribution from implant reporters, and wherein the corrected signal value is calculated in further dependence upon the measured third optical signal.

31. An optical detection device for monitoring an implant embedded in tissue of a mammalian body, the implant being capable of emitting, in response to excitation light within an excitation wavelength range, at least one analyte-dependent optical signal within an emission wavelength range, the device comprising:

a) a first light source arranged to transmit first excitation light in the excitation wavelength range through the tissue to the implant;

b) a first detector arranged to measure, in response to the first excitation light, a first optical signal emitted from the tissue in the emission wavelength range;

c) a second light source arranged to transmit second excitation light in the excitation wavelength range into the tissue; and

d) a second detector arranged to measure, in response to the second excitation light, a second optical signal emitted from the tissue within the emission wavelength range, wherein the second light source and the second detector are positioned with respect to each other such that the second excitation light and the light emitted in response to the second excitation light form a light path that is spaced laterally from the implant a sufficient distance to avoid significant contribution from implant reporters.

32. The device of claim 31, further comprising at least one processor arranged to receive data representative of the measured optical signals and programmed to calculate at least one corrected signal value in dependence upon the measured optical signals.

33. The device of claim 31, wherein the lateral spacing of the light path from the implant is greater than or equal to about 1 cm.

34. The device of claim 31, wherein the light path extends to a depth in the tissue that is substantially equal to the depth at which the implant is embedded.

35. The device of claim 31, wherein the implant is further capable of emitting, in response to excitation light having a second excitation wavelength range, at least one analyte-independent optical signal having a second emission wavelength range, and the device further comprises:

a third light source arranged to transmit third excitation light in the second excitation wavelength range through the tissue to the implant;

a third detector arranged to measure, in response to the third excitation light, a third optical signal emitted from the tissue in the second emission wavelength range;

a fourth light source arranged to transmit fourth excitation light into the tissue, wherein the fourth excitation light is substantially within the second emission wavelength range; and

a fourth detector arranged to measure, in response to the fourth excitation light, a fourth optical signal emitted from the tissue.

36. The device of claim 31, further comprising:

a third detector arranged to measure a third optical signal comprising light reflected from the tissue within the excitation wavelength range; and

at least one processor arranged to receive data representative of the measured optical signals and programmed to calculate at least one corrected signal value in dependence upon the measured optical signals.

37. The device of claim 31, further comprising:

a third light source arranged to transmit third excitation light into the tissue; and

a third detector arranged to measure, in response to the third excitation light, a third optical signal emitted from the tissue, wherein the third light source and the third detector are arranged with respect to each other such that the third excitation light and the light emitted in response to the third excitation light form a second light path that is spaced laterally from the implant a sufficient distance to avoid significant contribution from implant reporters.

38. The device of claim 31, wherein the light sources and detectors are arranged in a sensor patch adapted to be placed on a surface of skin, the first light source being positioned to transmit the first excitation light through a central via in the patch, and the detectors being arranged in a pattern of one or more rings around the central via.