Method and device for correcting optical signals

• US 10,045,722 B2
• Filed: 03/06/2014
• Issued: 08/14/2018
• Est. Priority Date: 03/14/2013
• Status: Active Grant

• Current Assignee: Profusa, Inc.
• Original Assignee: Profusa, Inc.
• Inventors: Kintz, Gregory J., McMillan, William, Wisniewski, Natalie
• Primary Examiner(s): Chen, Tse
• Assistant Examiner(s): HOFFMAN, JOANNE M
• Application Number:
  US14/199,497
• Publication Number:
  US 20140275869A1
• Time in Patent Office: 1,622 Days
• 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 device, comprising:

a sensor patch configured to be placed on a surface of a skin of a mammalian body, the sensor patch including a case;

a first light source disposed within the case and located within a center portion of the case, the first light source pre-configured to generate a first optical signal within an excitation wavelength range of a luminescent dye to illuminate an implant containing the luminescent dye embedded in tissue of the mammalian body, the luminescent dye configured to emit an analyte-dependent optical signal within an emission wavelength range in response to absorbing light within the excitation wavelength range;

a second light source disposed within the case and located within the center portion of the case, the second light source pre-configured to generate a second optical signal within the emission wavelength range to illuminate the tissue; and

a plurality of detectors disposed within the case and in a ring configuration around the central portion of the case, a first detector from the plurality of detectors configured to (1) receive a third optical signal emitted from the implant embedded in the tissue, the third optical signal being within the emission wavelength range and emitted by the implant in response to the implant being illuminated with the first optical signal and (2) receive a fourth optical signal in response to the tissue being illuminated by the second optical signal, the fourth optical signal being within the emission wavelength range.

2. The device of claim 1, further comprising at least one processor disposed within the case configured to:

receive data from the first detector representative of the third optical signal indicative of a concentration of the analyte and data representative of the fourth optical signal indicative of at least one of diffuse reflectance or scattering of light in the tissue,

calculate a correction factor using the data representative of the third optical signal and the data representative of the fourth optical signal, and

calculate at least one of a quantity or a concentration of analyte by applying the correction factor to the data representative of the third optical signal.

3. The device of claim 1, wherein a distance between the second light source and the first detector within the case is substantially equal to a distance between the first light source and the first detector within the case such that the first optical signal and the second optical signal each travel a light path that extends to a depth in the tissue that is substantially equal to a depth at which the implant is embedded.

4. The device of claim 1, wherein a distance between the second light source and the first detector within the case is greater than a distance between the first light source and the first detector within the case such that the second optical signal travels a light path that extends to a depth in the tissue that is greater than a depth at which the implant is embedded.

5. The device of claim 1, wherein the second light source is spaced apart from the first detector within the case such that the second optical signal travels a light path that extends to a depth of 1 to 5 mm under a surface of skin.

6. The device of claim 1, wherein the implant is embedded in subcutaneous tissue, and the second light source and a second detector from the plurality of detectors are configured 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.

7. The device of claim 1, wherein the first detector and the second light source spaced a first distance apart within the case such that the second optical signal and the fourth optical signal collectively define a first light path that extends to a first depth in the tissue, and the implant is embedded at a second depth in the tissue, the device further comprising:

a third light source disposed within the case and configured to generate a fifth optical signal to illuminate the tissue; and

a second detector disposed within the case and configured to receive a sixth optical signal emitted from the tissue, the third light source and the second detector spaced apart within the case a second distance different from the first distance such that the fifth optical signal and the sixth optical signal collectively define a second light path that extends to a third depth in the tissue, the second depth differing from the first depth and the third depth.

8. The device of claim 1, wherein the implant is embedded at a first depth in the tissue, the second light source and a second detector from the plurality of detectors are collectively configured such that the second optical signal travels a light path that extends to a second depth in the tissue, the device further comprising:

a processor disposed within the case configured to;

receive data representative of an analyte-independent optical signal emitted from the implant, and

determine the second depth using the data representative of the analyte-independent signal.

9. The device of claim 2, wherein the processor is further configured to:

receive data representative of an analyte-independent optical signal emitted from the implant, and

calculate the correction factor using the data representative of an analyte-independent optical signal.

10. The device of claim 1, wherein:

the analyte-dependent optical signal is a first analyte-dependent optical signal;

the emission wavelength range is a first emission wavelength range;

the excitation wavelength range is a first excitation wavelength range;

the luminescent dye is a first luminescent dye configured to emit the first analyte-dependent optical signal within the first emission wavelength range in response to absorbing light within the first excitation wavelength range;

the implant includes a second luminescent dye configured to emit an analyte-independent optical signal within a second emission wavelength range in response to absorbing light within a second excitation wavelength range, the device further comprising;

a third light source disposed within the case and pre-configured generate a fifth optical signal within the second excitation wavelength range to illuminate the implant, a second detector from the plurality of detectors configured to receive a sixth optical signal emitted from the implant, the sixth optical signal being within the second emission wavelength range and emitted from the implant in response to the implant being illuminated with the fifth optical signal; and

a fourth light source disposed within the case and pre-configured to generate a seventh optical signal within the second emission wavelength range to illuminate the tissue, the second detector configured to receive an eighth optical signal in response to the tissue being illuminated by the seventh optical signal.

11. The device of claim 2, wherein:

a second detector from the plurality of detectors is further configured to receive a fifth optical signal in response to the tissue being illuminated by a sixth optical signal, the sixth optical signal within the excitation wavelength range; and

the processor is further configured to calculate the correction factor using data representative of the fifth optical signal.

12. The device of claim 1, wherein the first light source and the second light source are light emitting diodes.

18. The device of claim 1, wherein:

the first light source is positioned to transmit the first generated light through a central via in the sensor patch.

19. The device of claim 1, wherein the excitation wavelength range and the emission wavelength range are mutually exclusive.

20. The device of claim 1, wherein:

the excitation wavelength range is 600 to 650 nm; and

the emission wavelength range is 670 to 750 nm.

21. The device of claim 1, further comprising:

a third light source disposed within the case and in the ring configuration in an outer ring portion of the case.

22. The device of claim 1, wherein:

the plurality of detectors is a first plurality of detectors; and

a third light source and a second plurality of detectors are disposed in a second ring configuration in an outer ring portion of the case outside the first ring configuration.

23. The device of claim 21, wherein:

the first light source is located in the center portion of the case and spaced apart from the outer ring portion of the case by at least 1 cm.

13. A device, comprising:

a case;

a plurality of light sources and a detectors disposed within the case, each detector from the plurality of detectors disposed adjacent to a light source from the plurality of light sources in a ring configuration in an outer ring portion of the case;

a first light source from the plurality of light sources disposed within a first portion of the case and pre-configured to generate a first optical signal within a first excitation wavelength range to illuminate an implant embedded in tissue of a mammalian body, the implant configured to emit an analyte-dependent optical signal within a first emission wavelength range in response to absorbing light within the first excitation wavelength range, the first emission wavelength range being different from the first excitation wavelength range, the implant configured to emit an analyte-independent optical signal within a second emission wavelength range in response to absorbing light within a second excitation wavelength range;

a first detector from the plurality of detectors disposed within the first portion of the case and configured to receive a second optical signal emitted from the implant in response to the implant being illuminated with the first optical signal, the second optical signal being within the first emission wavelength range;

a second light source from the plurality of light sources and pre-configured to generate a third optical signal to illuminate the implant with the second excitation wavelength range; and

a second detector from the plurality of detectors disposed within a second portion of the case and configured to receive a fourth optical signal emitted from the implant embedded in the tissue, the fourth optical signal being within a second emission wavelength range, the fourth optical signal emitted by the implant in response to the implant being illuminated with the third optical signal, the second portion of the case being mutually exclusive such that the first optical signal and the second optical signal define a first light path that is spaced laterally apart from a second light path defined by the third optical signal and the fourth optical signal.

14. The device of claim 13, further comprising:

a printed circuit board disposed within the case, the first detector and at least one processor disposed on the printed circuit board, the at least one processor configured to;

receive data representative of the second optical signal indicative of a concentration of the analyte and data representative of the fourth optical signal,

calculate a correction factor using the data representative of the second optical signal and the data representative of the fourth optical signal, and

calculate at least one of a quantity or a concentration of the analyte by applying the correction factor to the data representative of the second optical signal.

15. The device of claim 13, further comprising:

a third light source from the plurality of light sources pre-configured to generate a fifth optical signal within the first excitation wavelength range to illuminate the tissue within the first excitation wavelength range; and

a third detector from the plurality of detectors configured to receive a seventh optical signal emitted from the tissue, the seventh optical signal indicative of autofluorescence and emitted from the tissue in response to the tissue being illuminated with the fifth optical signal.

16. The device of claim 13, further comprising:

a third detector from the plurality of detectors configured to receive a fifth optical signal; and

at least one processor disposed within the case and configured to;

receive data representative of the second optical signal indicative of a concentration of the analyte and data representative of the fifth optical signal indicative of light reflected from the tissue within the first excitation wavelength range,

calculate a correction factor using the data representative of the second optical signal and the data representative of the fifth optical signal, and

calculate at least one of a quantity or a concentration of the analyte by applying the correction factor to the data representative of the second optical signal.

17. The device of claim 13, further comprising:

a third light source from the plurality of light sources configured to generate a fifth optical signal to illuminate the tissue; and

a third detector from the plurality of detectors disposed within a third portion of case and configured to receive a sixth optical signal emitted from the tissue in response to the tissue being illuminated with the fifth optical signal, the first portion of the case and the third portion of the case mutually exclusive such that the fifth optical signal and the sixth optical signal form a third light path that is spaced laterally from the implant when the first light source illuminates the implant such that the sixth optical signal does not include a significant contribution from the implant.

27. The device of claim 13, wherein:

a first subset of the plurality of detectors, including the first detector, is disposed in a first ring configuration around the central portion of the case; and

the second light source and a second subset of the plurality of detectors, including the second detector, are disposed in a second ring configuration in an outer ring portion of the case outside of the first ring configuration.

28. The device of claim 13, wherein the second light source is disposed in an outer ring portion of the case.

29. The device of claim 28, wherein:

the center portion of the case is spaced apart from the outer ring portion of the case by at least 1 cm.

24. A device, comprising:

a sensor patch configured to be placed on a surface of a skin of a mammalian body, the sensor patch including a case;

a first light source from a plurality of light sources disposed within the case, the first light source pre-configured to generate a first optical signal within an excitation wavelength range of a luminescent dye to illuminate an implant containing the luminescent dye embedded in tissue of the mammalian body, the luminescent dye configured to emit an analyte-dependent optical signal within an emission wavelength range in response to absorbing light within the excitation wavelength range;

a second light source from the plurality of light sources disposed within the case, the second light source pre-configured to generate a second optical signal within the emission wavelength range to illuminate the tissue; and

a plurality of detectors disposed within the case each detector from the plurality of detectors disposed adjacent to a light source from the plurality of light sources in a ring configuration in an outer ring portion of the case, a first detector from the plurality of detectors configured to (1) receive a third optical signal emitted from the implant embedded in the tissue, the third optical signal being within the emission wavelength range and emitted by the implant in response to the implant being illuminated with the first optical signal and (2) receive a fourth optical signal in response to the tissue being illuminated by the second optical signal, the fourth optical signal being within the emission wavelength range.

25. The device of claim 24, wherein the first detector and the first light source are disposed within a first portion of the case such that the first optical signal and the third optical signal travels a first light path that includes the implant and is associated with the first portion of the case, the device further comprising:

a third light source disposed within a second portion of the case, the third light source pre-configured to generate a fifth optical signal within the excitation wavelength range to illuminate the tissue; and

a second detector disposed within the second portion of the case, the second detector configured to receive a sixth optical signal emitted from the tissue, the sixth optical signal being within the emission wavelength range, the first portion of the case mutually exclusive from the first portion of the case such that the fifth optical signal and the sixth optical signal travel a second light path associated with the second portion of the case that is spaced laterally from the implant when the first light source illuminates the implant such that the sixth optical signal does not include a significant contribution from the implant.

26. A device, comprising:

a case;

a first light source disposed within a center portion of the case and pre-configured to generate a first optical signal within a first excitation wavelength range to illuminate an implant embedded in tissue of a mammalian body, the implant configured to emit an analyte-dependent optical signal within a first emission wavelength range in response to absorbing light within the first excitation wavelength range, the first emission wavelength range being different from the first excitation wavelength range, the implant configured to emit an analyte-independent optical signal within a second emission wavelength range in response to absorbing light within a second excitation wavelength range;

a plurality of detectors disposed within the case in a ring configuration around the central portion of the case;

a first detector from the plurality of detectors disposed within the first portion of the case and configured to receive a second optical signal emitted from the implant in response to the implant being illuminated with the first optical signal, the second optical signal being within the first emission wavelength range;

a second light source disposed within the case and pre-configured to generate a third optical signal to illuminate the implant with the second excitation wavelength range; and

a second detector from the plurality of detectors disposed within a second portion of the case and configured to receive a fourth optical signal emitted from the implant embedded in the tissue, the fourth optical signal being within a second emission wavelength range, the fourth optical signal emitted by the implant in response to the implant being illuminated with the third optical signal, the second portion of the case being mutually exclusive such that the first optical signal and the second optical signal define a first light path that is spaced laterally apart from a second light path defined by the third optical signal and the fourth optical signal.