Method and device for correcting optical signals

• US 11,134,871 B2
• Filed: 08/13/2018
• Issued: 10/05/2021
• Est. Priority Date: 03/14/2013
• Status: Active Grant

• Current Assignee: Profusa, Inc.
• Original Assignee: Profusa, Inc.
• Inventors: Kintz, Gregory J., McMillan, William A., Wisniewski, Natalie
• Primary Examiner(s): Hoffman, Joanne M
• Application Number:
  US16/102,070
• Publication Number:
  US 20190192057A1
• Time in Patent Office: 1,149 Days
• Field of Search: None
• 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, comprising:

sending a first generated light within an excitation wavelength range from a first light emitting diode (LED) of an optical device disposed on a skin of a mammalian body, the first generated light sent through tissue of the mammalian body to an implant embedded in the tissue, the implant configured to absorb light within the excitation wavelength range and fluoresce to emit an analyte-dependent optical signal within an emission wavelength range in response to absorbing light within the excitation wavelength range;

receiving, with at least one detector of the optical device disposed on the skin of the mammalian body and in response to the first generated light being sent through the tissue, a first optical signal emitted from the implant embedded in the tissue within the emission wavelength range;

calculate, with a processor of the optical device disposed on the skin of the mammalian body, an initial value indicative of a concentration of the analyte based on the first optical signal;

sending, from the optical device disposed on the skin of the mammalian body and into the tissue, a second generated light, the second generated light sent from a second LED pre-configured to emit light within the emission wavelength range;

receiving, with the at least one detector and in response to the second generated light, a second optical signal emitted from the tissue within the emission wavelength range;

calculating, with the processor, a correction factor based on the second optical signal, the correction factor indicative of background within the emission wavelength range; and

calculating, with the processor, the concentration of the analyte by applying the correction factor to the initial value indicative of the concentration of the analyte.

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 a depth at which the implant is embedded.

3. The method of claim 2, wherein the depth at which the implant is embedded is 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 a depth at which the implant is embedded.

5. The method of claim 1, wherein the correction factor is a first correction factor and the first generated light, the implant, and the first optical signal collectively define at least a portion of a first light path, the method further comprising:

sending a third generated light from the optical device into the tissue, the third generated light being within the excitation wavelength range;

receiving, with the at least one detector and in response to the third generated light, a third optical signal emitted from the tissue in the emission wavelength range; and

calculating, with the processor a second correction factor based on the third optical signal light, the second correction factor associated with autofluorescence of the tissue, the third generated light and the third optical signal collectively defining at least a portion of the second light path, at least a portion of the second light path spaced laterally from a corresponding portion of the first light path, the concentration of the analyte calculated by applying the first correction factor and the second correction factor to the initial value indicative of the concentration of the analyte.

6. The method of claim 1, wherein:

the implant is embedded in subcutaneous tissue; and

the second generated light 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 6 further comprising:

positioning the first LED on the skin of the mammalian body over the implant such that the first light source and the at least one detector are collectively configured such that the first light path intersects with the implant, the second LED spaced apart from the first LED such that when the first LED is positioned over the implant, such that the implant is illuminated by a lesser quantity of the third generated light relative to a quantity of the first generated light illuminating the implant.

8. The method of claim 1, wherein the implant is embedded at a first depth in the tissue, the second optical signal travels a first light path that extends to a second depth in the tissue, and the correction factor is a first correction factor, the method further comprising:

sending a third generated light from the optical device into the tissue such that the third generated light travels a second light path that extends to a third depth in the tissue, the third depth being different from the first depth and the second depth;

receiving, with the at least one detector and in response to the third generated light, a third optical signal emitted from the tissue; and

calculating with the processor a second correction factor based on the third optical signal the second correction factor associated with the second light path, the concentration of the analyte calculated by applying the first correction factor and the second correction factor to the initial value indicative of the concentration of the analyte.

9. The method of claim 1, wherein:

the excitation wavelength range is a first excitation wavelength range;

the implant is embedded at a first depth in the tissue; and

the second optical signal travels a first light path that extends to a second depth in the tissue, the method further comprising;

sending a third generated light from the optical device into the tissue, the third generated light sent before the second generated light, the third generated light being within a second excitation wavelength range; and

receiving, with the at least one detector and in response to the third generated light, an analyte-independent optical signal-emitted from the tissue; and

determining the second depth using the analyte-independent optical signal.

10. The method of claim 1, wherein the correction factor is a first correction factor, the method further comprising:

receiving, with the at least one detector, an analyte independent optical signal emitted from the implant; and

calculating, with the processor, a second correction factor based on an analyte-independent optical signal emitted from the implant, the concentration of the analyte calculated by applying the first correction factor and the second correction factor to the initial value indicative of the concentration of the analyte.

11. The method of claim 1, wherein the excitation wavelength range is a first excitation wavelength range, the emission range is a first emission range, the implant is configured to emit a signal having a second emission range in response to receiving an excitation signal within the second excitation wavelength range, the initial value is a first initial value, and the correction factor is a first correction factor, the method further comprising:

sending a third generated light from a third LED of the optical device pre-configured to emit light within the second excitation wavelength range through the tissue to the implant;

receiving, with the at least one detector and in response to the third generated light, a third optical signal emitted from the implant embedded within the tissue within the second emission wavelength range;

calculating, with the processor a second initial value indicative of excitation of the implant by the third generated light based on the third optical signal;

sending a fourth generated light from a fourth LED of the optical device into the tissue, the fourth LED pre-configured to emit light within the second emission wavelength range; and

receiving, with the at least one detector and in response to the fourth generated light, a fourth optical signal emitted from the tissue;

calculating, with the processor, a second correction factor based on the fourth optical signal, the concentration of the analyte calculated based on the initial value indicative of the concentration of the analyte, the initial value indicative of excitation of the implant by the third generated light, the first correction factor, and the second correction factor.

12. The method of claim 1, wherein the at least one detector is a first detector, the method further comprising:

sending a third generated light from a third LED of the optical device into the tissue, the third LED pre-configured to emit light within the excitation wavelength range;

receiving, with a second detector and in response to the third generated light, a third optical signal emitted from the tissue within the excitation wavelength range, the third LED and the second detector spaced apart from the first LED and the first detector within a housing of optical device such that when the first LED sends the first generated light to the implant, the third LED is spaced apart from the implant and the third optical signal is not sent to the implant;

calculating with the processor, a second correction factor based on the third optical signal, the second correction factor associated with autofluorescence of the tissue, the concentration of the analyte calculated by applying the first correction factor and the second correction factor to the initial value indicative of the concentration of the analyte.

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

14. The method of claim 1, wherein:

the excitation wavelength range is 600 to 650 nm; and

the emission wavelength range is 670 to 750 nm.

15. A method, comprising:

sending a first generated light from at least one light source disposed within a case of an optical device through tissue of a mammalian body to an implant embedded in the tissue, the at least one light source pre-configured to emit the first generated light within an excitation wavelength range, the implant configured to absorb light within the excitation wavelength range and emit an analyte-dependent optical signal within an emission wavelength range in response to absorbing light within the excitation wavelength range;

measuring, in response to the first generated light with at least one detector disposed within the case of the optical device, a first optical signal emitted from the implant embedded in the tissue within the emission wavelength range to produce a value indicative of a concentration of the analyte;

sending a second generated light within the excitation wavelength range into the tissue from the at least one light source;

determining a value indicative of tissue autofluorescence based on a second optical signal emitted from the tissue within the emission wavelength range in response to the second generated light, the second light source spaced apart from the first light source within the case such that the second optical signal travels a light path that is spaced laterally from the implant when the first light source sends the first generated light to the implant such that the second optical signal does not include a significant contribution from the implant;

calculating a correction factor using the value indicative of tissue autofluorescence; and

calculating the concentration of the analyte by applying the correction factor to the value indicative of the concentration of the analyte.

16. The method of claim 15, wherein the implant is embedded in subcutaneous tissue, and the light path extends to a depth in the tissue that is substantially equal to a depth at which the implant is embedded.

17. The method of claim 15, wherein the implant is embedded at a first depth in the tissue, the light path extends to a second depth in the tissue, the first light source is spaced a first distance apart from the at least one detector, and the second light source is spaced a second distance apart from the at least one detector, the method further comprises:

sending a third generated light into the tissue from a third light source within the case of the optical device, the third light source spaced a third distance apart from the at least one detector, the third distance being different from the first distance and the second distance such that the third optical signal travels a second light path that extends to a third depth in the tissue that differs from the first depth and the second depth; and

measuring a third optical signal emitted from the tissue in response to sending the third generated light into the tissue, the correction factor calculated using a value associated with the third optical signal.

18. The method of claim 15, wherein the excitation wavelength range is a first excitation wavelength range, and the emission wavelength range is a first emission wavelength range, the method further comprising:

sending a third generated light from a third light source disposed within the case of the optical device through the tissue to the implant, the third light source pre-configured to emit light within a second excitation wavelength range, the implant configured to absorb light within the second excitation wavelength range and emit a light in a second emission wavelength range in response to absorbing light within the second excitation wavelength range;

measuring, in response to the third light with the at least one detector, a third optical signal emitted from the implant embedded in the tissue within the second emission wavelength range to produce a value associated with the third optical signal;

sending a fourth generated light into the tissue from a fourth light source pre-configured to emit light within the second emission wavelength range; and

measuring, in response to the fourth generated light, a fourth optical signal emitted from the tissue to produce a value associated with the fourth optical signal, the correction factor calculated using the value associated with the third optical signal and the value associated with the fourth optical signal.

19. The method of claim 15, wherein the second light source is laterally spaced from the first light source by at least 1 cm, such that the light path is laterally spaced apart from the implant by at least 1 cm.

20. The method of claim 15, wherein the light path is a first light path, the method further comprising:

sending a third generated light into the tissue from a third light source pre-configured to emit light within the emission wavelength range; and

measuring, with the at least one detector and in response to the third generated light, a third optical signal emitted from the tissue to produce a value associated with diffuse reflectance in the tissue within the emission wavelength range, the third light source spaced apart from the first light source such that the third generated light and the third optical signal form a second light path that is spaced laterally from the implant when the first light source sends the first generated light to the implant such that the third optical signal does not include a significant contribution from the implant, the correction factor calculated using the value associated with the third optical signal.