Systems and methods for optode imaging

• US 10,159,434 B1
• Filed: 11/30/2015
• Issued: 12/25/2018
• Est. Priority Date: 11/30/2015
• Status: Active Grant

• Current Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Original Assignee: Verily Life Sciences LLC (Alphabet Inc.)
• Inventors: Alla, Suresh, Perreault, John D, Acosta, Victor Marcel, Lee, Seung Ah
• Primary Examiner(s): Winakur, Eric
• Assistant Examiner(s): Janoschka, Darin
• Application Number:
  US14/954,331
• Time in Patent Office: 1,121 Days
• Field of Search: 600300-399
• CPC Class Codes: A61B 2562/0233 Special features of optical sensors or probes classified in A61B5/00
• CPC Class Codes: A61B 2562/0238 Optical sensor arrangements for performing transmission measurements on body tissue
• CPC Class Codes: A61B 2562/0285 Nanoscale sensors
• CPC Class Codes: A61B 5/0059 using light, e.g. diagnosis by transillumination, diascopy, fluorescence A61B5/0093, A61B5/1455, A61B5/02416 and A61B5/0261 take precedence
• CPC Class Codes: A61B 5/0071 by measuring fluorescence emission
• CPC Class Codes: A61B 5/14503 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors A61B5/1459, A61B5/1464, A61B5/1473, A61B5/1482, A61B5/14865 take precedence
• CPC Class Codes: A61B 5/1451 for interstitial fluid
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/681 Wristwatch-type devices
• CPC Class Codes: A61B 5/7203 for noise prevention, reduction or removal
• CPC Class Codes: A61B 5/7278 Artificial waveform generation or derivation, e.g. synthesising signals from measured signals A61B5/327 takes precedence
• CPC Class Codes: A61M 2205/3303 Using a biosensor
• CPC Class Codes: G01N 2021/6434 Optrodes
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: Y10S 977/957 Of chemical property or presence

Abstract

Methods and systems disclosed herein may be operable to detect a presence or absence of an analyte in human tissue. An example method includes operating one or more light sources to illuminate a plurality of optodes with excitation light. Each optode is embedded in tissue at a respective location. The excitation light causes the optodes to emit emission light and the optodes are sensitive to at least one analyte such that the emission light emitted by the optodes is indicative of a presence or absence of at least one analyte in the tissue. An optical filter arrangement includes for each optode in the plurality of optodes a corresponding set of one or more optical filters. The method includes obtaining detector information from a detector arrangement optically coupled to the optical filter arrangement, and detecting the at least one analyte based on the detector information.

Claims

1. A system, comprising:

a plurality of optodes configured to be embedded in tissue, wherein each optode is at a respective location, wherein an excitation light causes the optodes to emit emission light, and wherein the optodes are sensitive to at least one analyte such that the emission light emitted by the optodes is indicative of a presence or absence of at least one analyte in the tissue;

one or more light sources, wherein the one or more light sources are configured to illuminate the plurality of optodes with the excitation light;

an optical filter array, wherein the optical filter array includes for each optode in the plurality of optodes a corresponding plurality of optical filters;

a detector array optically coupled to the optical filter array, wherein the detector array includes for each optode in the plurality of optodes a corresponding plurality of detectors configured to detect light received from the optode'"'"'s respective location via the optode'"'"'s corresponding plurality of optical filters; and

a controller comprising at least one processor, wherein the controller is programmed to carry out operations, the operations comprising;

operating the one or more light sources to illuminate the plurality of optodes with excitation light;

operating the detector array to obtain detector information, wherein the detector information includes for each optode a respective optode signal indicative of light that has been emitted from the optode'"'"'s respective location in response to the illumination from the one or more light sources, filtered through the optode'"'"'s corresponding plurality of optical filters, and detected by the optode'"'"'s corresponding plurality of detectors; and

detecting at least one analyte based on the detector information.

2. The system of claim 1, wherein the one or more light sources:

are disposed in an interleaved arrangement with respect to the detectors in the detector array, and

comprise at least one of;

a light-emitting diode or a laser diode.

3. The system of claim 1, further comprising a diffuser,

wherein the one or more light sources are optically-coupled to the diffuser, and wherein the diffuser is disposed around the detector array.

4. The system of claim 1, further comprising a spatial light modulator, wherein the operations further comprise selecting a target optode from the plurality of optodes and controlling the spatial light modulator to direct the excitation light from at least one of the one or more light sources toward the target optode in the plurality of optodes.

5. The system of claim 1, wherein the operations further comprise:

determining a background signal based on the detector information, wherein the background signal comprises a tissue autofluorescence signal; and

adjusting the detector information based on the background signal.

6. The system of claim 5, wherein adjusting the detector information based on the background signal comprises adjusting each of the optode signals based on a corresponding portion of the background signal.

7. The system of claim 6, wherein each optode'"'"'s respective optode signal includes an emission portion and a corresponding autofluorescence portion, wherein the emission portion is indicative of light from the optode'"'"'s location that is filtered by a first optical filter in the optode'"'"'s corresponding set of optical filters, wherein the autofluorescence portion is indicative of light from the optode'"'"'s location that is filtered by a second optical filter in the optode'"'"'s corresponding set of optical filters, and wherein adjusting each of the optode signals based on a corresponding portion of the background signal comprises adjusting the emission portions of the optode signals based on the corresponding autofluorescence portions.

8. The system of claim 1, wherein the one or more optical filters comprise at least one of:

a bandpass filter, a longpass filter, a shortpass filter, a dichroic filter, a polarization filter, an interference filter, or an absorptive filter.

9. The system of claim 8, wherein the characteristic waveband comprises a characteristic long wavelength cutoff and a characteristic short wavelength cutoff, wherein the plurality of optical filters further comprise a shortpass filter, wherein the shortpass filter has a cutoff wavelength less than the characteristic short wavelength cutoff.

10. The system of claim 8, wherein the characteristic waveband comprises a characteristic long wavelength cutoff and a characteristic short wavelength cutoff, wherein the one or more optical filters further comprise a longpass filter, wherein the longpass filter has a cutoff wavelength greater than the characteristic long wavelength cutoff.

11. The system of claim 1, wherein the emission light comprises a characteristic signal over a characteristic waveband, wherein the one or more optical filters comprise a bandpass filter, wherein the bandpass filter is configured to substantially transmit light over the characteristic waveband.

12. The system of claim 1, wherein the one or more light sources and the plurality of detectors are arranged in a checkerboard pattern corresponding with the respective locations of the plurality of optodes.

13. A method comprising:

operating a plurality of optodes embedded in tissue, wherein each optode is at a respective location, wherein an excitation light causes the optodes to emit emission light, wherein the optodes are sensitive to at least one analyte such that the emission light emitted by the optodes is indicative of a presence or absence of at least one analyte in the tissue;

operating one or more light sources to illuminate the plurality of optodes with the excitation light, wherein an optical filter array includes for each optode in the plurality of optodes a corresponding plurality of optical filters;

operating a detector array to obtain detector information, wherein the detector array is optically coupled to the optical filter array, wherein the detector array includes for each optode in the plurality of optodes a corresponding plurality of detectors operable to detect light received from the optode'"'"'s respective location via the optode'"'"'s corresponding plurality of optical filters, wherein the detector information includes for each optode a respective optode signal indicative of light that has been emitted from the optode'"'"'s respective location in response to the illumination from the one or more light sources, filtered through the optode'"'"'s corresponding plurality of optical filters, and detected by the optode'"'"'s corresponding plurality of detectors; and

detecting at least one analyte based on the detector information.

14. The method of claim 13, wherein the one or more light sources:

are disposed in an interleaved arrangement with respect to the detectors in the detector array, and

comprise at least one of;

a light-emitting diode or a laser diode.

15. The method of claim 13, further comprising:

determining a background signal based on the detector information, wherein the background signal comprises a tissue autofluorescence signal; and

adjusting the detector information based on the background signal.

16. The method of claim 15, wherein adjusting the detector information based on the background signal comprises adjusting each of the optode signals based on a corresponding portion of the background signal.

17. The method of claim 16, wherein each optode'"'"'s respective optode signal includes an emission portion and a corresponding autofluorescence portion, wherein the emission portion is indicative of light from the optode'"'"'s location that is filtered by a first optical filter in the optode'"'"'s corresponding set of optical filters, wherein the autofluorescence portion is indicative of light from the optode'"'"'s location that is filtered by a second optical filter in the optode'"'"'s corresponding set of optical filters, and wherein adjusting each of the optode signals based on a corresponding portion of the background signal comprises adjusting the emission portions of the optode signals based on the corresponding autofluorescence portions.

18. The method of claim 13, wherein the one or more optical filters comprise at least one of:

a bandpass filter, a longpass filter, a shortpass filter, a dichroic filter, a polarization filter, an interference filter, or an absorptive filter.

19. The method of claim 13, wherein the emission light comprises a characteristic signal over a characteristic waveband, wherein the one or more optical filters comprise a bandpass filter, wherein the bandpass filter is configured to substantially transmit light over the characteristic waveband.

20. The method of claim 13, further comprising:

determining a background signal based on at least one of;

detecting light via one or more detectors located at respective locations within the detector array or detecting light not having a characteristic optical response, wherein the characteristic optical response comprises the emission light emitted by the optodes that is indicative of the presence or absence of at least one analyte in the tissue, wherein the background signal comprises a tissue autofluorescence signal; and

adjusting the detector information based on the background signal.

21. The method of claim 13, wherein the one or more light sources and the plurality of detectors are arranged in a checkerboard pattern corresponding with the respective location of the plurality of optodes.