Systems, devices, and methods for time-resolved fluorescent spectroscopy

Patent metadata

Field	Value
Publication number	US-11630061-B2
Application number	US-202016849102-A
Country	US
Kind code	B2
Filing date	Apr 15, 2020
Priority date	Apr 1, 2016
Publication date	Apr 18, 2023
Grant date	Apr 18, 2023

Abstract

Provided herein are devices, systems, and methods for characterizing a biological sample in vivo or ex vivo in real-time using time-resolved spectroscopy. A light source generates a light pulse or continuous light wave and excites the biological sample, inducing a responsive fluorescent signal. A demultiplexer splits the signal into spectral bands and a time delay is applied to the spectral bands so as to capture data with a detector from multiple spectral bands from a single excitation pulse. The biological sample is characterized by analyzing the fluorescence intensity magnitude and/or decay of the spectral bands. The sample may comprise one or more exogenous or endogenous fluorophore. The device may be a two-piece probe with a detachable, disposable distal end. The systems may combine fluorescence spectroscopy with other optical spectroscopy or imaging modalities. The light pulse may be focused at a single focal point or scanned or patterned across an area.

First claim

What is claimed is:

1. A method for classifying or characterizing a sample, the method comprising:
radiating a sample with at least one light pulse at a predetermined wavelength to cause the sample to produce a responsive optical signal;
collecting the responsive optical signal from the sample; and
splitting the responsive optical signal at pre-determined wavelength ranges with a filter wheel comprising a plurality of spectral filters to obtain a plurality of temporally distinct spectral bands corresponding to the plurality of spectral filters, wherein the plurality of temporally split spectral bands is collected with a single pixel collection element; and
characterizing, in near real-time or real-time, the sample based on the plurality of temporally distinct spectral bands using time-resolved fluorescence spectroscopy.

2. The method of claim 1 , wherein each of the temporally distinct spectral bands is time delayed with respect to another.

3. The method of claim 1 , wherein the responsive optical signal comprises one or more of a fluorescence spectrum, a Raman spectrum, an ultraviolet-visible spectrum, or an infrared spectrum.

4. The method of claim 1 , wherein the single pixel collection element comprises a photomultiplier tube.

5. The method of claim 1 , wherein characterizing the sample comprises determining one or more of a concentration or a distribution of a molecule in the sample based on the plurality of temporally distinct spectral bands.

6. The method of claim 5 , wherein the molecule comprises an exogenous fluorescent molecule or an endogenous fluorescent molecule.

7. The method of claim 1 , wherein the sample is characterized in about 100 ms or less.

8. The method of claim 1 , further comprising encoding an identifier into one or more of the temporally distinct spectral bands using one or more of the spectral filters.

9. The method of claim 1 , further comprising scanning the at least one light pulse across a pre-determined portion of the sample.

10. The method of claim 9 , wherein scanning comprises raster scanning.

11. The method of claim 1 , wherein collecting the responsive optical signal from the sample comprises passing the responsive optical signal through an optical assembly comprising one or more optical components having a numerical aperture of 0.22 or greater.

12. The method of claim 11 , wherein the optical assembly is characterized by at least one numerical aperture and a total cross-sectional area for light passage, and wherein a square of the at least one numerical aperture multiplied by the total cross-sectional area is 0.018 mm2 at locations of the optical assembly conveying light.

13. The method of claim 12 , wherein the at least one numerical aperture is of one or more fibers of the optical assembly, and wherein the total cross-sectional area is based on the number of the one or more fibers and the diameter of the one or more fibers.

14. The method of claim of claim 1 , wherein a gain of the single pixel collection element is automatically adjusted.

15. The method of claim 1 , wherein the sample is obtained from a surgical procedure of a patient.

Assignees

• Black Light Surgical Inc
• Cedars Sinai Medical Center

Inventors

• Butte Pramod
• Black Keith
• Kavanaugh Jack
• BORTNIK Bartosz
• Nie Zhaojun

Classifications

• G01N21/6408 Primary

  with measurement of decay time, time resolved fluorescence · CPC title

• G01N21/6402 Primary

  Atomic fluorescence; Laser induced fluorescence · CPC title

• G01J3/32

  Investigating bands of a spectrum in sequence by a single detector · CPC title

• G01N2021/6484

  Optical fibres · CPC title

• G01J3/2889

  Rapid scan spectrometers; Time resolved spectrometry · CPC title