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

Patent metadata

Field	Value
Publication number	US-2020319108-A1
Application number	US-202016849102-A
Country	US
Kind code	A1
Filing date	Apr 15, 2020
Priority date	Apr 1, 2016
Publication date	Oct 8, 2020
Grant date	—

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

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, 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 plurality of temporally split spectral bands is collected with a single pixel collection element.

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

6 . 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.

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

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

9 . 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.

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

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.

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

• G01N2021/6484

  Optical fibres · CPC title

• G01N21/6402 Primary

  Atomic fluorescence; Laser induced fluorescence · CPC title

• G01J2003/1213

  Filters in general, e.g. dichroic, band · CPC title

• G01J3/0218

  using optical fibers · CPC title