System and method for classification of tissue based on Raman and fluorescence in high-wavenumber Raman spectrum

Inventors

Pandey, RishikeshKersey, Alan

Assignees

Cytoveris Inc

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Publication Number

US-11821841-B2

Patent

Publication Date

2023-11-21

Expiration Date


Abstract

A method and system for classifying a tissue specimen is provided. The method includes: a) interrogating a tissue specimen with a first interrogation light; b) detecting first light from the tissue specimen resulting from the interrogation, wherein the first light includes a first scattered light component and a first fluorescence light component, and producing first signals; c) interrogating the tissue specimen with a second interrogation light at a second excitation wavelength, wherein the first and second excitation wavelengths are within about 2 nm of each other; d) detecting second light from the tissue specimen resulting from the interrogation, wherein the second light includes a second scattered light component and a second fluorescence light component, and producing second signals; e) determining a difference between the first and second lights; f) determining a fluorescence spectrum produced by the interrogation of the tissue specimen; and g) classifying the tissue specimen.

Core Innovation

The invention relates to classifying a tissue specimen as a type of tissue using Raman spectroscopy combined with fluorescence information. The tissue specimen is interrogated with a first interrogation light at a first excitation wavelength, and first light from the tissue specimen is detected as including a first scattered light component and a first fluorescence light component to produce first signals. The specimen is further interrogated with a second interrogation light at a second excitation wavelength within about 2 nm of the first excitation wavelength, and second light is detected to produce second signals that include a second scattered light component and a second fluorescence light component.

A Raman spectrum difference is determined between the first light and the second light using the first signals and the second signals. A fluorescence spectrum is also determined as produced by the interrogation of the tissue specimen with at least one of the first interrogation light or the second interrogation light, and the determined Raman spectrum difference and the determined fluorescence spectrum are used together to classify the tissue specimen as a type of tissue. The approach leverages Raman spectrum difference information and fluorescence spectrum determination as inputs to a tissue classifier rather than relying on either Raman or fluorescence information alone.

The invention also supports producing a plurality of Raman bar codes based on peak wavenumber intensity ratios, and using those Raman bar codes for tissue type clustering and classification. The documented system architecture includes at least one light source, a spectrometer, at least one light detector, a system controller, and non-transitory memory storing instructions executed by the system controller to control interrogation, detection, determining the Raman spectrum difference and fluorescence spectrum, and classifying the tissue specimen.

Claims Coverage

The document includes two independent claims covering both a method and a system for classifying a tissue specimen. The independent claims include five inventive features: close excitation-wavelength interrogation with dual-component detection, Raman spectrum difference determination, fluorescence spectrum determination, classification using both outputs, and a corresponding system architecture.

Close excitation-wavelength interrogation with scattered and fluorescence detection

interrogating a tissue specimen with a first interrogation light at a first excitation wavelength; detecting first light from the tissue specimen resulting from the interrogation of the tissue specimen with the first interrogation light, wherein the first light includes a first scattered light component and a first fluorescence light component, and producing first signals representative of the first light thereof; interrogating the tissue specimen with a second interrogation light at a second excitation wavelength, wherein the second excitation wavelength is within about 2 nm of the first excitation wavelength; detecting second light from the tissue specimen resulting from the interrogation of the tissue specimen with the second interrogation light, wherein the second light includes a second scattered light component and a second fluorescence light component, and producing second signals representative thereof.

Raman spectrum difference determination for paired excitations

determining a Raman spectrum difference between the first light and the second light using the first signals and the second signals.

Fluorescence spectrum determination for paired excitations

determining a fluorescence spectrum produced by the interrogation of the tissue specimen with at least one of the first interrogation light or the second interrogation light.

Classification using Raman spectrum difference and fluorescence spectrum

classifying the tissue specimen as a type of tissue using the determined Raman spectrum difference and the determined fluorescence spectrum.

System for executing close excitation interrogation and dual-component detection

a system for classifying a tissue specimen as a type of tissue, comprising at least one light source, a spectrometer, at least one light detector, and a system controller in communication with the at least one light source, the at least one light detector, and a non-transitory memory storing instructions, which instructions when executed cause the system controller to perform the interrogation, detection, determining the Raman spectrum difference, determining the fluorescence spectrum, and classifying the tissue specimen.

Across both independent claims, the core claim coverage centers on using two excitation wavelengths within about 2 nm, detecting scattered and fluorescence light components to produce first and second signals, determining a Raman spectrum difference, determining a fluorescence spectrum, and classifying tissue using both the Raman spectrum difference and the fluorescence spectrum.

Stated Advantages

Documented Applications

Tissue specimen classification into a type of tissue using Raman spectroscopy and fluorescence information.

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