Method and system for detecting cancerous tissue and tumor margin using raman spectroscopy
Inventors
Kersey, Alan • Pandey, Rishikesh
Assignees
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Publication Number
US-12326404-B2
Publication Date
2025-06-10
Expiration Date
Abstract
A method and system for determining the presence or absence of cancerous cells within subject tissue. The method includes: providing a material that includes a peptide component configurable in a non-binding form when disposed in a neutral pH environment, and in a binding form when disposed in an acidic pH environment, wherein the peptide component is configured to produce a first Raman spectrum when subjected to one or more predetermined wavelengths of light; administering the material to a subject tissue; interrogating the subject tissue with light; sensing the subject tissue for light emitted from the subject tissue, and producing signals representative of the sensed emitted light; analyzing the signals to determine a presence or absence of the first Raman spectrum; and determining the presence or absence of cancerous cells based on the presence or absence of the first Raman spectrum within the sensed light emitted from the subject tissue.
Core Innovation
The invention relates to Raman-based cancer detection in subject tissue using a material that includes at least one pH-configurable peptide component. The peptide component is configurable in a non-binding form when disposed in a neutral pH environment, and in a binding form when disposed in an acidic pH environment. The peptide component includes a pH (low) insertion peptide (pHLIP) and a Raman Reporter (RR) configured to produce a first Raman spectrum when subjected to one or more predetermined wavelengths of light.
The first Raman spectrum is distinguishable from Raman spectra produced by the subject tissue under the same one or more predetermined wavelengths of light. The first Raman spectrum is located within a Raman silent region defined by a wavelength region within a range of about 1800 cm−1 to about 2800 cm−1. This placement within the Raman silent region supports discriminating the RR signal from tissue Raman spectra.
The method and system determine the presence or absence of cancerous cells based on whether the first Raman spectrum is present or absent in the sensed light emitted from the subject tissue. The approach includes administering the material, allowing it to reside with the subject tissue for an incubation period, washing to remove any unbound peptide components, interrogating the tissue with light, sensing emitted light with one or more light detectors, and analyzing signals using an analyzer.
Claims Coverage
The patent includes two independent claims: a method claim and a system claim. Across these independent claims, the core inventive features are a pH-responsive pHLIP-RR peptide probe producing a distinguishable first Raman spectrum within a Raman silent region, and determining cancer presence/absence by detecting that spectrum, with narrow-pass band filters in the system claim.
pH-configurable peptide component for Raman spectrum generation
A material that includes at least one type of peptide component configurable in a non-binding form when disposed in a neutral pH environment, and in a binding form when disposed in an acidic pH environment, wherein the peptide component is configured to produce a first Raman spectrum when subjected to one or more predetermined wavelengths of light.
pHLIP Raman Reporter producing distinguishable first Raman spectrum in Raman silent region
The peptide component includes a pH (low) insertion peptide (pHLIP) and a Raman Reporter (RR), the RR configured to produce the first Raman spectrum when subjected to the one or more predetermined wavelengths of light, and the first Raman spectrum is distinguishable from Raman spectra produced by the subject tissue when subjected to the one or more predetermined wavelengths of light, wherein the first Raman spectrum resides within a Raman silent region defined by a wavelength region within a range of about 1800 cm−1 to about 2800 cm−1.
Incubate, wash, and interrogate to detect presence or absence of first Raman spectrum
Administering the material to a subject tissue and allowing the material to reside with the subject tissue for an incubation period of time; washing the subject tissue after the incubation period to remove any unbound peptide components; interrogating the subject tissue with light at the one or more predetermined wavelengths of light produced by one or more light sources after the subject tissue has been washed after the incubation period; sensing the subject tissue for light emitted from the subject tissue using one or more light detectors and producing signals representative of the sensed emitted light; analyzing the signals representative of the sensed emitted light using an analyzer to determine a presence or absence of the first Raman spectrum; and determining the presence or absence of cancerous cells within the subject tissue based on the presence or absence of the first Raman spectrum.
System with narrow-pass band filters and analyzer for presence/absence determination
A system comprising at least one light source configured to interrogate a subject tissue with light at the one or more predetermined wavelengths of light; at least one light detector configured to detect light emitted from the subject tissue, the emitted light resulting from the light interrogation of the subject tissue, and configured to produce signals representative of the detected emitted light; one or more narrow-pass band filters configured to permit passage limited to the signals representative of the detected emitted light that are also representative of the first Raman spectrum within the Raman silent region; and an analyzer in communication with the at least one light source, the at least one light detector, and a non-transitory memory storing instructions that cause the analyzer to control interrogation, receive signals representative of the first Raman spectrum within the Raman silent region from the one or more narrow-pass band filters, analyze the signals to determine a presence or absence of the first Raman spectrum, and determine the presence or absence of cancerous cells based on the presence or absence of the first Raman spectrum within the sensed light emitted from the subject tissue.
Across the independent claims, the inventive concept is the use of a pH-configurable pHLIP-RR peptide probe that generates a distinguishable first Raman spectrum within a Raman silent region (about 1800 cm−1 to about 2800 cm−1), followed by interrogation, sensing, and analysis to determine cancerous cell presence/absence based on whether that first Raman spectrum is present.
Stated Advantages
Provides a first Raman spectrum that is distinguishable from Raman spectra produced by subject tissue.
Places the first Raman spectrum within a Raman silent region defined by a wavelength region within about 1800 cm−1 to about 2800 cm−1.
Enables determining presence or absence of cancerous cells based on the presence or absence of the first Raman spectrum within sensed emitted light.
In the system, narrow-pass band filters permit passage limited to signals representative of the first Raman spectrum within the Raman silent region.
Documented Applications
Determining the presence or absence of cancerous cells within subject tissue using a Raman-based method and a Raman-based system employing a pHLIP and Raman Reporter generating a first Raman spectrum in a Raman silent region.
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