SERS Nanoparticle Imaging for Multiplex Tissue Biomarker Detection
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Solution Overview
Problem
Current optical histology imaging techniques for cancer diagnosis are limited by their inability to efficiently interrogate multiple biomarkers within a single tissue section, often requiring destructive, laborious, and time-consuming processes that introduce artifacts and destroy the sample, while existing multiplexed imaging methods are costly, complex, or require repetitive staining and bleaching, limiting their clinical applicability.
Innovation Solution
Development of surface-enhanced Raman spectroscopy nanoparticles (SERS-NPs) with a Raman active core, layer, and optional shell, chemically modified to target multiple biomarkers, enabling rapid molecular profiling of a whole tissue section in a single image with ultra-high sensitivity and specificity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Loss of information
If immunohistochemical staining is used to interrogate multiple biomarkers, then molecular information can be obtained, but the process is time-consuming and requires multiple tissue sections
Solution Approach 1:
The patent divides the detection task into multiple independent SERS nanoparticle probes, each targeting a specific biomarker. These segmented probes can simultaneously detect multiple biomarkers in a single tissue section, eliminating the need for sequential staining of multiple sections and significantly reducing the time required while preserving all molecular information.
Solution Approach 2:
The patent develops a universal platform using SERS nanoparticles that can simultaneously perform multiple detection functions. By functionalizing nanoparticles with different antibodies or ligands, the system can interrogate multiple biomarkers (HER2, ER, PR, Ki-67, etc.) in parallel within the same tissue section, making the process both faster and more comprehensive.
2Loss of information
If mass cytometry is used to interrogate multiple biomarkers, then comprehensive molecular data can be obtained, but the tissue sample is destroyed and cannot be used for further examination
Solution Approach 1:
The patent uses SERS nanoparticles as intermediary probes that bind to biomarkers on the tissue surface without requiring tissue destruction. These nanoparticles act as mediators that transfer molecular information from the tissue to the detector through Raman scattering, allowing comprehensive molecular data acquisition while preserving the tissue sample for subsequent pathological examination and other analyses.
Solution Approach 2:
The patent replaces the mechanical ablation process of mass cytometry with an optical detection method. Instead of using ion beams to sputter and destroy tissue for mass spectrometry analysis, the system uses Raman spectroscopy to detect nanoparticle signals, eliminating mechanical destruction while maintaining the ability to acquire comprehensive molecular data.
3Loss of information
If multiplexed fluorescence microscopy is used to characterize multiple analytes, then sub-cellular resolution can be achieved, but repetitive staining and bleaching are required which destroys essential antigens
Solution Approach 1:
The patent discards the need for repetitive bleaching steps inherent in fluorescence microscopy. By using SERS nanoparticles with Raman-active reporters that do not photobleach, the system maintains stable signals through multiple imaging sessions without requiring destructive bleaching, thereby preserving essential antigens and allowing repeated imaging of the same tissue section.
Solution Approach 2:
The patent changes the detection parameter from fluorescence emission (which is susceptible to photobleaching) to Raman scattering (which is photostable). This parameter change eliminates the need for repetitive bleaching and washing steps, preserving tissue antigens while maintaining the ability to characterize multiple analytes with sub-cellular resolution.
4Loss of information
If photo-cleavable oligonucleotide tags are used for multiplexed imaging, then multiple biomarkers can be detected, but cellular-level resolution is not achieved and data interpretation is challenging
Solution Approach 1:
The patent transitions from a chemical tagging approach (oligonucleotide hybridization) to a physical nanoparticle approach that provides spatial localization. By using solid SERS nanoparticles that can be imaged with optical microscopy, the system achieves cellular-level and sub-cellular spatial resolution while maintaining the ability to detect multiple biomarkers through spectral differentiation of different nanoparticle reporters.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The SERS-NPs provide exceptional multiplexing capabilities for rapid, accurate, and non-destructive molecular imaging, enhancing diagnostic sensitivity to femtomolar levels, reducing sample destruction and processing time, and improving clinical utility.
Implementation Method 1
surface-enhanced Raman spectroscopy nanoparticles (SERS-NP) as contrast agents that exhibit unsurpassed multiplexing capabilities to offer exceptional specificity
Implementation Method 2
Raman active metallic core, a Raman active layer... enhance Raman scattering and are thereby suitable for surface-enhanced Raman spectroscopy (SERS)
Implementation Method 3
The labeling agent may include a water soluble homobifunctional, heterobifunctional, or photoreactive crosslinker that may have a chemical group that can react with a functional group of an antibody or another biotargeting species
Implementation Method 4
utilizes Raman spectroscopy to interrogate the molecular expression of samples, for example, histology samples
Data Source
AI summary
This disclosure relates to a rapid molecular imaging strategy that utilizes Raman spectroscopy to interrogate the molecular expression of samples, for example, histology samples. This disclosure also relates to surface-enhanced Raman spectroscopy nanoparticles (SERS-NP) as contrast agents that exhibit unsurpassed multiplexing capabilities to offer exceptional specificity. This disclosure also relates to a SERS-NP comprising a Raman active metallic core, a Raman active layer, and a shell that may offer ultra-high diagnostic sensitivity (e.g., femtomolar level). This disclosure also relates to chemically modifying these new contrast agents to target a plurality of biomarkers within the sample. This disclosure also relates to rapid assessment of the molecular expression profile of the entire sample, for example, a whole tissue section, in a single image.