SERS Nano-particle for CTC Detection via ROC Thresholding
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Solution Overview
Problem
Current SERS-based methods for detecting circulating tumor cells (CTCs) face challenges in distinguishing CTCs from white blood cells (WBCs) due to nonspecific adsorption of SERS probes, leading to increased missed detection rates.
Innovation Solution
Development of a SERS nano-particle composed of core magnetic particles, noble metal nano-particles, Raman signal molecules, hydrophilic molecules, and target antibodies such as anti-trop2, which specifically binds to trop2 expressed on CTCs, combined with the use of a ROC curve to set a SERS signal intensity threshold for differentiation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If SERS probes are used to detect CTCs, then detection capability is improved, but nonspecific adsorption to WBCs increases leading to missed detection
Solution Approach 1:
The detection system is segmented into multiple functional components: magnetic particles for capture, noble metal nanoparticles for SERS signal enhancement, and hydrophilic molecules for reducing nonspecific adsorption. Each component addresses a specific aspect of the detection challenge, allowing selective improvement of CTC detection while minimizing WBC interference.
Solution Approach 2:
The invention uses composite nano-particles combining magnetic particles, noble metal nanoparticles, and hydrophilic molecules. This composite structure integrates multiple functions: magnetic separation capability, SERS signal enhancement, and reduced nonspecific adsorption to WBCs, thereby improving both detection precision and reliability simultaneously.
2Measurement precision
If SERS probes bind to receptors on tumor cells, then tumor cell recognition is improved, but WBCs also carry Raman signals due to nonspecific adsorption
Solution Approach 1:
The nano-particle surface is designed with different local properties: hydrophilic molecules are distributed on the surface to specifically reduce nonspecific adsorption to WBCs, while target antibodies are positioned to bind specifically to tumor cell receptors. This local differentiation allows selective improvement of tumor cell recognition without increasing WBC interference.
Solution Approach 2:
The invention converts the harmful nonsspecific adsorption phenomenon into a beneficial selective binding mechanism. By using hydrophilic molecules to prevent nonspecific WBC adsorption, the system ensures that only specific tumor cell-SERS probe interactions produce strong Raman signals, thereby converting potential interference into enhanced specificity.
3Productivity
If EpCAM-based immunomagnetic bead capture is used, then CTC capture is improved, but tumors undergoing EMT lead to loss of EpCAM molecules increasing missed detection
Solution Approach 1:
The invention changes the detection parameter from EpCAM-specific binding to a more general approach using target molecules that can recognize tumor cells regardless of EpCAM expression status. This parameter change allows the system to maintain high capture efficiency for epithelial tumors while also detecting mesenchymal-transformed cells that have lost EpCAM expression.
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 nano-particle effectively captures and identifies CTCs by enhancing SERS signals and reducing interference from WBCs, while the ROC curve analysis ensures accurate differentiation based on SERS intensity thresholds, thereby improving detection specificity and sensitivity.
Implementation Method 1
a surface-enhanced Raman scattering (SERS) probe is bound to a corresponding receptor on the surface of a tumor cell by means of the specificity of an antibody coupled thereto, and then tumor cells are recognized by detecting Raman signals of the SERS probe targeted to the surface of cells
Implementation Method 2
CTC capture techniques include density gradient precipitation, size-exclusion filtration, self-driven micro-machines, magnetic beads
Data Source
AI summary
Disclosed are a SERS nano-particle, a preparation method therefor, and an application thereof to a method for distinguishing CTCs from WBCs. The SERS nano-particle are formed by core magnetic particles, noble metal nano-particles, Raman signal molecules, hydrophilic molecules and target molecules. A method for distinguishing CTCs from WBCs comprises: enabling a SERS nano-particle to make contact with a to-be-detected solution containing CTCs and/or WBCs; performing incubation; then detecting SERS signal intensity of a cell combined with the SERS nano-particle; setting SERS signal intensity threshold; if SERS signal intensity of the cell combined with the SERS nano-particle exceeds SERS signal intensity threshold, determining the cell as CTS; otherwise, determining the cell as WBC. A ROC curve is used for the first time to assist the SERS technique in distinguishing CTCs from WBCs.