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Three-Principal-Substrate SERS Profiling Enables Reliable Screening of Serum Biomarkers: A General Approach
Xuecheng Dong1, Zhengyuan Zhao1, Yuanhao Zheng1
1Key Laboratory of Advanced Materials (MOE), School of Materials Science and Engineering, Tsinghua University, Beijing 100084, China.
Analytical Chemistry
|March 20, 2026
Summary
A novel three-principal-substrate Surface-Enhanced Raman Scattering (SERS) method efficiently screens for cancer biomarkers in serum. This cost-effective technique identifies potential metabolites for early cancer diagnosis and treatment.
Area of Science:
- Biomedical Engineering
- Analytical Chemistry
- Cancer Research
Background:
- Biomarker discovery is vital for early cancer diagnosis and personalized treatment.
- Conventional methods like genomics are costly and time-consuming.
- Surface-Enhanced Raman Scattering (SERS) offers a sensitive and efficient alternative for trace-level detection.
Purpose of the Study:
- To develop a novel SERS-based strategy for efficient serum biomarker screening in cancer.
- To utilize a multi-substrate approach for enhanced biomarker identification.
- To validate the SERS strategy using breast cancer as a model.
Main Methods:
- Developed a three-principal-substrate SERS strategy using Ag-Au nanorods.
- Selected optimal substrates via Principal Component Analysis (PCA) of serum SERS spectra.
- Employed Partial Least-Squares Discriminant Analysis (PLS-DA) and the unanimity principle for biomarker screening.
- Validated candidate biomarkers using MALDI-TOF MS.
Main Results:
- Identified eleven candidate metabolites using SERS spectral differences and Variable Importance Projection (VIP) values.
- Confirmed trends of candidate metabolites with MALDI-TOF MS.
- Nine identified candidates are known breast cancer biomarkers; two are relevant metabolic derivatives.
Conclusions:
- The three-principal-substrate SERS framework is an effective approach for serum biomarker discovery.
- This method is particularly valuable for identifying biomarkers in diseases with unknown markers.
- SERS offers a cost-effective and time-efficient alternative to traditional biomarker discovery techniques.
