Cervical cancer screening by biomarker-free Serum-SERS technique: A three-principal-substrate approach

The complexity of serum constituents and the lack of knowledge on biomarkers bring obstacles for reliable cancer screening with the limited information obtained by surface-enhanced Raman scattering (SERS) on a single substrate. We report here an extremely high-accurate approach for cancer screening by biomarker-free serum-SERS technique which employs three principal SERS substrates that are of specially designed surface properties. With three substrates rich information on serum can be obtained from SERS spectra, of which quadratic discriminant analysis (QDA) yields excellent classifications of serum samples independently. Diagnosis with an accuracy of ∼100% can be achieved based on the three independent QDA classifications, by the unanimity principle. In this study, a screening accuracy of 100% was achieved by this approach for 122 diagnosed out of the 194 serum samples. The mechanism for the extremely high accuracy of this approach was also theoretically investigated. The three-principal-substrate approach opens up a path towards highly accurate biomarker-free cancer screening by serum-SERS technique.