A simple paper-based surface enhanced Raman scattering (SERS) platform and magnetic separation for cancer screening

Abstract Early and precise diagnosis of cancer is critical for a better prognosis. Here, we describe a simple and cost-effective plasmonic paper as a surface enhanced Raman scattering (SERS) substrate in combination with magnetic separation for cancer screening. The plasmonic paper was fabricated by immersing plain filter paper into gold nanorod solution and the SERS property of the paper was evaluated using 4-mercaptobenzoic acid (4-MBA) and rhodamine 6 G (R6 G), which showed an enhancement factor (EF) in the range of 106–108. HT-29, a colorectal cancer cell line that highly expresses epithelial cell adhesion molecule (EpCAM), served as the target cells; non-EpCAM-expressing cells, namely fibroblasts and red blood cells (RBCs), were used as negative controls. Intrinsic SERS spectra of the target and control cells showed distinctive patterns on the plasmonic paper due to differences in their structure and components. A combination of principal component analysis (PCA) and k-nearest-neighbor algorithm (k-NN) was employed to analyze and distinguish the acquired HT-29 and fibroblast SERS spectra, demonstrating a diagnostic sensitivity and specificity of 84.8% and 82.6%, respectively, whereas the differentiation between HT-29 and RBCs SERS spectra showed a sensitivity and specificity of 96.4% and 100%, respectively. The magnetic separation was applied to capture the target cells from cell mixtures followed by PCA and k-NN analysis. The identification of the captured cells as cancerous cells from the HT-29 and fibroblast mixture indicated an accuracy of 83.7%, while that from a mixture of HT-29 and RBCs was 98.2%. Thus, the simple paper-based SERS substrate with the assistance of magnetic enrichment and multivariate analysis offers a potent new platform for cancer cell detection and screening.