Novel Nitrocellulose Membrane Substrate for Efficient Analysis of Circulating Tumor Cells Coupled with Surface-Enhanced Raman Scattering Imaging

The capture and detection of circulating tumor cells (CTCs) in the bloodstream of patients with cancer is crucial for the clinical diagnosis and therapy. In the present work, a facile and integrated approach based on novel nitrocellulose membrane substrate and large-scale surface-enhanced Raman scattering (SERS) imaging technology has been developed for CTCs' sensitive detection and enumeration. The system mainly consists of three aspects: capture of CTCs in bloodstream, SERS probes labeling of the captured CTCs and large-scale SERS imaging readout of CTCs enumeration. The NC membrane was used to prepare the novel CTC-capture substrate through antibody self-assembled. It was low-cost, easily prepared and completely nontoxic. Furthermore, excellent capture efficiency of the substrate was demonstrated using nonsmall-cell lung cancer (NSCLC) cells (NCI-H1650) as target cells. As the most sensitive detection technology, SERS holds huge potential in CTCs analysis. Large-scale SERS imaging was employed in CTCs enumeration for the first time, instead of the conventional fluorescence imaging. Our SERS probes, with a simplified structure, offered highly enough sensitivity to recognize every single cell clearly. In the simulation experiment of spiking 100 cancer cells into 1 mL of human whole blood, 34 cells were captured and counted successfully according to the SERS imaging result. Our experimental results demonstrate the potential feasibility of novel NC membrane substrate coupled with large-scale SERS imaging technology for the accurate enumeration of CTCs in human whole blood.