Octahedral silver oxide nanoparticles enabling remarkable SERS activity for detecting circulating tumor cells.

The detection of circulating tumor cells (CTCs) is a crucial tool for early cancer diagnosis, prognosis, and postoperative evaluation. However, detection sensitivity remains a major challenge because CTCs are extremely rare in peripheral blood. To effectively detect CTCs, octahedral Ag2O nanoparticles (NPs) with high dispersibility, good biocompatibility, remarkable surface-enhanced Raman scattering (SERS) enhancement, and obvious enhancement selectivity are designed as an SERS platform. Ag2O NPs with many oxygen vacancy defects are successfully synthesized, which exhibit an ultra-high SERS enhancement factor (1.98×106) for 4-mercaptopyridine molecules. The remarkable SERS activity of octahedral Ag2O NPs is derived from the synergistic effect of the surface defect-promoted photo-induced charge transfer (PICT) process and strong vibration coupling resonance in the Ag2O-molecule SERS complex, greatly amplifying the molecular Raman scattering cross-section. The promoted PICT process is confirmed using ultraviolet-visible (UV-Vis) absorption spectroscopy, demonstrating that obvious PICT resonance occurs in Ag2O SERS system under visible light. An additional growth step of SERS bioprobe is proposed by modifying the Raman signal molecules and functional biological molecules on Ag2O NPs for CTC detection. The Ag2O-based SERS bioprobe exhibits excellent detection specificity for different cancer cells in rabbit blood. Importantly, the high-sensitivity Ag2O-based SERS bioprobe satisfies the requirement for rare CTC detection in the peripheral blood of cancer patients, and the detection limit can reach 1 cell per mL. To our knowledge, this study is the first time that a semiconductor SERS substrate has been successfully utilized in CTC detection. This work provides new insights into CTC detection and the development of novel semiconductor-based SERS platforms for cancer diagnosis.