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 Ag 2 O nanoparticles (NPs) with high dispersibility, good biocompatibility, remarkable surface-enhanced Raman scattering (SERS) enhancement, and obvious enhancement selectivity are designed as an SERS platform. Ag 2 O NPs with many oxygen vacancy defects are successfully synthesized, which exhibit an ultra-high SERS enhancement factor (1.98×10 6 ) for 4-mercaptopyridine molecules. The remarkable SERS activity of octahedral Ag 2 O 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 Ag 2 O-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 Ag 2 O 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 Ag 2 O NPs for CTC detection. The Ag 2 O-based SERS bioprobe exhibits excellent detection specificity for different cancer cells in rabbit blood. Importantly, the high-sensitivity Ag 2 O-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.