Ultrahigh SERS activity of the TiO 2 @Ag nanostructure leveraged for accurately detecting CTCs in peripheral blood.

Circulating tumor cells (CTCs) usually shed from primary and metastatic tumors serve as an important tumor marker, and easily cause fatal distant metastasis in cancer patients. Accurately and effectively detecting CTCs in a peripheral blood sample is of great significance in early tumor diagnosis, efficacy evaluation, and postoperative condition monitoring. In this work, a TiO 2 @Ag nanostructure is structured as a SERS substrate, rhodamine 6G (R6G) is used as a Raman signal molecule, the reduced bovine serum protein (rBSA) acts as a protective agent, and folic acid (FA) acts as a target molecule to specifically recognize cancer cells. A TiO 2 @Ag-based SERS bioprobe is successfully prepared with the feature of ultrahigh sensitivity, good specificity, low toxicity, and high accuracy in CTC detection. The remarkable SERS activity of the TiO 2 @Ag nanostructure is synergistically contributed by surface plasmon resonance and photon-induced charge transfer mechanism. The limit of detection for rhodamine 6G (R6G) molecules adsorbed on the TiO 2 @Ag SERS substrate is 5 × 10 -14 M, and the corresponding SERS enhancement factor can reach 7.61 × 10 7 . The designed TiO 2 @Ag-R6G-rBSA-FA SERS bioprobe is effectively utilized in detecting various cancer cells in rabbit blood, and the limit of detection (LOD) for the target cancer cell is 1 cell per mL. Notably, CTCs in peripheral blood of six clinical liver cancer patients are successfully recognized via the TiO 2 @Ag-based SERS bioprobe. Accurately recognizing CTCs in peripheral blood based on the TiO 2 @Ag-R6G-rBSA-FA SERS bioprobe is also carefully verified by in situ immunofluorescence staining experiments, which directly supports the CTC detection accuracy of the SERS strategy. These results demonstrate that the TiO 2 @Ag-based SERS bioprobe has great application potential in early screening and diagnosis of tumors.