金属氧化物较弱的SERS增强因子严重制约了其在生物传感、诊疗领域的发展前景，为了突破这一瓶颈，本项目提出制备生物兼容性好、具有选择性增强特性和高灵敏度的表面缺陷态/非晶态金属氧化物SERS基底应用于循环肿瘤细胞的高效检测。通过研究金属氧化物表/界面电子结构增大目标分子拉曼散射截面，及选择性增强拉曼振动模式的作用机制，是提升金属氧化物SERS增强因子的有效途径。结合实验测试和模拟计算，明确材料表面电偶极子、静电势、费米能级、能带结构与目标分子轨道能级耦合作用方式，总结出提升金属氧化物SERS性能的实验证据和理论模型，优化合成路线，获得高SERS增强因子的金属氧化物纳米材料。随后，对表面缺陷态/非晶态金属氧化物进行功能化分子及抗体修饰，研发出可对肝癌循环肿瘤细胞高效检测的SERS生物探针，拓展金属氧化物纳米材料在循环肿瘤细胞SERS检测技术中的应用，对于恶性肿瘤的早期筛查具有重要的研究意义。

Due to the relatively weak SERS enhancement factor, which severely restricts the application of metal oxides-based SERS platforms in biosensing and biodiagnosis. In order to break through the bottleneck, in this project, a strategy of fabricating amorphous/surface defect metal oxide SERS substrates with the feature of good biocompatibility, selective enhancement, high sensitivity and good stability is proposed, and successfully utilized in circulating tumor cells (CTCs) detection. The boosted SERS activity can be obtained by modulating surface electronic structure, which will effectively amplify molecular Raman scattering cross-section and selectively enhance molecular Raman vibration mode. Combined with SERS experimental results and theoretical simulation calculations, the coupling interaction between surface electric dipole, electrostatic potential, Fermi level, band structure and molecular orbital energy level is detailed studied, which effectively promotes vibration coupling effect in the substrate-molecule system and obtain high SERS performance. Subsequently, high-sensitivity metal oxide-based SERS bioprobe is prepared by modifying functionalized molecules and antibody proteins, allowing efficient CTCs detection. These research results will establish a significant relationship between the surface electronic structure and intrinsic enhancement mechanism of metal oxide nanostructure, and the metal oxide-based SERS bioprobe will pave the way for developing new SERS biosensor in CTC detection, which has great significance for cancer diagnosis.