Surface Enhanced Raman Scattering Analysis Based On Non-metallic Nanomaterials

Surface-enhanced Raman scattering?SERS?generally refers to the phenomenon that when molecules are adsorbed on the surface of rough noble metals,the Raman spectrum of molecules is significantly enhanced,with an enhancement factor of 10¹² or even higher.Therefore,surface-enhanced Raman scattering has the characteristics of high sensitivity,rich structural information,and rapid response.It is widely used in many fields such as materials science,physical science,analytical science,and biological science.Currently,SERS materials are mainly composed of noble metal nanomaterials with various morphologies?nanoparticles,nanoshells,nanorods,nanoflowers,nanostars,nanoclusters,etc.?.For SERS mechanism,the main reason for the SERS activity of noble materials is the localized electric field enhancement based on the localized surface plasmon resonance?LSPR?on the surface of the materials,thereby enhancing the molecular Raman signal adsorbed on the surface of the materials.Generally,the SERS enhancement effect based on LSPR has high sensitivity,so it is very suitable for the analysis and detection of trace substances in the system.However,for bioanalysis,such materials often suffered from self-aggregation,surface oxidation,and non-specific adsorption in complex analysis environments,which greatly affects their SERS signal output and reliability.In contrast to noble metal materials,non-metallic nanomaterials SERS substrates,which are mainly based on the charge transfer process between molecules and materials,have stable surface structures,are not easy to be oxidized and aggregate,resulting in high molecular selectivity,and high biocompatibility.However,the SERS enhancement factor of non-metallic nanomaterials is very low,only 10-100,which makes it difficult to achieve qualitative and quantitative analysis and real-time monitoring of multiple trace substances in living systems.In addition,the excitation wavelength of non-metallic nanomaterial SERS substrates is usually in the ultraviolet and visible light regions,but there is no obvious SERS signal response in the near-infrared light region.Therefore,the development of non-metallic nanomaterials with near-infrared SERS response to reduce damage and penetration of cellular tissues is still present great challenges.To solve the above problems,my doctoral dissertation mainly carried out the following three aspects:?1?A binary non-metallic nanocomposite graphene-titanium dioxide?EG-TiO₂?was constructed by anodic oxidation method and electrochemical deposition method.Utilizing the?-?interaction between the molecule and the graphene structure and the lifting effect of TiO₂ on the graphene Fermi level,the charge transfer phenomenon between molecules and materials is strengthened,and then enhancing the Raman signal of copper phthalocyanine?CuPc?on EG-TiO₂.In addition,the specific binding of CuPc to the telomerase G-rich base chain was used to detect the telomerase activity of mesenchymal stem cells and neural stem cells in the process of proliferation and differentiation.The detection limit was as low as single cell level.Moreover,it was found that the important role of telomerase in the process of proliferation and differentiation of mesenchymal stem cells and neural stem cells.?2?With Fe₃O₄ as the core,a new ternary heterogeneous nanocomposite material,ferric oxide@graphene oxide@titanium dioxide?Fe₃O₄@GO@TiO₂?,was prepared.the Raman signal of CuPc molecule were enhanced with factor 8.08×10⁶.Furthermore,detailed analysis of its enhancement mechanism through experiments and theoretical simulations shows that the Raman enhancement effect of this material on CuPc molecules is mainly due to?i?the resonance Raman enhancement of CuPc molecules under 633 nm laser.?ii?Obvious charge transfer between materials and molecules.?iii?Enrichment of CuPc molecules by TiO₂ shell.Moreover,the PD-L1 antibody was specifically immobilized on the surface of the material by chemically modifying to prepare a PD-L1-specific SERS probe,realizing quantitative study and real-time monitoring of PD-L1 expression on breast cancer cell surface.?3?Cu_2-x-x S nanocages with different morphologies were synthesized using Cu₂O as a template.It was found that Cu_2-x-x S with different morphologies had different contents of Cu holes.Because of this,Cu_2-xS nanocages with different morphologies have different levels of Raman enhancement on Raman molecules.In addition,the enhanced activity of Cu_2-xS showed a significant excitation wavelength dependence.Through the investigation of the energy level of nanostructures and molecules,we supposed that the SERS activity of Cu_2-xS is mainly due to the matching degree of the incident photon energy with the energy level difference between molecules and materials,and the LSPR effectof Cu_2-x-x S.In addition,a COX-2 probe with Raman signal in the biologically silent region and matched energy level with Cu_2-xS was prepared.Using Cu_2-xS nanocubes as SERS subtrates,a reliable,stable and sensitive detection of COX-2 was successfully achieved with high enhanmcent factor of 1.38×10⁹.These studies not only greatly help the development of new SERS nano-substrate materials and mechanism research,but also provide new ideas for the application of non-metallic SERS nano-materials in biological analysis.