SERS Analysis Of Brain Disease-related Molecules Based On Semiconductor Raman Substrates

Brain related diseases such as glioma,AD,PD,etc.are currently hot topics in various fields of research.Glioma is a common tumor of the central nervous system,showing the characteristics of easy recurrence and high invasiveness.The clinical etiological manifestations of AD are still unclear,but most of them are memory,cognitive impairment,and aphasia.These brain-related diseases generally lack early diagnosis methods and good treatment methods,resulting in a generally short median survival of patients.Therefore,it is urgent to develop analytical methods for early diagnosis of brain-related diseases.Biomolecular markers related to brain diseases can be identified by simple and non-invasive methods,which are beneficial to identify cancer risk,help in early diagnosis,and accurately grade.At present,the analysis methods of biomolecular markers include fluorescence method,electrochemiluminescence method,electrochemical method,etc.These methods have the advantages of high resolution and high sensitivity,but they are easily interfered by autofluorescence and cannot perform in situ and non-destructive cell imaging.Surface-enhanced Raman scattering（SERS）is a powerful spectroscopic detection technology with the advantages of high sensitivity and in-situ real-time detection.SERS can rapidly realize dynamic monitoring of changes in small molecules,proteins and other substances.Compared with noble metal substrates,semiconductor materials have advantages in molecular selectivity,biocompatibility,anti-interference ability,etc.,which makes semiconductor-based SERS substrates widely used in the recognition and sensing of biomolecules.This paper has carried out has carried out in-depth exploration and research on the above problems.First of all,we constructed a ratiometric SERS probe（Rh B-PLGM@CN）based on semiconducting graphitic carbon nitride for the detection of MMP-9（a protease associated with glioma invasion）and further applied to imaging and biosensing of MMP-9 in living cells.The g-C₃N₄ nanosheets play a dual role,on the one hand,g-C₃N₄ can be used as a SERS substrate material with an enhancement factor of up to 2.0×10~6 for the Raman signaling molecule Rh B,thus showing good linearity in the detection of MMP-9 with a detection limit as low as 0.035 pg/m L.On the other hand,g-C₃N₄ nanosheets were also used as photosensitizers,which produced photodynamic effects.Based on SERS spectroscopic analysis and imaging with high sensitivity and selectivity of the probe to MMP-9,we also found that photodynamic therapy（PDT）was able to inhibit the invasion of glioma cells by downregulating MMP-9.Then,we developed a SERS probe based on MXenes material for the detection of S100βprotein,and further applied to S100βbiosensing in living cells.The incidence of Alzheimer’s disease is high in the elderly,and there is no good clinical treatment.The content of S100βprotein is closely related to Alzheimer’s disease,and its level is increased in neuritic plaques.The content of S100βprotein in the organism is lower than that of MMP-9,so the choice of substrate material is very important in SERS detection.MXenes,as typical two-dimensional semiconductor nanomaterials,exhibit the advantages of metal-like conductivity,tunable electronic structure,and high carrier mobility,making S100βprotein-specific organic ligands as Raman signaling molecules with an enhancement factor up to 2.7×10~8.Finally,using the SERS probe we constructed,the detection and Raman imaging of S100βwith high sensitivity,high selectivity,and high accuracy were realized,with a linear range of 10 n M～10μM and LOD of 3 n M.