Surface-enhanced Raman Scattering Technology Based On Semiconductor Nanomaterials For Analysis Of Molecule Associated With Neurodegenerative Disease

Alzheimer’s disease（AD）is a neurodegenerative disease.It is an increasingly heavy economic burden on society in terms of medical costs,accommodation and informal care.Therefore,early diagnosis and treatment of AD is urgent.Surface enhanced Raman spectroscopy（SERS）is an effective technique for disease diagnosis.It has broad application prospect of trace chemical and biological analysis with the characteristics of rapid,non-destructive,high sensitivity and fingerprint diagnosis.This paper has carried out exploration and research based on the above aspects.In Chapter 2,we designed a tri-modal paper device based on flower-like Cu Se for the selective,sensitive and fast point-of-care testing（POCT）of AD-associated mi R-34c using colorimetric,photothermal and Raman mode.Cu Se catalyzed the one-electron oxidation of colorless 2,2-azino-bis（3-ethylbenzothiazoline-6-sulfonic acid）（ABTS）to produce dark green ABTS·⁺with photothermal effect to realize colorimetric and photothermal analysis.In addition,flower-like Cu Se has selective SERS enhancement effect on ABTS·⁺with EF up to 2.14×10~7,realizing the ratio SERS analysis of mi R-34c with high sensitivity and high selectivity,and the detection limit（LOD）as low as 0.5 f M,the false negative rate of early AD was successfully reduced.Compared with traditional paper chip,the developed three-mode detection platform has higher sensitivity and selectivity,avoiding false negative diagnosis in early AD screening,and providing an ideal method of POCT of AD.In Chapter 3,we designed a SERS probe based on perovskite-organic semiconductor composite material,and realized the in situ,sensitive and selective quantitative analysis of the dynamic changes of mi R-146a in the brain of AD mice as well as the diagnosis and treatment of AD.Firstly,the water-stable perovskite-organic semiconductor nanocomposite SERS substrate was successfully prepared,and the selective Raman enhancement effect on MB molecules was realized,with EF up to1.11×10¹⁰.Subsequently,the Y-motif that could specifically recognize mi R-146a and carry out signal cycles amplification was further designed,and the SERS diagnostic and therapeutic integrated probe was successfully constructed.Based on the dual role of Raman signal molecules and therapeutic molecules of MB in the diagnosis and treatment of AD,combined with the in situ implantation of fiber microarray in the rat brain,this work successfully achieved the in situ analysis and detection of mi R-146a in the rat brain with high sensitivity,high stability and high selectivity（LOD as low as0.08 f M）and rapid diagnosis and treatment（treatment cycle of 12 days）,which is of great significance in the clinical research and treatment of AD.