Application And Fabrication Of Substrates For Human Body Fluid Analysis Through Surface-enhanced Raman Spectroscopy

In recent years,the global cancer incidence and mortality rate are increasing rapidly.If early detection and diagnosis can be made,most cancers can be treated.Therefore,early detection of cancer is of great significance in clinical medicine,but the method of early diagnosis is expensive,inconvenient and invasive.Therefore,a simple and fast method for early diagnosis is urgently needed.Surface-enhanced Raman spectroscopy(SERS)can provide fast and convenient detection,and can be used for immediate care or screening test of biological fluids,especially the label-free SERS spectra of serum and plasma.Therefore,it has attracted widespread attention in the rapid diagnosis of pathogens and abnormal biological states.In this work,researching on the application and fabrication of substrates for human body fluid analysis through SERS.The specific research is as follows:(1)The fabrication of SERS substrate is the core of SERS technology.First,the finite-difference time-domain(FDTD)was used to simulate the electric field distribution between the gold nanoparticles(Au NPs),the tilted gold nanorods and other models.It was found that both the particles and the gold nanorods showed a strong electromagnetic field enhancement effect,and the SERS substrate required rough nanostructures on the surface,and the pitch is between nanometers.And based on this theory,this paper combines the advantages of the research group’s electronic plating,five methods of hydrothermal synthesis of gold nanoparticles,electron beam evaporation oblique angle deposition method,electrochemical deposition method,chemical deposition method,and electric displacement method were used to prepare the active substrate,and perform SEM characterization and SERS performance test on it.(2)Application of SERS technology in the diagnosis of colorectal cancer.In this work,a simple,fast and inexpensive optical sensing platform is developed by the design of SERS sampling and data analysis.The pretreatment of spectral mea-surement employed gold nanoparticle colloid mixing with the serum from patients with colorectal cancer(CRC).The droplet of particle-serum mixture formed coffee-ring-like region at the rim,providing strong and stable SERS profiles.The obtained spectra from cancer patients and healthy volunteers were analyzed by unsupervised principal component analysis(PCA)and supervised machine learning model,such as support-vector machine(SVM),respectively.The results demonstrate that the SVM model provides the superior performance in the classification of CRC diagnosis compared with PCA.In addition,an innovative attempt to combine the carcinoembryonic antigen value(CEA)in the blood sample with the corresponding SERS spectrum for SVM calculation,with an accuracy rate of over 90%.(3)Feasibility research of SERS technology in the detection of blood drug concentration of regorafenib.Including Raman collection,pure substance SERS collection,SERS collection under serum environment of regorafenib pure substance.The experimental results showed that regorafenib powder has strong and stable Raman Signal:The SERS spectrum of the pure substance of regorafenib still has a number of prominent characteristic peaks after pre-processing,which can be used for subsequent analysis;Regorafenib has better performance in the serum environment,with strong signal and large peak difference intensity which is convenient for later spectral analysis and feature classification and recognition.And the research results also show that regorafenib drug is more suitable for detection under the silver substrate and 532 nm laser.In summary,regorafenib blood concentration detection is feasible.