Controllable Fabrication Of Paper-based SERS Chips And Its Application In The Biological Analysis

As people’s living standards improve,health issues require increasing attention.However,various chemical components in human body are important information for evaluating human health,and are important indicators for the diagnosis and treatment of various diseases.The timely detection of these chemical components and contents is very important for human health judgment.However,limited social medical resources,it limits the comprehensive and professional physical condition monitoring for most people.Based on this,we propose to apply the paper-based sensors to the detection of chemical components related to human health,which is expected to monitor the state of human health at any time through the paper-based system,and determine the health status according to the analysis of the obtained data.It can effectively prevent or diagnose some diseases.In recent years,Surface Enhanced Raman Spectroscopy（SERS）has shown rich characteristic"fingerprint"information through plasma resonance effect,and has been increasingly applied in biology,food,environment fields.Nevertheless,for construction of a SERS sensing method with stability and reliability,it is necessary to prepare an efficient,flexible,stable and reproducible SERS substrate,which enables highly sensitive and specific adsorption of target analytes.At the same time,SERS sensing technology was combined with other detection methods as a multi-channel sensing system,which can significantly raise the detection sensitivity,debase the detection limit and provide a greater possibility for rapid and specific analysis.Therefore,this paper constructs a controllable paper-based SERS sensor to realize the rapid identification and accurate detection of lung cancer markers in human exhalation,as well as the rapid and sensitive detection of glucose and caffeine in urine,which has potential application value in biological analysis.The chapter 1,the introduction part introduces the background and practical significance of the research,and also introduces the principle of Raman spectroscopy,SERS enhancement mechanism and substrate preparation,and introduces the key application fields of paper-based SERS materials.The chapter 2,we developed a vapor generation paper-based thin film microextraction（VG-PTFM）system based on core-shell gold nanorods-quantum dots@metal-organic framework（GNRs-QDs@NU-901）functional materials for fluorescence and SERS dual-mode sensing of gas benzaldehyde（BA）molecules.Firstly,GNRs-QDs assembly and core-shell GNRs-QDs@NU-901 nanostructure were prepared by electrostatic interaction and layer-by-layer assembly strategy.The amino-modified GNRs and carboxyl-covered QDs can directly assembled with each other by electrostatic interaction,which leads to almost complete emission quenching of QDs.After VG-PTFM,the gaseous BA flows through the porous NU-901 to experience the“cavity-diffusion”effect,providing increased analyte-metal interaction on the surface of the GNRs core.Meanwhile,Schiff base reactions is triggered by interaction between aldehyde group of BA and amine group of 4-mercaptonoaniline（PATP）modified on GNRs,leading to the disassembly of GNRs-QDs and recovery of fluorescence signals,which can be used to visualize BA molecules.Moreover,the BA-induced schiff base reaction products have specific SERS signals and can be used for SERS detection of BA molecules with high specificity and sensitivity.The system can be used for selective capture and highly sensitive detection of trace BA molecules in complex media and is very suitable for immediate detection and rapid screening.The dual mode analysis technique can accurately distinguish the concentrations of BA in exhaled of lung cancer and health subjects,so it has a good application prospect in preclinical early diagnosis and treatment evaluation of lung cancer.In chapter 3,a simple and reliable paper-based sensor was developed for the rapid and sensitive detection of glucose and caffeine in human urine.Firstly,amino-functionalized luminescent metal-organic frameworks containing gold nanoparticles were prepared by hydrothermal method（GNPs@NH₂-MIL-53（Al））.GNPs@NH₂-MIL-53（Al）has high peroxidase activity and biocompatibility,which can catalyze hydrogen peroxide（H₂O₂）to produce hydroxyl radicals（·OH）,and convert colorless 3,3′,5,5′-tetramethylbenzidine（TMB）into blue oxidation TMB(_OXTMB),and act as a SERS substrate to enhance the Raman signal of the _OXTMB.Then,glucose oxidase（GOx）was immobilized by oxidative coupling reaction to form GNPs@NH₂-MIL-53（Al）/GOx integrated nanozymes for glucose detection.NH₂-MIL-53（Al）with luminescent properties interacts with caffeine through hydrogen bonding N-H…O-H,leading to a obvious increase in fluorescence,realizing its sensing performanceasafluorescentprobeagainstcaffeine.Therefore,GNPs@NH₂-MIL-53（Al）/GOx-TMB and GNPs@NH₂-MIL-53（Al）nanomaterials were loaded on test strips to establish a capillary action side flow kit to achieve the purpose of portable detection of glucose and caffeine,and to visualize the distinction between glucose and caffeine.The side flow kit can specifically detect glucose and caffeine by colorimetric,fluorescent and SERS multi-sensing techniques,and has low detection limit and high sensitivity.Therefore,it has important application prospect in biosensing,life analysis and so on.