Design Of Label-free Multifunctional Fluorescence Sensor Array And Its Applications In Biochemical Analysis

With the new challenges in the fields of environmental monitoring,food and drug safety,the demand for high-sensitivity and specificity analytical methods is growing.As an important part of the emerging high-tech industry in the 21^st century,biosensors have experienced rapid development in recent decades due to their characteristics of good selectivity,high sensitivity,fast analysis,and continuous online monitoring.However,traditional sensor analysis usually use a sensor to specifically identify a target,so it usually requires a lot of effort and material resources to develop sensors with different target-specific responses.In order to solve this problem,inspired by mammalian taste and olfactory sensor systems,researchers combined sensor units with highly cross-sensitive characteristics into sensor arrays.Combined with appropriate pattern recognition algorithms and multivariate analysis methods,pattern recognition discrimination and detection of a large number of targets are realized.At present,sensing technology based on this"chemical nose/tongue"has been widely used in precision agriculture,health monitoring,and food fields.Although various sensor array systems are constantly proposed,the manufacturing process of most sensing units often requires complex processes and considerable costs,which limits their widespread application.Therefore,designing new multifunctional array sensors with low cost,easy operation,good reproducibility,and simple scale is still a long-term challenge.Herein,taking advantages of the key issues in the field of intelligent"chemical nose/tongue"multi-functional sensor arrays and fluorescence characteristics of biomimetic polydopamine nanomaterials,we first proposed a"chemical nose/tongue"sensor array based on biomimetic polydopamine nanomaterials.At the same time,combined with pattern recognition,non-invasive analysis and other technologies,it is applied to the pattern recognition and detection of various substances in biological fluids?including metal ions and thiols?,which has broadened the application research of polydopamine nanomaterials in chemical sensing array systems.On the other hand,taking advantages of rare-earth fluorescent complexes to eliminate background fluorescence signals,we have developed a highly sensitive time-resolved fluorescence analysis technology based on rare earth ion-protein-sensitized ligand fluorescence array sensors,which is used for the transmission of rare earth ion-protein interactions.The analysis method provides new ideas and realizes important applications in the early diagnosis of related diseases.This article is divided into three parts,as follows:Chapter 1:IntroductionFirst,this chapter introduces biosensors and their research progress,and then focuses on pattern recognition-based sensor arrays,including the design principle,composition,and applications of"chemical nose/tongue"sensor arrays.Finally,the significance and main contents of the research in this article are explained.Chapter 2:Design of Unlabeled Fluorescent“Chemical Nose/Tongue”Sensor Array Based on Biomimetic Polydopamine Nanomaterials and Its Application in Biochemical AnalysisIn this chapter,based on the fluorescence characteristics of polydopamine materials,we used three different concentrations of polyethyleneimine to synthesize a group of polydopamine materials with different fluorescent properties and build a label-free intelligent"chemical nose/tongue"sensor array based on this material.The fluorescence sensor array realizes the pattern recognition analysis of metal ions in biological fluids,and provides a new and efficient solution for the differential detection of multiple metal ions in biological fluids.By combining the principal component analysis method,this sensor array can successfully achieve highly efficient and sensitive detection of 18 metal ions using only three probes(PDA/PEI₆,PDA/PEI₁₈,and PDA/PEI₄₈),and has realized a fluorescence-based lifetime model.The probe is cleverly designed,easy to synthesize,and has good analytical performance.It was successfully applied to the detection of metal ions in complex biological samples.In addition,inspired by the ease with which copper ions(Cu²⁺)can be combined with amino and thiol coordination,we designed a label-free non-invasive fluorescent copolymer(PDA/PEI_n-Cu²⁺)sensor array based on pH regulation.Combined with artificial urine samples,non-invasive pattern recognition analysis of 8 thiols and the differentiation effect of chiral cysteine molecules were realized.It showed the outstanding advantages of adjustable and simple polydopamine fluorescence for diagnostics,environmental testing and other uses provide practical ideas.Chapter 3:Construction of a Novel Time-Resolved Fluorescence Sensor Array Based on the Interaction between Proteins and Rare Earth Ions to Identify Metal Ions in Biological FluidsIn this chapter,a protein/rare earth complex(BSA/Tb³⁺)is designed using the interaction of bovine serum albumin?BSA?and rare earth ions(Tb³⁺),and a new type of time-resolved fluorescence sensor is constructed by adjusting its optical properties through pH.The array can realize the pattern recognition and analysis of metal ions in biological fluids.BSA as an antenna ligand sensitizes the fluorescence of rare earth Tb³⁺.In the presence of metal ions,it can bind to BSA and change the structure of BSA,thereby affecting the antenna effect of BSA on Tb³⁺.We confirmed this principle through experimental verification and coarse-grained molecular dynamics?CG-MD?.BSA/Tb³⁺fluorescence was regulated by two kinds of pH?pH 7.4,8.5?to form a sensor array,which realized the detection of 17 kinds of metal ions,and the identification and analysis of samples with different concentrations of the same metal ions and different metal ions.In addition,using the designed sensor array,we can realize the detection of metal ions in biological fluids,which verifies its practical application.The BSA/Tb³⁺fluorescence sensor array is simple to synthesize and easy to operate,which provides new ideas for the design of time-resolved sensors based on protein/rare earth interactions.