Rational Design Of Phenylboronic Acid Functionalized Stimuli- Responsive Polymer And Its Application

As we all know,saccharides are involved in many physiological and pathological processes in the human body.Among all saccharides,the quantification of glucose is one of the most interesting topics for researchers around the world.Diabetes,the biggest health threat of this century,is also caused by dysregulated glucose metabolism and the continuous accumulation of glucose concentrations in the blood.For diabetics,regular blood glucose testing has become routine.However,the pain and pressure caused by repeated finger puncture has given researchers more motivation to explore non-invasive monitoring technology.Because saliva glucose has a certain relationship with blood glucose concentration,it is desirable to measure glucose in saliva for detection.However,their relatively low concentration in saliva and the coexisting chemicals present challenges to the sensitivity and selectivity of detection.In this paper,we have rationally designed and constructed a salivary glucose sensor by modifying the inner wall of the Au-decorated glass nanopore with stimuli-responsive copolymer poly(3-(acryloylthioureido)phenylboronic acid-co-N-isopropyl acrylamide)(denoted as PATPBA-co-PNIPAAm)via Au-S interaction.The nanopores with welldemonstrated analytical performance were finally applied for monitoring glucose in saliva.Together,this work unveiled a new platform for glucose detection in saliva,and promised to provide a new strategy for detecting other biomolecules in accessible biofluid involved in physiological and pathological events.Specifically,the full text is divided into three parts,as follows: Charpter 1: OverviewThis chapter first introduces nanopores.According to the different materials used,the nanopores are classified and elaborated into biological nanopores and artificial solid nanopores.The preparation,modification and application of glass nanopores in artificial solid nanopores are emphasized.Then,we also summarized the design ideas and working principles of stimulus-responsive polymers,and related applications of new sensors made by stimuli-responsive polymers based on artificial nanochannels.In addition,the detection method of glucose concentration is also introduced,with emphasis on electrochemical detection methods,fluorescence and colorimetric methods based on boric acid modification.Finally,the research significance and main content of this thesis are clarified.Charpter 2: Synthesis and characterization of functional monomer and functional modification of benzene boric acid polymerFollowing the design ideas and principles of stimulus-responsive polymers,we first synthesized monomer with a saccharide response,3-(acryloylthioureido)phenylboronic acid and 3-aminophenylboronic acid.Using a reversible additionfracture chain transfer polymerization(RAFT)reaction,we designed and synthesized a three-unit stimulus-responsive polymer with phenylboronic acid as the recognition unit,N-isopropylacrylamide as the function unit,and thiourea as the mediating unit.In order to verify that we successfully synthesized the monomer and polymers,we performed nuclear magnetic resonance spectrum(NMR),FTIR spectra,XPS spectra.Charpter 3: Detection of glucose in saliva by glass conical nanopore modified by phenylboric acid copolymerIn this chapter,we have rationally designed and constructed a salivary glucose sensor by modifying the inner wall of the Au-decorated glass nanopore with stimuli-responsive copolymer poly(3-(acryloylthioureido)phenylboronic acid-co-N-isopropyl acrylamide)(denoted as PATPBA-co-PNIPAAm)via Au-S interaction.Notably,upon recognition of glucose,the copolymer could undergo wettability switch and p Ka shifts in the boronic acid functional groups,which significantly regulated the ion transport through nanopores,thus showing improved sensitivity with the detection limit of 1 nM.Moreover,benefiting from the multivalent boronic acid–glucose interaction and the cooperation of thiourea units,the copolymer exhibited good selectivity for glucose detection against the coexisting saccharides and other biological molecules in saliva.The nanopores with well-demonstrated analytical performance were finally applied for monitoring glucose in saliva.Together,this work unveiled a new platform for glucose detection in saliva,and promised to provide a new strategy for detecting other biomolecules in accessible biofluid involved in physiological and pathological events.