Electrochemical Detection Of ?-Amyloid Based On Signal Amplification Strategy Of Microelectrode

It has been reported that the neurotoxicity of?-amyloid?A??has an important effect on the pathological progress of Alzheimer's disease?AD?.However,the concentration of brain-derived A?is low and the brain environment is complex.Therefore,the sensitive and selective detection of A?has important implications for further investigate the pathogenesis of AD,which is critical for early diagnosis of AD.There is growing concern about electrochemical sensors based on microelectrode in clinical diagnosis field due to its easy operation,high sensitivity,small sample amount and miniaturization.Besides,metal nanoparticles have the advantages of large specific surface area,good electrical conductivity and easily functionalized,so metal nanoparticles often appear on the construction of high-sensitivity electrochemical biosensors.In this paper,we synthesized functional gold nanoprobe.Based on A?-directed the assembly of nanoprobes on a Au microelectrode interface,which was beneficial for the enrichment of A?and AuNPs on the electrode interface,we developed electrochemical biosensors for ultrasensitive monitoring of A?.Moreover,the designed electrochemical biosensors were applied to monitor A?level in cerebrospinal fluid?CSF?of AD mice.The full text is divided into three parts,as follows:Charpter 1:OverviewThis chapter mainly introduces the research background and detection method of AD-related A?,applications of microelectrodes in electrochemical sensing,and signal amplification strategies based on nanomaterials.We focus on the signal amplification strategies based on metal nanoparticles.Finally,the significance and content of this paper are expounded.Charpter 2:Interface engineering of microelectrodes toward ultrasensitive monitoring of?-amyloid peptidesIt is of prime importance to study the pathological process of Alzheimer's disease?AD?to realize ultrasensitive detection of monomeric?-amyloid peptides?A??.In this article,by facilely engineering a gold microelectrode interface,we developed an electrochemical biosensor for sensitive and selective monitoring of A?monomers.Through specific Cu²⁺-A?-hemin coordination,we synthesized dual functional gold nanoprobe(Cu²⁺-PEI/AuNPs-hemin).A?monomers induced the nanoprobes to assemble on the microelectrode interface forming network aggregates,which promoted the enrichment of A?monomers on the microelectrode.Besides,the AuNP aggregates catalyze the deposition of silver nanoparticles.Utilizing the stripping voltammetric signal produced by AgNPs,ultrasensitive detection of A?monomer can be achieved,with the detection limit down to 0.2 pM.The electrochemical biosensor also has high selectivity.We successfully applied the electrochemical biosensor to detect A?monomers in CSF of AD mice.This work promotes the study of the role that A?monomers play in brain events.The microelectrode interface we designed has value of practical applications.Charpter 3:Signal amplification detection of?-amyloid(A?₁–_40/1–₄₂)fibrils based on the aggregation of Congo red-functionalized gold nanoparticle probesSensitive and selective monitoring of A?fibrils in cerebral nervous system is of great importance for studying the role that A?plays in the pathological process of AD and screening of A?aggregation inhibitors.In this work,Congo red-functionalized gold nanoparticles probe was synthesized.We developed an electrochemical biosensor based on microelectrode for selective and sensitive detection of A?_{?1?–40/1–42}fibrils.Based on the specific recognition between CR and A?fibrils,A?fibrils were captured on the microelectrode surface,which induced nanoprobes gathering on the surface resulting in the formation of AuNP aggregates.The AuNPs aggregates promoted the enrichment of AuNPs on the microelectrode.Furthermore,the AuNPs aggregates promoted the deposition of numerous silver nanoparticles,which were utilized for the electrochemical stripping analysis of the A?_{?1?–40/1–42}fibrils.A?_{?1?–40/1–42}fibrils could be detected with a detection limit down to 8 pM.Besides,this method exhibited good selectivity.The electrochemical biosensor with remarkable analytical performance was successfully applied to evaluate the change of A?_{?1?–40/1–42}fibrils level in CSF of live mouse brain with AD.This work provides an effective analytical method based on microelectrode for the detection of AD-related biomolecules.