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

It has been reported that the neurotoxicity ofβ-amyloid（Aβ）has an important effect on the pathological progress of Alzheimer’s disease（AD）.However,the concentration of brain-derived Aβis low and the brain environment is complex.Therefore,the sensitive and selective detection of Aβhas 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 Aβ-directed the assembly of nanoprobes on a Au microelectrode interface,which was beneficial for the enrichment of Aβand AuNPs on the electrode interface,we developed electrochemical biosensors for ultrasensitive monitoring of Aβ.Moreover,the designed electrochemical biosensors were applied to monitor Aβlevel 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 Aβ,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 ofβ-amyloid peptidesIt is of prime importance to study the pathological process of Alzheimer’s disease（AD）to realize ultrasensitive detection of monomericβ-amyloid peptides（Aβ）.In this article,by facilely engineering a gold microelectrode interface,we developed an electrochemical biosensor for sensitive and selective monitoring of Aβmonomers.Through specific Cu²⁺-Aβ-hemin coordination,we synthesized dual functional gold nanoprobe(Cu²⁺-PEI/AuNPs-hemin).Aβmonomers induced the nanoprobes to assemble on the microelectrode interface forming network aggregates,which promoted the enrichment of Aβmonomers on the microelectrode.Besides,the AuNP aggregates catalyze the deposition of silver nanoparticles.Utilizing the stripping voltammetric signal produced by AgNPs,ultrasensitive detection of Aβmonomer 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 Aβmonomers in CSF of AD mice.This work promotes the study of the role that Aβmonomers play in brain events.The microelectrode interface we designed has value of practical applications.Charpter 3:Signal amplification detection ofβ-amyloid(Aβ₁–_40/1–₄₂)fibrils based on the aggregation of Congo red-functionalized gold nanoparticle probesSensitive and selective monitoring of Aβfibrils in cerebral nervous system is of great importance for studying the role that Aβplays in the pathological process of AD and screening of Aβaggregation 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 Aβ_{（1）–40/1–42}fibrils.Based on the specific recognition between CR and Aβfibrils,Aβfibrils 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 Aβ_{（1）–40/1–42}fibrils.Aβ_{（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 Aβ_{（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.