An Electrochemiluminescent Alpha Synuclein Oligomer Aptasensor Based On Metal-Organic Frameworks

Parkinson's disease(PD)is a neurodegenerative disease commonly found in the elderly.Alpha-synuclein(a-syn)causes gene mutations,as a result,scientists often associate it with the pathogenesis of PD.Studies have shown that its soluble oligomer can destroy synapsis and ion gradients in neuron,who also possesses the strongest neurotoxicity.As one of the early diagnostic biomarkers of PD,the efficient and sensitive detection of ?-syn oligomer is of great significance for the prevention of disease and the judgment of conditionCurrently,the detection methods of ?-syn oligomer mainly include mass spectrometry,fluorescence,capillary electrophoresis,surface plasmon resonance,enzyme-linked immunosorbent assay and so on.However,these methods have some disadvantages,such as high price and tedious operation.Therefore,it is very important to design and develop a sensitive,convenient and fast detection method.Electrochemical luminescence(ECL)aptasensors have become one of the choices for the detection of biomarkers due to their high sensitivity and good selectivity.In this research,we used metal-organic framework(MOFs)materials to functionalize indium tin oxide(ITO)glass to provide an adequate platform.Two ECL biosensors with aptamers as the recognition elements of ?-syn oligomers were prepared.To prepare nano-modified electrodes,the hydrolysis product of 3-aminopropyltrimethoxysilane(APTMS)or glutaraldehyde was used as a binder for AuNPs@MOFs composites or single MOFs.On the aforementioned two electrodes,luminol is used as a luminescent reagent,which can both produce strong ECL emission even under weak alkaline conditions Subsequently,aptamers could be modified to functional electrodes by Au-S bond or amide bond.After the ?-syn oligomer was combined with the aptamer,the sensor's ECL signal was significantly inhibited due to the large steric hindrance.Finally,a good linear relationship was established between the ECL signal inhibition rate and the logarithm of?-syn oligomer concentration(R=0.999 and 0.995),with linear ranges of 2.43 fM to 0.486 pM and 1.39 fM to 0.243 pM,and detection limits as low as 0.42 fM and 0.38 fM,respectively.Both aptasensors have high sensitivity,good selectivity,reproducibility,and can be used to detect ?-syn oligomer in human serum.