Nanochannel array-based platform for aggregation monitoring and high-sensitive identification of neurotoxic amyloid-β oligomers

Abstract

The soluble amyloid-β oligomer (AβO) has been recognized as an important neuropathological hallmark for severity assessment of Alzheimer’s disease (AD) due to its more neurotoxicity than the larger and mature fibrillar Aβ. However, considering the time-scale aggregation pathway, AβO are transient, metastable and heterogeneous, developing reliable and straightforward methods able to directly monitor dynamics of AβO formation and conversion remains challenging. For this purpose, we fabricated a nanochannel array-based biosensor by immobilizing AβO aptamers (AβO-Apt) on the inner surface of the nanaochannels. The AβO-Apt could specificly bind AβO popoulations with high affinity, which would occur to growing rectified ion-current (at -1 V) within the nanochannels owing to lower nanospace occupancy of aptamers. Based on this principle, the nanochannel-aptamer-based (NC-Apt-based) biosensor we constructed could monitor the dynamics of AβO formation and conversion along with incubating timescale. Further investigation, we observed accelerating effects of external factors (such as increasing monomer concentrations and Al (Ⅲ) binding) on aggregation rate and state during AβO formation and conversion. This nanochannel-aptamer-based (NC-Apt-based) platform provides a chemically label-free and reliable assay to study dynamics of AβO formation and conversion without perturbing Aβ aggregation behavior. We expect it could be developed into a promising tool for estimating the toxicity degree of Aβ aggregates in clinical diagnosis.