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

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