An excellent electrochemical aptasensor for amyloid-β oligomers based on a triple-helix aptamer switch via target-triggered signal transduction DNA displacement events

An excellent aptasensor for electrochemical detection of amyloid-β oligomers (AβOs) at trace levels was fabricated based on a triple-helix aptamer switch (THAS) via target-triggered signal transduction DNA displacement events. Specifically, a single-stranded anti-AβO aptamer (Apt) carrying two symmetrical arm segments was first attached via Au-S binding to an Au electrode. Gold nanoparticle (GNP)-tagged signal transduction probes (GNP-STPs) were simultaneously hybridized with the two arm segments of the Apt, and a rigid THAS was formed on the Au electrode. Compared to the conventional hybrid, the number of GNPs on the Au electrode increased significantly with the THAS, effectively improving the stability of the Apt to avoid lodging. Trithiocyanuric acid (TA) was utilized to further gather the GNPs and form network-like TA/GNPs. As a result, the differential pulse voltammetry (DPV) response of GNPs was clearly enhanced. When AβOs were present, target-triggered signal transduction DNA displacement events were carried out from THAS via the reaction of the Apt with the AβOs, which caused the GNP-STP to dissociate from the Au electrode, and thus a significant reduction in the DPV response was observed. The assay was able to sensitively detect trace AβOs by monitoring the AβO-controlled DPV response change. It exhibited a wide linear range from 1 fM to 10 pM with a low detection limit of 0.5 fM, and was successfully employed for the determination of AβOs in 20 serum samples, with good recovery. Moreover, the developed assay can provide a sensitive and selective platform for many studies or investigations related to Alzheimer’s disease (AD) monitoring and treatment. Graphical abstract