An electrochemical aptasensor for amyloid-β oligomer based on double-stranded DNA as "conductive spring"

In order to overcome the antibody-based sensor's shortcomings, an electrochemical aptamer (Apt)-based sensor was developed for amyloid-β₄₀ oligomer (Aβ_40-O). The aptasensor was constructed by locating Apt and ferrocence (Fc) on streptavidin-modified gold (SA-gold) nanoparticles. The obtained AptFc@SA-gold nanoparticles were linked onto the Au electrode via the connection of double-stranded DNA (dsDNA) as a "conductive spring." The determination of Aβ_40-O was performed with square-wave voltammetry (SWV). Upon bio-recognition between Apt and Aβ_40-O, the conformation of Apt changed and the formed Apt/Aβ_40-O complex separated from the SA-gold surface. As a result, the surface charge of SA-gold positively shifted, weakening the electrostatic attraction between the SA-gold and the positively charged Au electrode surface (at potential range of 0.1~0.5 V, corresponding to the Fc redox transformation), and stretching the dsDNA chain. Based on the exponential decay of dsDNA's electron transfer efficiency on its chain stretching, the oxidation current density from Fc decreased and displayed linear correlation to the concentration of Aβ_40-O. A wide linear range of 0.100 nM to 1.00 μM with a low detection limit of 93.0 pM was obtained. The aptasensor displayed excellent selectivity toward Aβ_40-O in contrast to other possible interfering analogs (Aβ₄₀ monomer, Aβ₄₂ monomer, and oligomer) at × 100 higher concentrations. The recoveries for Aβ_40-O-spiked artificial cerebrospinal fluid and healthy human serum were 94.0~104% and 92.8~95.4%, respectively. The electrochemical aptasensor meets the demands of clinic determination of Aβ_40-O, which is significant for the early diagnosis of AD. Graphical abstract Schematic representation of the electrochemical aptasensor for amyloid-β oligomer based on the surface charge change induced by target binding.