Molecular machine powered catalytic hairpin assembly for signal-on electrochemical detection of Alzheimer’s amyloid-β oligomer

We have developed a bipedal driven catalytic hairpin assembly for the electrochemical detection of highly sensitive amyloid-β oligomers. Aptamers specifically recognize of amyloid-βoligomers can activate catalytic hairpin assembly and form bipedal molecular machines. Catalytic hairpin assembly hybridizes with surface-fixed hairpin DNA1 (HP1) through proximity effect, exposing the pre-locking foot domain of HP1 for fusion with ferrocene labeled hairpin DNA2 (HP2-Fc). The electrochemical signal molecule Fc approaches the electrode under the action of fulcrum mediated chain shift reaction, and the bipedal molecular machines generated by catalytic hairpin assembly crosses the surface of the sensor, where a large number of ferrocenes HP1-HP2 bipedal structures towards the electrode are formed, which realizes the amplification of the electrochemical signal. The linear detection range of this component is 0.1 pM∼1 nM, and the detection limit is 38 fM. As an enzyme-free detection method, it can realize the high sensitivity and specificity detection of multiple target proteins through the appropriate DNA-based affinity probe, which has great reference significance and application value in the field of biological detection. •A novel signal-on electrochemical aptasensor for sensing AβO was developed.•Bipedal DNA walkers was driven by CHA exhibit faster walking kinetics.•The whole process does not need the assistance of enzymes.