Internal-driven DNA nanowindmill: Multi-fulcrum mediated amplified rolling nanomachine for fast and ultrasensitive electrochemical detection of tau

Inspired by the wind driving windmill rolling to generate electrical energy, we have fabricated a multi-fulcrum mediated amplified rolling nanomachine (MFN) for Tau detection with the internal drive. The MFN backbone is DNA nanowindmill (DM) self-assembled from DNA, which is initially ineffective and finally activated into an effective DM through interaction with Tau followed by the magnetic separation. The DM is introduced to the electrode interface where it continues rolling under the drive of the multi-fulcrum and signal probe to achieve signal amplification. On one hand, the modular design and DM rolling feeds the impediment of signal transduction and amplification due to spatial hindrance during protein detection. On the other hand, it endows fast response and high sensitivity. The proposed MFN electrochemical biosensor is successfully applied to detect Tau ranging from 10 pg/mL to 2 μg/mL with low detection limit of 127 fg/mL, which is much lower than the pathological state concentration of Tau ∼400 pg/mL. Furthermore, our findings proves that MFN can successfully differentiate normal individuals from Alzheimer’s disease (AD) patients based on clinical samples analysis.