Versatile Luminol/Dissolved Oxygen/Fe@Fe2O3 Nanowire Ternary Electrochemiluminescence System Combined with Highly Efficient Strand Displacement Amplification for Ultrasensitive microRNA Detection

Herein, a versatile ECL biosensor was fabricated for ultrasensitive detection of microRNA-21 (miRNA-21) from cancer cells based on a novel H₂O₂-free electrochemiluminescence (ECL) system (luminol/dissolved oxygen/Fe@Fe₂O₃ nanowires). Compared with the previously reported coreaction accelerator that needed a negative potential to produce reactive oxygen species (ROS), these newly discovered Fe@Fe₂O₃ nanowires could generate ROS in the detection solution immediately without the application of voltage, which narrowed down the detection potential range to avoid side reactions, favoring their practical application in biological systems. Especially, the Fe@Fe₂O₃ nanowires could produce H^• for activating dissolved oxygen into ROS to improve the ECL intensity dramatically, which initiates a novel pathway to promote the generation of ROS for the ECL system. In addition, an original strand displacement amplification coupled with strand displacement reaction (SDA-SDR) was developed to improve the conversion efficiency of the target for sensitive detection of miRNA-21. By virtue of the SDR, a quadruple quenching effect was achieved through each output DNA strand of SDA; hence, the nucleic acid signal amplification efficiency was effectively enhanced. As expected, on account of the superb activation performance of Fe@Fe₂O₃ nanowires and the outstanding amplification efficiency of the SDR-SDA strategy, the fabricated ECL biosensor realized ultrasensitive detection of miRNA-21 with a detection limit down to 52.5 aM. The established ECL sensing platform ushered a new route for H₂O₂-free detection and a promising biomarker assay method for clinical diagnosis.