CeO/MXene heterojunction-based ultrasensitive electrochemiluminescence biosensing for BCR-ABL fusion gene detection combined with dual-toehold strand displacement reaction for signal amplification.

An "on-off" nonenzymatic and ultrasensitive electrochemiluminescence (ECL) biosensing platform has been constructed to detect BCR-ABL fusion gene based on CeO/MXene heterojunction and configuration-entropy driven dual-toehold strand displacement reaction (DT-SDR) for signal amplification. The CeO/MXene heterojunction were prepared via one-step hydrothermal method through in situ synthesis of CeO nanocubes on the surface of TiC-MXene nanosheets. Surprisingly, the prepared CeO/MXene heterojunction with good dispersion and excellent conductivity not only significantly enhanced ECL emission of SO/O system, but also acted as good electrode modification materials to provide massive active sites for three-stranded ST/AS/BK complex immobilization. In the presence of target BCR-ABL fusion gene and Bio-FS, target BCR-ABL fusion gene bound to dual-toehold exposed at the ends of ST, replacing AS and BK and obtaining ST/target with a loop. Subsequently, Bio-FS bound to the loop (as toehold) in ST strand of ST/target to form ST/Bio-FS, replacing the target to further trigger a new SDA cycle. This configuration-entropy driven DT-SDR made three-stranded ST/AS/BK complex transform into dual-stranded ST/Bio-FS in the electrode interface. Ultimately, the quenching labels of streptavidin modified Pt nanoparticles functionalized polydopamine composites (SA-Pt@PDA) were introduced via biotin and streptavidin recognition, realizing ECL emission quenching of SO/O system for "on-off" detection of BCR-ABL fusion gene. The developed ECL biosensor for BCR-ABL fusion gene detection achieves the wide concentration variation from 1 fM to 100 pM with low limit of detection down to 0.27 fM, which provides new enlightenment and basis for molecular diagnosis of chronic myelogenous leukemia in clinical practice.