Metal-organic framework-enabled surface state passivation integrating with single-nuclease-propelled multistage amplification for ultrasensitive lab-on-paper photoelectrochemical biosensing

The surface states and photoinduced corrosion in the photoelectrode can severely reduce the photocurrent signal and stability of photoelectrochemical (PEC) sensor, which imposes a great challenge on the improvement of analytical performance. Herein, metal-organic framework (MOF)-enabled surface passivation strategy is proposed to passivate surface states, suppress photocorrosion and facilitate interfacial charge transport. In the concrete, zeolitic imidazolate framework-8 (ZIF-8), which serves as the passivation layer, is in-situ assembled on the surface of paper-based ZnO nanorods (NRs) array to restrain the charge trapping at the surface states and keep ZnO NRs from photocorrosion, thereby substantially enhancing the photocurrent signal and durability. Moreover, the unique single-nuclease-propelled multistage amplification (SNMA) and triple-helix molecular switch (THMS)-conformation-transition-mediated signal quenching strategies are also designed to further improve the sensitivity. The SNMA process can convert target microRNA-141 into quadruple amount of useful output DNA strands (trigger DNA) in one duplex-specific nuclease (DSN) cleavage cycle assisted by succedent DSN cleavage of DNA duplexes, guaranteeing a higher target amplification efficiency. Subsequently, the THMS structure which anchors double amount of signal enhancers to the photoelectrode surface can be disassembled by the resulted trigger DNA, therefore achieving powerful signal amplification. Profiting from the MOF-enabled surface state passivation and elegantly designed signal amplification strategies, the ultrasensitive detection of microRNA-141 is realized with a liner range from 0.2 fM to 2 nM and detection limit of 72 aM, which provides a promising paradigm for developing high-performance lab-on-paper PEC biosensing platform.