Dynamic switching circuit modulated by intramolecular conformation transition of DNA translator for versatile fluorescence biosensors

It might be intriguing and desirable to explore the stimuli-responsive modulation of dynamic switching circuit (DSC) for constructing versatile fluorescence biosensors via two-step sequential independent displacement reactions. Here, a switchable DNA translator (DT) encoding three functional modules is proposed to implement DSC for interpreting specific Key triggers (i.e. DNA segment, miRNA or small molecule) by activating intramolecular conformation transition. Upon presenting Key to regulate strand displacement, the Lock-blocked DT is liberated and self-folded into "active" on-state hairpin structure, so that two ended toeholds are oriented closely to execute proximal hybridization cooperatively for Key-responsive signal readout. Benefited from fast kinetics, efficient transduction, simplified operation and flexible programming, the Key-actuated DSC strategy achieved label-free assay of various target species by employing tunable Ag nanocluster as fluorescent reporter adjacent to or away from hemin/G-quadruplex complexes, which would be more potential and applicable in versatile fluorescence biosensors, identifiable cell imaging or customized tasks than typical strand displacements.