An orbitron-like 3D DNA clip-based nanomachine and its application for sensitive fluorescent bioassay of MicroRNA

Herein, an orbitron-like three-dimensional (3D) DNA clip-based nanomachine was proposed for ultrasensitive fluorescent bioassay of microRNA, which was constructed by mechanically interlocking double-DNA-ring with two single-stranded DNAs, performing an orbitron-like 3D structure with double freely rotated DNA rings as the open state. In the presence of target microRNA, the proposed orbitron-like 3D DNA clip can alter its structure from open to closed state in identification of the target microRNA, generating the closure between the previously modified fluorescent dyes and the quenchers to perform a "signal off" fluorescent signal correlated with the concentration of target microRNA. Compared with the normal DNA nanomachines, such as DNA tweezers constructed by self-assembly of three single-stranded DNAs which regulated the open and closed states on the basis of linear conformational changes, the proposed 3D DNA clip-based nanomachine with high mechanical rigidity realized the conformational changes in 3D space with the assistance of target microRNA, which could effectively increase the adjustable distance range and reduce the background signal. Furthermore, the 3D DNA clip-based nanomachine was applied in the fluorescent detection of microRNA-21 with favorable performances for the sensitive detection of microRNA in cells, providing a new avenue for early clinical diagnoses of disease.