Structure and function encoding of a bidirectional activatable synergetic DNA machine for speeded and ultrasensitive determination of microRNAs

This work describes the unique design of a bidirectional activatable synergetic DNA machine (BAS-DNA machine) for speeded and ultrasensitive determination of microRNA-21 (miR-21), a well-known biomarker for biomedical research and early diagnosis of lung cancer. The BAS-DNA machine is composed by a pair of track strands (Track 1 and Track 2) encoding with two regions in the opposite direction for miR-21 recognition. Introduction of miR-21 can hybridize either with Track 1 or with Track 2 to activate the BAS-DNA machine with a synergistic effect for speeded amplifying the fluorescence signal. Moreover, compared with common DNA machine with only one switch for exogenous target recognition, the BAS-DNA machine with two switches for miR-21 binding allows the speeded and strong operation of the autonomous strand scission, replication, and displacement on Track 1 and Track 2 simultaneously. This behavior makes the BAS-DNA machine powerful for ultrasensitive, specific, and fast screening of miR-21 even from real biological samples, and the fluorescence signal was found to be linear from 1 pM to 10 nM with a detection limit of 703.6 fM. We envision this BAS-DNA machine with its superior assay performance will provide a new avenue for simple, sensitive, and affordable biomedical assays.