Ingenious entropy-driven DNA circuit intercommunicating with DNAzyme-powered DNA walker for dual-mode biosensing

Abstract

Conventional DNA motor-based cascaded amplification methods have relative low DNA utilization efficiency and lack of self-feedback. Herein, a novel dual-mode biosensor of miRNA-155 was constructed based on a waste-free entropy-driven DNA circuit (EDC) cascaded with a self-feedback DNAzyme-powered DNA walker (DNAzyme Walker). The target (T)-triggered EDC generates two same single-stranded DNA (ssDNA) labelled with CdTe QDs as the signal probes (CdTe-O) and one double-stranded DNA (dsDNA) S/F to unlock the downstream blocked DNAzyme (D), which could then be activated in the presence of Mn²⁺ ions cofactor, and stochastically walk on the surfaces of SiO₂ nanospheres, producing a lot of target analogue (T*) for self-feedback. With the assistance of Fe₃O₄@SiO₂-capture DNA, the released CdTe-O can be rapidly extracted for the following self-validating dual-mode biosensing. The autocatalytic EDC module possesses a high operation efficiency and atomic economy, since it is not only hairpin- and leak-free, but also enzyme- and waste-free. The interactive EDC-DNAzyme Walker network-based fluorescent and colorimetric biosensor has a limit of detection low to 0.35 amol L⁻¹ and 1.87 fmol L⁻¹ at 3σ/S, respectively. The as-designed biosensor not only enables reliable and robust detection of miRNA expression levels, but also provides a remarkable signal cascaded amplification platform with self-feedback and high atom economy.