In virtue of the inherent molecular recognition and programmability, DNA has recently become the most promising for high-performance biosensors. The rationally engineered nucleic acid architecture will be very advantageous to hybridization efficiency, specificity, and sensitivity. Herein, a robust and split-mode photoelectrochemical (PEC) biosensor for miRNA-196a was developed based on an entropy-driven tetrahedral DNA (EDTD) amplifier coupled with superparamagnetic nanostructures. The DNA tetrahedron structure features in rigidity and structural stability that contribute to obtain precise identification units and specific orientations, improving the hybridization efficiency, sensitivity, and selectivity of the as-designed PEC biosensor. Further, superparamagnetic Fe3O4@SiO2@CdS particles integrated with DNA nanostructures are beneficial for the construction of a split-mode, highly selective, and reliable PEC biosensor. Particularly, the enzyme- and hairpin-free EDTD amplifier eliminates unnecessary interference from the complex secondary structure of pseudoknots or kissing loops in typical hairpin DNAs, significantly lowers the background noise, and improves the detection sensitivity. This PEC biosensor is capable of monitoring miRNA-196a in practical settings with additional advantages of efficient electrode fabrication, stability, and reproducibility. This strategy can be extended to various miRNA assays in complex biological systems with excellent performance.
Keywords: DNA tetrahedron; biosensing; entropy-driven amplifier; microRNAs; superparamagnetism.