Self-assembled “feather-like” CuS@MIL-101 nanostructure for CL-FL-PT triple-modal signal amplification: PER-controlled AND logic gate detection of miR-21&miR-155

The accurate detection of microRNA (miRNA) biomarkers is of paramount importance for early cancer diagnosis. However, it remains challenging due to their low abundance and complex dysregulation patterns in biofluids. Current detection methods often struggle to simultaneously achieve both precision and reliability. To address these limitations, we developed a novel biosensing platform that integrates a primer exchange reaction (PER)-controlled AND logic gate with signal-amplifying “feather-like” nanostructures (FLNs) constructed vis hybridization chain reaction (HCR) for the simultaneous detection of miR-21 and miR-155. This platform employs a core-shell CuS@MIL-101 nanocomposite as a triple-functional signal tag, enabling colorimetric (CL), fluorescent (FL), and photothermal (PT) readouts. The HCR-constructed FLNs provides a high density of binding sites for the signal tags, facilitating cascade signal amplification with up to 2.7-fold, 4.7-fold and 2.7-fold enhancement in three modes, respectively. The PER-mediated logic operation ensures that the signal probe assembly is triggered only in the simultaneous presence of both target miRNAs, enabling attomole-level detection with excellent specificity. The biosensor showed high robustness in spiked human serum, underscoring its strong potential for clinical miRNA analysis and cancer diagnostics.