Programmable Electric Double Layer at Metal–Organic Framework Interfaces for miRNA Resolution

Abstract

MicroRNA (miRNA) assays often rely on solid–liquid interfaces for enrichment and signal transduction, but programmable regulation of interfacial adsorption, recognition, and release remains largely unexplored. Here, we propose an electric double layer (EDL)-programmable nucleic-acid interfacial switch on metal–organic framework (MOF) interfaces. In this system, EDL-mediated interfacial stabilization, andcoordination anchoring at coordinatively unsaturated metal sites retain probes and posthybridization duplexes within a near-surface quenching region, producing a stable signal-off state. Increasing ionic strength and introducing competitive polyphosphate anions (PPi/STPP) weaken interfacial anchoring and trigger release of the complexes into the surrounding solution, thereby generating a signal-on response. Based on this mechanism, we developed two complementary miRNA assays: a MIL-101(Cr)-based multiplex fluorescence platform with quencher strands to suppress background, and a Zn2Ph2Da-enabled duplex-release strategy that generates DNA templates for extraction-free, reverse-transcription-free one-step qPCR with a detection limit of 10–18 M. Both readouts discriminated liver cancer patients from healthy controls in plasma, demonstrating the potential of EDL-programmable interfacial chemistry for miRNA analysis.