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

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.