Nanoconfined biosensor for attomolar molecule detection and recycling via DNA strand displacement.

Attomolar-level biomolecular detection remains challenging due to inefficient molecular collisions and weak signal transduction at ultralow concentrations. Here, we introduce a recyclable nanoconfined biosensing platform (ABA@NCBS) for adenosine triphosphate (ATP) detection. This platform integrates a programmable DNA strand displacement reaction (SDR) directly within solid-state nanochannels, establishing a strong coupling between molecular recognition and ion transport. Under nanoconfinement, SDR-induced DNA conformational transitions actively modulate channel geometry and ionic migration pathways, converting molecular recognition into amplified and reversible transmembrane current signals. This confined reaction-transport coupling enables attomolar-level sensitivity (LOD = 83.4 aM) with dual linear response regimes, reflecting a transition in the dominant sensing mechanism across concentration ranges. Moreover, the cascade strand displacement circuit enables multistage logic signal transduction and reversible sensor regeneration. The ABA@NCBS system exhibits stable performance through five detection-regeneration cycles and outstanding anti-interference capability in complex artificial sweat matrices. This work establishes a distinct confined reaction-transport-logic sensing paradigm that goes beyond conventional nanoconfined sensors or SDR-based reversible systems, offering a versatile platform for ultrasensitive biosensing and intelligent molecular signal processing.