An Electrically Activated Nanobody Biosensor for On-Demand Detection.

The development of systems capable of dynamic, on-demand target detection marks a transformative advance for biomanufacturing, diagnostics, and environmental monitoring. Nanobodies can recognize targets ranging from bacteria and proteins to small molecules, yet conventional platforms remain static, with perpetually exposed binding sites that hinder control in dynamic settings. We introduce an adaptive, on-demand sensing nanobody platform that leverages electrically responsive oligopeptides to gate antigen-binding sites between OFF (shielded) and ON (exposed) states. Upon electrical activation, binding sites are revealed with >80% efficiency, enabling real-time, selective detection. The system achieves pg/mL sensitivity over a broad dynamic range (pg/mL-μg/mL), performs reliably in serum and cell culture media, and supports multiplexed detection via independently addressable electrodes. This electroresponsive architecture defines a new paradigm for programmable, high-performance molecular detection.