Quantum Mechanical Tunnelling Probes with Redox Cycling for Ultra‐Sensitive Detection of Biomolecules

Abstract Quantum mechanical tunnelling sensors (QMTs) have emerged as a promising technology for next‐generation single‐molecule detection. Furthermore, QMT sensors can be combined with redox species resulting in repeated oxidation and reduction (redox cycling).. We developed robust QMT probes with electrode gap distances below 2 nm. Using the generator‐collector (GC) mode, we verified that redox cycling of the ferrocyanide/ferricyanide (Fe(CN) 6 3−/4− ) couple occurs both in the tunnelling regime and on the electrode surface. Our findings indicated that the current enhancement is affected by both the gap distance and surface modifications of the probes. These QMT probes exhibited remarkable sensitivity, capable of detecting Fe(CN) 6 3−/4− concentrations down to sub‐picomolar levels. Utilising this ability to modulate redox reactions, we adapted the QMT probes to serve as electrochemical sensors for detecting viral proteins. By modifying the electrode surfaces, our functionalised QMT probes achieved sub‐pM detection limits with high selectivity in biofluids such as nasopharyngeal secretions. These findings highlight the potential of QMT probes to develop into a new class of electrochemical tunnelling sensors, offering significant advancements in biomedical diagnostics.