Lin Wang, Zitai Jiang
Ultrasensitive detection at the single-molecule level is crucial for advancing biomedical diagnostics, environmental monitoring, and chemical synthesis. Among various strategies, single-molecule junctions (SMJs) stand out as they convert molecular-scale events into detectable electrical signals, offering a versatile and sensitive platform for real-time, label-free, and non-destructive sensing with single-molecule resolution. This review provides an overview of the primary SMJ measurement techniques, with a particular focus on the fundamental mechanisms driving SMJ-based sensing, including the molecular chemical structure influenced by the local environment, supramolecular interactions and molecule-electrode interface. We also highlight recent progress in utilizing SMJs for monitoring chemical reactions, chiral recognition, and biomedical diagnostics. Finally, we have analyzed the current challenges in single-molecule electrical detection in terms of signal reliability, sensitivity, and selectivity, offering corresponding solutions for each to provide valuable insights for designing more effective detection systems.