| Summary: | Abstract Single‐biomolecule electronic sensing techniques are of great importance in many fields, from medical diagnosis to disease surveillance. As the physiological changes of single biomolecules can be converted into measurable electrical signals, single‐molecule electronic biosensors can realize real‐time, highly sensitive, and high‐bandwidth detection of individual intra‐ or inter‐molecular interactions. These powerful single‐molecule sensing devices have demonstrated key advantages in precisely providing rare and detailed intermediate information along reaction pathways and revealing unique properties hidden in ensemble measurements. This review summarizes significant advances in single‐molecule electronic biosensors, emphasizing biomolecule recognition, interaction, and reaction dynamics at the single‐molecule level. Sensor configurations, sensing mechanisms, and representative applications are also discussed. Furthermore, a perspective on the use of photoelectric integrated systems for synchronous sensing of the electrical and optical signals of single biomolecules is provided.
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