Observing Mesoscopic Nucleic Acid Capacitance Effect and Mismatch Impact via Graphene Transistors

Abstract This work reports a molecular‐scale capacitance effect of the double helical nucleic acid duplex structure for the first time. By quantitatively conducting large sample measurements of the electrostatic field effect using a type of high‐accuracy graphene transistor biosensor, an unusual charge‐transport behavior is observed in which the end‐immobilized nucleic acid duplexes can store a part of ionization electrons like molecular capacitors, other than electric conductors. To elucidate this discovery, a cascaded capacitive network model is proposed as a novel equivalent circuit of nucleic acid duplexes, expanding the point‐charge approximation model, by which the partial charge‐transport observation is reasonably attributed to an electron‐redistribution behavior within the capacitive network. Furthermore, it is experimentally confirmed that base‐pair mismatches hinder the charge transport in double helical duplexes, and lead to directly identifiable alterations in electrostatic field effects. The bioelectronic principle of mismatch impact is also self‐consistently explained by the newly proposed capacitive network model. The mesoscopic nucleic acid capacitance effect may enable a new kind of label‐free nucleic acid analysis tool based on electronic transistor devices. The in situ and real‐time nucleic acid detections for virus biomarkers, somatic mutations, and genome editing off‐target may thus be predictable.