Revealing the direct effect of individual intercalations on DNA conductance toward single-molecule electrical biodetection

Monitoring complex interactions of biological systems at the molecular level provides new opportunities to uncover fundamental details of the basic processes of life, of crucial importance to biology, diagnosis and drug discovery. Here, we detailed a reliable single-molecule electrical approach for achieving label-free, ultrasensitive electrical detection of DNA functions, using DNA intercalations by individual EB/SGs as a representative, based on DNA-functionalized molecular junctions. The analysis principle relies on the distortion mechanism of intercalative binding on the structural integrity of DNAs at the single-event level, resulting in significant step-wise changes in DNA charge transport. Such an understanding led to direct, rapid intercalator detection with subfemtomolar sensitivity. This single-molecule electrical approach provides a foundation for future molecular dynamics studies with single-molecule sensitivity, which will lead to direct observation of new effects and fundamental discoveries of the details of the most basic processes of life.