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Abstract Cancer is a significant healthcare issue, and early screening methods based on biomarker analysis in liquid biopsies are promising avenues to reduce mortality rates. Electrical detection of nucleic acids at the single molecule level could enable these applications. We examine the electrical detection of RNA cancer biomarkers (KRAS mutants G12C and G12V) as a single-molecule proof-of-concept electrical biosensor for cancer screening applications. We show that the electrical conductance is highly sensitive to the sequence, allowing discrimination of the mutants from a wild-type KRAS sequence differing in just one base. In addition to this high specificity, our results also show that these biosensors are sensitive down to an individual molecule with a high signal-to-noise ratio. These results pave the way for future miniaturized single-molecule electrical biosensors that could be groundbreaking for cancer screening and other applications. 

The last half-century has witnessed the birth and development of a new multidisciplinary field at the edge between materials science, nanoscience, engineering, and chemistry known as Molecular Electronics. This field deals with the electronic properties of individual molecules and their integration as active components in electronic circuits and has also been applied to biomolecules, leading to BioMolecular Electronics and opening new perspectives for single-molecule biophysics and biomedicine. Herein, we provide a brief introduction and overview of the BioMolecular electronics field, focusing on nucleic acids and potential applications for these measurements. In particular, we review the recent demonstration of the first single-molecule electrical detection of a biologically-relevant nucleic acid. We also show how this could be used to study biomolecular interactions and applications in liquid biopsy for early cancer detection, among others. Finally, we discuss future perspectives and challenges in the applications of this fascinating research field.