Experimental comparison of electrochemical and quantum transport-based biodetection methods for RNA cancer biomarkers

Cancer remains a leading cause of death worldwide and early‑stage detection is essential to improve patient outcomes. Recent advances in nanoscale sensing have opened up new pathways for ultrasensitive, label-free detection of nucleic acid biomarkers. In this work, we compare two sensor platforms for a KRAS G12V RNA biomarker: (i) a classical bioelectrochemical sensor that exploits the redox activity of methylene blue modified DNA probes, and (ii) a recently reported quantum transport-based single-molecule sensor that measures conductance changes of individual DNA: RNA hybrids using scanning ‑ tunneling‑microscopy break‑junctions (STM‑BJ). By comparing both approaches, we evaluate their key performance metrics -limit of detection, specificity, and robustness- in biologically relevant complex media. The electrochemical sensor reaches a femtomolar detection limit, but fails to discriminate a single‑base mismatch under the tested conditions. In contrast, the STM-BJ platform delivers attomolar sensitivity and single-base resolution; however, its operation is hindered in complex media, particularly in protein-rich environments. However, this weakness is also shared with the electrochemical approach. Our comparative analysis highlights the complementary strengths of these platforms, suggesting that integrating both could improve point-of-care cancer screening by combining sensitivity, specificity, and robustness in complex samples.