Investigating Modulation of Surface Charge on Nucleic Acid/MoS2 Interface: An Electrochemical Study

This study examines the modulation of interfacial charge (Qsur) at nucleic acid/MoS₂ interfaces using chronocoulometry, with the goal of elucidating the roles of the charge on metal ions and nucleic acid properties in developing adsorption-based platforms for nucleic acid detection. Specifically, we investigated the adsorption of locked nucleic acid (LNA) and DNA oligomers on MoS₂ surfaces in the presence of Mg2+ and Na+, employing [Ru(NH3)6]3+ as an electrostatically adsorbed redox probe. Qsur was determined by removing the diffusion-controlled contribution and subtracting the adsorbed charge (Qads) from the total measured charge (Qtotal). Our results show that interfacial charge is highly sensitive to metal ion identity, nucleic acid backbone chemistry, strand conformation, and nonspecific adsorption—factors that significantly influence diffusion-limited charge transfer. Mg²⁺, owing to its higher charge density, induces strong electrostatic interactions with both nucleic acids and MoS₂, resulting in pronounced charge accumulation, whereas Na⁺ produces weaker and less predictable effects. Duplex formation reduced surface electropositivity relative to single-stranded probes, while nonspecific adsorption of noncomplementary strands caused large charge perturbations that could mimic hybridization, underscoring potential risks for false positives and the critical need for blocking layers in such biosensing interfaces. Overall, these findings emphasize that interfacial charge, not solely steric hindrance from probe–target complexes, governs redox probe diffusion on nucleic acid/MoS2 interfaces. By clarifying these charge-dependent dynamics, this work provides a framework to minimize artifacts and improve the specificity and reliability of 2D material–based nucleic acid biosensors.