Charge Modulation at Nucleic Acid/MoS2 Interfaces: Insights from Chronocoulometry for 2D Material-Based Biosensing.

This study examines the modulation of interfacial charge (Q sur) at nucleic acid/MoS2 interfaces using chronocoulometry with the goal of elucidating the roles of the charge on metal ions and properties of nucleic acids in developing adsorption-based platforms for nucleic acid detection. Specifically, we investigated the adsorption of locked nucleic acid and DNA oligomers on MoS2 surfaces in the presence of Mg2+ and Na+, employing [Ru-(NH3)6]3+ as an electrostatically adsorbed redox probe. Q sur was determined by removing the diffusion-controlled contribution and subtracting the adsorbed charge (Q ads) from the total measured charge (Q total). Our results show that interfacial charge is highly sensitive to metal ion identity, nucleic acid backbone chemistry, strand conformation, and nonspecific adsorptionfactors that may influence diffusion-limited charge transfer at the nucleic acid/MoS2 interface. Owing to its higher charge density, Mg2+ induces strong electrostatic interactions with both nucleic acids and MoS2, resulting in pronounced charge accumulation, whereas Na+ produces weaker and less predictable effects. Duplex adsorption and duplex formation on the surface reduced interfacial electropositivity relative to single-stranded oligomers, 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 mere steric hindrance from probe-target complexes, governs redox probe diffusion on nucleic acid/MoS2 interfaces. By elucidating charge-dependent dynamics, this study establishes a framework for reducing artifacts and enhancing the specificity and reliability of 2D material-based nucleic acid biosensors.