Charge Transfer Study of Artificial Nucleic Acid/MoS₂ Interface for Nucleic Acid Detection

Locked nucleic acids (LNAs) possess distinctive properties, including a rigid, negatively charged backbone and a high affinity for complementary nucleic acids, making them highly promising for biosensing applications. Surface-tethered LNA probes have demonstrated exceptional sensitivity and selectivity for detecting complex RNA targets. However, simpler and more cost-effective alternatives, such as adsorption-based assays on two-dimensional (2D) nanomaterials (e.g., molybdenum disulfide, MoS2), could further streamline detection mechanisms. In this study, we explore the first adsorption-based LNA/MoS2 interface for DNA biosensing via label-free interfacial charge transduction. The charge transfer process, driven by diffusion of a soluble redox probe at the interface, is influenced by the presence of metal ions in the surrounding matrix. Compared to a DNA probe of the same sequence, LNA exhibits a stronger affinity for the MoS2 surface, along with a gradual and concentration-dependent response. Additionally, the LNA–RNA duplex displayed a lower affinity for the MoS2 surface than the LNA–DNA and DNA–RNA duplexes but caused a higher concentration responsive change in interfacial charge transfer. The LNA-based interface achieves attomolar-level target detection and offers remarkable selectivity by effectively discriminating between specific and nonspecific targets. This systematic investigation of interactions of LNA and LNA–RNA duplexes with MoS2 provides valuable insights for designing next-generation adsorption-based biosensing assays with improved sensitivity and specificity.