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, MoS 2 ), could further streamline detection mechanisms. In this study, we explore the first adsorption-based LNA/MoS 2 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 MoS 2 surface, along with a gradual and concentration-dependent response. Additionally, the LNA–RNA duplex displayed a lower affinity for the MoS 2 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 MoS 2 provides valuable insights for designing next-generation adsorption-based biosensing assays with improved sensitivity and specificity.