MoS₂ Modified Au-Locked Nucleic Acid (LNA) Nanocomposites for Enhanced Multi-Detection of miRNAs for Surface-Enhanced Raman Spectroscopy (SERS) Biosensing

Surface-enhanced Raman spectroscopy (SERS) is a powerful analytical technique for ultrasensitive detection of biological markers. Relying on the amplification of an analyte adsorbed on a noble metal surface for sensitive detection of molecules, in this study, we develop and report a novel indirect SERS biosensor combining the chemical synergies and enhancement properties of molybdenum disulfide (MoS<inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf>), plasmonic capabilities of AuNPs, the oligo-specific hybridization chemistry of locked nucleic acids (LNAs), resulting in a MoS<inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf>@Au-LNA nanocomposite optimized for multiplex detection of miR-210-3p and miR-9-3p. MoS<inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf> nanosheets, exfoliated via liquid-phase sonication, are functionalized with the in-situ synthesis of gold nanoparticles (AuNPs) through chemical reduction, forming an MoS<inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</inf>@Au composite which is exploited for detecting a wide range of miRNA from 9 nM to <tex xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">$\text{4 5 ~ n M}$</tex>. We discovered the nanocomposite's maximum functionalization limit below 45 nM. The nanocomposite exhibited strong SERS activity, amplifying the Raman signal of Cy3, Cy5.5, labeled LNA-miRNA nanohybrids to a LOD of 0.3 nM. This sensor exhibits significant next-generation biosensing capabilities.