In-situ growth of heterogeneous Au on MoS2 nanosheets for SERS detection of breast cancer-derived miR-210-3p and miR-9-3p

In-situ growth of gold nanoparticles (AuNPs) on two-dimensional materials has emerged as a promising route to engineer broadband and tunable surface-enhanced Raman scattering (SERS)-based platforms. Here, we demonstrate the synthesis of heterogeneous AuNPs directly on MoS₂ nanosheets to construct a versatile, low-energy SERS platform to detect cellular-derived microRNAs (miRNAs). The optimization of AuNP loading ratios on MoS₂ reveals heterogeneous morphologies generating abundant plasmonic hotspots and enhancing localized surface plasmon resonances across a wide spectral window. Au growth on a MoS₂ substrate via the Ostwald ripening phenomenon promotes morphological and size dispersions, which improve the stability of the hybrid nanostructure while providing large hotspot densities for analyte attachment. Using Cy3 and Cy5.5 as Raman reporters conjugated to locked nucleic acid (LNA) probes, the sensitive detection of synthetic targets miR-9-3p and miR-210-3p was validated with a LOD of 4 pM. We confirm the platform's sensing capabilities for cell-derived miRNAs, demonstrating a low. The detection limit is 0.1 nM, which validates relevant quantification capabilities. This work highlights the synergistic and interfacial integration of MoS₂ with heterogeneously grown Au, creating stronger SERS active hotspots with improved sensitivity and mode-selective chemical enhancement effects and also establishes its potential as a platform for translation and clinically focused studies for miRNA diagnostics from complex disease sources.