ABSTRACT MicroRNAs (miRNAs) are powerful minimally invasive biomarkers for early cancer diagnosis, prognosis, and therapeutic monitoring. Conventional detection technologies, including quantitative reverse transcription‐ polymerase chain reaction (qRT‐PCR), microarrays, in situ hybridization, and next‐generation sequencing, have been essential for defining disease‐specific miRNA signatures; however, their clinical translation is limited by workflow complexity, high cost, restricted multiplexing, and dependence on centralized infrastructure. To address these limitations, oligonucleotide‐based probes and amplification strategies have been developed to enhance binding affinity, nuclease resistance, and analytical sensitivity. Nevertheless, many probe‐based platforms still rely on enzymatic amplification or complex surface chemistries, introducing variability and limiting reproducibility, scalability, and robustness. Two‐dimensional (2D) nanomaterials such as graphene, MXenes, and molybdenum disulfide (MoS 2 ) have recently emerged as alternative sensing platforms, enabled by high surface‐to‐volume ratios and strong affinity‐driven interactions with nucleic acids. Among these materials, MoS 2 nanostructures offer distinct advantages, including tunable morphology, versatile synthesis routes, and favorable electronic and optical properties. Nevertheless, MoS 2 alone often exhibits limited signal transduction efficiency, necessitating integration with plasmonic nanoparticles to achieve clinically relevant detection limits. Accordingly, engineered MoS 2 –plasmonic hybrid nanostructures have become a central strategy for advancing miRNA biosensing, with surface‐enhanced Raman scattering (SERS) gaining prominence as a sensitive detection modality. Emerging SERS‐based MoS 2 platforms demonstrate promise for ultrasensitive and reliable miRNA detection through chemical enhancement mechanisms. This review traces the evolution of miRNA detection from conventional molecular techniques to oligonucleotide engineering and nanomaterial‐enabled sensing, highlighting MoS 2 ‐based SERS architectures as promising candidates for next‐generation robust diagnostics. Finally, the review examines unresolved challenges, including reproducibility, biofluid matrix effects, standardization, and clinical translation.
Zablon et al. (Mon,) studied this question.