Quantitative and Specific Detection of Exosomal miRNAs for Accurate Diagnosis of Breast Cancer Using a Surface‐Enhanced Raman Scattering Sensor Based on Plasmonic Head‐Flocked Gold Nanopillars

Abstract MicroRNAs in exosomes (exosomal miRNAs) have attracted increased attention as cancer biomarkers for early diagnosis and prognosis owing to their stability in body fluids. Since strong association exists between exosomal miRNA expression levels and breast cancer, the development of effective methods that can monitor exosomal miRNA expression both over broad concentration ranges and in ultralow amounts is critical. Here, a surface‐enhanced Raman scattering (SERS)‐based sensing platform is developed for the quantitative determination of exosomal miRNAs. Ultrasensitive exosomal miRNA detection with single‐nucleotide specificity is obtained from enhanced SERS signals from a uniform plasmonic head‐flocked gold nanopillar substrate, which generates multiple hotspots and enables hybridization between short oligonucleotides, i.e., miRNAs and locked nucleic acid probes. The proposed SERS sensor shows an extremely low detection limit without any amplification process, a wide dynamic range (1 a m to 100 n m ), multiplex sensing capability and sound miRNA recovery in serum. Furthermore, this sensor allows reliable observation of exosomal miRNA expression patterns from breast cancer cell lines and can discriminate breast cancer subtype based on the difference between these patterns. The results suggest that this sensor can be used for universal cancer diagnosis and further biomedical applications through the quantitative measurement of exosomal miRNAs in bodily fluids.