Liposome-mediated EC-SERS signal boost enables ultrasensitive detection of microRNA

Aberrant microRNA (miRNA) expression is a critical biomarker for various diseases, yet its low abundance in biofluids poses significant detection challenges, limiting clinical utility. To overcome the sensitivity limitations of conventional methods, this paper developed a novel liposome-assisted electrochemical surface-enhanced Raman scattering (EC-SERS) sensor for ultrasensitive miRNA detection. This platform uniquely integrates three synergistic amplification strategies: (1) catalytic hairpin assembly (CHA) for exponential target miRNA recycling and capture, (2) high-capacity liposomal nanocarriers densely loaded with cationic Rhodamine 6G (R6G) SERS reporters, and (3) a low-cost silver nanowire-coated screen-printed electrode (AgNW-SPE) generating intense electromagnetic fields under electrochemical modulation. Target miRNA initiates CHA cycling, immobilizing numerous DNA-tagged liposome probes on the SPE. Subsequent electrostatic attraction between the anionic AgNW-SPE and cationic R6G released from lysed liposomes concentrates the reporters at electromagnetic hotspots on the nanowires. This synergistic cascade enables ultrasensitive and specific detection. The EC-SERS sensor achieves a remarkably low detection limit of 28 fM and a wide linear range (1.0 × 10 −13 to 1.0 × 10 −9  M) for target miRNA, with high specificity against mismatched sequences. Demonstrated in complex biological serum samples, this robust and cost-effective platform provides a powerful tool for highly sensitive miRNA profiling. It holds significant potential for advancing biomarker discovery, enabling early diagnosis of disease, and facilitating personalized therapeutic strategies within precision medicine.