A dual catalytic hairpin-based cyclic self-assembly reaction system for sensitive detection of miRNA21 using Zn@HRP snowflake metal-organic frameworks

MicroRNAs are remarkably stable and detectable, making them ideal candidates for non-invasive diagnostics. The clinical relevance of fluid-specific miRNA profiling has implications for early disease detection, prognostic prediction, and therapeutic monitoring. A novel colorimetric biosensor for the highly sensitive detection of miRNA-21 is presented, integrating a dual catalytic hairpin-based cyclic self-assembly reaction system with Zn@HRP snowflake metal-organic frameworks (MOFs). This system leverages the unique snowflake structure and high catalytic activity of Zn@HRP MOF for signal amplification. Upon target miRNA-21 recognition, the system undergoes a cascade amplification process, leading to a significant increase in absorbance that is directly proportional to miRNA-21 concentration. The developed biosensor exhibits an ultra-low detection limit of 0.27 fM, demonstrating exceptional sensitivity, specificity, and anti-interference capabilities. Furthermore, the biosensor performs robustly in complex plasma samples, showing reliable recovery rates and excellent correlation with qRT-PCR results. This work not only provides a robust platform for precise miRNA detection but also offers significant potential for clinical diagnostics and biomarker profiling, paving the way for more accessible and reliable diagnostic tools in personalized medicine.