Urchin-Shaped COFs Empower Dual-Mode Sensor Integrating Multiple Signal Amplification for Ultrasensitive miRNA-21 Detection

MicroRNAs (miRNAs) are promising biomarkers for cancer, offering a minimally invasive approach for liquid biopsy. However, their low abundance in clinical samples poses a major challenge for detection sensitivity and analytical reliability. Herein, this study report a fluorescence-electrochemical dual-mode sensor that integrates multiple signal amplification strategies for the ultrasensitive detection of miRNA-21. MXene–gold nanoparticles (AuNPs) composites were first modified on the electrode surface to enable efficient probe loading and enhanced electron transfer to amplify signal. The urchin-shaped covalent organic frameworks (COFs) facilitated more efficient methylene blue loading, with the unique structure further enhancing signal response. Combined with the miRNA-21 triggered entropy-driven catalysis (EDC)–DNA catalysis (DNAzyme) cascade amplification, the sensor realized a multi-level synergistic signal enhancement, demonstrating remarkable sensitivity. Notably, the urchin-shaped COFs served dual roles as both fluorescent reporters and nanocarriers, facilitating dual-mode signal readout. Under optimized conditions, the sensor exhibited a linear response to miRNA-21 in the range of 1–10 5 fmol∙L –1 , with detection limits of 0.285 and 0.342 fmol∙L –1 for the electrochemical and fluorescence modes, respectively. The platform enabled accurate detection of miRNA-21 in human serum and cancer cells. It provides a viable pathway for early cancer diagnosis with sensitivity and reliability.