Flavin mononucleotide-based biomimetic redox flow biosensor for rapid miRNA-21 detection in colorectal cancer diagnostics

Detection of tumor biomarkers in serum and cellular samples is essential for early diagnosis and precision treatment of colorectal cancer, and miRNA-21 is well-established as a pivotal oncogenic biomarker for this malignancy. Conventional nucleic acid detection methods typically rely on complex enzymatic amplification and lengthy workflows, severely restricting their application in point-of-care clinical screening and long-term dynamic disease monitoring. In this work, a novel biomimetic redox flow biosensor based on flavin mononucleotide (FMN) is developed for rapid quantitative detection of miRNA-21, marking the first application of FMN as an electroactive tag for trace nucleic acid analysis. The sensing mechanism centers on Ti⁴⁺ as a multifunctional coordination bridge, which forms stable bonds simultaneously with phosphate moieties of FMN and the phosphate backbone of target miRNA-21. This multisite coordination strategy enables ultrahigh detection sensitivity without additional signal amplification procedures. The fabricated biosensor exhibits an excellent linear response for miRNA-21 detection across 1∼10000 pM, with a detection limit as low as 0.18 pM. It converts biological recognition events into distinguishable electrochemical signals within 1 h under mild conditions, and shows outstanding selectivity and anti-interference capability in complex biological matrices. Notably, the system supports real-time data viewing and storage via mobile terminals, enabling IoT-compatible personalized health management and long-term dynamic monitoring. This portable biosensor suits high-throughput clinical colorectal cancer screening, facilitating early clinical intervention and precise tumor treatment.