A fluorescence biosensor was designed for the sensitive detection of microRNA (miR)-144-3p, a potential miR biomarker for nasopharyngeal cancer, by integrating magnetic beads (MBs) into a hybridization chain reaction-silver nanoclusters (HCR-AgNCs) system. Through careful design, each component in the MB-HCR-AgNCs biosensor was able to perform well without affecting subsequent steps, where target miR was magnetically separated, followed by amplification via HCR and detection via AgNCs in a ratiometric manner. The novel MB-HCR-AgNCs biosensor exhibits a good fluorescence response towards the target miR with a wide linear detection range of 10 fM–1 μM and a detection limit of 4.88 fM. Moreover, it shows remarkable selectivity towards the target miR, and good reproducibility even in raw human serum samples. Our findings suggest that the MB-HCR-AgNCs can be a promising tool for sensitive miR detection in clinical diagnostics, without the need for complex sample preparation.
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