Flexible photoelectrochemical biosensor for ultrasensitive microRNA detection based on concatenated multiplex signal amplification

Precise microRNA (miRNA) analysis is significant importance for early disease diagnosis. Herein, a novel flexible photoelectrochemical (PEC) biosensor for miRNA determination was developed by employing CdS NPs-modified carbon cloth (CC) on polyimide (PI) film as photoelectric material to provide the PEC responses and an efficient four-stage reaction system as the target recognition and signal amplification unit to improve the analytical performance. In this PEC biosensor, the presence of target miR-21 would trigger the catalytic hairpin assembly (CHA) and the following hybridization chain reaction (HCR) to produce a long dsDNA labeled with numerous biotins, which would further capture a large amount of alkaline phosphatase (ALP) for catalyzing the generation of ascorbic acid (AA). As an efficient electron donor, AA could be oxidized by the photoelectrode, which would initiate a redox cycling amplification process to regenerate AA, resulting in the enhancement of the photocurrent response. Benefitting from the synergistic nucleic acid-based, enzyme catalytic, and chemical signal amplification strategies, the proposed biosensing strategy enabled ultrasensitive miRNA determination. As expected, the PEC biosensor performed satisfactory analytical performances with a linear range of 1 fM to 1 nM and the detection limit down to 0.41 fM. Furthermore, the PEC biosensing strategy exhibited recommendable selectivity, stability, flexibility, and practical applicability. Therefore, this sensing platform provides promising potential for application in bioassay and early diagnosis of disease. •A flexible PEC biosensor was constructed for miRNA assay.•CdS NPs-modified CC on PI film was prepared to provide the PEC responses.•Concatenated four stage signal amplification was used to improve the sensitivity.•The biosensor shows good performance for miRNA with low LOD and wide linear range.•The sensor exhibits excellent practicability for miRNA assay in human serum samples.