Ultrasensitive electrochemical paper-based biosensor for microRNA via strand displacement reaction and metal-organic frameworks

•Au nanoparticles and Cu-MOFs cooperatively catalyze the oxidation of glucose.•The target initiates strand displacement reaction cycle for signal amplification.•An origami electrochemical device with portable owns extremely high sensitivity. A novel electrochemical biosensor based on hairpin assembly target recycling for signal amplification and Au nanoparticles (AuNPs) modified Cu-based metal-organic frameworks (Cu-MOFs) for catalysis was constructed for highly sensitive detection of microRNA (miRNA). It was worth noting that the recycling of target was finished only based on strand displacement reaction without nuclease. In addition, a novel catalytic material of Cu-MOFs was prepared, which could provide more large surface area for AuNPs enveloping and DNA strand 1 (S1) immobilization. In this sensing process, the released target was available for initiating many of cycles, and the prepared S1-AuNPs@Cu-MOFs was linked to the modified electrode by chain hybridization, which was promising for signal amplification. All electrical signal measurements and chain displacement reactions are carried out on a compatibly designed origami electrochemical device (OECD). In the presence of glucose, AuNPs and Cu-MOFs cooperatively catalyzed the oxidation of glucose, resulting in the wide linear detection range from 1.0fM to 10nM and the detection limit of 0.35fM for miRNA-155 with extremely high sensitivity. As we expect, the newly designed biosensor was successfully applied to the detection of miRNA-155 in serum samples from healthy people to cancer patients. Therefore, this proposed method could provide a promising and safe pathway for sensitive detection of miRNAs in clinical applications.