Ultrasensitive lab-on-paper device via Cu/Co double-doped CeO2 nanospheres as signal amplifiers for electrochemical/visual sensing of miRNA-155

•A dual-mode lab-on-paper device for ultrasensitive electrochemical/visual sensing of miRNA-155.•Synthesis of Cu/Co double-doped CeO2 nanospheres with abundant oxygen vacancies as signal probes.•DNA-functionalized nanomaterial complexes were used as electrochemical probes for amplification strategies.•The device has high sensitivity, stability and selectivity. In this work, an ultrasensitive lab-on-paper device via Cu/Co double-doped CeO2 (CuCo-CeO2) nanospheres as signal amplifiers, being acquiescent to quantitative assay with the dual mode signal readout of electrochemical and visual screening, was constructed for ultrasensitive sensing of miRNA-155. To improve the performance of biosensor, an Au-modified paper-based working electrode was manufactured by a secondary in-situ growth method, thereby enhancing its conductivity and facilitating the modification of hairpin probe with miRNA-155 through Au-S bonds. For constructing the lab-on-paper device, CuCo-CeO2 nanospheres were introduced as signal amplifiers, which exhibited remarkable enhanced performance in catalyzing H2O2 to generate ·OH to achieve electrochemical signal amplification compared with CeO2, and further improved the sensitivity of the lab-on-paper device. By combining hybridization chain reaction and classic competitive recognition interaction mechanism between aptamers and targets, ultrasensitive detection of miRNA-155 based on the lab-on-paper device was achieved. Meanwhile, color reaction could be realized on account of the oxidation of 3,3′5,5′-tetramethylbenzidine in the presence of H2O2 with the help of CuCo-CeO2, thereby achieving dual mode signal output. Under optimal conditions, a low detection limit of 0.05 fM with a linear range of 0.1 fM–10 nM for sensing miRNA-155 was reached by electrochemical method. And the low detection limit of 4.89 fM was obtained by visual method with a linear range of 10 fM–10 nM. The proposed lab-on-paper device was also successfully applied in serum samples to detect miRNA-155.