It is of great significance to accurately and sensitively detect oral cancer-related biomarker (ORAOV 1) for the early diagnosis of oral cancer. Present here is a novel electrochemical biosensor based on Cu2+-doped zeolitic imidazolate frameworks and gold nanoparticles (AuNPs@ZIF-8/Cu) nanocomposites and one-step strand displacement reaction for label-free, simple and sensitive detection of ORAOV 1 in saliva. It is worth noting that AuNPs@ZIF-8/Cu nanocomposites show large electrochemical effective surface area, good electrical conductivity and electrocatalytic activity due to the synergistic effect of metal nanoparticles (MNPs) and ZIF-8. Consequently, the newly developed electrochemical sensor displays a wide linear range of 0.1-104 pM and a low limit of detection (LOD) of 63 fM. Meanwhile, the electrochemical biosensor can distinguish single base mismatch. The relative standard deviation (RSD) of intra-assays and inter-assays is 1.46% and 1.76%, respectively, and the peak current values decline by 9.20% with RSD value of 1.35% after being stored at 4oC for 7 days, suggesting the newly designed electrochemical sensor exhibits good selectivity, reproducibility and stability to detect ORAOV 1. More importantly, this novel electrochemical sensor is found to be applicable for detecting ORAOV 1 in human saliva sample with a satisfactory result. The RSD values range from 1.15% to 1.77%, and the recoveries range from 95.46% to 112.98 %.

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