Using signal off-to-on strategy for designing precise and ultrasensitive biosensor towards hepatocellular carcinoma through protein variant detection based on biocompatible bimetallic MOF.

The high mortality rate of patients with hepatocellular carcinoma (HCC) is an ever-increasing worldwide concern. Fortunately, the newest research has found that the proportion of a protein variant in total alpha-fetoprotein (AFP) over 10 % can accurately predict the incidence of HCC. Therefore, a signal off-to-on strategy was designed for developing a novel precise and ultrasensitive biosensor towards HCC through protein variant detection based on bimetallic metal-organic framework (MOF). In this study, the biocompatible FeNi-MOF was used as an electrochemically immobilized carrier, which provided abundant active sites and exhibited a synergistic effect between Fe and Ni ions for dramatically promoting the electron transfer and improving the electrochemical reduction efficiency, prominently facilitating signal amplification of the biosensing platform. Then, we designed a novel ordered labeling method to distinguish AFP-L3 from overall AFP and introduced a signal off-to-on strategy for achieving highly efficient determination of AFP-L3 %. This proposed biosensor demonstrated a satisfactory linear range, along with a very low detection limit of 69 pg/mL for AFP-L3, which was far below the medically relevant threshold level. Furthermore, the adopted biosensor presented preeminent specificity, and favorable reproducibility.