Abstract: Traditional protein molecularly imprinted polymers (MIPs) are used to develop biosensors for highly specific protein recognition based on generated three-dimensional cavities that are completely complementary to the imprinted template molecules. As a new generation of artificial identification probes, protein MIPs can realize the recognition specificity, but the analytical sensitivity and limit of detection (LOD) are not optimal. Here, a highly sensitive protein MIPs biosensor was constructed, in which conductive and biocompatible graphdiyne (GDY) nanosheets, antifouling and specific MIPs were combined, to achieve the highly sensitive and selective recognition of human C-reactive protein. Dopamine, owing to its simple polymerization procedure and the verified low fouling property of polydopamine, was used as the functional monomer to form steady complex with the template molecule through hydrogen bonding and multipoint electrostatic attraction. GDY with high biocompatibility and conductivity was independently synthesized and initially introduced into the C reactive protein imprinted polymers (C-MIPs) to enhance the electrochemical response and provide a suitable microenvironment for the bioactive protein molecules. In addition to the highly specific MIPs, antifouling material was also utilized to further improve the recognition selectivity. Herein, our developed C-MIPs biosensor performed with a wider linear detection range from 10-5 to 103 ng/mL and the LOD was found to be 0.41 x 10-5 ng/mL. Moreover, the C-MIPs biosensor showed excellent selectivity, reversibility and reusability, a short rebinding time, and long-term stability. Notably, the developed C-MIPs biosensor performed well even in complex serum samples without discernible signal suppression, indicating its good antifouling ability, as well as high sensitivity and selectivity. The developed C-MIPs biosensor behaved well in human blood samples, declaring its potential practical application capability
Author keywords: Graphdiyne, Protein molecularly imprinted polymer, Antifouling interface, C-reactive protein, Biosensor