A novel quartz crystal microbalance (QCM) biosensor with high selectivity and sensitivity has been developed for ribonuclease A determination. Macroporous protein imprinted films have been fabricated on the surface of QCM electrode using 2,2,3,4,4,4-hexafluorobutyl methacrylate (HFBMA) as the main matrix monomer, N-methacryloyl-histidine (MAH) as the functional monomer, and trimethylolpropane trimethacrylate (TRIM) as the cross-linker. The imprinted special surface area and the quantity of the imprinted sites were increased by the formation of macropores that were generated by employing calcium carbonate nanoparticles as the porogen. The selectivity factor was improved obviously for the fluoromonomer containing system, especially in dilute protein solution, which gets benefit from the reducing of the nonspecific adsorption of proteins. Furthermore, MAH can not only play the role as the functional monomer, but also improve the hydrophilicity of surface of the imprinted film, which makes for the adsorption of proteins. At last, the rigid skeleton structure made the films durable in the recycled tests.
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