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In this study, we present experimental, modeling and simulation results for affinity binding between human immunoglobulin G (IgG) and protein A using an AT-cut quartz crystal microbalance (QCM) biosensor. A multilayer configuration transmission line model was built to predict the IgG-Protein A binding affinity on the QCM surface. The influence of antibody-antigen bonding effect on resonance frequency was analyzed by varying the IgG concentrations. The experiments registered 440 Hz, 360 Hz, 215 Hz and 110 Hz for IgG concentrations of 100 μg/ml, 50 μg/ml, 10 μg/ml and 5 μg/ml respectively, while the simulation resulted in 480 Hz, 409 Hz, 298 Hz and 130 Hz, respectively.