Electrical properties of core-shell nanoparticles with protein shell layers have not been fully surveyed, although such nanoparticles have been studied widely as model biomimetic particles. In this study, we demonstrated that the capacitance changes of a silica (SiO 2 )/bovine serum albumin (BSA) core-shell nanoparticle (SiO 2 @BSA) could be monitored with variation of BSA shell thickness using AC impedance spectroscopy combined with conductive atomic force microscopy (c-AFM). Impedance spectra showed that the resistance and capacitance of SiO 2 @BSA core-shell nanoparticles increased with increasing BSA shell thickness. Within the range of experimental conditions studied, the capacitance of SiO 2 @BSA increased linearly with increasing number of BSA layers, corresponding to a 5.4 pF rise per single layer of BSA after the first two layer deposition of BSA. This result demonstrated that the minute changes of the electrical properties that were induced by the shell protein layer can be monitored and quantified using impedance spectroscopy.AC impedance spectroscopy is a widely studied method useful for the characterization of capacitive and non-conductive materials. The AC impedance spectrum contains diverse electrical information on the target substances, such as capacitance and inductance, which cannot be measured by the resistance responses from DC stimuli. 1-3 Due to its versatility in electrical characterization, AC impedance spectroscopy has been commonly applied for the analyses of macroscopic substances and for monitoring electrochemical reactions in aqueous media. Recently, AC impedance spectroscopy has been applied for the analysis of dry materials at the nanoscale by combining it with c-AFM. Using the c-AFM tip as an electrode, AC stimuli of a wide range of frequencies was applied to individual particles of nanoscale substances, and the obtained impedance signal was analyzed further using an electrical circuit model for the characterization and/or identification of individual nanoparticles. This method was exploited to characterize the capacitive properties of a thin inorganic nanoparticle layer or a polymeric thin film. [4][5][6][7] Aside from the studies noted above on non-biological substances, AC impedance spectroscopy is an attractive method for characterizing biological substances because it can collect detailed information on the electrical properties of biomolecules, although this area has been explored only a little. Biological transformations such as DNA hybridization, immunological antibody-antigen interactions, and enzymatic reactions have been clearly indicated by AC impedance spectroscopy, with significant electrical signal changes observed during those biological developments. 8-10 Combination with c-AFM broadened the scope of AC impedance spectroscopy to the characterization of biological substances at the nanoscale. Identification of virion under 100 nm was achieved using AC-impedance spectroscopy combined with c-AFM. 4,11 The differences in the capsid proteins of each virus particle made...