Ultra-Wideband Impedance Spectroscopy of the Nucleus in a Live Cell

This paper describes the first application of a double-shell model in ultra-wideband impedance spectroscopy of a live cell. The impedance spectrum measured from 9 kHz to 9 GHz is analyzed by using the double-shell cell model to separate the contribution of the nucleus from that of the cytoplasm. The model parameters include the nucleus-to-cell radius ratio (r) and a parallel R-C circuit for each of the four cell compartments: the cell membrane (CM), the cytoplasm (CP), the nuclear membrane (NM), and the nucleoplasm (NP). In general, the extracted radius ratio agrees with that measured by optical microscopy, and the extracted resistances and capacitances agree with the literature and order-of-magnitude estimates. For example, for a human lymphocytes cell with r ≈ 0.8, the nuclear contribution is approximately linear. Therefore, the membrane parameters are constant so that RCM = 1.5 MΩ, CCM = 1.5 pF, RNM = 0.05 MΩ, and CNM = 1.2 pF, but the plasma parameters are linearly scaled so that RCP → 0.5(1 − r) MΩ, CCP → 6.7/(1 − r) fF, RNP → 0.12r MΩ, and CNP → 9.4/r fF. Because morphological and structural changes of a cell nucleus are important screening, diagnostic, and prognostic markers, these results suggest that ultra-wideband impedance spectroscopy may be a fast, compact, and label-free technique in cancer cytology.