On the Dielectric Properties of Human Skin (2015)

Electrochemical impedance spectroscopy has become a powerful tool to assess the response of human skin to external stimuli. Two approaches have been taken to analyze the skin impedance data. The skin properties have been assumed to be independent of spatial position but dependent on frequency,[1] and, alternatively, skin properties have been assumed to be independent of frequency but dependent on spatial position.[2] Recent data published by White et al.[3] provides a unique opportunity to assess the validity of the two distinct approaches. The data used in the present study were part of a larger study intended to correlate changes in the flux of p-chloronitrobenzene and 4-cyanophenol in response to physical and chemical damage. Split-thickness human cadaver skin (300-400 microns thick) from the back was purchased from the National Disease Research Interchange (NDRI, Philadelphia, PA). The skin was collected within 24 h post mortem, frozen immediately, and stored at temperatures less than -60 C until used. The protocol described by White et al.[4] was used to ensure that skin samples had sufficient integrity for meaningful measurements of in-vitro chemical permeability. The impedance was measured in the four-electrode configuration, in which two Ag/AgCl (In Vivo Metric, Healdsburg, CA) reference electrodes were used to sense the potential drop across the skin, and two Ag/AgCl working electrodes were used to drive the current. The skin was exposed on both sides for roughly eight hours to a phosphate buffered saline solution (PBS) (0.01 M, pH 7.4, Sigma P-3813) prepared in de-ionized water. The impedance measurements were collected with a 10 mV potential perturbation after two eight-hour long, permeation experiments in which 4-cyanophenol-saturated PBS was placed in the donor chamber and PBS was placed in the receptor chamber. After the first 4-cyanophenol permeation experiment, the frame holding the skin was removed from the diffusion cell, the skin was pierced by a 26 gauge needle (with a 464 micron outside diameter), the cell was reassembled, and the donor and receptor chambers refilled with fresh 4-cyanophenol-saturated PBS and PBS, respectively, for the second permeation experiment. Before perforation with a needle, the impedance diagrams showed a capacitive loop with a depressed semi-circle, consistent with a CPE model. The impedance measured after perforation with the needle could be fit by a CPE model, but the capacitive loop was substantially smaller. Perforation by a needle also caused a substantial shift in the characteristic frequency. These data were used to evaluate models for the impedance response of skin under the hypothesis that perforation by a needle introduces an additional parallel pathway for current to flow, but should not change the dielectric properties of the skin. Under the assumption that skin properties are a function of frequency, this hypothesis means that the frequency-dependent dielectric response should not be altered by perforation of the skin. The observed frequency shift provides a means of assessing different proposed distributions of skin properties. The analysis presented in this paper supports the hypothesis that skin may be described as a system with frequency-independent properties that are functions of position within the skin. The frequency-dependent relative permittivity and resistivity were changed substantially by perforation of the skin. References S. Grimnes and O­. G. Martinsen, Bioimpedance and Bioelectricity Basics, 3 rd edition (Amsterdam: Academic Press, 2015). M. E. Orazem, B. Tribollet, V. Vivier, S. Marcelin, N. Pebere, A. L. Bunge, E. A. White, D. P. Riemer, I. Frateur, and M. Musiani, J. Electrochem. Soc., 160 (2013) C215-C225. E. A. White, M. E. Orazem, and A. L. Bunge, Pharm. Res., 30 (2013), 2036-2049. E. A. White, M. E. Orazem, and A. L. Bunge, J. Electrochem. Soc., 159 (2012) G161-G165.