Microdosimetry for Nanosecond Pulsed Electric Field Applications: A Parametric Study for a Single Cell

Abstract

A microdosimetric study of nanosecond pulsed electric fields, including dielectric dispersivity of cell compartments, is proposed in our paper. A quasi-static solution based on the Laplace equation was adapted to wideband signals and used to address the problem of electric field estimation at cellular level. The electric solution was coupled with an asymptotic electroporation model able to predict membrane pore density. An initial result of our paper is the relevance of the dielectric dispersivity, providing evidence that both the transmembrane potential and the pore density are strongly influenced by the choice of modeling used. We note the crucial role played by the dielectric properties of the membrane that can greatly impact on the poration of the cell. This can partly explain the selective action reported on cancerous cells in mixed populations, if one considers that tumor cells may present different dielectric responses. Moreover, these kinds of studies can be useful to determine the appropriate setting of nsPEF generators as well as for the design and optimization of new-generation devices.

A Microdosimetric Study of Electropulsation on Multiple Realistically Shaped Cells: Effect of Neighbours

“…At the same time, great attention has been given to the development of models that could justify and explain experimental observations. Such models can be based on molecular simulations (Casciola et al 2014;Ho et al 2013) or can be built in the continuum at the macroscopic (Denzi et al 2015a;Corovic et al 2007;Neal and Davalos 2009) or microscopic scale (Denzi et al 2013;Merla et al 2011;Gowrishankar et al 2013).…”

“…In principle, the different spectral contents of pulses can cause different responses in the time trends of the TMP induced in real cells. To obtain a general, predictive model for all pulse durations (from few nanoseconds to hundreds of microseconds) the dielectric dispersion of all cells in the medium has been taken into account (Joshi and Hu 2011;Merla et al 2011Merla et al , 2012Denzi et al 2013;Guo et al 2013). Furthermore with our approach it is possible to extract the shape of internal organelles and investigate their response.…”

Dielectric model for Chinese hamster ovary cells obtained by dielectrophoresis cytometry

“…The range of variation for each parameter is chosen such that it encompasses the values previously reported in literature for other mammalian cells. 11,20,21,38,39,[56][57][58][59] Sensitivity of each parameter is calculated with respect to the nominal values: 20,38 Since the medium conductivity has a substantial influence, the sensitivities are presented for five media conductivities (0.17, 0.3, 0.4, and 0.5 S/m media as employed in our measurements and a very low conductivity medium, 0.01 S/m, which has been used in many other dielectric parameter studies 10,11,39,41,59,60 ). As our measurements are in the 0.6-10 MHz frequency range, the sensitivity to the membrane conductivity is low as this parameter predominantly affects the low frequency part of the RefK CM g spectrum (less than 200 kHz).…”

Effects of nanosecond pulsed electric fields on the activity of a Hodgkin and Huxley neuron model

“…Both N and A depend on the TMP and hence on time. A can be estimated on the bases of the TMP calculated as in [20]; as an example, for a nsPEF of 10 ns and an intensity of 2.2 MV/m, A showed a first significant peak with a fast decay (in the time scale < 1 µs) down to a value approximately equal to 0.1 m 2 . Typically N exhibits a very sharp increase (in a time scale of ns) up to a maximum level (N MAX ), which, due to the resealing process of the pores, slowly decays (in the time scale up to s) to the initial value N 0 .…”

“…The pore formation and destruction is a stochastic process following, in general, the Smolukowski equation [15]; in the nanosecond time scale, it can be simplified leading to the asymptotic electroporation model [15], [16], where pores with a fixed size (≈ 1 nm) are considered [17]- [19]. Pore density exhibits a highly non-linear dependence on the trans-membrane potential (TMP) induced by the particular nsPEF used, which can be obtained as the outcome of microdosimetric studies [20].…”