A microdosimetry analysis of reversible electroporation in scattered, overlapping, and cancerous cervical cells

Abstract

We present a numerical method for studying reversible electroporation on normal and cancerous cervical cells. This microdosimetry analysis builds on a unique approach for extracting contours of free and overlapping cervical cells in the cluster from the Extended Depth of Field (EDF) images. The algorithm used for extracting the contours is a joint optimization of multiple-level set function along with the Gaussian mixture model and Maximally Stable Extremal Regions. These contours are then exported to a multi-physics domain solver, where a variable frequency pulsed electric field is applied. The trans-Membrane voltage (TMV) developed across the cell membrane is computed using the Maxwell equation coupled with a statistical approach, employing the asymptotic Smoluchowski equation. The numerical model was validated by successful replication of existing experimental configurations that employed low-frequency uni-polar pulses on the overlapping cells to obtain reversible electroporation, wherein, several overlapping clumps of cervical cells were targeted. For high-frequency calculation, a combination of normal and cancerous cells is introduced to the computational domain. The cells are assumed to be dispersive and the Debye dispersion equation is used for further calculations. We also present the resulting strength-duration relationship for achieving the threshold value of electroporation between the normal and cancerous cervical cells due to their size and conductivity differences. The dye uptake modulation during the high-frequency electric field electroporation is further advocated by a mathematical model.

Giant pore formation in vesicles under msPEF-induced electroporation: role of charging time and waveform

“…Their initial study on the local analysis of a planar membrane could predict highly non-linear pore formation and growth and the simultaneous coupled variation of the transmembrane potential. The physics of electroporation on a cellular level can be much more complex than those of a local small planar patch of the membrane, predominantly on account of spatial variation of the electric field [26, 7, 27, 18]. Using computational simulations, a number of studies demonstrated that for spherical biological cells, the TMP, pore number, and pore size are nonlinearly coupled, resulting in nonintuitive transient variations in TMP along the membrane [17, 14, 11, 34, 13].…”