An FDTD Interaction Scheme of a High-Intensity Nanosecond-Pulsed Electric-Field System for In Vitro Cell Apoptosis Applications

A finite-difference time-domain analysis of a high-intensity nanosecond-pulsed electric-field (nsPEF) system, composed of a pulse-forming line (PFL) and a universal electroporation cuvette, is described. The simulation scheme is based on interactions of 1-D transmission-line equations for the PFL and 3-D Maxwell's curl equations for the cuvette volume. Simulations incorporate system adjustment to facilitate maximum transfer of electrical energy from the PFL to the cuvette medium. Experimental validation of the voltage across the cuvette electrodes through the laboratory-constructed nsPEF system with an energy density of ~1 J/cm3 reveals an overall agreement with some discrepancies. The distribution profiles of the transient field inside the cell suspension area during the excitation of 5-kV 10-ns pulses would adequately account for the feasibility of using an integrated model as a design benchmark for the interaction physics of the generated nanosecond pulses and culture vessel. The observed nsPEF effects on cells include increased transmembrane potentials across organelle membranes without permanently damaging the cell membrane, increasing the probability of electric field interactions with intracellular structures.

[1]  A nanosecond pulse generator for intracellular electromanipulation , 2000, Conference Record of the 2000 Twenty-fourth International Power Modulator Symposium.

[2]  M. Hengartner.  The biochemistry of apoptosis , 2000, Nature.

[3]  K. Schoenbach,et al.  Nanosecond, high‐intensity pulsed electric fields induce apoptosis in human cells , 2003, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[4]  Zhen Ji,et al.  FDTD analysis of a gigahertz TEM cell for ultra-wideband pulse exposure studies of biological specimens , 2006, IEEE Transactions on Biomedical Engineering.

[5]  R. B. Standler,et al.  A frequency-dependent finite-difference time-domain formulation for dispersive materials , 1990 .

[6]  E. Neumann,et al.  Electroporation and Electrofusion in Cell Biology , 1989, Springer US.

[7]  S. Cory,et al.  The Bcl2 family: regulators of the cellular life-or-death switch , 2002, Nature Reviews Cancer.

[8]  Dennis M. Sullivan,et al.  Comparison of measured and simulated data in an annular phased array using an inhomogeneous phantom , 1992 .

[9]  T. Tsong,et al.  Electroporation of cell membranes. , 1991, Biophysical journal.

[10]  Kenneth R. Foster,et al.  Thermal and nonthermal mechanisms of interaction of radio-frequency energy with biological systems , 2000 .

[11]  U. Zimmermann,et al.  Reversible Electropermeabilization of Mammalian Cells by High-Intensity, Ultra-Short Pulses of Submicrosecond Duration , 2001, The Journal of Membrane Biology.

[12]  K. Schoenbach,et al.  Intracellular effect of ultrashort electrical pulses , 2001, Bioelectromagnetics.

[13]  Laura Marcu,et al.  Calcium bursts induced by nanosecond electric pulses. , 2003, Biochemical and biophysical research communications.

[14]  A. Kuthi,et al.  Electrical modeling of pulsed power systems for biomedical applications , 2003, Digest of Technical Papers. PPC-2003. 14th IEEE International Pulsed Power Conference (IEEE Cat. No.03CH37472).

[15]  Juergen F. Kolb,et al.  Nanosecond pulsed electric fields cause melanomas to self-destruct , 2006 .

[16]  K. Schoenbach,et al.  Time domain dielectric spectroscopy measurements of HL-60 cell suspensions after microsecond and nanosecond electrical pulses , 2004, IEEE Transactions on Plasma Science.

[17]  K. Schoenbach,et al.  Bioelectrics-new applications for pulsed power technology , 2001, PPPS-2001 Pulsed Power Plasma Science 2001. 28th IEEE International Conference on Plasma Science and 13th IEEE International Pulsed Power Conference. Digest of Papers (Cat. No.01CH37251).

[18]  Ulrich Zimmermann,et al.  Electromanipulation of cells , 1996 .

[19]  Ravindra P. Joshi,et al.  Ultrashort electrical pulses open a new gateway into biological cells , 2004 .

[20]  Dennis M. Sullivan,et al.  A frequency-dependent FDTD method for biological applications , 1992 .

[21]  K. Yee.  Numerical solution of initial boundary value problems involving maxwell's equations in isotropic media , 1966 .

[22]  Martin A. Gundersen,et al.  Compact nanosecond pulse generator for cell electroperturbation experiments , 2002, Conference Record of the Twenty-Fifth International Power Modulator Symposium, 2002 and 2002 High-Voltage Workshop..

[23]  S. Gedney.  An anisotropic perfectly matched layer-absorbing medium for the truncation of FDTD lattices , 1996 .

[24]  Laura Marcu,et al.  Pulse generators for pulsed electric field exposure of biological cells and tissues , 2003 .

[25]  J. Engstrom.  Electrodiagnostic medicine, 2nd edition , 2003 .

[26]  K. Schoenbach,et al.  Nanosecond pulsed electric field (nsPEF) effects on cells and tissues: apoptosis induction and tumor growth inhibition , 2001, PPPS-2001 Pulsed Power Plasma Science 2001. 28th IEEE International Conference on Plasma Science and 13th IEEE International Pulsed Power Conference. Digest of Papers (Cat. No.01CH37251).

[27]  Kenneth S. Cole.  Electric impedance of marine egg membranes , 1937 .

[28]  Allen Taflove,et al.  Computational Electrodynamics the Finite-Difference Time-Domain Method , 1995 .

[29]  U. Zimmermann,et al.  Electrical breakdown, electropermeabilization and electrofusion. , 1986, Reviews of physiology, biochemistry and pharmacology.

[30]  James C. Weaver,et al.  Electroporation of cells and tissues , 2000 .