Optimization of electroporation waveforms for cell sterilization
ABSTRACT Pores occur naturally in cell membranes. Application of an electric field generates a force which tends to open the pore, a mechanism known as electroporation. The force generated depends on the electric field in the pore and the difference in dielectric constant between the fluid in the pore and the membrane. In this paper, we use transient finite-element analysis to investigate the field as a function of time in a system which consists of an electrolyte, an ellipsoidal bacterial cell membrane, and cytoplasm within the cell membrane. For this shape of cell, the field in the cell membrane is caused largely by the relaxation of the field in the cytoplasm. In addition, we compute the force on the pore wall, both in an analytic approximation and numerically as a function of time during a variety of applied voltage waveforms, using transient finite-element analysis. The numerical data are in good agreement with the analytic approximation and provide a basis for judging the efficacy of waveforms for sterilization based on a "figure of merit" which is suggested in the paper.
[show abstract] [hide abstract]
ABSTRACT: The transmembrane potential (TMP) of a cell exposed to harmonic or transient electric fields is the main parameter for a successful permeabilization of a cell. Obviously, TMP can be computed with a finite-element method, but the high contrast between sizes and electromagnetic properties of the cytoplasm, the membrane, and the extra-cellular medium leads sometimes to inaccurate numerical results. Influences of membrane conductivity and frequency on the accuracy are studied. Optimization of transient waveforms is proposed for various shapes of cellsIEEE Transactions on Magnetics 05/2007; · 1.36 Impact Factor
[show abstract] [hide abstract]
ABSTRACT: Electroporation is a method of disrupting the integrity of cell membrane by electric pulses (EPs). Electrical modeling is widely employed to explain and study electroporation, but even most advanced models show limited predictive power. No studies have accounted for the biological consequences of electroporation as a factor that alters the cell's susceptibility to forthcoming EPs. We focused first on the role of EP rate for membrane permeabilization and lethal effects in mammalian cells. The rate was varied from 0.001 to 2,000 Hz while keeping other parameters constant (2 to 3,750 pulses of 60-ns to 9-µs duration, 1.8 to 13.3 kV/cm). The efficiency of all EP treatments was minimal at high rates and started to increase gradually when the rate decreased below a certain value. Although this value ranged widely (0.1-500 Hz), it always corresponded to the overall treatment duration near 10 s. We further found that longer exposures were more efficient irrespective of the EP rate, and that splitting a high-rate EP train in two fractions with 1-5 min delay enhanced the effects severalfold. For varied experimental conditions, EPs triggered a delayed and gradual sensitization to EPs. When a portion of a multi-pulse exposure was delivered to already sensitized cells, the overall effect markedly increased. Because of the sensitization, the lethality in EP-treated cells could be increased from 0 to 90% simply by increasing the exposure duration, or the exposure dose could be reduced twofold without reducing the effect. Many applications of electroporation can benefit from accounting for sensitization, by organizing the exposure either to maximize sensitization (e.g., for sterilization) or, for other applications, to completely or partially avoid it. In particular, harmful side effects of electroporation-based therapies (electrochemotherapy, gene therapies, tumor ablation) include convulsions, pain, heart fibrillation, and thermal damage. Sensitization can potentially be employed to reduce these side effects while preserving or increasing therapeutic efficiency.PLoS ONE 01/2011; 6(2):e17100. · 4.09 Impact Factor