Electric field modulation in tissue electroporation with electrolytic and non-electrolytic additives Antoni Ivorra ⁎ , Boris Rubinsky Department of Bioengineering, University of California at Berkeley, California, Berkeley, CA 94720, USA Department of Mechanical Engineering, University of California at Berkeley, California, Berkeley, CA 94720, USA Received 6 September 2006; received in revised form 10 January 2007; accepted 6 February 2007 Available online 13 February 2007 Abstract Electroporation, cell membrane permeabilization with short electrical field pulses, is used in tissue for in vivo gene therapy, drug therapy and minimally invasive tissue ablation. For the electroporation to be successful, the electrical field that develops during the application of the pulses needs to be precisely controlled. In this study we investigate the use of electrolytic and non-electrolytic gels to generate the precise electrical fields required for controlled electroporation, in heterogeneous and irregular tissues, in vivo. Finite element computer simulations are used to illustrate various applications, such as the treatment of irregularly shaped organs and interior cavities. The feasibility of the concept is demonstrated experimentally in vivo with a rat liver subjected to irreversible electroporation. © 2007 Elsevier B.V. All rights reserved. Keywords: Electroporation; Electropermeabilization; Electrolytic gel; Gene therapy; Irreversible electroporation 1. Introduction Electroporation, or electropermeabilization, is the phenomenon in which cell membrane permeability to ions and macromolecules is increased by exposing the cell to short (microsecond to millisecond) high electric field pulses [1]. Reversible electropora- tion of living tissues is the basis for different therapeutic maneuvers on clinical use or under study [2]: in vivo introduction of genes into cells (electrogenetherapy) [3–5], introduction of anti-cancer drugs into undesirable cells (electro-chemotherapy) [6] and introduction of photosensitizers into tumor cells for photodynamic therapy [7]. Irreversible electroporation has also found a use in tissues as a minimally invasive surgical procedure to ablate undesirable tissue without the use of adjuvant agents [8–10]. Electroporation is a dynamic phenomenon that depends on the local transmembrane voltage at each cell membrane point. It is generally accepted that for a given pulse duration and shape, a specific transmembrane voltage threshold exists for the manifes- tation of the electroporation phenomenon (from 0.5 V to 1 V). This leads to the definition of an electric field magnitude threshold for electroporation (E th ). That is, only the cells within areas where E ≥ E th are electroporated. If a second threshold (E th _ irr ) is reached or surpassed, electroporation will compromise the viability of the cells, i.e., irreversible electroporation. It is obvious, from the above, that precise control over the electric field that develops in tissues is important for electroporation therapies [11–14]. For instance, in reversible electroporation it is desirable to generate a homogeneous electric field (E th ≤ E b E th_irr ) in the region of interest and a null electric field in the regions not to be treated. Currently, optimization of the electric field distribution during electro- poration is done through design of optimal electrode setups [15]. However, there are situations in which an electrode setup alone is not sufficient for obtaining an optimal electrical field, particularly in situations such as the electroporation of irregularly shaped tissues or when the protection of specific tissue regions is required. Here we propose and investigate the use of additives for modulating the electric properties of the treated tissues or for modifying the geometry of tissues or electrodes as a means of optimizing the electric field during tissue electroporation. As an Bioelectrochemistry 70 (2007) 551 – 560 www.elsevier.com/locate/bioelechem ⁎ Corresponding author. Department of Bioengineering and Department of Mechanical Engineering, University of California at Berkeley, Berkeley, CA 94720, USA. Tel./fax: +1 510 643 1866. E-mail address: antoni.ivorra@gmail.com (A. Ivorra). 1567-5394/$ - see front matter © 2007 Elsevier B.V. All rights reserved. doi:10.1016/j.bioelechem.2007.02.001