Modeling of electroporation mediated molecular delivery

In electroporation, electric fields are used to transiently permeabilize the cellular membrane to facilitate molecular exchange. This technique is extensively employed to deliver biologically active molecules into the cell compartment, to perform a variety of tasks such as electrochemotherapy and directed stem-cell differentiation. Despite its great potential and broad applications, electroporation still suffers from low delivery efficiency and/or significant cell death, in part due to a lack of fundamental understanding and quantitative prediction tools for the complex processes involved. The aim of this dissertation is to overcome these limitations by providing the much need capabilities. We have developed the first spatially- and temporally-resolved numerical model to predict molecular transport via electroporation. The model framework is used to study the delivery of small molecules such as calcium and propidium iodide. The results are compared directly with experimental data in the literature, and reveal that electrophoresis, not diffusion, is the dominant model of delivery. Furthermore, the maximum achievable concentration within the cell is reciprocally correlated with the extracellular electrical conductivity. This behavior is mediated by an electrokinetic mechanism known as field- amplified sample stacking. Based on the simulation, we have also developed a compact model to predict delivery with a simple formula. This formula can be conveniently used in place of the complex full-model simulation. This dissertation contributes to the field by generating predictions that are previously not available, identifying mechanisms for the underlying physical processes, and providing a high-fidelity optimization tool. The results offered are currently utilized to improve and optimize eletroporation as a promising cell-manipulation technique.Ph. D.Includes bibliographical referencesIncludes vitaby Jianbo L