Numerical Assessments of Subcellular Electroporation Driven by Ultrashort Electric Pulses

The field of electroporation has risen to prominence in recent years as a new technique useful for a wide array of biomedical applications, including electro- chemotherapy. Accurate and rapid simulation of the occurrence and effects of the electroporation (EP) are necessary for the continued advancement of this field as it moves towards larger experimental trials. Most simulations of electric field driven bioeffects have considered spherical cellular geometries or probed symmetrical structures for simplicity. Furthermore, EP studies have tended to focus mostly on the outer cell membrane. This thesis presents quantitative predictions and simulation-based assessments of cellular transmembrane potential build-up and electroporation in a Jurkat cell, which is non-spherical in nature. It also includes potential EP processes at the endoplasmic reticulum (ER) and mitochondria, both of which have complex shapes, in response to external nanosecond electric pulses. The simulations are based on a time-domain nodal analysis that incorporates membrane poration utilizing the Smoluchowski model with angular-dependent changes in membrane conductivity. Consistent with prior experimental reports, the simulations show that the ER requires the largest electric field for electroporation, while the inner mitochondrial membrane (IMM) is the easiest membrane to porate. Repeated pulsing and/or using multiple electrodes are shown to create a stronger poration. The roles of mutual coupling, screening, and proximity effects in bringing about electric field modifications are also probed.