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A unified model of electroporation and molecular transport

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dc.contributor.advisor James C. Weaver. en_US Smith, Kyle Christopher en_US
dc.contributor.other Harvard University--MIT Division of Health Sciences and Technology. en_US 2011-05-23T18:15:20Z 2011-05-23T18:15:20Z 2011 en_US
dc.description Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, February 2011. en_US
dc.description "February 2011." Cataloged from PDF version of thesis. en_US
dc.description Includes bibliographical references. en_US
dc.description.abstract Biological membranes form transient, conductive pores in response to elevated transmembrane voltage, a phenomenon termed electroporation. These pores facilitate electrical and molecular transport across cell membranes that are normally impermeable. By applying pulsed electric fields to cells, electroporation can be used to deliver nucleic acids, drugs, and other molecules into cells, making it a powerful research tool. Because of its widely demonstrated utility for in vitro applications, researchers are increasingly investigating related in vivo clinical applications of electroporation, such as gene delivery, drug delivery, and tissue ablation. In this thesis, we describe a quantitative, mechanistic model of electroporation and concomitant molecular transport that can be used for guiding and interpreting electroporation experiments and applications. The model comprises coupled mathematical descriptions of electrical transport, electrodiffusive molecular transport, and pore dynamics. Where possible, each of these components is independently validated against experimental results in the literature. We determine the response of a discretized cell system to an applied electric pulse by assembling the discretized transport relations into a large system of nonlinear differential equations that is efficiently solved and analyzed with MATLAB. We validate the model by replicating in silico two sets of experiments in the literature that measure electroporation-mediated transport of fluorescent probes. The model predictions of molecular uptake are in excellent agreement with these experimental measurements, for which the applied electric pulses collectively span nearly three orders of magnitude in pulse duration (50 ts -20 ms) and an order of magnitude in pulse magnitude (0.3 -3 kV/cm). The advantages of our theoretical approach are the ability to (1) analyze in silico the same quantities that are measured by experimental studies in vitro, (2) simulate electroporation dynamics that are difficult to assess experimentally, and (3) quickly screen a wide array of electric pulse waveforms for particular applications. We believe that our approach will contribute to a greater understanding of the mechanisms of electroporation and provide an in silico platform for guiding new experiments and applications. en_US
dc.description.statementofresponsibility by Kyle Christopher Smith. en_US
dc.format.extent 292 p. en_US
dc.language.iso eng en_US
dc.publisher Massachusetts Institute of Technology en_US
dc.rights M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. en_US
dc.rights.uri en_US
dc.subject Harvard University--MIT Division of Health Sciences and Technology. en_US
dc.title A unified model of electroporation and molecular transport en_US
dc.type Thesis en_US Ph.D. en_US
dc.contributor.department Harvard University--MIT Division of Health Sciences and Technology. en_US
dc.identifier.oclc 725958797 en_US

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