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dc.contributor.advisorJames C. Weaver.en_US
dc.contributor.authorSmith, Kyle Christopheren_US
dc.contributor.otherHarvard University--MIT Division of Health Sciences and Technology.en_US
dc.date.accessioned2011-05-23T18:15:20Z
dc.date.available2011-05-23T18:15:20Z
dc.date.issued2011en_US
dc.identifier.urihttp://hdl.handle.net/1721.1/63085
dc.descriptionThesis (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.descriptionIncludes bibliographical references.en_US
dc.description.abstractBiological 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.statementofresponsibilityby Kyle Christopher Smith.en_US
dc.format.extent292 p.en_US
dc.language.isoengen_US
dc.publisherMassachusetts Institute of Technologyen_US
dc.rightsM.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.urihttp://dspace.mit.edu/handle/1721.1/7582en_US
dc.subjectHarvard University--MIT Division of Health Sciences and Technology.en_US
dc.titleA unified model of electroporation and molecular transporten_US
dc.typeThesisen_US
dc.description.degreePh.D.en_US
dc.contributor.departmentHarvard University--MIT Division of Health Sciences and Technology
dc.identifier.oclc725958797en_US


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