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theses

The main theme of this dissertation is to investigate the effects of electric field on biological cells and tissue. This highly multidisciplinary research involves the fields of electrohydrodynamics, cell mechanics, drug delivery, high-throughput signal/image processing, and design and development of medical devices. In the first part of this study, electrodeformation-relaxation is utilized to bring forth new insights to mechanical properties of biological cells. Electrodeformation is a contact-free and label-free method, and has high-throughput capability to simultaneously characterize a large cell population in a relatively short time. It is found that mechanical properties of cells display different characteristics depending on the pulse duration. Two distinctive regimes were discovered: in the first relaxation durations are proportional to pulsing duration, which corresponds to soft glass rheology (SGR); in the second, they are independent, which is consistent with the worm-like-chain (WLC) regime. A quantification of the “naïve” cell mechanical properties is only possible in the latter. In the second and third parts of this dissertation, electroporation, a technique popular in the fields of drug/gene delivery, is studied both on the cellular and tissue levels. In Part 2, we conducted a series of two-pulse electroporation experiments at the cellular level, focusing on the delivery efficiency of two different-sized molecules using different pulsing parameters. We further systematically studied the effect of delay times between pulses on the delivery efficiency. Using an alternating-current (AC) first pulse to porate the membrane, and a direct-current (DC) second pulse for transport, we were able to probe resealing dynamics over timescales ranging from milliseconds to minutes. We found for these cells and pulsing parameters electroporation-mediated delivery scaled with the logarithm of the delay time regardless of the molecule size, and 50% of resealing happened in the first 100 ms after pulsation. However, complete resealing took hundreds of seconds. This result may unify the inconsistent membrane resealing times reported in the literature for different experiments. In Part 3, at the tissue level, we have developed an electroporation device to improve targeted transdermal gene transfection. The feasibility and mass production capability of electroporation chips have been demonstrated by upgrading and revising the design and assembly approach. These micro-electrode-based devices have been extensively tested on animals (rats) to demonstrate efficacies on gene expression.

ETD_10381

Ph.D.

Includes bibliographical references

doi:10.7282/t3-39kr-fj60

ETD doctoral

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