Chemical and Biomedical Engineering - Theses
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ItemQuantifying interactions between nanoengineered particles and cells( 2018)Nanoengineering has recently emerged as a promising technology for the understanding, treatment, and diagnosis of disease. One of its most compelling potential uses is in the design of particles with controlled interactions with particular cell types. Significant research effort has been devoted to developing particles that exhibit a variety of interesting behaviors, including stealth, targeting, cargo carrying capabilities, or responsiveness to biological environments. In vitro experiments with cultured cells are fundamental to understanding and studying the interface between nanoengineered particles and biological systems. However, partially due to the wide range of physicochemical properties nanomaterials exhibit, quantification and generalization of data from in vitro bio-nano experiments has unique challenges when compared to traditional small-molecule drugs or materials in bulk. As the fields of bio-nano research and nanomedicine have matured, in vitro quantification has become a significant barrier to understanding, characterizing, and comparing newly developed particle systems. This thesis addresses three interrelated areas that are necessary to accurately quantify in vitro interactions between nanoengineered particles and cells. First, particle-dependent variation between the amount of material administered and that which reaches the surface of cells (in vitro dosimetry) is studied. Second, instrument independent quantification of cell-particle association is used to study differences in association induced by labeling and cytometry technique. Third, a theoretical framework to isolate the biological kinetics of association is developed, and is used to compare cell-particle association results from experiments varying in particle type and cell line. Though the primary focus of this thesis is computational, a mixture of experimental, mathematical, and computational strategies are utilized. This thesis addresses three interrelated areas that are necessary to accurately quantify in vitro interactions between nanoengineered particles and cells. First, particle-dependent variation between the amount of material administered and that which reaches the surface of cells (in vitro dosimetry) is studied. Second, instrument independent quantification of cell-particle association is used to study differences in association induced by labeling and cytometry technique. Third, a theoretical framework to isolate the biological kinetics of association is developed, and is used to compare cell-particle association results from experiments varying in particle type and cell line. Though the primary focus of this thesis is computational, a mixture of experimental, mathematical, and computational strategies are utilized.