Microfluidics for translating multifunctional nanomaterials
Sei, Yoshitaka John
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Conflicting results between benchtop experiments, animal models, and clinical trials have posed a significant challenge in translational medical research, motivating the development of technologies with which to assess and screen experimental therapeutics. Among these new technologies are microfluidic platforms that allow for the synthesis of nanoparticles and the tuning of microenvironments to replicate the ideal physiological conditions to study living responses in vitro. The advantages of using microfluidic technologies in order to accomplish these feats are attributed to volumetrically minimal usage of expensive reagents while also having the capacity to be run continuously for high-throughput and large-scale applications. Some of the challenges still associated to the general adoption of microfluidic technologies are those typically found in the early stages of new technological advancements: (1) a lack of standardization in work flow and platform design, and (2) a limited accessibility to specialized equipment. This thesis focuses on contributing to the standardization of the microfluidic workflow through exploring both platform designs for the synthesis and screening of nanoparticles, and exploring key translational questions with experiments that are uniquely enabled with microfluidics. The microfluidic platforms that are presented in this work are a mixer for nanoparticle synthesis and a monitor for the permeability of a cellular monolayer. These platforms were implemented in experiments studying the functionality of high-density lipoprotein mimetic nanoparticles and their interactions with endothelial cells within the context of cardiovascular disease. We report how the functionality of the high-density lipoprotein mimetic nanoparticles is affected by its protein composition, and how its interactions with the endothelial monolayer are modulated depending on the oscillatory flow stimulated inflammatory condition of the endothelial cells.