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Randhawa, Avineet

University of British Columbia

The microfluidic organ-on-chip platform exhibits promise for helping bridge the in vitro-in vivo gap through incorporating key elements of the in vivo microenvironment absent in traditional cell culture models. A prime example of such an element is fluid flow; tissues and their constituent cells are sensitive to a myriad of environmental stimuli, one of which is the mechanical forces that arise from wall shear stress exerted by these fluids. The work reported in the following thesis is focused on the small airways of the human lung and, particularly, how a microfluidic model of this physiology can be used in the study of aerosol exposure. Beginning with more traditional and well-established methods for the study of aerosol exposure in vitro, an aerosol generation apparatus was designed and employed to extract a panel of aerosols into solution for the assessment of cytotoxicity induced upon exposure in an airway epithelial cell line. A PDMS-based microfluidic small-airway-on-chip was, then, designed based on models reported in literature with optimizations included to balance physiological mimicry with established in vitro culture yields. A recirculating flow regime was developed, which enabled the application of wall-shear-stresses in ranges experienced by airway epithelia in vivo while minimizing consumption of reagents and maintaining the presence of excreted factors and chemokines. The microfluidic design and operating protocols were validated using both functional assays (permeability, inflammatory mediator release) and morphological features (F-actin localization). The small-airway-on-chip was, then, deployed in a novel experiment comprising the exposure of airway epithelium to aerosol generated from burnt wood at a dynamic ALI. Finally, an emerging method for characterization was explored: future applications of the silicon photonics platform to potential sensing and detection of biomolecules secreted by cells residing in organs-on-chip. Proof of concept experiments demonstrating the detection of recombinant interleukin 8 in buffer at natively expressed concentrations in vitro were performed.

Text

2022-10-19

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/82922

Biomedical Engineering

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/