A moving contact line is the idealized line of intersection between two immiscible fluids as one displaces the other along a solid boundary. The displacement process has been the subject of a large amount of theoretical and experimental research; however, the fundamental processes that govern contact line motion are still unknown. The challenge from an experimental perspective is to make measurements with high enough resolution to validate competing theories. An experimental method has been developed to simultaneously measure interface motion, dynamic contact angles, and local fluid velocity fields using micron-resolution Particle Image Velocimetry (µPIV). Capillary numbers range from 1.7 x 10^(⁻⁴) to 6.2 x 10^(⁻⁴). Interface velocities were measured between 1.7 µm/s and 33 µm/s. Dynamic contact angles were manually measured between 1.1 µm and 120 µm from the contact line, and calculated from µPIV data to within several hundred nanometers from the contact line. Fluid velocities were measured over two orders of magnitude closer to the contact line than published values with an increase in resolution of over 3400%. The appearance of a recirculation zone similar to controversial prediction below previously published limits demonstrates the power and significance of the method.

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Many drugs and environmental chemicals, such as antibiotics and chemotherapeutic agents, are nephrotoxic (toxic to the kidney) and are a common cause of acute kidney injury and chronic kidney disease. Conventional tissue models for assessment of drug-induced nephrotoxicity rely on animals or simple cell culture models, which lack tissue characteristics of the human kidney required to accurately predict a drug’s effect in clinical trials. Microfluidic kidney-on-chips can generate tissue with improved human relevance compared to traditional models, however, generally lack high-throughput and multiparametric data collection capabilities for evaluation of nephrotoxic drug exposures. Standard data collection techniques remain limited to fluorescent imaging or colorimetric assays that often focus on single endpoints, are invasive due to the addition of labels, and fail to capture dynamic changes in tissue function. Additionally, conventional toxicological readouts rely on bulk measures of injury, such as cell death, which are less sensitive than sub-lethal changes in cell function and morphology that occur prior to cell death. Due to the challenges above, there is a need for new measurement approaches that enable collection of kinetic, multi-parametric, and sub-lethal readouts of injury in kidney-on-chip systems. In this work, we developed and characterized several measurement approaches for evaluation of tissue function in kidney-on-chip systems and assessment of drug-induced nephrotoxicity. In chapter 2, we developed a novel optical-based oxygen sensing technique for measurement of sub-lethal mitochondrial dysfunction in an array of kidney-on-chips. In chapter 3, we investigated an approach for simultaneous transepithelial electrical resistance (TEER) sensing and flow control to enable near-continuous monitoring of tissue barrier function under different flow conditions. In chapter 4, we demonstrated the use of different data collection modalities, including multiple sensors, fluorescent imaging, and colorimetric-based assays, to generate multi-parametric readouts for evaluation of drug-induced nephrotoxicity in kidney-on-chips. / 2024-05-24T00:00:00Z

Multiphase flow in porous media is important in a wide range of industrial and environmental processes. It is well-known that the fluids’ relative affinity to the porous media (i.e., wettability) is a crucial factor controlling multiphase flow in porous media. Despite having a good understanding of multiphase flow in porous media under uniform wettability conditions, our knowledge of how fluids flow in mixed-wet porous media is more limited. Mixed-wet porous media (i.e., porous media with spatially heterogeneous wettability) is prevalent in nature, from groundwater aquifers to oil-bearing rocks. This Thesis aims to better understand the complexities of multiphase flow in mixed-wet porous media. The study begins with investigating fluid-fluid displacement in mixed-wet microfluidic flow cells. We performed experiments over a range of capillary numbers and mixed-wettability conditions, and our results show that the fluid-fluid interface in mixed-wet pores resembles an S shaped saddle with very low capillary pressure. In the next step, we derive analytical expressions for fluid-fluid interface evolution through mixed-wet pore throats. These analytical expressions are incorporated into a dynamic pore network model, which enables us to develop a numerical framework capable of simulating fluid-fluid displacement in mixed-wet porous media. Next, we leverage our model to simulate multiphase flow in simple mixed-wet porous micro-models consisting of distinct water-wet and oil-wet regions whose fractions are systematically varied to yield a variety of displacement patterns over a wide range of capillary numbers. Our simulations reveal that mixed-wettability impacts are most prominent at low capillary numbers, and it depends on the complex interplay between the wettability fraction and the intrinsic contact angle of the water-wet regions. We also investigate the dynamics of multiphase flow in mixed-wet porous media under quasi-static conditions and discover that it exhibits self-organized criticality (SOC). Finally, we determine the correlation between spatial and temporal aspects of this dynamical system. / Thesis / Doctor of Science (PhD)

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