| The field of microfluidics has grown steadily over the last decade and a half, due in part to the large variety of applications for manipulating fluids in nanoliter volumes. Specifically for biomedical engineering, microfluidics has been employed for creating small, well-controlled microenvironments for reliable analysis of small populations of cells. Thus, a thoughtfully designed microfluidic device can be extremely powerful toward assaying various cell functions, including the analysis of the cellular secretome. The focus of this thesis involves creating precisely engineered microfluidic devices to analyze small cell populations contained within carefully considered geometries.;By integrating biosensors (electrochemical and optical) with these cellular microenvironments, we can achieve near real-time quantitative analysis of cell-secreted products in response to external stimuli. Combined with computational modeling techniques, we can calculate secretion rates for these products. Moreover, these microenvironments can also serve protective functions and toggle cellular communication, yielding novel information and insights into cellular responses. Through series of experiments such as these, we can develop novel methods for addressing and manipulating cell performance, especially in the context of disease or cellular dysfunction.;My work involved microfluidic device design, prototyping, fabrication, and testing to obtain meaningful, quantitative results based on cellular function. Chapter 2 describes a microfluidic device capable of detecting two pro-inflammatory cytokines from cells. In Chapter 3, a reconfigurable microfluidic device was designed to protect cells while regenerating a sensor surface. Chapter 4 describes a microfluidic co-culture of liver cells, monitoring the paracrine interactions between hepatocytes and stellate cells. Chapter 5 reports on the detection of cell-secreted cytokines, analyzed in a reconfigurable device facilitating intercellular communication. In chapter 6, a microfluidic device with integrated valves was designed to assay cellular response to a predictably evolving chemical gradient.;These devices with their disparate applications have produced a variety of interesting results pertaining to cellular function and intercellular communication. To this end, future work may be useful for shedding insights into disease pathogenesis and treatment, especially in terms of quantifying dose-dependent responses. |
