Microbioreactors with controlled perfusive and adhesive microenvironment for on -chip cellular studies.
Zhu, Xiaoyue
2005
Abstract
Recent advances in micro- and nanotechnologies coupled with the need in biology and medicine to perform cellular scale studies and productions have led to the emergence of a variety of microscale biological reaction systems. These microbioreactors are promising as low cost modules for optimizing bioproduction processes, highly parallel analytical platforms for screening pharmaceutical drugs, therapeutic implements for treating disorders and deficiencies, and examination tools for exploring basic physiological responses and biological reactions. This thesis summarizes the concepts, designs and applications of two important microbioreactor components with a special focus on medical pharmaceutical and cell biological applications. First, a passive gravity-driven fluidic pumping system was developed and evaluated. This gravity-driven pump was shown to effectively generate spatial-temporal patterns of chemical gradients, maintain perfusion cell culture, assay drug toxicity, and sort motile sperm from non-motile sperm in semen from patients undergoing infertility treatment. An active pumping and valving mechanism has been achieved by locally deforming microfluidic channels using computerized Braille-pins. Second, a reconfigurable protein matrix was developed and used to reversibly control cell morphology and enable the study of transient cellular responses. Arrays of micro and nanometer width protein lines were patterned on elastic polymer surfaces by cracking. Reversibly stretching and relaxing the rubbery material widened and narrowed the width of the protein patterns, which in turn triggered dynamic cell morphogenic alterations. A three-dimensional reconfigurable protein matrix created arrays of square-shaped cells that span the width of microstructures/microchannels. These surface patterning works are compatible with a wide range of microbioreactor platforms dedicated to cell cultures and assays. The needs to obtain more physiologically-related cellular responses from <italic> in vitro</italic> culture conditions and develop innovative methods and assays to regulate and examine cells continuously drive the development of novel tools. This thesis demonstrates the application of microfluidic pumps and surface adhesive patterns to regulate cell responses. The two techniques are noteworthy and especially useful in their ability to dynamically regulate the cell environment. The experimental simplicity, low cost, unique regulatory capabilities, and potential for integration with other microchip components and systems make these techniques promising for cell culture and assays on microchips. It is also promising for broad use in pharmaceutical, medical, clinical, and biological fields.Subjects
Adhesive Cellular Controlled Microbioreactors Microenvironment On-chip Perfusive Studies
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