Microfluidic systems and analytical tools for genetic screening, optogenetics, and neuroimaging of C. elegans
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This thesis seeks to address the critical bottlenecks of current technologies that have slowed the neuroscience research in C. elegans. The objective of this research is to enhance the currently developed systems through the design and construction of simple microdevices and quantitative analytical tools for high-throughput phenotyping C. elegans to investigate functions of nervous systems. First, we developed and used the integrated system combining user-friendly single-layer microfluidics and quantitative analytical tools to study the genetic regulation of target gene expression. We found several putative mutants based on large-scale screens, which would have previously been too labor-intensive to attempt. Second, we developed a simple mathematical model that describes the regulation of a target gene expression. Using the model developed, we simulated phenotypical space of hypothetical mutants to suggest plausible genetic pathways some isolated mutants may affect. Lastly, we developed a high-density multichannel device for rapid trapping, parallel selective stimulating, long-term culturing, and (often repeatedly). We used this integrated system to study the neurodegenerative process based on selective ablation of multiple animals using an optogenetic tool, which would have been taken at least 1 order of magnitude longer. Taken together, we expect that these developments will greatly facilitate a broad range of fundamental, and application studies including aging, neurodegeneration, circuit and behavior.