| This thesis describes the use of microfluidics for studying the worm Caenorhabditis elegans, a popular model organism in modern biology. Chapter 1 discusses the potential value of C. elegans as a model organism for chemists studying living systems, and how the worm could be used to connect molecular-level details to organism-level phenotypes. The chapter provides an overview of chemically-relevant research with C. elegans, and reviews chemical, physical, and biological tools that are available for studying the worm. In addition, this chapter provides an overview of C. elegans biology, and highlights similarities and differences between worms and humans. Chapters 2, 3, and 4 describe specific microfluidic devices for studying the worm. The general characteristics of these devices are that they (i) enable the physical manipulation and observation of many worms in parallel, (ii) create well-defined, and tunable, chemical and physical environments for the worm, and (iii) are compatible with the application of a broad range of stimuli. Chapter 2 describes a device containing an array of 128 worm clamps---tapered microfluidic channels, which physically immobilize live worms for high-resolution imaging and laser-mediated microsurgery. Chapter 3 describes the maintenance of worms inside a microfluidic device for their entire adult lifespans. This device enabled the observation and characterization of age-related changes in locomotory behavior and body size. Chapter 4 describes a method of measuring the toxicity of compounds to C. elegans in a microfluidic device using locomotion as the endpoint of the toxicity assay. This chapter describes the potential use of C. elegans as an inexpensive model organism for testing the toxicity of putative environmental toxins and candidate drugs. The Appendices present work related to the theme of developing microfluidic and microfabricatcd tools for studying biological systems. Appendix A describes a microfluidic device for directing the motion of swimming cells of Escherichia coli . Appendix B describes a method for fabricating valves that are easily inserted into microfluidic devices. The microfluidic device described in Chapter 3 employs these valves to control and direct flow. |
