| This dissertation presents a set of microfluidic devices and a mode of operation to advance droplet-based microfluidics for applications in site-specific therapeutics. Droplet microfluidic technology offers superior monodispersity and control of the emulsion relative to conventional means of production, yet is commonly viewed as unviable as a bulk manufacturing technique owing to low rates of generation. In response, this body of work focuses on methods to generate droplets and microbubbles in quantities suitable for the clinical scale. First, a multiarray microfluidic module is used to produce dual-layer microbubbles with the capacity to carry lipophilic chemotherapeutics. Production from eight flow-focusing orifices reached 1.34 x 105 Hz, at microbubble diameters ~ 20 μm, demonstrating that scale-up for high output production of multilayer bubbles is possible while maintaining consistency in size. Second, this work examines three modes of droplet formation, and uses dripping in a single droplet generator to generate highly monodisperse droplets of liquid perfluoropentane at rates exceeding 105 Hz. These volatile droplets are stable for weeks at room temperature yet undergo rapid liquid-to-gas phase transition above a uniform activation threshold. The opportunity exists to potentiate locoregional cancer therapies using thermal or acoustic vaporization of these droplets for gas embolotherapy. An approach for more general applications is thirdly developed, combining microfluidic scale-up with dripping to generate droplets ~ 10 ?m in diameter at rates in the hundreds of kilohertz. Generation in the parallel module exceeded 3.69 x 105 Hz at a mean diameter of 9.8 μm, improving upon past shear-based scale-up systems by one to two orders of magnitude in terms of droplet size and generation frequency. Lastly, a hand-controlled pressure pumping system provides means to form droplet streams at low cost. This system is used in a series of exercises to instruct in the art of droplet formation, including the dripping and jetting modes, with additional implications for creating droplets in the field or at point-of-care. |
