Microfluidic Device Technology for Cell and Droplet Sorting, Encapsulation, Storage, and Lysis

Abstract

Microfluidics enables researchers and clinicians to manipulate fluids, particles, and cells at the micron scale, providing a vast array of potential methods for studying cell populations at the single-cell level. In this thesis, I present techniques and methods that improve the use of microfluidics for particle and fluid manipulation by incorporating surface acoustic waves and passive flow techniques for cell sorting, droplet generation, sample encapsulation, cell lysis, and droplet storage. I provide a general overview of surface acoustic waves (SAW) based microfluidic mechanisms for particle manipulation, and present two microfluidic devices using these mechanisms for rapid fluorescence activated cell sorting (FACS). I demonstrate a new technique for droplet generation using SAW and step-emulsification channel geometries. Using this technique, I present a variety of applications such as: the ability to selectively encapsulate samples into droplets upon fluorescent detection, thus eliminating or minimizing the production of empty droplets, or the need to sort droplets based on their contents; the ability to lyse and encapsulate cells, and the ability to inject small volumes of fluids into individual droplets. I also present a microfluidic device that generates and passively stores up to hundreds of water-in-oil droplets, preserving the order in which they are produced. By drawing an analogy between fluid flow and electrical resistance networks, I present a model to determine the geometry of devices that can store a controllable number of droplets. The device may assist microfluidic applications incorporating droplet incubation and long-term observation.