Development of droplet microfluidic platforms for the synthesis of monodisperse lipid vesicles and polymer particles

This body of work presents my approaches to the design and development of microfluidic platforms for synthesizing monodisperse polymer particles and phospholipid vesicles. There is interest in both of these particles for use in a variety of biomedical applications. Poly(D,L-lactide-co-glycolic acid) (PLGA) particles in particular have been sought out as vehicles for drug delivery due to their biocompatibility and because the rate of degradation -- hence cargo release - can be controlled. On the other hand, liposomes possess membrane structures resembling that of cells, an ability to adopt both hydrophilic and hydrophobic molecules, and are easily functionalized, which make lipid vesicles the ideal candidate for applications ranging from targeted therapeutic delivery to formation of artificial cells. However, current methods of production for both of these particles result in a wide range of sizes and poor cargo uptake efficiency. We address these challenges by utilizing a flow focusing droplet generation design, which allows for fine control over droplet size and improves encapsulation efficiencies. The size of these droplets can be determined by channel geometry and the ratio of fluid flow rates.I will discuss the work I have done to improve upon current technologies to form nano- to micrometer sized PLGA particles and cell-sized lipid vesicles. Solvent evaporation and solvent extraction methods were implemented and tested in several device designs to optimize the formation process. The particles produced were characterized for their stability, size variation, and ability to encapsulate a model drug. The release profiles of PLGA particles were also measured to determine the length of delivery. In addition, I worked on the generation of monodisperse lipid vesicles to investigate the application of liposomes as an artificial cell. As a proof of principle, expression of green fluorescent protein (GFP) was successfully carried out in the lipid vesicles. This demonstrates the versatility of the microfluidic device for generating a range of particles of controlled size for therapeutic agent delivery and artificial cell applications.