Analysis of monodisperse microfluidic droplet generation and its biochemical applications

Abstract

Droplet fluidic systems have dramatically improved precision in many applications, such as polymerase chain reaction, biochemical analysis, and particle synthesis in which accurate control of sample volume plays a significant role. Despite the well-understood physics of squeezing regime droplet formation in two-phase flow systems, the long-sought-after goal of generating identical, equal size droplets is challenging. Although the individual parameters that affect the droplet size were identified as channel dimension, wettability, viscosity, and flow rate or pressure ratio of the two immiscible fluids, the governing mechanism of droplet size variation is not completely analyzed. More importantly, the limit of monodispersity for droplet generation systems is still unknown. This is due to the difficulty in analytical modeling of droplet formation that is usually compensated by experimental approaches, which fall short in leading to universal conclusions. In this thesis, depending on the flow source used for driving fluids we present an analytical approach that takes into account all the system dynamics and internal and external factors that disturb monodispersity. We use the analogy between fluidic and electrical circuits to analyze the factors that influence droplet monodispersity. Interestingly, we enable to model the dynamics of a segmented two-phase flow system using a single-phase flow analogy, electron flow, in electrical circuits. Doing so, we reveal the sources of disturbances that lead to variation in droplet volume. We offered a unique solution and designed guidelines to ensure ultramonodisperse droplet generation. Our analytical conclusions are experimentally verified using a T-junction and flow-focusing droplet generator design driven by a pressure supply. Equally importantly, we show the limiting experimental factors for reaching the theoretical maximum of monodispersity. For the displacement pump case, we propose a more effective and widely applicable solution to improve flow stability, by controlling off-chip compliances to minimize fluctuations due to the flow source. Eventually, we compare the performance of the two common drive units (pressure-driven and displacement pump) in terms of droplet monodispersity, while using our proposed methods and guidelines. Finally, we did study in reaction kinetics of poly dopamine and hydrogen peroxide and synthesize silica and polyethylene glycol (PEG) particles and supramolecular polymer capsules with high monodispersity using ultra-monodisperse droplets.