Magnetophoretic All-Aqueous Droplet Microfluidics

Abstract

<p>Droplet microfluidics is the science of manipulation of discrete volumes of fluid in the nanoliter to femtolitre range. One of the important applications of droplet microfluidics is cargoencapsulation. The droplets can be loaded with live cells or therapeutics, with applications in single-cell analysis or drug delivery, respectively. </p> <p>The conventional system in droplet microfluidics is water-oil, where droplets of water that encapsulate the cargo are generated in an immiscible phase of oil. Because of the presence of the non-biocompatible oil phase, this traditional two-phase system poses complications for biomedical applications. </p> <p>Over the past decade, aqueous two-phase systems (ATPS) have emerged as an alternative for the conventional water-oil systems. ATPSs are composed of immiscible aqueous solutions of two incompatible polymers or a polymer and a salt. Owing to the aqueous nature of both phases, these systems are biocompatible. </p> <p>In this thesis, I explain the development of a magnetophoretic all-aqueous droplet microfluidic platform by the integration of a commonly used polymeric ATPS and aqueous based ferrofluids—a colloidal suspension of iron oxide nanoparticles. I have applied this platform to two major applications of droplet microfluidics: single-cell analysis and drug delivery. </p> <p>In the first part of my thesis, I show that ATPS droplets can be functionalized with ferrofluid for magnetic droplet manipulation. I show control over droplet manipulation by changing various parameters in the system such as the magnetic field and ferrofluid concentration. Additionally, I modify an existing mathematical model which was previously developed for modeling the deflection of magnetic beads in microfluidics and apply it to my droplet microfluidic system and show a good agreement between the model and the experimental data. </p> <p>Next, I show that by coupling cell-triggered Rayleigh-Plateau instability and diamagnetism in an ATPS droplet microfluidic platform, a pure population of cell-encapsulating droplets can be generated. Such a pure sample of single-cell encapsulating droplets is an essential component of droplet-based single-cell analysis. I generate single-cell encapsulating droplets by passive methods and separate cell-encapsulating droplets from the empty waste droplets by size-based diamagnetic droplet sorting. I show that by changing the magnetic field, the separation efficiency of empty and cell-encapsulating droplets increases, and cells used in such a microfluidic system show a high level of viability. </p> <p>In the last part of my thesis, I use the magnetic droplet microfluidic platform, reported in the first part of the thesis, for the fabrication of magnetic polyelectrolyte microcapsules. Polyelectrolytes are polymers with an electrolyte group. Once dissolved in deionized water, they become charged. Using two oppositely charged polyelectrolytes in the two phases of an ATPS droplet microfluidic system, and by careful tuning of the concentrations, I fabricate magnetic polyelectrolyte microcapsules. Such microcapsules have applications in targeted drug delivery. Therefore, I characterize the delivery profile of these microcapsules using pseudo-drugs with different molecular weights and show triggered release of their cargo by exposing the microcapsules to different stimuli such as osmotic pressure and change in pH. </p> <p>This magnetophoretic all-aqueous droplet microfluidic platform will find applications in single-cell analysis and fabrication of functionalized drug carriers for targeted drug delivery.</p>