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Complex Microparticle Fabrication Using Optical Transient Liquid Molding and Cell Microcarriers

Abstract

There is need of applications of microparticles in various fields including tissue engineering, biosensing, photonic crystal, and drug delivery. It has been proven that porosity control using microparticles enhances wound healing while anisotropically-shaped microparticles are utilized for different types of Lab-on-a-Chip technologies. Ability of 3D shaping in microparticle fabrication plays a crucial role to not only improve the performance of current technologies but also create novel applications. Conventionally microparticles are fabricated using droplet generator, 3D printing, and stop flow lithography. However, it is challenging for droplet generator to produce asymmetric microparticles as 3D printing generates designed structure in a relatively slow speed. Stop flow lithography is operated in an intermediate speed to create 2D-extruded microparticles. 3D shaping microparticles in high throughput manner is highly demanded and promising for next-generation microparticle systems. In this dissertation, we briefly discuss on current microfluidics-assisted microparticle fabrications and applications, show our ability to control flow shape of photo-crosslinkable polymer precursor in the out-of-plane direction using inertial flow engineering, demonstrate a novel manufacturing system of 3D-shaped microparticle based on inertial flow engineering, and present an innovative cell microcarriers synthesized using high throughput version of the system for advancing cellular studies. First, we provide three cases of microparticle fabrications and applications to show the significance of “microfluidically-fabricated materials” in the modern bioengineering fields. Secondly, we create “fundamental inertial flow transformations” of a flow stream in a co-flow experimentally and theoretically, showing that inertial flow engineering can generate increased complexity and asymmetry on micro-scale photolinkable polymer precursor. Third, “optical transient liquid molding” is introduced to be the core of a novel manufacturing system, which generates microparticles with shape of intersection of two 2D patterns by engineering inertial flows of photo-crosslinkable polymer precursor. Finally, we designed, manufactured, and characterized “cell microcarriers” with shape of intersection of a dumbbell and a slit with notches. We further develop a new version of optical transient liquid molding with high production rate for repeated biological experiments. The microcarrier system is demonstrated to be an innovative cell-culture platform, where the high-speed cell imaging and analysis can be achieved without bringing cells away from adherent status. To sum up, the integration of optical transient liquid molding and inertial flow engineering creates a new domain of microparticles with complexly asymmetrical shape, allowing wide applications including a new paradigm of cell culture using cell microcarriers.

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