Microfluidic synthesis, characterization, and applications of bioinspired deformable microparticles

Abstract

Polymeric microparticles have a wide variety of uses, ranging from traditional applications in paints and coatings, to specialized applications in medical therapeutics and diagnostics. For biological applications - including drug delivery, analytical assays, and tissue engineering - it is important to tailor the interactions between the microparticles and their external environment. To do this, it is necessary to precisely control the physical and chemical properties of the engineered microparticles. Recently, it has become apparent that in addition to particle chemistry, the physical properties of a particle - for example, size, shape, internal structure, and mechanical deformability - play an important role in determining particle behaviour in biological environments. However, it remains largely unknown exactly how these various physical properties influence particle behaviour and function, and how these properties should be exploited for different applications. This thesis focuses on the development and characterization of polymeric hydrogel microparticles with well-controlled physical and chemical properties, and shows several applications of these custom microparticles. In particular, we explore particle motifs inspired by biological entities, designing particles with different shapes, internal structure, and mechanical deformability, functionalized with proteins and nucleic acids. We employ microfluidic tools for synthesis and characterization of these hydrogel microparticles, and also investigate the interaction of functionalized particles with nucleic acids and cells, in the context of biomolecule detection and specific cell capture, respectively. Based on the microfluidic particle synthesis technique, stop flow lithography, we fabricate custom particles - including non-spherical 3D capsules and 2D extruded cylindrical rings with systematically varied internal architecture. We design microfluidic channels to study the flow and deformation of these particles, investigating the effects of internal structure, size, and stiffness on passage through microfluidic constrictions. We expand on this work, designing a microfluidic platform to specifically position particles in hydrodynamic traps, based on particle physical properties. This platform enables subsequent encapsulation of immobilized particles in monodisperse, isolated aqueous droplets. We demonstrate the platform's utility with chemically functionalized microparticles enabling sensitive, multiplexed microRNA detection. To further explore the interactions of functionalized microparticles with biological systems, we study how antibody-functionalized microparticles of varying shape can capture specific cells for future diagnostic applications.