Continuous and Forced Dynamic Operation to Achieve  Kinetically Controlled Crystallization

Crislip, Jacob

Etd

Continuous and Forced Dynamic Operation to Achieve Kinetically Controlled Crystallization

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Crystallization is a vital step in nearly every field of chemical manufacturing including production of refinery catalysts, isolation of active pharmaceutical ingredients, and purification of specialty materials. While centuries of research have defined what crystals are down to the atomic level, the field continues to be challenged by the fundamental questions of what physical and chemical pathways occur during synthesis, why certain morphologies are favored over others, and how these processes and properties can be controlled. In particular, the common thread in each of these barriers is the ambiguity in scaling relationships from the formation of a single crystal to the macroscopic behavior throughout the body of the crystallizer. This work answers each of these questions through the lens of reaction engineering by transforming the way crystallization is performed. Rather than synthesizing individual batches that are prone to nonuniform internal conditions, the cutting-edge reactor designs described herein demonstrate how highly reproducible crystals can be made continuously using segmented flow microfluidics. Each self-contained microdroplet acts as a mobile batch reactor whose temperature can be rapidly and isothermally changed by virtue of fast heat and mass transfer at the minimized length scale. These near step changes in reaction environment unlock operating regimes that would otherwise be impossible. Quickly oscillating between hot and cold environments prevents the system from reaching equilibrium, and this work proves through population balance modeling that operating within this kinetically limited window facilitates the inverse ripening of seed crystals into highly monodisperse fine crystallites. This approach to continuous bottom-up crystallization substitutes the numerous unit operations typically required in traditional crystallizers for an elegant continuous reactor design that eliminates wasted material and excessive solvents.

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