(182a) Design and Control of Novel Droplet-Based System for Estimating Protein Crystallization Kinetics
AIChE Annual Meeting
Monday, November 8, 2021 - 3:30pm to 3:45pm
Crystallization technology for large-molecule therapeutic proteins is much less mature than for small molecules and is mostly still in research and development other than a few isolated products [1,3,6,7]. Protein crystallization is mainly studied by micro-batch scale protein crystallization experiments, focused on high-throughput protein crystallization screening. Few studies consider operation at the production scale. Crystallization kinetics are required for the design and control of such process but only a limited quantity of protein is available during the initial stage of process development.
This presentation describes the design of a droplet-based evaporative system for the evaluation of candidate crystallization conditions and the estimation of kinetics using only a minimum quantity of protein. The temperature and humidity of air are controlled for evaporation and rehydration of the droplet, which are used for manipulating supersaturation. Multi-angle images of the droplet are taken and analyzed on-line to obtain the droplet volume and crystal sizes. Crystallization kinetics are estimated based on a first-principles process model and experimental data. Tight control of temperature and humidity of the air, fast and accurate image analysis, and accurate estimation of crystallization kinetics are experimentally demonstrated for a model protein lysozyme.
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