Work

Droplet-Based Evaporative System for the Estimation of Protein Crystallization Kinetics

Year: 2021

Type: article

Abstract: Crystallization is a potential cost-effective alternative to chromatography for the purification of biotherapeutic proteins. Crystallization kinetics are required for the design and control of such processes, but only a limited quantity of proteins is available during the initial stage of process development. This article describes the design of a droplet-based evaporative system for the evaluation of candidate crystallization conditions and the estimation of kinetics using only a droplet (on the order of μL) of protein solution. The temperature and humidity of air fed to a flow cell containing the droplet are controlled for evaporation and rehydration of the droplet, which are used for manipulating supersaturation. Dual-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. The estimated kinetics are suitable for the model-based design and control of protein crystallization processes.

Source: Crystal Growth & Design

DOI: 10.1021/acs.cgd.1c00231

Authors: Moo Sun Hong, Amos E. Lu, Jaehan Bae, Jong Min Lee, Richard D. Braatz

Institutions: Massachusetts Institute of Technology, Seoul National University

Language: English

Topic: Crystallization and Solubility Studies

Subfield: Materials Chemistry

Field: Materials Science

Domain: Physical Sciences

Open Access status: hybrid

Estimated APC paid: $5,000

Funder: Bill and Melinda Gates Foundation