化学
洗脱
吸附
色谱法
离子交换
胶粒
离子色谱法
胶体
粒子(生态学)
离子
有机化学
海洋学
地质学
作者
Till Briskot,Tobias Hahn,Thiemo Huuk,Gang Wang,Simon Kluters,Joey Studts,Felix Wittkopp,Johannes Winderl,Peter Schwan,Isabell Hagemann,Klaus Kaiser,Anja Trapp,Serge M. Stamm,Jadranka Koehn,Gunnar Malmquist,Jürgen Hubbuch
标识
DOI:10.1016/j.chroma.2021.462439
摘要
• A kinetic model of protein adsorption on ion exchange media was derived. • The model is able to capture complex elution profiles in preparative CEX processes. • The formation of a peak shoulder can be observed at high protein load densities. • The shoulder is formed during salt and pH gradient elution and on different CEX media. A fundamental understanding of the protein retention mechanism in preparative ion exchange (IEX) chromatography columns is essential for a model-based process development approach. For the past three decades, the mechanistic description of protein retention has been based predominantly on the steric mass action (SMA) model. In recent years, however, retention profiles of proteins have been reported more frequently for preparative processes that are not consistent with the mechanistic understanding relying on the SMA model. In this work, complex elution behavior of proteins in preparative IEX processes is analyzed using a colloidal particle adsorption (CPA) model. The CPA model is found to be capable of reproducing elution profiles that cannot be described by the traditional SMA model. According to the CPA model, the reported complex behavior can be ascribed to a strong compression and concentration of the elution front in the lower unsaturated part of the chromatography column. As the unsaturated part of the column decreases with increasing protein load density, exceeding a critical load density can lead to the formation of a shoulder in the peak front. The general applicability of the model in describing preparative IEX processes is demonstrated using several industrial case studies including multiple monoclonal antibodies on different IEX adsorber systems. In this context, the work covers both salt controlled and pH-controlled protein elution.
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