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Adsorption of colloidal proteins in ion-exchange chromatography under consideration of charge regulation.

Authors
  • Briskot, Till1
  • Hahn, Tobias2
  • Huuk, Thiemo2
  • Hubbuch, Jürgen3
  • 1 GoSilico GmbH, Kaiserstraße 183, Karlsruhe 76133, Germany; Institute of Engineering in Life Sciences, Section IV: Biomolecular Separation Engineering, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 2, Karlsruhe 76131, Germany. , (Germany)
  • 2 GoSilico GmbH, Kaiserstraße 183, Karlsruhe 76133, Germany. , (Germany)
  • 3 Institute of Engineering in Life Sciences, Section IV: Biomolecular Separation Engineering, Karlsruhe Institute of Technology (KIT), Fritz-Haber-Weg 2, Karlsruhe 76131, Germany. Electronic address: [email protected] , (Germany)
Type
Published Article
Journal
Journal of chromatography. A
Publication Date
Oct 09, 2019
Pages
460608–460608
Identifiers
DOI: 10.1016/j.chroma.2019.460608
PMID: 31629491
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Mechanistic modeling of protein adsorption has gained increasing importance in the development of ion-exchange (IEX) chromatography processes. The most common adsorption models use a stoichiometric representation of the adsorption process based on the law of mass action. Despite the importance of these models in model-based development, the stoichiometric representation of the adsorption process is not accurate for the description of long-range electrostatic interactions in IEX chromatography, limiting the application and mechanistic extension of these models. In this work an adsorption model is introduced describing the non-stoichiometric electrostatic interaction in IEX chromatography based on the linear Poisson-Boltzmann equation and a simplified colloidal representation of the protein. In contrast to most recent non-stoichiometric models, the introduced model accounts for charge regulation during the adsorption process. Its capability of describing the adsorption equilibrium is demonstrated by simulating partitioning coefficients of multiple proteins on different adsorber systems as a function of ionic strength and pH. Despite model simplifications the physical meaning and predictive value of the model could be preserved. By transferring model parameters of a monoclonal antibody (mAb) from one adsorber system to another, it could be demonstrated that protein parameters are theoretically not only valid on a specific adsorber system but freely transferable to other adsorbers. The predictive value of the mechanistic model on the new adsorber system was highlighted by predicting the elution behavior of charge variants of the mAb. Copyright © 2019 Elsevier B.V. All rights reserved.

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