Patterns of protein adsorption in ion-exchange particles and columns: Evolution of protein concentration profiles during load, hold, and wash steps predicted for pore and solid diffusion mechanisms

•Artificial CSLM images to study intraparticle mass transfer effects.•Solid diffusion continues unhindered during hold and wash steps.•Different transport type effects distinct wash out profiles during column adsorption. Elucidation of protein transport mechanism in ion exchanges is essential to mod...

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Bibliographic Details
Published in:Journal of Chromatography A 2021-09, Vol.1653, p.462412, Article 462412
Main Authors: Beck, Jürgen, von Lieres, Eric, Zaghi, Negar, Leweke, Samuel, Carta, Giorgio, Hahn, Rainer
Format: Article
Language:English
Subjects:
Confocal laser scanning microscopy
Ion exchange chromatography
Mechanistic modelling
Pore diffusion
Solid diffusion
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Summary:•Artificial CSLM images to study intraparticle mass transfer effects.•Solid diffusion continues unhindered during hold and wash steps.•Different transport type effects distinct wash out profiles during column adsorption. Elucidation of protein transport mechanism in ion exchanges is essential to model separation performance. In this work we simulate intraparticle adsorption profiles during batch adsorption assuming typical process conditions for pore, solid and parallel diffusion. Artificial confocal laser scanning microscopy images are created to identify apparent differences between the different transport mechanisms. Typical sharp fronts for pore diffusion are characteristic for Langmuir equilibrium constants of KL ≥1. Only at KL = 0.1 and lower, the profiles are smooth and practically indistinguishable from a solid diffusion mechanism. During hold and wash steps, at which the interstitial buffer is removed or exchanged, continuation of diffusion of protein molecules is significant for solid diffusion due to the adsorbed phase concentration driving force. For pore diffusion, protein mobility is considerable at low and moderate binding strength. Only when pore diffusion if completely dominant, and the binding strength is very high, protein mobility is low enough to restrict diffusion out of the particles. Simulation of column operation reveals substantial protein loss when operating conditions are not adjusted appropriately.
ISSN:0021-9673
DOI:10.1016/j.chroma.2021.462412