…in ion exchange chromatography using an asymmetric activity coefficient
Within the past few years, model-based approaches have emerged as flexible, fast and cheap tools for industrial process development, optimization and characterization, as well as adapting facilities. The commonly used model for ion exchange chromatography is the “Steric Mass Action” (SMA) model. This isotherm bases on the assumption that the behavior of proteins is thermodynamically ideal, which, in fact, is not always the case in industrial applications.
Taking thermodynamic effects into account
Complex elution behavior is a challenge for the modeling of industrial applications. The predictability of high protein load densities is one key requirement for the successful implementation of model-based process development in the industry. The SMA model for ion exchange chromatography does not consider thermodynamic non-idealities. To account for these, concentration-dependent activities are necessary.
Applying an asymmetric activity coefficient to the steric mass action isotherm
The SMA isotherm was extended by an additional coefficient to generate a generalized ion exchange isotherm. The asymmetric activity coefficient was approximated by means of two protein-specific parameters. These could be identified using the inverse curve fitting method of the ChromX simulation software. The data needed to calibrate the model was generated using just three different gradient elution experiments with varying load densities and gradient slopes.
The new isotherm opens various possibilities for future applications
Now, processes with high-load densities can be modeled and simulated. Furthermore, it allows, for instance, model-based process development for continuous ion exchange chromatography or the operational mode of “overloaded chromatography”.