Modelling gradient elution of bioactive multicomponent systems in non-linear ion-exchange chromatography

Area of Science:

• Biochemical Engineering
• Separation Science
• Chromatography

Background:

• Non-linear ion-exchange chromatography is crucial for purifying bioactive substances.
• Existing models often simplify complex binding interactions, limiting process design accuracy.

Purpose of the Study:

• Develop a theoretical framework for non-linear ion-exchange chromatography of bioactive substances.
• Create a model basis for production-scale ion-exchange chromatography process design.

Main Methods:

• Developed a theoretical model incorporating ion-exchange and adsorption mechanisms.
• Utilized Gouy-Chapman theory for counter-ion distribution and extended it for selectivity.
• Simulated adsorption-elution cycles, varying column loading, eluent concentration, and multicomponent systems.

Main Results:

• Experimental data showed a transition from Langmuir to sigmoidal isotherms at higher eluent concentrations.
• The model accurately predicted non-linear elution profiles with desorption fronting.
• Simulations revealed that column loading significantly impacts separation more than elution gradients.

Conclusions:

• The developed model provides insights into biochromatography phenomena, including non-linear binding and the influence of contaminants.
• Separation is predominantly governed by the loading step, challenging conventional process design strategies.
• The framework supports the design of production-scale ion-exchange chromatography for diverse bioactive molecules.