Parameter-by-parameter method for steric mass action model of ion exchange chromatography: Theoretical considerations...

Area of Science:

• Biochemistry
• Chemical Engineering
• Analytical Chemistry

Background:

• Ion exchange chromatography (IEC) is a key technique for protein separation.
• Mechanistic models, like the steric mass action (SMA) model, are valuable but hindered by complex calibration.
• Efficient model calibration is crucial for optimizing IEC processes.

Purpose of the Study:

• To introduce a novel, simplified calibration methodology for the SMA model in IEC.
• To reduce the complexity and time associated with determining SMA model parameters.
• To enhance the predictive accuracy of IEC models across various loading conditions.

Main Methods:

• Development of the parameter-by-parameter (PbP) method, involving sequential determination of characteristic charge, equilibrium coefficient, shielding factor, and kinetic coefficient.
• Utilizing linear regression (LR1, LR2), linear approximation (LA), and inverse method (IM) for parameter estimation.
• Validation through numerical single-component experiments and comparison with the Yamamoto method.

Main Results:

• The PbP method successfully determined SMA parameters, reducing unknown parameters per species to one.
• PbP demonstrated excellent agreement between simulated and experimental results for single-component systems.
• PbP exhibited higher accuracy and robustness compared to the Yamamoto method, especially under varying loading conditions.
• A five-experiment strategy was proposed to minimize calibration costs.
• Feasibility confirmed through a real-world multi-component separation experiment.

Conclusions:

• The PbP method provides a reliable and physically grounded approach for estimating SMA parameters in IEC.
• This method significantly improves the accuracy of retention prediction across a broad range of loading conditions.
• The PbP method streamlines IEC process development by simplifying model calibration.