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

Area of Science:

• Biochemical Engineering
• Chromatographic Separations
• Process Analytical Technology

Background:

• Mechanistic models are vital for ion-exchange chromatography (IEC) process development.
• Accurate estimation of the steric shielding factor (σ) in the steric mass action (SMA) model is critical but challenging.
• Previous linear approximation (LA) methods involved complex calculations for multi-component systems.

Purpose of the Study:

• To develop a straightforward and efficient method for estimating the steric shielding factor (σ).
• To improve the accuracy and reduce computational complexity in parameter estimation for IEC.
• To accelerate the process development of multi-component IEC separations.

Main Methods:

• Proposed a combined approach of simplified linear approximation (SLA) and inverse method (IM).
• SLA provides an initial, unique, and positive estimation of σ.
• IM refines the σ estimation for accurate parameter determination.

Main Results:

• The SLA+IM method significantly reduced time complexity from O(n³) to O(n) compared to LA.
• Numerical experiments showed reduced error (one-sixth) in elution profiles using SLA+IM.
• Real-world experiments with monoclonal antibody separation confirmed lower error and better physical understanding.

Conclusions:

• SLA+IM offers a novel, straightforward, and efficient approach for determining σ in multi-component IEC.
• The method simplifies calibration experiments and accelerates IEC process development.
• This simplification facilitates wider adoption of mechanistic modeling in biopharmaceutical process optimization.