Modulator Dynamics Shape the Design Space for Stepwise-Elution Simulated Moving Bed Chromatographic Separations.

Area of Science:

• Biochemical Engineering
• Separation Science
• Chromatography

Background:

• Simulated Moving Bed (SMB) chromatography is crucial for separating biological macromolecules.
• Non-isocratic operation enhances SMB efficiency but introduces complex mobile-phase modulator dynamics.
• Quantitative understanding of these dynamics is lacking, limiting optimization of the SMB design space.

Purpose of the Study:

• To quantitatively explain how mobile-phase modulator dynamics impact non-isocratic SMB separation success.
• To introduce new design constraints for predicting and optimizing non-isocratic SMB operations.
• To redefine the SMB design space based on these new constraints.

Main Methods:

• Explicitly accounting for modulator dynamics (e.g., salts in ion exchange/hydrophobic interaction chromatography).
• Developing two new dimensionless numbers to quantify modulator effects.
• Utilizing computational and experimental studies to validate predictions.

Main Results:

• Elucidation of two novel design constraints presented as dimensionless numbers.
• Quantification of modulator phenomena's effect on non-isocratic SMB separation success.
• Redefinition of the SMB design space, enabling more efficient and robust operating conditions.

Conclusions:

• The new design constraints provide a quantitative framework for understanding non-isocratic SMB chromatography.
• The redefined SMB design space facilitates the development of optimized separation protocols.
• This work enables more efficient and robust purification of proteins and biological macromolecules using SMB chromatography.