A Diagnostic Procedure for Identifying Isotherm Models in Liquid Chromatography
Konstantinos Katsoulas, Federico Galvanin, Luca Mazzei, Eva Sorensen
TL;DR
This paper introduces a diagnostic method to improve isotherm models in liquid chromatography, enhancing accuracy without sacrificing interpretability.
Contribution
A novel diagnostic procedure using a Lagrange multiplier test to refine isotherm models in chromatography.
Findings
The diagnostic procedure improves model accuracy for complex separations like peptides.
The method avoids black-box models, preserving physical insight and interpretability.
Three in-silico case studies validated the effectiveness of the approach.
Abstract
Liquid chromatography is a pivotal purification process widely used in pharmaceutical development and manufacturing. Efficient optimal design and control of the process rely heavily on mechanistic models such as the lumped pore diffusion model (POR) and the Equilibrium Dispersion Model (EDM), both popular choices owing to their simplicity and good accuracy for a wide range of applications. However, the choice of the functional form of the isotherm models, which describe the component adsorption equilibria, strongly affects the predictions of the chromatography model. While traditional isotherms perform well for simple compounds (e.g., small molecules), they often fall short for more complex separations (e.g., peptides), thus resulting in process-model mismatch, even following rigorous parameter estimation. As a remedy to this, recent advances have introduced hybrid models that integrate…
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Taxonomy
TopicsProtein purification and stability · Analytical Chemistry and Chromatography · Chromatography in Natural Products