Summary
Packed-bed liquid chromatography is an important method used to separate biological molecules, but existing models are fragmented and complicated. The authors created a new unified and flexible system that brings many different models together in a clear and structured way. This system allows people to choose and combine components to build models best suited for their specific needs, supporting everything from detailed 3D simulations to simpler designs. They also provide a web tool that helps users assemble models and get clear mathematical descriptions, improving consistency and transparency in this field. The framework makes it easier to extend and improve chromatography modeling software for complex biological separations.
What this means in practice
- •For process engineers: Create tailored bioseparation models for designing and optimizing packed-bed chromatography setups using the unified modular framework.
- •For software developers: Integrate and extend chromatography simulation tools with the modular components and model hierarchy introduced in a consistent framework.
Authors
Jan Michael Breuer, Samuel Leweke, Johannes Schmölder, Antonia Berger, Gregor J. Gassner, Eric von Lieres
Abstract
Packed-bed chromatography is a cornerstone of bioseparation, yet its modeling landscape remains fragmented by numerous model variants, inconsistent terminology, and limited structural clarity. While prior work has categorized and contrasted individual variants, our approach shifts the focus to unification. We present a unified, modular, and composable framework that integrates diverse mechanistic packed-bed chromatography models into a coherent structure. Starting from a high-resolution three-dimensional model, the framework systematically derives a hierarchy of reduced-order models through formal model order reduction. It encompasses a broad range of bulk transport phenomena, intraparticle mass transfer processes, binding mechanisms, and chemical reactions. Formulated orthogonally, these modules are independently meaningful and can be systematically combined into mathematically consistent models tailored to specific applications. The framework recovers and generalizes existing models, establishes a consistent taxonomy, and enables novel model combinations and extensions, including alternative column and particle geometries, particle-size and particle-type distributions, component-specific pore accessibility, rapid-equilibrium binding and reaction formulations, and size-exclusion with simultaneous binding. The framework is accessible through CADET-Equations, an interactive web application for model assembly and automatic generation of governing equations in LaTeX, promoting standardization and transparency. Its design principles are increasingly reflected throughout the CADET ecosystem, whose modular architecture supports the majority of the proposed model family. The generality and composable design of the framework provide a foundation for extending chromatography modeling software toward integrated bioseparation processes and advanced computational biotechnology applications.