Advanced score system and automated search strategies for parameter estimation in mechanistic chromatography modeling

Least squares estimation of unknown parameters from measurement data is a well-established standard method in chromatography modeling but can suffer from critical disadvantages. The description of real-world systems is generally prone to unaccounted mechanisms, such as dispersion in external holdup volumes, and systematic measurement errors, such as caused by pump delays. In this scenario, matching the shape between simulated and measured chromatograms has been found to be more important than the exact peak positions. We have therefore developed a new score system that separately accounts for the shape, position and height of individual peaks. A genetic algorithm is used for optimizing these multiple objectives. Even for non-conflicting objectives, this approach shows superior convergence in comparison to single-objective gradient search, while conflicting objectives indicate incomplete models or inconsistent data. In the latter case, Pareto optima provide important information for understanding the system and improving experiments. The proposed method is demonstrated with synthetic and experimental case studies of increasing complexity. All software is freely available as open source code (https://github.com/modsim/CADET-Match).