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Modell-based cause of error diagnostics for liquid-chromatographic applications

Aims & Objectives

This project facilitates model-based approaches in development of chromatographic processes. With the help of cause of error diagnostics, the possibilities of bio-mathematical methods in process design shall be demonstrated with respect to process analytical technologies and quality by design The basis is a sensitivity analysis that examines typical causes of error and uncertainty in chromatographic processes and reveals links with the model parameters. With the help of inverse modelling, it is possible to determine small fluctuations in the process, their possible cause and appropriate counter measures for quality assurance – after completion (offline) as well as process-accompanying (online). The theoretical work in this project is backed-up and validated in all stages with laboratory experiments.

Research Topics

Besides the challenges in experimentally characterizing and quantifying the influences of different parameters and parameter combinations on the process, mathematical challenges include sensitivity analyses of the parameters and correlations between them. For online diagnostics, an algorithm has to be developed, that allows for high precision parameter estimation from partial experimental results in real time, including simulations of the underlying model several times faster. The coupling of both the theoretical and experimental results allows for error detection, analysis and possibly correction during the chromatographic process.


The project is partly funded by the Ministry of Science, Research and the Art of Baden-Württemberg in the framework of the “Ideenwettbewerb Biotechnologie und Medizintechnik”.


Chair Biomolecular Separation Engineering (Molekular Aufarbeitung von Bioprodukten MAB)

The chair on Biomolecular Separation Engineering  of Prof. Dr. Jürgen Hubbuch focuses on all aspects of modern downstream processing: protein purification, formulation as well as analytics in the biopharmaceutical industry. The area of research ranges from assessing structural parameters of proteins on a molecular level, transport and surface interaction phenomena of proteins, purification and characterization of bio-nanoparticles to industrial process development.



Dipl.-Math. techn. Tobias Hahn


  • T. Hahn, A. Osberghaus, V. Heuveline, J. Hubbuch, Model-based diagnostics and control of processes in ion exchange chromatography (Poster), 2nd Indo-German Workshop on "Advances in Reaction and Separation Processes", Bad Herrenalb, 20. - 22.02.2012
  • A. Osberghaus, T. Hahn, V. Heuveline, J. Hubbuch, J. Kratzke, Simulation and parameter estimation in protein separation (Poster), Summer School and Workshop: Fluid-Structure Interaction for Biomedical Applications, Prague, 29.8. - 2.9.2011
  • A. Osberghaus, T. Hahn, V. Heuveline, J. Hubbuch, Model-based diagnostics and control of processes in ion exchange chromatography (Poster), DECHEMA Vortrags- und Diskussionstagung: Bioverfahrenstechnik an Grenzflächen, Potsdam, 30.05.2011 - 01.06.2011