KIT | KIT-Bibliothek | Impressum

Optimizing a chromatographic three component separation: A comparison of mechanistic and empiric modeling approaches

Osberghaus, Anna; Hepbildikler, Stefan; Nath, Susanne; Haindl, Markus; Lieres, Eric von; Hubbuch, Jürgen

Abstract:
The search for a favorable and robust operating point of a separation process represents a complex multi-factor optimization problem. This problem is typically tackled by design of experiments (DoE) in the factor space and empiric response surface modeling (RSM); however, separation optimizations based on mechanistic modeling are on the rise. In this paper, a DoE–RSM-approach and a mechanistic modeling approach are compared with respect to their performance and predictive power by means of a case study – the optimization of a multicomponent separation of proteins in an ion exchange chromatography step with a nonlinear gradient (ribonuclease A, cytochrome c and lysozyme on SP Sepharose FF). The results revealed that at least for complex problems with low robustness, the performance of the DoE-approach is significantly inferior to the performance of the mechanistic model. While some influential factors of the system could be detected with the DoE–RSM-approach, predictions concerning the peak resolutions were mostly inaccurate and the optimization failed. The predictions of the mechanistic model for separa ... mehr


Zugehörige Institution(en) am KIT Institut für Bio- und Lebensmitteltechnik (BLT)
Publikationstyp Zeitschriftenaufsatz
Jahr 2012
Sprache Englisch
Identifikator DOI: 10.1016/j.chroma.2012.03.029
ISSN: 0021-9673
KITopen ID: 1000046597
Erschienen in Journal of Chromatography A
Band 1237
Seiten 86-95
KIT – Die Forschungsuniversität in der Helmholtz-Gemeinschaft KITopen Landing Page