True Moving Bed Centrifugal Partition Chromatography Unit
Zusammenfassung der Projektergebnisse
Liquid-liquid chromatography (LLC), also known as Centrifugal Partition Chromatography and Counter-Current Chromatography, is a powerful and versatile separation technique that shares the principles of extraction and chromatography. In LLC a separation of a mixture is realized owing to the compounds different partitioning between two liquid phases, whereas one of the phases is kept stationary by means of centrifugal forces. LLC has been successfully used at lab scale for more than 50 years. The technical limitations (equipment design) impeding its application at production scale have been solved recently. The overall objective of this project is to contribute toward the fast technology breakthrough in the industry by establishing general guidelines for design of LLC separation process in the field of natural and life science products. The research methodology comprises mathematical model-based process design on the course “from molecule to process”. The equipment financed by this project (liquid-liquid chromatographic unit and high-throughput screening liquid handling station) was used to generate necessary data for the method development and to validate the proposed concepts. The first step in the development of LLC process, batch or continuous, is the selection of two-liquid phase system. The currently used approaches (rules of thumb and experimental screening) comprise high experimental effort and do not always lead to the optimal system. In the frame of this project, a priori method for screening and selection of biphasic system using a predictive thermodynamic model (Conductorlike Screening Model for Real Solvents, COSMO-RS) was developed. The method uses the molecular structure of solvents and compounds to be separated as input information, considers cost and safety relevant issues, and enables creating tailor-made biphasic systems for a particular LLC separation task. Downstream processing comprises 50-80% of the entire production cost. Implementation of a continuous mode of operation is one of the options for the reduction of the separation cost. In a publication (J. Völkl, W. Arlt, M. Minceva, AIChE J., 59, 241–249, 2013) a short-cut method for the selection of operating parameters of the novel continuous LLC process (patented in 2005 by IFP, France) was developed. Predicted or experimentally determined partition coefficients of the solutes present in the mixture to be separate are used as input information. The method was validated experimentally using the LLC unit (True Moving Bed Centrifugal Partition Chromatograph, TMB-CPC) financed by this project. A detailed mathematical model, needed for the simulation and optimization of the process performances, and experimental methods for the determination of the model parameters are presented in J. Chromatogr. A, 1229, 140–147, 2012. The benefits of using continuous instead of batch operation are demonstrated for a difficult separation task (components which molecular structure differs in only one double bound). The derived short-cut design method and mathematical model for process simulation are the first engineering inputs to this new continuous separation technology. Currently, the LLC technology application in the field of bio-components is impeded due to the incompatibility of the physical properties of the conventional polymer/polymer or polymer/salt aqueous twophase systems (high phase viscosity and low interfacial tension). In DFG project “Application of Ionic liquid based two-aqueous phase systems in centrifugal partition chromatography” we study the applicability of the recently introduced new class of aqueous two-phase systems (ATPS), formed by combining a hydrophilic ionic liquid, an inorganic salt and water. The main feature of the ionic liquids, i.e. versatility of anion and cation combinations, is used to tune the partition coefficient of the proteins in the mixture as well as the physical properties of the biphasic liquid system.
Projektbezogene Publikationen (Auswahl)
- Solvent system selection in counter-current chromatography using conductor-like screening model for real solvents. J. Chromatogr. A, 1218, 242-250,2011
E. Hopmann, W. Arlt, M. Minceva
- A priori selection of the mobile and stationary phase in centrifugal partition chromatography and counter-current chromatography. J. Chromatogr. A, 1238, 68-76, 2012
E. Hopmann, A. Frey, M. Minceva
- Separation of a binary mixture by sequential centrifugal partition chromatography. Journal of Chromatography A, 1229,140-147, 2012
E. Hopmann, M. Minceva
- Sequential centrifugal partition chromatography: a new continuous chromatographic technology. Chemical Engineering & Technology., 35 (1), 72-82, 2012
E. Hopmann, J. Goll, M. Minceva
- Development of a Centrifugal Partition Chromatography: from molecule to process. Dissertation, Verlag Dr. Hut, München 2013
E. Hopmann
- Model-based design of preparative liquid-chromatography processes. Habilitationsschrift, 2013
M. Minceva
- Study of the separation limits of continuous solid support free liquid-liquid chromatography: Separation of capsaicin and dihydrocapsaicin by centrifugal partition chromatography. Journal of Chromatography A, 1284,59-68, 2013
J. Goll, A. Frey, M. Minceva
- Theoretical study of sequential centrifugal partition chromatography. AIChE J, 59 (1), 241-249, 2013
J. Völkl, W. Arlt, M. Minceva
