Continuous Process of Protein Crystallization

• Applicant: Professor Dr.-Ing. Achim Kienle
• Subject Area: Chemical and Thermal Process Engineering
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 544924858

Objective of this project is to develop an new class ofcontinuous processes for the production of highly pure bioactive proteins in cooperation between the Antos group at Rzeszów University of Technology (PRz) in Poland (project lead), the Striedner group at BOKU University in Vienna in Austria and the Kienle group at Otto von Guericke University (OVGU) in Magdeburg/Germany. Further cooperation partner is Prof. Robert Dürr from the Magdeburg-Stendal University of Applied Sciences, who is not applying for extra funding within this proposal. BOKU will develop novel growth decoupled continuous production technologies for recombinant proteins in Bacterial cell cultures. PRz and OVGU will develop a new continuous process for the crystallization of bioactive proteins using forced convection crystallization (FCC). The process uses a warm air stream for controlled evaporation of the solvent to induce crystallization. Furthermore, exploitation of the wet-bulb phenomenon ensures mild temperatures which are favorable for protein crystallization. Control of the solution's supersaturation level is enabled by the variation of the solution temperature and the properties of the convective fluid. The novel process avoids local concentration gradients leading to unfavorable protein aggregation and the formation of an amorphous phase, which are major problems in conventional protein crystallization. Preparatory work at PRz has focused on a batch process. It has been proven that FCC is a promising process with high yield and good quality of the crystalline phase. In the present project we aim at the development of a continuous process using an Archimedian screw. The screw allows an efficient but gentle mixing of the protein solution. The development of the new process requires a thorough knowledge of the underlying thermodynamics, crystallization kinetics as well as heat and mass transfer. To design and optimize the new process, mathematical models will be developed by the group from OVGU based on the experimental investigations to be performed by the group from PRz. For the modeling, focus is first on the batch process. Afterwards the model will be extended to the continuous process and will be used for process design. The proposed concept will be implemented and validated experimentally at PRz. Finally, a refined process model will be used for model based mathematical optimization of the novel continuous forced convection crystallization process and its integration with the novel continuous bacterial production process.

• DFG Programme: Research Grants
• International Connection: Austria, Poland
• Partner Organisation: Fonds zur Förderung der wissenschaftlichen Forschung (FWF)
• Cooperation Partners: Professorin Dr.-Ing. Dorota Antos, Ph.D.; Professor Dr. Gerald Striedner
• Co-Investigator: Professor Dr.-Ing. Robert Dürr