Development of integrated continuous flow systems for transient transfection, cultivation and monitoring of mammalian cells

• Applicant: Professorin Dr. Janina Bahnemann
• Subject Area: Biological Process Engineering
• Term: from 2017 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 346772917

Benefits of continuous cultivation and production processes have been widely demonstrated by a variety of manufacturing industries in recent years. With growing demand for biopharmaceuticals, higher productivity and ever-increasing pressure to reduce manufacturing costs, the biotech industry seems to exhibit a persisting interest in the development of continuous bio-manufacturing systems. Although there are emerging continuous bioprocessing technologies available in the market, there are almost no concrete examples for successful implementation of a fully continuous process for biological products. To accelerate the process optimization it is advantageous to implement the bioreactor with appropriate technology for continuous monitoring and regulation of critical cultivation parameters. In addition, the market is seeking for rapid gene delivery technologies that would allow flexible production of individual target proteins and parallelization of production processes. To further enhance this development process, the construction of a novel controlled and continuous cell transfection and cultivation system for recombinant protein production and simultaneous analyte monitoring by integration of different functional microfluidic lab-on-a-chip (LOC) devices is proposed. LOC devices offer many advantages for bioprocesses such as small sample volume, defined and reproducible working conditions, portability, point-of-care (POC) diagnosis, and the potential of reducing process costs. Main challenges for continuous bioreactor cultivation are the development and integration of functional units and monitoring systems, which are suitable for both upstream and downstream processes. Herein, this project will focus on the upstream process and development of new sensors to monitor cell culture systems. As an important part of the upstream process, this project aims to design, fabricate and integrate a LOC for continuous and controlled transient gene transfer to the host cells for recombinant protein production. Furthermore, a novel electromechanical aptamer-based biosensor for rapid monitoring of target proteins as well as for early detection of potential microbial contamination is proposed.

• DFG Programme: Independent Junior Research Groups
• International Connection: Israel, USA
• Major Instrumentation: High-resolution 3D printer
• Instrumentation Group: 2110 Formen-, Modellherstellung und gießereitechnische Maschinen
• Cooperation Partners: Professor Michael R. Hoffmann; Professorin Dr. Ester Segal