No abstract

In this article we describe the development, the characterization and the evaluation of a novel bioreactor type for the cultivation of different pro- and eukaryotic cell-systems: the mist-chamber bioreactor. This innovative bioreactor meets the demand of cultivation systems for shear stress sensitive cells with high requirements for gas supply. Within the mist-chamber bioreactor the cells are cultivated inside an aerosol of vaporized medium generated by ultrasonic vaporization. In contrast to many established bioreactor systems the mist-chamber bioreactor offers an environment with an excellent gas supply without any impeller or gas bubble induced shear stress. A mist-chamber bioreactor prototype has been manufactured and characterized during this work. In the technical and chemical characterization we evaluated the vaporization process, resulting in a vaporization performance of 32 mL/h at working conditions. On this basis we calculated a biomass of 1.4 g (S. cerevisiae, qs  = 3.45 × 10-3 mol/g/h) and 3.4 g (Aspergillus niger, qs  = 1.33 × 10-3 mol/g/h) where the growth rate becomes limited by transport processes. Additionally, we determined a homogenous cultivation area to a height of 3 cm giving a total volume of 0.45 L for the cultivation. Medium components were examined according to their stability during vaporization with the result that all components are stable for at least 5 days. After the technical characterization we demonstrated the feasibility to cultivate S. cerevisiae and F. velupites in the mist-chamber bioreactor. The results demonstrated that the mist-chamber bioreactor is able to transport a sufficient amount of nutrients consistently to the cell samples and offers an excellent oxygen supply without any shear stress inducing aeration. Furthermore we successfully cultivated F. velupites in a solid state cultivation in a long term experiment. The data indicate that the new bioreactor concept can contribute to improve various fermentations and cell culture processes depending on the cultured cell types.

The hydrodynamic characterization of bioreactors is an integral element in the industrial development of cell and gene therapy platforms where mild process conditions with low power inputs are desired. In this technology, modular single‐use equipment is frequently used for which accurate techniques to measure or predict scaling parameters, such as power input, are of high interest. In this work, computational fluid dynamics as well as two experimental approaches are used to determine the power input in a small‐scale bioreactor and validate the employed techniques. Particular attention is given to the implications arising from low‐speed operation with low power input conditions.

No abstract

Ein neuer Bioreaktortyp, der Nebelkammer-Reaktor, wird vorgestellt. Im Unterschied zu den bisherig verwendeten submersen Kultur-bzw. Bioreaktorverfahren werden im Nebelkammer-Reaktor Zellverbände mittels eines Aerosols aus ultraschallzerstäubtem Nährmedium umhüllt. Die kontinuierlich erzeugten Aerosoltröpfchen setzen sich auf den Zellen ab und ermöglichen so eine besonders effektive und scherstressarme Versorgung der Zellen mit Gasen und Nährstoffen sowie eine größere Unabhängigkeit von Form und Größe der eingesetzten Konstrukte. The Mist Chamber Reactor -Novel Bioreactor Concept for Challenging CultivationsThe mist chamber reactor is described as a new bioreactor type in which cell structures, in contrast to conventional submerged culture systems, are surrounded by an aerosol of a culture medium derived by ultrasonic vaporization. The continuously produced aerosol droplets sediment on the cells, which leads to an effective supply with gases and nutrients with low shear stress as well as greater independence of shape and size of the constructs used.