Tscheschke Bernd, Dreimann Janis, von der Ruhr Jürgen W, Schmidt Timo, Stahl Frank, Just Lothar, Scheper Thomas
Institut für Technische Chemie der Leibniz Universität Hannover, Callinstr. 5, D-30167, Hannover, Germany.
Biotechnol Bioeng. 2015 Jun;112(6):1155-64. doi: 10.1002/bit.25523. Epub 2015 Apr 17.
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.
在本文中,我们描述了一种用于培养不同原核和真核细胞系统的新型生物反应器的开发、特性及评估:雾室生物反应器。这种创新型生物反应器满足了对气体供应有高要求的剪切应力敏感细胞培养系统的需求。在雾室生物反应器中,细胞在通过超声蒸发产生的汽化培养基气溶胶内进行培养。与许多已建立的生物反应器系统不同,雾室生物反应器提供了一个气体供应极佳的环境,且不存在任何由叶轮或气泡引起的剪切应力。在此项工作中制造并表征了一个雾室生物反应器原型。在技术和化学表征过程中,我们评估了蒸发过程,在工作条件下蒸发性能为32 mL/h。在此基础上,我们计算出当生长速率受传输过程限制时,生物量分别为1.4 g(酿酒酵母,qs = 3.45×10-3 mol/g/h)和3.4 g(黑曲霉,qs = 1.33×10-3 mol/g/h)。此外,我们确定了高度为3 cm的均匀培养区域,培养总体积为0.45 L。对培养基成分在蒸发过程中的稳定性进行了检测,结果是所有成分至少在5天内保持稳定。经过技术表征后,我们证明了在雾室生物反应器中培养酿酒酵母和绒毛状镰孢菌的可行性。结果表明,雾室生物反应器能够持续为细胞样品输送足够量的营养物质,并提供极佳的氧气供应,且不存在任何引起剪切应力的曝气。此外,我们在长期实验中成功地以固态培养方式培养了绒毛状镰孢菌。数据表明,根据所培养的细胞类型,这种新型生物反应器概念有助于改进各种发酵和细胞培养过程。