Kempken R, Büntemeyer H, Lehmann J
Institute for Cell Culture Technology, University of Bielefeld, Germany.
Cytotechnology. 1991 Oct;7(2):63-74. doi: 10.1007/BF00350912.
The perfusion mode of a continuous cell culture bioreactor was modified to establish a closed loop system. Eighty percent of the spent medium was re-used twice. The medium cycle bioreactor unit was operated sterile and uncomplicated without a technical retention system for the high molecular weight substances. Therefore, only 20% of the actual medium was necessary to run the recycling process. During seven days culture time in a two liter scale 5 grams of IgG1 type monoclonal antibody was produced. During that period the cell specific productivity was constant. Renewal of proteins was omitted because the protein content in the system persisted at a high level. Therefore, self-conditioning substances of the cells were retained in the system as well as the expensive medium components (proteins with catalytic or stimulating function). Seventy to 80% of medium costs and medium quantity were saved for each medium recycling step. Only cheap metabolites that are consumed by the cells had to be supplemented. Uptake rates of glucose and amino acids were calculated to establish a suitable supplementation mixture for the recirculated medium.
对连续细胞培养生物反应器的灌注模式进行了改进，以建立一个闭环系统。80%的用过的培养基被重复使用两次。培养基循环生物反应器单元在无菌且简单的条件下运行，无需用于高分子量物质的技术保留系统。因此，运行循环过程仅需20%的实际培养基。在两升规模的七天培养时间内，产生了5克IgG1型单克隆抗体。在此期间，细胞比生产率保持恒定。由于系统中的蛋白质含量维持在较高水平，因此省略了蛋白质更新。因此，细胞的自我调节物质以及昂贵的培养基成分（具有催化或刺激功能的蛋白质）都保留在系统中。每个培养基循环步骤可节省70%至80%的培养基成本和培养基用量。仅需补充细胞消耗的廉价代谢物。计算了葡萄糖和氨基酸的摄取率，以建立用于再循环培养基的合适补充混合物。
