Bräuchle Eric, Knaub Maria, Weigand Laura, Ehrend Elisabeth, Manns Patricia, Kremer Antje, Fabre Hugo, Bonig Halvard
Institute for Transfusion Medicine and Immunohematology, German Red Cross Blood Service Baden-Württemberg-Hessen, 60528 Frankfurt, Germany.
Faculty of Biological Science, Goethe University, 60439 Frankfurt, Germany.
Bioengineering (Basel). 2025 Jun 12;12(6):644. doi: 10.3390/bioengineering12060644.
Bioreactors enable scalable cell cultivation by providing controlled environments for temperature, oxygen, and nutrient regulation, maintaining viability and enhancing expansion efficiency. Automated systems improve reproducibility and minimize contamination risks, making them ideal for high-density cultures. While fed-batch bioreactors dominate biologics production, continuous systems like perfusion cultures offer superior resource efficiency and productivity. The Quantum hollow-fiber perfusion bioreactor supports cell expansion via semi-permeable capillary membranes and a closed modular design, allowing continuous media exchange while retaining key molecules. We developed a multiple-harvest protocol for suspension cells in the Quantum system, yielding 2.5 × 10 MEL-745A cells within 29 days, with peak densities of 4 × 10 cells/mL-a 15-fold increase over static cultures. Viability averaged 91.3%, with biweekly harvests yielding 3.1 × 10 viable cells per harvest. Continuous media exchange required more basal media to maintain glucose and lactate levels but meaningfully less growth supplement than the 2D culture. Stable transgene expression suggested phenotypic stability. Automated processing reduced hands-on time by one-third, achieving target cell numbers 12 days earlier than 2D culture. Despite higher media use, total costs for the automated were lower compared to the manual process. Quantum enables high-density suspension cell expansion with cost advantages over conventional methods.
生物反应器通过提供温度、氧气和营养调节的可控环境，实现可扩展的细胞培养，维持细胞活力并提高扩增效率。自动化系统提高了重现性并将污染风险降至最低，使其成为高密度培养的理想选择。虽然补料分批生物反应器在生物制品生产中占主导地位，但像灌注培养这样的连续系统具有更高的资源效率和生产率。量子中空纤维灌注生物反应器通过半透性毛细管膜和封闭式模块化设计支持细胞扩增，允许连续更换培养基，同时保留关键分子。我们为量子系统中的悬浮细胞开发了一种多次收获方案，在29天内产生了2.5×10个MEL-745A细胞，峰值密度为4×10个细胞/毫升，比静态培养增加了15倍。活力平均为91.3%，每两周收获一次，每次收获可产生3.1×10个活细胞。连续更换培养基需要更多的基础培养基来维持葡萄糖和乳酸水平，但与二维培养相比，生长补充剂的用量明显减少。稳定的转基因表达表明表型稳定。自动化处理将人工操作时间减少了三分之一，比二维培养提前12天达到目标细胞数量。尽管培养基用量较高，但与手动操作相比，自动化操作的总成本更低。量子系统能够实现高密度悬浮细胞扩增，与传统方法相比具有成本优势。
