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k_La as a predictor for successful probe-independent mammalian cell bioprocesses in orbitally shaken bioreactors

机译:k_La作为轨道摇动生物反应器中与探针无关的成功哺乳动物细胞生物过程的成功预测因子

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The aim of this study was to gain a better understanding of orbitally shaken bioreactors (OSRs) operated without controllers for pH and dissolved oxygen (DO) concentration. We used cylindrical OSRs with working volumes ranging from 250 mL to 200 L to determine that the volumetric mass transfer coefficient of oxygen (k_La) is a good predictor of the performance of OSRs at different scales. We showed that k_La values of 7–10 hour~(-1) were required to avoid DO limitations and to prevent conditions of low pH during the cultivation of CHO cells. Overall, cell cultures in probe-independent OSRs of different nominal volumes ranging from 250 mL to 200 L achieved similar cell densities, recombinant protein concentrations, and pH and DO profiles when having the same k_La. We conclude that k_La is a key parameter for probe-independent bioprocesses in OSRs and can be used as a scale-up factor for their operation.
机译:这项研究的目的是更好地了解在没有pH和溶解氧(DO)浓度控制器的情况下运行的轨道摇动生物反应器(OSR)。我们使用工作容积为250 mL至200 L的圆柱OSR,确定氧气的体积传质系数(k_La)是不同规模OSR性能的良好预测指标。我们表明,在CHO细胞培养过程中,需要k_La值为7-10小时〜(-1),以避免溶解氧的限制并防止pH值过低的情况。总体而言,当具有相同的k_La时,在标称体积为250 mL至200 L的不同标称体积的独立于探针的OSR中,细胞培养获得了相似的细胞密度,重组蛋白浓度以及pH和DO曲线。我们得出的结论是,k_La是OSRs中与探针无关的生物过程的关键参数,可以用作其操作的放大因子。

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