Henry Olivier, Kwok Ezra, Piret James M
Dépt. de Génie Chimique, Ecole Polytechnique de Montréal, Campus de l'Université de Montréal, Montréal, QC, Canada H3C 3A7.
Biotechnol Prog. 2008 Jul-Aug;24(4):921-31. doi: 10.1002/btpr.17.
Perfusion culture optimization in multiple noninstrumented small-scale flasks allows reduced expense and time associated with process development. These cultures normally use a different process mode because at small scales it is not practical to retain the cells for medium perfusion. In this work, the kinetics of growth, nutrient consumption, metabolite, and product formation were compared in spinner cultures operated in batch, semicontinuous, chemostat, and perfusion modes. Fed-batch was also included to provide an added comparison. Using logistic fitting for more reliable specific rate estimates in transient conditions, the growth phase of batch cultures predicted similar kinetics to fed-batch and continuous processes. For daily medium exchange rates up to 50%, the semicontinuous mode also predicted the perfusion process kinetics. Differences between the chemostat and semicontinuous culture results were only observed at higher exchange rates with the greatest daily culture perturbation. Overall, the batch or semicontinuous cultures were shown to readily provide results similar to the far more complex to operate chemostat or perfusion cultures.
在多个非仪器化的小规模烧瓶中进行灌注培养优化,可以降低与工艺开发相关的成本和时间。这些培养通常采用不同的工艺模式,因为在小规模下保留细胞进行培养基灌注是不实际的。在这项工作中,比较了在分批、半连续、恒化器和灌注模式下操作的旋转培养物中生长、营养物质消耗、代谢物和产物形成的动力学。还包括补料分批培养以提供额外的比较。在瞬态条件下使用逻辑拟合以获得更可靠的比速率估计,分批培养的生长阶段预测出与补料分批和连续过程相似的动力学。对于高达50%的每日培养基更换率,半连续模式也预测了灌注过程动力学。仅在更高的更换率和最大的每日培养扰动下才观察到恒化器和半连续培养结果之间的差异。总体而言,分批或半连续培养显示出能够轻松提供与操作复杂得多的恒化器或灌注培养相似的结果。