Prediction and verification of centrifugal dewatering of P. pastoris fermentation cultures using an ultra scale‐down approach
Prediction and verification of centrifugal dewatering of P. pastoris fermentation cultures using an ultra scale‐down approach
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使用超缩小方法预测和验证巴斯德毕赤酵母发酵培养物的离心脱水
DOI：
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发表时间：
2012
影响因子：
3.8
通讯作者：
E. Keshavarz‐Moore
中科院分区：
文献类型：
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作者：
A. Lopes;E. Keshavarz‐Moore
近年来，发酵液细胞密度急剧上升，并转向微生物细胞中的胞外产物表达。因此，细胞分离期间的脱水特性是重要的，因为任何截留在沉积物中的液体都会导致产物的损失，从而降低产物回收率。在这项研究中，开发了一种超缩小（USD）方法，以快速评估间歇固体排放的中试离心机的脱水性能。然后对两种类型的中试规模离心机的结果进行了规模验证：管式碗设备和叠盘离心机。初始实验表明，采用基于与中试规模离心机相当的进料浓度的实验室规模离心模拟装置，无法成功预测规模下的脱水性能（P值<0.05）。然而，使用USD方法（P值≥0.05）成功预测了脱水水平，该方法基于使用小规模进料浓度（模拟与中试规模离心机中相同的固体高度）。最初的实验使用面包酵母饲料悬浮液，然后是新鲜的巴斯德毕赤酵母发酵培养物。这项工作提出了一种简单而新颖的USD方法，用于预测两种使用少量原料（<50 mL）的中试规模离心机的脱水水平。它是一个有用的工具，可用于确定中试离心机需要运行的最佳条件，从而减少工艺开发早期阶段重复中试运行的需要。Biotechnol. Bioeng. 2012; 109：2039-2047.© 2012 Wiley Periodicals，Inc.
Recent years have seen a dramatic rise in fermentation broth cell densities and a shift to extracellular product expression in microbial cells. As a result, dewatering characteristics during cell separation is of importance, as any liquor trapped in the sediment results in loss of product, and thus a decrease in product recovery. In this study, an ultra scale‐down (USD) approach was developed to enable the rapid assessment of dewatering performance of pilot‐scale centrifuges with intermittent solids discharge. The results were then verified at scale for two types of pilot‐scale centrifuges: a tubular bowl equipment and a disk‐stack centrifuge. Initial experiments showed that employing a laboratory‐scale centrifugal mimic based on using a comparable feed concentration to that of the pilot‐scale centrifuge, does not successfully predict the dewatering performance at scale (P‐value <0.05). However, successful prediction of dewatering levels was achieved using the USD method (P‐value ≥0.05), based on using a feed concentration at small‐scale that mimicked the same height of solids as that in the pilot‐scale centrifuge. Initial experiments used Baker's yeast feed suspensions followed by fresh Pichia pastoris fermentation cultures. This work presents a simple and novel USD approach to predict dewatering levels in two types of pilot‐scale centrifuges using small quantities of feedstock (<50 mL). It is a useful tool to determine optimal conditions under which the pilot‐scale centrifuge needs to be operated, reducing the need for repeated pilot‐scale runs during early stages of process development. Biotechnol. Bioeng. 2012; 109:2039–2047. © 2012 Wiley Periodicals, Inc.