Simulated oxygen and glucose gradients as a prerequisite for predicting industrial scale performance a priori.

Biotechnology and Bioengineering
Maike Kuschel, Ralf Takors

Abstract

Transferring bioprocesses from lab to industrial scale without loss of performance is key for the successful implementation of novel production approaches. Because mixing and mass transfer is usually hampered in large scale, cells experience heterogeneities eventually causing deteriorated yields, that is, reduced titers, productivities, and sugar-to-product conversions. Accordingly, reliable and easy-to-implement tools for a priori prediction of large-scale performance based on dry and wet-lab tests are heavily needed. This study makes use of computational fluid dynamic simulations of a multiphase multi-impeller stirred tank in pilot scale. So-called lifelines, records of 120,000 Corynebacterium glutamicum cells experiencing fluctuating environmental conditions, were identified and used to properly design wet-lab scale-down (SD) devices. Physical parameters such as power input, gas hold up, k L a , and mixing time showed good agreement with experimental measurements. Analyzing the late fed-batch cultivation revealed that the complex double gradient of glucose and oxygen can be translated into a wet-lab SD setup with only few compartments. Most remarkably, the comparison of different mesh sizes outlined that even the coarsest ap...Continue Reading

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Citations

Apr 10, 2021·Essays in Biochemistry·Felix Thoma, Bastian Blombach
Sep 11, 2021·Biotechnology and Bioengineering·Philipp DemlingLars M Blank

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