Modelling of Industrial-Scale Bioreactors Using the Particle Lifeline Approach

Gisela Nadal-Rey,John M. Kavanagh,Benny Cassells,Sjef Cornelissen,David F. Fletcher,Krist V. Gernaey,Dale D. McClure

Biochemical Engineering Journal（2023）SCI 3区SCI 2区

Tech Univ Denmark

Cited 6|Views15

Abstract

A key factor in improving the performance of large-scale bioreactors is understanding the conditions experienced by the cells inside the reactor. This can be challenging due to the practical difficulties involved, hence there is increasing use of simulation to quantify the environmental conditions found in large-scale bioreactors. In this work we have used the particle lifeline approach to quantify the effect of the reactor design on the conditions experienced by two very commonly used industrial organisms (Escherichia coli and Saccharomyces cerevisiae). It was found that the cells in the stirred tank reactor tended to experience longer fluctuations of both starvation and overflow metabolism when compared with those in the bubble column, this behaviour being caused by differences in mixing between the two reactor designs. It was found that a significant (60%) fraction of the population in the stirred tank reactors experienced starvation conditions for a large fraction (>70%) of the time, with exposure to such conditions being likely to affect the cellular metabolism. Results from this work provide a detailed insight into the conditions experienced inside industrial-scale bioreactors operated at realistic conditions. Such data can be leveraged to optimise large-scale reactor designs as well as for the development of scale-down systems.

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Key words

CFD Modelling,Kinetics,Large-scale bioreactor,Mixing,Particle lifelines

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【要点】：本文采用粒子生命周期方法，研究了工业规模生物反应器设计对细胞环境条件的影响，发现了搅拌罐式反应器与气泡柱式反应器中细胞经历的不同条件，为优化反应器设计提供了依据。

【方法】：研究运用粒子生命周期方法模拟了两种常用工业微生物（大肠杆菌和酵母菌）在生物反应器中的环境条件。

【实验】：通过模拟实验，使用的是假设的工业规模数据集，发现搅拌罐式反应器中的细胞更容易经历较长时间的饥饿和过度代谢波动，而气泡柱式反应器中的细胞则波动较小；在搅拌罐式反应器中，有60%的细胞群体在超过70%的时间内经历了饥饿条件，这些条件可能会影响细胞代谢。