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使用扩散方程对大规模生物反应器进行建模。第二部分:对基质、氧、温度、二氧化碳和 pH 值分布进行特征描述。

Modeling large-scale bioreactors with diffusion equations. Part II: Characterizing substrate, oxygen, temperature, carbon dioxide, and pH profiles.

机构信息

Faculty of Engineering and Natural Sciences, Tampere University, Tampere, Finland.

出版信息

Biotechnol Bioeng. 2024 Mar;121(3):1102-1117. doi: 10.1002/bit.28635. Epub 2023 Dec 27.

Abstract

Large-scale fermentation processes involve complex dynamic interactions between mixing, reaction, mass transfer, and the suspended biomass. Empirical correlations or case-specific computational simulations are usually used to predict and estimate the performance of large-scale bioreactors based on data acquired at bench scale. In this two-part-study, one-dimensional axial diffusion equations were studied as a general and predictive model of large-scale bioreactors. This second part focused on typical fed-batch operations where substrate gradients are known to occur, and characterized the profiles of substrate, pH, oxygen, carbon dioxide, and temperature. The physically grounded steady-state axial diffusion equations with first- and zeroth-order kinetics yielded analytical solutions to the relevant variables. The results were compared with large-scale Escherichia coli and Saccharomyces cerevisiae experiments and simulations from the literature, and good agreement was found in substrate profiles. The analytical profiles obtained for dissolved oxygen, temperature, pH, and were also consistent with the available data. Distribution functions for the substrate were defined, and efficiency factors for biomass growth and oxygen uptake rate were derived. In conclusion, this study demonstrated that axial diffusion equations can be used to model the effects of mixing and reaction on the relevant variables of typical large-scale fed-batch fermentations.

摘要

大规模发酵过程涉及混合、反应、质量传递和悬浮生物量之间复杂的动态相互作用。通常使用经验相关性或特定于案例的计算模拟来根据在台架规模获得的数据预测和估计大规模生物反应器的性能。在这项两部分研究中,一维轴向扩散方程被研究为大规模生物反应器的通用和预测模型。第二部分重点研究了典型的分批补料操作,其中已知存在底物梯度,并对底物、pH 值、氧气、二氧化碳和温度的分布进行了特征描述。具有一级和零级动力学的基于物理的稳态轴向扩散方程为相关变量提供了解析解。将结果与大型大肠杆菌和酿酒酵母的实验和文献中的模拟进行了比较,在底物分布方面发现了很好的一致性。获得的溶解氧、温度、pH 和 的解析分布也与可用数据一致。定义了底物的分布函数,并推导出了生物量生长和氧气摄取率的效率因子。总之,这项研究表明,轴向扩散方程可用于模拟混合和反应对典型大规模分批补料发酵中相关变量的影响。

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