Developing a Computational Framework To Advance Bioprocess Scale-Up

Wang, Guan; Haringa, Cees; Noorman, Henk; Chu, Ju; Zhuang, Yingping

doi:10.1016/j.tibtech.2020.01.009

Cited by 60 publications

(33 citation statements)

References 73 publications

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“…The scale-up of bioreactors and biotechnological processes is a critical operation in industrial biotechnology. In many cases, due to limitations in the applied methodology, a scale-up results in reduced titers, yields or productivities [147] . For the layout and design of bioreactors, mainly of the stirred tank type, there was a strong focus on the numerical simulation and analysis of local effects in the 1980's [148] , [149] , [150] .…”

Section: Current Research and Future Trendsmentioning

confidence: 99%

“…The application of these approaches in real-time is nowadays still restricted to comparably simple systems at lower resolutions, as merging CFD and dynamic models for microbially catalyzed reactions is accompanied by a high demand of processing power. In the future, these integrated approaches are a promising trend for a truly knowledge-based bioreactor scale-up and layout [147] . Eventually, once real-time operation is made feasible, this approach can be advanced to a framework for online control of bioprocesses.…”

Section: Current Research and Future Trendsmentioning

confidence: 99%

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History and Evolution of Modeling in Biotechnology: Modeling & Simulation, Application and Hardware Performance

Noll

Henkel

2020

Computational and Structural Biotechnology Journal

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Section: Current Research and Future Trendsmentioning

confidence: 99%

Section: Current Research and Future Trendsmentioning

confidence: 99%

History and Evolution of Modeling in Biotechnology: Modeling & Simulation, Application and Hardware Performance

Noll

Henkel

2020

Computational and Structural Biotechnology Journal

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“…Although the interplay between cell systems and their production conditions can be measured, the underlying mechanism is partially unknown, which is, however, seldom accounted for during lab-scale research and development [3,4]. Representatively, the nonideal mixing and mass transfer limitations at the large scale in most cases are not rigorously considered in lab-scale designs, and thus the outcome of the environmental impacts cannot match the reality at the large scale [5,6]. In industrial settings, the environmental gradients, such as those of substrate, dissolved oxygen and pH, caused by insufficient mixing and mass transfer restrictions, and of the shear force caused by the impellers, often exert a negative impact on the resulting commercial indicators (i.e., titer, yield and productivity) and thus the economic benefits [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Impact of Altered Trehalose Metabolism on Physiological Response of Penicillium chrysogenum Chemostat Cultures during Industrially Relevant Rapid Feast/Famine Conditions

et al. 2021

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Due to insufficient mass transfer and mixing issues, cells in the industrial-scale bioreactor are often forced to experience glucose feast/famine cycles, mostly resulting in reduced commercial metrics (titer, yield and productivity). Trehalose cycling has been confirmed as a double-edged sword in the Penicillium chrysogenum strain, which facilitates the maintenance of a metabolically balanced state, but it consumes extra amounts of the ATP responsible for the repeated breakdown and formation of trehalose molecules in response to extracellular glucose perturbations. This loss of ATP would be in competition with the high ATP-demanding penicillin biosynthesis. In this work, the role of trehalose metabolism was further explored under industrially relevant conditions by cultivating a high-yielding Penicillium chrysogenum strain, and the derived trehalose-null strains in the glucose-limited chemostat system where the glucose feast/famine condition was imposed. This dynamic feast/famine regime with a block-wise feed/no feed regime (36 s on, 324 s off) allows one to generate repetitive cycles of moderate changes in glucose availability. The results obtained using quantitative metabolomics and stoichiometric analysis revealed that the intact trehalose metabolism is vitally important for maintaining penicillin production capacity in the Penicillium chrysogenum strain under both steady state and dynamic conditions. Additionally, cells lacking such a key metabolic regulator would become more sensitive to industrially relevant conditions, and are more able to sustain metabolic rearrangements, which manifests in the shrinkage of the central metabolite pool size and the formation of ATP-consuming futile cycles.

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“…To calculate the load bearing capacity and failure probability of corroded RC members, the calculation of the minimum cross-sectional area is of vital importance. To meet the convenience of engineers, the indicator R was adopted to determine directly the minimum crosssectional area, regardless of complicated corrosion topography of the rebar [9,10]. Statistical analysis found that the indicator R of corroded rebar can be characterized by Gumbel distribution and both the location parameter and the scale parameter increased linearly with increase in the corrosion degree [10].…”

Section: Introductionmentioning

confidence: 99%

Probability Distribution of Cross-sectional radius of Corroded Steel Bars in Concrete and Its application

Chongkai

Zhang

et al. 2018

MATEC Web Conf.

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The impress current method is applied to acquire corroded steel bars embedded in concrete, and three-dimensional(3D) laser scanning techniques are applied on corroded steel bars to obtain the cross-sectional radius of corroded steel bars. Statistical analysis shows that with the increase of corrosion degree, the variation of radius of corroded steel bars increases linearly. For different types of steel bars, plain round steel bars have a larger sensitivity to corrosion than ribbed ones. Original radius of steel bars and mixture proportion of concrete have negligible effect on the variability of radius of corroded steel bars. A normal distribution model is obtained to describe radius data of corroded steel bars. For the convenience of practical application, the indicator, R, which is the ratio of the average to the minimum cross-sectional areas of corroded steel bars, is introduced to quantify the longitudinal variation of the cross-sectional areas. By using Monte-Carlo simulation, the indicator, R, of corroded steel bars are achieved based on the probability distribution of radius. The indicator R can be fitted well by the Gumbel distribution, and the distribution parameters increase linearly with the increases of corrosion degree.

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Developing a Computational Framework To Advance Bioprocess Scale-Up

Cited by 60 publications

References 73 publications

History and Evolution of Modeling in Biotechnology: Modeling & Simulation, Application and Hardware Performance

History and Evolution of Modeling in Biotechnology: Modeling & Simulation, Application and Hardware Performance

Impact of Altered Trehalose Metabolism on Physiological Response of Penicillium chrysogenum Chemostat Cultures during Industrially Relevant Rapid Feast/Famine Conditions

Probability Distribution of Cross-sectional radius of Corroded Steel Bars in Concrete and Its application

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