Recent advances in fed-batch microscale bioreactor design

Teworte, Sarah; Malcı, Koray; Walls, Laura E.; Halim, Murni; Rios‐Solis, Leonardo

doi:10.1016/j.biotechadv.2021.107888

Cited by 34 publications

(25 citation statements)

References 86 publications

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“…This indicates that, although succinic acid concentration was deemed to have a significant effect on bisabolene production by the statistical model (Figure 1), it was largely unconsumed at bioreactor scale. The differences in operational mode between scales may have contributed to the discrepancies observed as recent studies have shown that the ability of microscale batch screening experiments to predict performance of larger scale fed-batch processes is limited (Teworte et al, 2022). Future optimisation studies should therefore focus on the incorporation of fed-batch microscale tools to allow closer mimicry of large scale bioreactor conditions from the outset.…”

Section: Resultsmentioning

confidence: 99%

“…shown that the ability of microscale batch screening experiments to predict performance of larger scale fed-batch processes is limited (Teworte et al, 2022). Future optimisation studies should therefore focus on the incorporation of fed-batch microscale tools to allow closer mimicry of large scale bioreactor conditions from the outset.…”

Section: Gb2485 Bioreactor Cultivation With Ph-controlled Acid Feedingmentioning

confidence: 99%

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Toward sustainable jet fuels: bioconversion of cellulose into isoprenoid biojet candidates using rumen bacteria and non-conventional yeast

Walls

Otoupal

Ledesma-Amaro

et al. 2022

Preprint

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In this study, organic acids were demonstrated as a promising carbon source for bisabolene production by the non-conventional yeast, Rhodosporidium toruloides, at microscale with a maximum titre of 1055 mg/L. A 125-fold scale-up of the optimal process, enhanced bisabolene titres 2.5-fold to 2606 mg/L. Implementation of a pH controlled organic acid feeding strategy at this scale lead to a further threefold improvement in bisabolene titre to 7758 mg/L, the highest reported microbial titre. Finally, a proof-of-concept sequential bioreactor approach was investigated. Firstly, the cellulolytic bacterium Ruminococcus flavefaciens was employed to ferment cellulose, yielding 4.2 g/L of organic acids. R. toruloides was subsequently cultivated in the resulting supernatant, producing 318 mg/L of bisabolene. This highlights the feasibility of a sequential bioprocess for the bioconversion of cellulose, into biojet fuel candidates. Future work will focus on enhancing organic acid yields and the use of real lignocellulosic feedstocks to further enhance bisabolene production.

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Section: Resultsmentioning

confidence: 99%

Section: Gb2485 Bioreactor Cultivation With Ph-controlled Acid Feedingmentioning

confidence: 99%

Toward sustainable jet fuels: bioconversion of cellulose into isoprenoid biojet candidates using rumen bacteria and non-conventional yeast

Walls

Otoupal

Ledesma-Amaro

et al. 2022

Preprint

Self Cite

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“…Frontiers in Bioengineering and Biotechnology frontiersin.org have entered the market (Tapia et al, 2016;Granicher et al, 2019). It has been found that through improved culture strategies, such as fed-batch (Gutiérrez-Granados et al, 2018) and perfusion strategies (Teworte et al, 2021), high cell density can be obtained. However, high cell density culture will decrease cell-specific virus production and appear the cell density effect (i.e., the drop in the specific productivity in the virus-cells expression system when cells are infected at high cell densities).…”

Section: High Cell Density Virus Culturementioning

confidence: 99%

“…By the end of the 20th century, it reached a scale of 10,000 L ( Griffiths, 1990 ). Currently, with the development of fed-batch culture ( Gutiérrez-Granados et al, 2018 ), perfusion culture ( Teworte et al, 2021 ), and genetic engineering ( Pino et al, 2020 ), bioreactors have developed into a platform in which cells are used to produce a variety of viral vectors, live viruses, and virus-based vaccines. These bioreactors combine the low shear environment of traditional systems with the scalability of automated systems, and have a broader application prospect ( Von den Eichen et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Application of bioreactor technology for cell culture-based viral vaccine production: Present status and future prospects

Fang

Lyu

et al. 2022

Front. Bioeng. Biotechnol.

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Bioreactors are widely used in cell culture-based viral vaccine production, especially during the coronavirus disease 2019 (COVID-19) pandemic. In this context, the development and application of bioreactors can provide more efficient and cost-effective vaccine production to meet the global vaccine demand. The production of viral vaccines is inseparable from the development of upstream biological processes. In particular, exploration at the laboratory-scale is urgently required for further development. Therefore, it is necessary to evaluate the existing upstream biological processes, to enable the selection of pilot-scale conditions for academic and industrial scientists to maximize the yield and quality of vaccine development and production. Reviewing methods for optimizing the upstream process of virus vaccine production, this review discusses the bioreactor concepts, significant parameters and operational strategies related to large-scale amplification of virus. On this basis, a comprehensive analysis and evaluation of the various process optimization methods for the production of various viruses (SARS-CoV-2, Influenza virus, Tropical virus, Enterovirus, Rabies virus) in bioreactors is presented. Meanwhile, the types of viral vaccines are briefly introduced, and the established animal cell lines for vaccine production are described. In addition, it is emphasized that the co-development of bioreactor and computational biology is urgently needed to meet the challenges posed by the differences in upstream production scales between the laboratory and industry.

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“…Additionally, defined volumetric gas flow rates as in fermenters can be applied. 3) Fed-batch mode for multiple components can be implemented in a very cost-effective way ( Jeude et al, 2006 ; Panula-Perälä et al, 2008 ; Krause et al, 2010 ; Bähr et al, 2012 ; Krause et al, 2016 ; Philip et al, 2017 ; Habicher et al, 2019 ; Keil et al, 2019 ; Müller et al, 2019 ; Teworte et al, 2021 ). This even includes pH control and, thus, by reducing buffer concentrations, similar osmotic conditions as commonly used in stirred tank bioreactors can be applied ( Scheidle et al, 2011 ; Philip et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Implementation of Perforated Concentric Ring Walls Considerably Improves Gas-Liquid Mass Transfer of Shaken Bioreactors

Hansen

Gumprecht

Micheel

et al. 2022

Front. Bioeng. Biotechnol.

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Since their first use in the 1930s, shake flasks have been a widely used bioreactor type for screening and process development due to a number of advantages. However, the limited gas-liquid mass transfer capacities—resulting from practical operation limits regarding shaking frequency and filling volumes—are a major drawback. The common way to increase the gas-liquid mass transfer in shake flasks with the implementation of baffles is generally not recommended as it comes along with several severe disadvantages. Thus, a new design principle for shaken bioreactors that aims for improving the gas-liquid mass transfer without losing the positive characteristics of unbaffled shake flasks is introduced. The flasks consist of cylindrical glass vessels with implemented perforated concentric ring walls. The ring walls improve the gas-liquid mass transfer via the formation of additional liquid films on both of its sides, whereas the perforations allow for mixing between the compartments. Sulfite oxidation experiments revealed over 200% higher maximum oxygen transfer capacities (OTRmax) compared to conventional shake flasks. In batch cultivations of Escherichia coli BL21 in mineral media, unlimited growth until glucose depletion and oxygen transfer rates (OTR) of up to 138 mmol/L/h instead of an oxygen limitation at 57 mmol/L/h as in normal shake flasks under comparable conditions could be achieved. Even overflow metabolism could be prevented due to sufficient oxygen supply without the use of unconventional shaking conditions or oxygen enrichment. Therefore, we believe that the new perforated ring flask principle has a high potential to considerably improve biotechnological screening and process development steps.

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Recent advances in fed-batch microscale bioreactor design

Cited by 34 publications

References 86 publications

Toward sustainable jet fuels: bioconversion of cellulose into isoprenoid biojet candidates using rumen bacteria and non-conventional yeast

Toward sustainable jet fuels: bioconversion of cellulose into isoprenoid biojet candidates using rumen bacteria and non-conventional yeast

Application of bioreactor technology for cell culture-based viral vaccine production: Present status and future prospects

Implementation of Perforated Concentric Ring Walls Considerably Improves Gas-Liquid Mass Transfer of Shaken Bioreactors

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