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Open AccessArticle

Automated Conditional Screening of Multiple Escherichia coli Strains in Parallel Adaptive Fed-Batch Cultivations

1
Technische Universität Berlin, Institute of Biotechnology, Chair of Bioprocess Engineering, Strasse des 17. Juni 135, 10623 Berlin, Germany
2
AIT Austrian Institute of Technology GmbH, Giefingasse 2, 1210 Vienna, Austria
3
DataHow AG, ETH Zürich-HCI, F137, Vladimir-Prelog-Weg 1, 8093 Zurich, Switzerland
*
Author to whom correspondence should be addressed.
Bioengineering 2020, 7(4), 145; https://doi.org/10.3390/bioengineering7040145
Received: 15 September 2020 / Revised: 7 November 2020 / Accepted: 9 November 2020 / Published: 11 November 2020
In bioprocess development, the host and the genetic construct for a new biomanufacturing process are selected in the early developmental stages. This decision, made at the screening scale with very limited information about the performance in larger reactors, has a major influence on the efficiency of the final process. To overcome this, scale-down approaches during screenings that show the real cell factory performance at industrial-like conditions are essential. We present a fully automated robotic facility with 24 parallel mini-bioreactors that is operated by a model-based adaptive input design framework for the characterization of clone libraries under scale-down conditions. The cultivation operation strategies are computed and continuously refined based on a macro-kinetic growth model that is continuously re-fitted to the available experimental data. The added value of the approach is demonstrated with 24 parallel fed-batch cultivations in a mini-bioreactor system with eight different Escherichia coli strains in triplicate. The 24 fed-batch cultivations were run under the desired conditions, generating sufficient information to define the fastest-growing strain in an environment with oscillating glucose concentrations similar to industrial-scale bioreactors. View Full-Text
Keywords: high-throughput screening; rapid phenotyping; model-based experimental design; Escherichia coli; automated bioprocess development high-throughput screening; rapid phenotyping; model-based experimental design; Escherichia coli; automated bioprocess development
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MDPI and ACS Style

Hans, S.; Haby, B.; Krausch, N.; Barz, T.; Neubauer, P.; Cruz-Bournazou, M.N. Automated Conditional Screening of Multiple Escherichia coli Strains in Parallel Adaptive Fed-Batch Cultivations. Bioengineering 2020, 7, 145. https://doi.org/10.3390/bioengineering7040145

AMA Style

Hans S, Haby B, Krausch N, Barz T, Neubauer P, Cruz-Bournazou MN. Automated Conditional Screening of Multiple Escherichia coli Strains in Parallel Adaptive Fed-Batch Cultivations. Bioengineering. 2020; 7(4):145. https://doi.org/10.3390/bioengineering7040145

Chicago/Turabian Style

Hans, Sebastian; Haby, Benjamin; Krausch, Niels; Barz, Tilman; Neubauer, Peter; Cruz-Bournazou, Mariano N. 2020. "Automated Conditional Screening of Multiple Escherichia coli Strains in Parallel Adaptive Fed-Batch Cultivations" Bioengineering 7, no. 4: 145. https://doi.org/10.3390/bioengineering7040145

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