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Main Title: Automated Conditional Screening of Multiple Escherichia coli Strains in Parallel Adaptive Fed-Batch Cultivations
Author(s): Hans, Sebastian
Haby, Benjamin
Krausch, Niels
Barz, Tilman
Neubauer, Peter
Cruz-Bournazou, Mariano Nicolas
Type: Article
Abstract: 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.
Subject(s): high-throughput screening
rapid phenotyping
model-based experimental design
Escherichia coli
automated bioprocess development
Issue Date: 11-Nov-2020
Date Available: 28-Dec-2020
Is Part Of: 10.14279/depositonce-12144
Language Code: en
DDC Class: 570 Biowissenschaften; Biologie
Sponsor/Funder: BMBF, 031L0018A, ERASysAPP2 - Verbundprojekt: LEANPROT - Entwicklung einer Systembiologie-Plattform für die Entwicklung von lean-proteome-Escherichia coli-Stämmen - Deutsches Teilprojekt A
TU Berlin, Open-Access-Mittel – 2020
Journal Title: Bioengineering
Publisher: MDPI
Volume: 7
Issue: 4
Article Number: 145
Publisher DOI: 10.3390/bioengineering7040145
EISSN: 2306-5354
TU Affiliation(s): Fak. 3 Prozesswissenschaften » Inst. Biotechnologie » FG Bioverfahrenstechnik
Appears in Collections:Technische Universität Berlin » Publications

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