Hans, SebastianHaby, BenjaminKrausch, NielsBarz, TilmanNeubauer, PeterCruz-Bournazou, Mariano Nicolas2020-12-282020-12-282020-11-11https://depositonce.tu-berlin.de/handle/11303/12257http://dx.doi.org/10.14279/depositonce-11133In 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.en570 Biowissenschaften; Biologiehigh-throughput screeningrapid phenotypingmodel-based experimental designEscherichia coliautomated bioprocess developmentArticle2020-12-182306-5354