dc.contributor.author	Anane, Emmanuel
dc.contributor.author	García, Ángel Córcoles
dc.contributor.author	Haby, Benjamin
dc.contributor.author	Hans, Sebastian
dc.contributor.author	Krausch, Niels
dc.contributor.author	Krewinkel, Manuel
dc.contributor.author	Hauptmann, Peter
dc.contributor.author	Neubauer, Peter
dc.contributor.author	Cruz-Bournazou, Mariano Nicolas
dc.date.accessioned	2020-02-13T14:53:39Z
dc.date.available	2020-02-13T14:53:39Z
dc.date.issued	2019-07-30
dc.description.abstract	Concentration gradients that occur in large industrial‐scale bioreactors due to mass transfer limitations have significant effects on process efficiency. Hence, it is desirable to investigate the response of strains to such heterogeneities to reduce the risk of failure during process scale‐up. Although there are various scale‐down techniques to study these effects, scale‐down strategies are rarely applied in the early developmental phases of a bioprocess, as they have not yet been implemented on small‐scale parallel cultivation devices. In this study, we combine mechanistic growth models with a parallel mini‐bioreactor system to create a high‐throughput platform for studying the response of Escherichia coli strains to concentration gradients. As a scaled‐down approach, a model‐based glucose pulse feeding scheme is applied and compared with a continuous feed profile to study the influence of glucose and dissolved oxygen gradients on both cell physiology and incorporation of noncanonical amino acids into recombinant proinsulin. The results show a significant increase in the incorporation of the noncanonical amino acid norvaline in the soluble intracellular extract and in the recombinant product in cultures with glucose/oxygen oscillations. Interestingly, the amount of norvaline depends on the pulse frequency and is negligible with continuous feeding, confirming observations from large‐scale cultivations. Most importantly, the results also show that a larger number of the model parameters are significantly affected by the scale‐down scheme, compared with the reference cultivations. In this example, it was possible to describe the effects of oscillations in a single parallel experiment. The platform offers the opportunity to combine strain screening with scale‐down studies to select the most robust strains for bioprocess scale‐up.	en
dc.description.sponsorship	EC/H2020/643056/EU/Rapid Bioprocess Development/Biorapid	en
dc.description.sponsorship	TU Berlin, Open-Access-Mittel - 2019	en
dc.identifier.eissn	1097-0290
dc.identifier.issn	0006-3592
dc.identifier.uri	https://depositonce.tu-berlin.de/handle/11303/10769
dc.identifier.uri	http://dx.doi.org/10.14279/depositonce-9664
dc.language.iso	en
dc.rights.uri	https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subject.ddc	570 Biowissenschaften; Biologie	en
dc.subject.other	Escherichia coli	en
dc.subject.other	mini‐bioreactors	en
dc.subject.other	modeling	en
dc.subject.other	scale‐down	en
dc.subject.other	scale‐up effects	en
dc.title	A model‐based framework for parallel scale‐down fed‐batch cultivations in mini‐bioreactors for accelerated phenotyping	en
dc.type	Article	en
dc.type.version	publishedVersion	en
dcterms.bibliographicCitation.doi	10.1002/bit.27116
dcterms.bibliographicCitation.issue	11
dcterms.bibliographicCitation.journaltitle	Biotechnology and Bioengineering	en
dcterms.bibliographicCitation.originalpublishername	Wiley	en
dcterms.bibliographicCitation.originalpublisherplace	New York, NY	en
dcterms.bibliographicCitation.pageend	2918
dcterms.bibliographicCitation.pagestart	2906
dcterms.bibliographicCitation.volume	116
tub.accessrights.dnb	free
tub.affiliation	Fak. 3 Prozesswissenschaften::Inst. Biotechnologie::FG Bioverfahrenstechnik	de
tub.affiliation.faculty	Fak. 3 Prozesswissenschaften	de
tub.affiliation.group	FG Bioverfahrenstechnik	de
tub.affiliation.institute	Inst. Biotechnologie	de
tub.publisher.universityorinstitution	Technische Universität Berlin	de

A model‐based framework for parallel scale‐down fed‐batch cultivations in mini‐bioreactors for accelerated phenotyping

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