Please use this identifier to cite or link to this item: https://doi.org/10.15480/882.2735
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dc.contributor.authorMöller, Johannes-
dc.contributor.authorRosenberg, Marcel-
dc.contributor.authorRiecken, Kristoffer-
dc.contributor.authorPörtner, Ralf-
dc.contributor.authorZeng, An-Ping-
dc.contributor.authorJandt, Uwe-
dc.date.accessioned2020-04-02T12:07:17Z-
dc.date.available2020-04-02T12:07:17Z-
dc.date.issued2020-03-04-
dc.identifier.citationAnalytical and Bioanalytical Chemistry 9 (412): 2065-2080 (2020-04-01)de_DE
dc.identifier.issn1618-2642de_DE
dc.identifier.urihttp://hdl.handle.net/11420/5597-
dc.description.abstractCell population heterogeneities and their changes in mammalian cell culture processes are still not well characterized. In this study, the formation and dynamics of cell population heterogeneities were investigated with flow cytometry and stably integrated fluorescent markers based on the lentiviral gene ontology (LeGO) vector system. To achieve this, antibody-producing CHO cells were transduced with different LeGO vectors to stably express single or multiple fluorescent proteins. This enables the tracking of the transduced populations and is discussed in two case studies from the field of bioprocess engineering: In case study I, cells were co-transduced to express red, green, and blue fluorescent proteins and the development of sub-populations and expression heterogeneities were investigated in high passage cultivations (total 130 days). The formation of a fast-growing and more productive population was observed with a simultaneous increase in cell density and product titer. In case study II, different preculture growth phases and their influence on the population dynamics were investigated in mixed batch cultures with flow cytometry (offline and automated). Four cell line derivatives, each expressing a different fluorescent protein, were generated and cultivated for different time intervals, corresponding to different growth phases. Mixed cultures were inoculated from them, and changes in the composition of the cell populations were observed during the first 48 h of cultivation with reduced process productivity. In summary, we showed how the dynamics of population heterogeneities can be characterized. This represents a novel approach to investigate the dynamics of cell population heterogeneities under near-physiological conditions with changing productivity in mammalian cell culture processes.en
dc.language.isoende_DE
dc.publisherSpringerde_DE
dc.relation.ispartofAnalytical and bioanalytical chemistryde_DE
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAutomated flow cytometryde_DE
dc.subjectClonal stabilityde_DE
dc.subjectLeGOde_DE
dc.subjectPopulation heterogeneityde_DE
dc.subjectProcess variabilityde_DE
dc.subject.ddc540: Chemiede_DE
dc.subject.ddc600: Technikde_DE
dc.titleQuantification of the dynamics of population heterogeneities in CHO cultures with stably integrated fluorescent markersde_DE
dc.typeArticlede_DE
dc.identifier.doi10.15480/882.2735-
dc.type.diniarticle-
dcterms.DCMITypeText-
tuhh.identifier.urnurn:nbn:de:gbv:830-882.085399-
tuhh.oai.showtruede_DE
tuhh.abstract.englishCell population heterogeneities and their changes in mammalian cell culture processes are still not well characterized. In this study, the formation and dynamics of cell population heterogeneities were investigated with flow cytometry and stably integrated fluorescent markers based on the lentiviral gene ontology (LeGO) vector system. To achieve this, antibody-producing CHO cells were transduced with different LeGO vectors to stably express single or multiple fluorescent proteins. This enables the tracking of the transduced populations and is discussed in two case studies from the field of bioprocess engineering: In case study I, cells were co-transduced to express red, green, and blue fluorescent proteins and the development of sub-populations and expression heterogeneities were investigated in high passage cultivations (total 130 days). The formation of a fast-growing and more productive population was observed with a simultaneous increase in cell density and product titer. In case study II, different preculture growth phases and their influence on the population dynamics were investigated in mixed batch cultures with flow cytometry (offline and automated). Four cell line derivatives, each expressing a different fluorescent protein, were generated and cultivated for different time intervals, corresponding to different growth phases. Mixed cultures were inoculated from them, and changes in the composition of the cell populations were observed during the first 48 h of cultivation with reduced process productivity. In summary, we showed how the dynamics of population heterogeneities can be characterized. This represents a novel approach to investigate the dynamics of cell population heterogeneities under near-physiological conditions with changing productivity in mammalian cell culture processes.de_DE
tuhh.publisher.doi10.1007/s00216-020-02401-5-
tuhh.publication.instituteBioprozess- und Biosystemtechnik V-1de_DE
tuhh.identifier.doi10.15480/882.2735-
tuhh.type.opus(wissenschaftlicher) Artikel-
dc.type.driverarticle-
dc.type.casraiJournal Article-
tuhh.container.issue9de_DE
tuhh.container.volume412de_DE
tuhh.container.startpage2065de_DE
tuhh.container.endpage2080de_DE
dc.relation.projectIBÖ-04: mDoE-Toolbox - Software zur modellgestützten Optimierung biotechnologischer Prozessede_DE
dc.relation.projectIBÖM04:mDoE-Toolbox2-Neue mDoE Software-Toolbox zur modellgestützten Optimierung biotechnologischer Prozessede_DE
dc.rights.nationallicensefalsede_DE
local.status.inpressfalsede_DE
local.funding.infoFunding by German Federal Ministry of Education and Research (BMBF, Grant 031B0222). Funding by BMBF (Grants 031B0305 and 031B0577A).Funding from DFG Sonderforschungsbereich SFB841 (SP2).de_DE
item.creatorOrcidMöller, Johannes-
item.creatorOrcidRosenberg, Marcel-
item.creatorOrcidRiecken, Kristoffer-
item.creatorOrcidPörtner, Ralf-
item.creatorOrcidZeng, An-Ping-
item.creatorOrcidJandt, Uwe-
item.openairetypeArticle-
item.openairecristypehttp://purl.org/coar/resource_type/c_6501-
item.fulltextWith Fulltext-
item.mappedtypeArticle-
item.creatorGNDMöller, Johannes-
item.creatorGNDRosenberg, Marcel-
item.creatorGNDRiecken, Kristoffer-
item.creatorGNDPörtner, Ralf-
item.creatorGNDZeng, An-Ping-
item.creatorGNDJandt, Uwe-
item.cerifentitytypePublications-
item.grantfulltextopen-
item.languageiso639-1en-
crisitem.project.funderBundesministerium für Bildung und Forschung (BMBF)-
crisitem.project.funderBundesministerium für Bildung und Forschung (BMBF)-
crisitem.project.funderid501100002347-
crisitem.project.funderid501100002347-
crisitem.project.funderrorid04pz7b180-
crisitem.project.funderrorid04pz7b180-
crisitem.project.grantno031B0305-
crisitem.project.grantno031B0577A-
crisitem.author.deptBioprozess- und Biosystemtechnik V-1-
crisitem.author.deptBioprozess- und Biosystemtechnik V-1-
crisitem.author.deptBioprozess- und Biosystemtechnik V-1-
crisitem.author.deptBioprozess- und Biosystemtechnik V-1-
crisitem.author.orcid0000-0001-9546-055X-
crisitem.author.orcid0000-0001-9050-6766-
crisitem.author.orcid0000-0003-1163-9718-
crisitem.author.orcid0000-0001-9768-7096-
crisitem.author.orcid0000-0001-8221-5176-
crisitem.author.parentorgStudiendekanat Verfahrenstechnik-
crisitem.author.parentorgStudiendekanat Verfahrenstechnik-
crisitem.author.parentorgStudiendekanat Verfahrenstechnik-
crisitem.author.parentorgStudiendekanat Verfahrenstechnik-
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