Enhanced harvest performance predictability through advanced multivariate data analysis of mammalian cell culture particle size distribution.
automated cell counter
centrifugation
monoclonal antibodies
multivariate data analysis (MVDA)
particle size distribution
shear
Journal
Biotechnology and bioengineering
ISSN: 1097-0290
Titre abrégé: Biotechnol Bioeng
Pays: United States
ID NLM: 7502021
Informations de publication
Date de publication:
02 Nov 2023
02 Nov 2023
Historique:
revised:
12
09
2023
received:
30
04
2023
accepted:
21
09
2023
medline:
2
11
2023
pubmed:
2
11
2023
entrez:
2
11
2023
Statut:
aheadofprint
Résumé
The industry's pursuit for higher antibody production has led to increased cell density cultures that impact the performance of subsequent product recovery steps. This increase in cell concentration has highlighted the critical role of solids concentration in centrifugation yield, while recent product degradation cases have shed light on the impact of cell lysis on product quality. Current methods for measuring solids concentration and cell lysis are not suited for early-stage high-throughput experimentation, which means that these cell culture outputs are not well characterized in early process development. This article describes a novel approach that leveraged the data from a widely-used automated cell counter (Vi-CELL™ XR) to accurately predict solids concentration and a common cell lysis indicator represented as lactate dehydrogenase (LDH) release. For this purpose, partial least squares (PLS) models were derived with k-fold cross-validation from the particle size distribution data generated by the cell counter. The PLS models showed good predictive potential for both LDH release and solids concentration. This novel approach reduced the time required for evaluating the solids concentration and LDH for a typical high-throughput cell culture system (with 48 bioreactors in parallel) from around 7 h down to a few minutes.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : AstraZeneca
ID : EP/L01520X/1
Organisme : Engineering and Physical Sciences Research Council
Informations de copyright
© 2023 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.
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