Development, characterization, and application of a 2-Compartment system to investigate the impact of pH inhomogeneities in large-scale CHO-based processes.
2‐Compartment system
CHO
inhomogeneities
large‐scale
pH excursions
scale‐down
Journal
Engineering in life sciences
ISSN: 1618-0240
Titre abrégé: Eng Life Sci
Pays: Germany
ID NLM: 101193313
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
13
02
2020
revised:
08
04
2020
accepted:
29
04
2020
entrez:
11
8
2020
pubmed:
11
8
2020
medline:
11
8
2020
Statut:
epublish
Résumé
Large-scale bioreactors for the production of monoclonal antibodies reach volumes of up to 25 000 L. With increasing bioreactor size, mixing is however affected negatively, resulting in the formation of gradients throughout the reactor. These gradients can adversely affect process performance at large scale. Since mammalian cells are sensitive to changes in pH, this study investigated the effects of pH gradients on process performance. A 2-Compartment System was established for this purpose to expose only a fraction of the cell population to pH excursions and thereby mimicking a large-scale bioreactor. Cells were exposed to repeated pH amplitudes of 0.4 units (pH 7.3), which resulted in decreased viable cell counts, as well as the inhibition of the lactate metabolic shift. These effects were furthermore accompanied by increased absolute lactate levels. Continuous assessment of molecular attributes of the expressed target protein revealed that subunit assembly or
Identifiants
pubmed: 32774209
doi: 10.1002/elsc.202000009
pii: ELSC1307
pmc: PMC7401239
doi:
Types de publication
Journal Article
Langues
eng
Pagination
368-378Informations de copyright
© 2020 The Authors. Engineering in Life Sciences published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim.
Déclaration de conflit d'intérêts
The authors have declared no conflict of interest.
Références
Curr Opin Biotechnol. 2010 Feb;21(1):114-21
pubmed: 20185293
J Biotechnol. 2010 Jun;147(3-4):186-97
pubmed: 20416347
Appl Microbiol Biotechnol. 2005 Sep;68(4):425-35
pubmed: 16001256
Biotechnol Appl Biochem. 2007 Aug;47(Pt 4):197-204
pubmed: 17362203
J Biotechnol. 2015 Jan 20;194:100-9
pubmed: 25529344
Cytotechnology. 2012 May;64(3):249-65
pubmed: 21870215
Biotechnol Bioeng. 2007 Aug 15;97(6):1479-88
pubmed: 17318909
Biotechnol Bioeng. 2015 Jun;112(6):1165-76
pubmed: 25545631
Biotechnol Bioeng. 1999;66(3):171-9
pubmed: 10577471
Biotechnol Bioeng. 2018 Aug;115(8):1890-1903
pubmed: 29603726
J Biotechnol. 2012 Dec 31;162(2-3):210-23
pubmed: 22974585
Microb Biotechnol. 2018 May;11(3):486-497
pubmed: 29333753
Biotechnol Prog. 2002 Mar-Apr;18(2):346-53
pubmed: 11934306
J Biotechnol. 2017 Mar 20;246:52-60
pubmed: 28159614
Biotechnol Bioeng. 2015 Jun;112(6):1220-31
pubmed: 25728062
J Biotechnol. 2014 Sep 30;186:98-109
pubmed: 25014402
Biotechnol Prog. 2018 May;34(3):756-766
pubmed: 29464875
Nat Rev Drug Discov. 2018 Mar 28;17(4):232
pubmed: 29588516
MAbs. 2019 Apr;11(3):569-582
pubmed: 30668249
Cytotechnology. 1996 Jan;22(1-3):87-94
pubmed: 22358918
Biotechnol Bioeng. 2001 Oct 5;75(1):63-73
pubmed: 11536128
Biotechnol Prog. 2004 Jul-Aug;20(4):1293-6
pubmed: 15296466
Biotechnol J. 2011 Dec;6(12):1532-46
pubmed: 21818860
Bioprocess Biosyst Eng. 2018 Dec;41(12):1731-1741
pubmed: 30088083
Biotechnol Bioeng. 2002 Aug 20;79(4):398-407
pubmed: 12115403
Biotechnol Bioeng. 2017 Aug;114(8):1733-1743
pubmed: 28322433
Adv Biochem Eng Biotechnol. 2014;139:35-68
pubmed: 24153406
Biotechnol Prog. 2011 Sep-Oct;27(5):1358-64
pubmed: 21626722
Biotechnol J. 2017 Jul;12(7):
pubmed: 28078826
Biotechnol Bioeng. 2006 Aug 20;94(6):1033-44
pubmed: 16736530
Biotechnol J. 2016 Sep;11(9):1190-200
pubmed: 27213298
Metab Eng. 2012 Mar;14(2):138-49
pubmed: 22244936
Cytotechnology. 2010 Jul;62(3):175-88
pubmed: 20502964
Eng Life Sci. 2017 Dec 19;18(3):204-214
pubmed: 32624899
Biotechnol Bioeng. 2007 Sep 1;98(1):141-54
pubmed: 17657776
MAbs. 2015;7(1):9-14
pubmed: 25529996
Biotechnol Bioeng. 2009 Jul 1;103(4):733-46
pubmed: 19280669
Biotechnol J. 2011 Aug;6(8):934-43
pubmed: 21695785