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Cell function profiling to assess clone stability
Author(s) -
Dobson Paul D.,
Coss Karen P.,
Doherty Carolanne,
Clifford Jerry,
Thompson Ben,
James David C.
Publication year - 2020
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27336
Subject(s) - chinese hamster ovary cell , bioprocess , computational biology , cell culture , biology , titer , function (biology) , clone (java method) , microbiology and biotechnology , cell function , biological system , cell , computer science , genetics , antibody , dna , paleontology
In cell line development the identification of stable Chinese hamster ovary cells for production is a critical but onerous task. The stability trial focus upon high‐level attributes can mask profound underlying cellular changes, leading to unstable clones mistakenly being chosen for production. The challenge is to assay underlying cell pathways and subsystems without pushing up cell line development costs. ChemStress® cell function profiling is a simple, multiwell plate‐based assay that uses a panel of active chemicals to mimic known bioprocess stresses and challenge key pathways. After 3 days of static culture on the plate, functional responses are assayed, for example, titer and growth. Here this approach is used to monitor 131 clones as they change over real stability trials. A novel stability metric is defined over the data to identify stable clones that remain unperturbed across many components of cell function. This allows stability trials to look beneath the titer to identify clones that are internally more stable.

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