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Shear stress analysis of mammalian cell suspensions for prediction of industrial centrifugation and its verification
Author(s) -
Hutchinson N.,
Bingham N.,
Murrell N.,
Farid S.,
Hoare M.
Publication year - 2006
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.21029
Subject(s) - centrifuge , bioprocess , centrifugation , shear stress , shear rate , materials science , shear (geology) , scale up , particle size , chromatography , volumetric flow rate , process engineering , chemistry , composite material , rheology , mechanics , engineering , chemical engineering , physics , classical mechanics , nuclear physics
This article describes the use of ultra scale‐down studies requiring milliliter quantities of process material to study the clarification of mammalian cell culture broths using industrial‐scale continuous centrifuges during the manufacture of a monoclonal antibody for therapeutic use. Samples were pretreated in a small high‐speed rotating‐disc device in order to mimic the effect on the cells of shear stresses in the feed zone of the industrial scale centrifuges. The use of this feed mimic was shown to predict a reduction of the clarification efficiency by significantly reducing the particle size distribution of the mammalian cells. The combined use of the rotating‐disc device and a laboratory‐scale test tube centrifuge successfully predicted the separation characteristics of industrial‐scale, disc stack centrifuges operating with different feed zones. A 70% reduction in flow rate in the industrial‐scale centrifuge was shown to arise from shear effects. A predicted 2.5‐fold increase in throughput for the same clarification performance, achieved by the change to a centrifuge using a feed zone designed to give gentler acceleration of the bioprocess fluid, was also verified at large‐scale. © 2006 Wiley Periodicals, Inc.