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Mammalian cell and protein distributions in ultrafiltration hollow fiber bioreactors
Author(s) -
Piret James M.,
Cooney Charles L.
Publication year - 1990
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.260360905
Subject(s) - ultrafiltration (renal) , concentration polarization , bioreactor , chemistry , fiber , chromatography , membrane , shell (structure) , biophysics , chemical engineering , materials science , biochemistry , biology , composite material , organic chemistry , engineering
The heterogeneous nature of hollow fiber reactors for cell cultivation requires special considerations for proper design and operation. Downstream concentration of high‐molecular‐weight proteins has been measured in the shell side of ultrafiltration hollow fiber bioreactors. This distribution resulted from shell‐side convective fluxes which caused a concentration polarization of proteins retained by the ultrafiltration membranes (nominal 3 × 10 4 D cutoff). Measurements of the axial hybridoma cell distribution also revealed a downstream concentration of viable cells during the first month of perfusion operation. This is believed to result from the shell‐side convective flow and its influence on the inoculum and high‐molecular‐weight growth factor distributions. The heterogeneous distribution of cells leads to reduced cell numbers and reactor productivities. The mechanisms responsible for these phenomena have been investigated and their implications in process design and operation are considered. The heterogeneous protein and cell distributions on the shell side of hollow fiber bioreactors have been reduced significantly by periodic alternation of the direction of recycle flow and the reactor antibody productivities have been doubled.