Premium
Process parameter shifting: Part II. Biphasic cultivation—A tool for enhancing the volumetric productivity of batch processes using Epo‐Fc expressing CHO cells
Author(s) -
Trummer Evelyn,
Fauland Katharina,
Seidinger Silke,
Schriebl Kornelia,
Lattenmayer Christine,
Kunert Renate,
VorauerUhl Karola,
Weik Robert,
Borth Nicole,
Katinger Hermann,
Müller Dethardt
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.20958
Subject(s) - bioprocess , bioreactor , productivity , cell growth , yield (engineering) , fermentation , microbiology and biotechnology , cell , chemistry , process (computing) , biochemical engineering , process engineering , biochemistry , biology , computer science , materials science , engineering , paleontology , organic chemistry , metallurgy , economics , macroeconomics , operating system
Regulation of cell growth and protein expression potentially results in a sustainable enhancement of the volumetric productivity in a fermentation process. Following a biphasic cultivation strategy the process initially passes through a cell proliferation phase to generate a sufficiently high viable cell mass. In the subsequent production phase cells are maintained viable and productive without significant cell proliferation leading to increased viable cell days and product yields. In a previous work we have shown that the well directed alteration of the process environment based on process parameter shifting is a promising tool to regulate cell growth and protein expression. In continuation of this work we investigated process parameters which have been identified to affect cell proliferation in favor of an increased specific productivity and total product yield in a series of biphasic batch cultivation experiments. In most of these processes the integral of viable cells and the specific productivity were increased leading to a significant improvement of both final product concentration and volumetric productivity. In addition, combined parameter shifts (pH 6.90/30°C and pH 6.90/33°C) exerted a synergistic effect on product quality. The loss of product sialylation which occurred at reduced temperatures was prevented by simultaneously reducing the external pH. In conclusion, biphasic cultivation based on combined shifting of process parameters is a suitable tool for controlling cell proliferation and protein expression of mammalian cells in a batch bioreactor leading to enhanced volumetric productivities and therefore offers an enormous potential for bioprocess optimization. © 2006 Wiley Periodicals, Inc.