Biomedical Engineering Reference
In-Depth Information
19.
Microb Cell Fact
. 2009 Aug 5;8:44.
Comparisons of optically
monitored small-scale stirred
tank vessels to optically
controlled disposable bag
bioreactors. Hanson MA,
Brorson KA, Moreira AR, Rao G.
Center for Advanced Sensor
Technology, Chemical and
Biochemical Engineering
Department, University of
Maryland Baltimore County,
Baltimore, MD, 21250.
grao@
umbc.edu
.
Upstream bioprocesses are extremely complex since
living organisms are used to generate active
pharmaceutical ingredients (APIs). Cells in culture
behave uniquely in response to their environment;
thus, culture conditions must be precisely defined
and controlled in order for productivity and product
quality to be reproducible. Thus, development
culturing platforms are needed where many
experiments can be carried out at once and pertinent
scale-up information can be obtained. Here we have
tested a high-throughput bioreactor (HTBR) as a
scale-down model for a lab-scale wave-type
bioreactor (CultiBag). Mass transfer was
characterized in both systems and scaling based on
volumetric oxygen mass transfer coefficient (K
L
a)
was sufficient to give similar DO trends. HTBR and
CultiBag cell growth and mAb production were
highly comparable in the first experiment, where DO
and pH were allowed to vary freely. In the second
experiment, growth and mAb production rates were
lower in the HTBR as compared to the CultiBag,
where pH was controlled. The differences in
magnitude were not considered significant for
biological systems. Similar oxygen delivery rates
were achieved in both systems, leading to
comparable culture performance (growth and mAb
production) across scales and mode of mixing. The
HTBR model was most fitting when neither system
was pH-controlled, providing an information-rich
alternative to typically nonmonitored mL-scale
platforms.
