Biomedical Engineering Reference
In-Depth Information
In the Tsunami Bioreactor, up to six rocker units integrated into one rack
housing 5 bags (each with 160 Liters Culture Volume (L CV) or 64 bags (each
with 5 L) move in opposite directions. This is no longer available.
Oxygen transfer (which is described by the volumetric oxygen transfer
efficiency rate (K
L
a) values) and its influence on the cultivation result have
been investigated for the majority of the systems. For Newtonian culture
broths, K
L
a values between 5 and 30 per hour were reported as being typi-
cal for animal cell cultivations in the BioWave, the Wave, and the AppliFlex.
Oxygen limitations may be virtually disregarded during such a process as
increasing the rocking rate, and angle is more effective in increasing the oxy-
gen transfer than increasing the aeration rate.
The required high oxygen level can be achieved by operating a BIOSTAT
CultiBag RM with low CV (50 L bag with 5 L CV) or the CELL-tainer. In
contrast to the version for cell cultures (CELL-tainer Bioreactor) where K
L
a
values exceed 100 per hour, values above 200 per hour are possible in the ver-
sion for microbial cultures (CELL-tainer Microbial Bioreactor). This is attrib-
uted to the 2D movement of the CELL-tainer, which ensures higher oxygen
transfer rates for microorganisms.
In the WUB, the wave propagated inside the bag is generated by periodic
upward movement of the movable head and/or foot section of the horizon-
tal table (platform) on which the bag is located; the K
L
a values of the WUB
are similar to those achieved with the BioWave. The parameters having the
most impact on the K
L
a data are the angle of the platform, the percentage of
the CV located on and lifted by the platform, the aeration rate, and the time
taken for the platform to complete one oscillation.
The Wave Bioreactor, BioWave, and BIOSTAT CultiBag RM differ in their
sensors and control units.
The wave-mixed bag bioreactors have secured a solid position in mam-
malian cell-derived seed train manufacturing and process developments
aimed at producing therapeutic proteins. These bioreactors are run in a
batch, fed-batch (feeding processes), or perfusion mode and are preferred
reactors for transient transfections; they are becoming widely used in sim-
ple, medium-volume processes such as the production of viruses for gene
therapies (e.g., recombinant adeno-associated virus vectors) and veterinary
as well as human vaccines (e.g., Aujeszky's disease virus, porcine influenza
virus, porcine parvovirus, mink enteritis virus, smallpox virus). Traditional
disposable virus production bioreactors (roller flasks, Cell Factories) have
been successfully replaced by wave-mixed bag bioreactors.
To date, wave-mixed bag bioreactors have proved acceptable for the culti-
vation of plant cell and tissue cultures in research and development (R&D).
Focusing on biomanufacturing, secondary metabolite productions (taxanes,
harpagosides, hyoscya-mine, alliin, ginsenosides, isoflavones) have been real-
ized in the BioWave and the WUB. Suspension cells, embryogenic cells, and
hairy roots were grown. In addition, the first proteins (e.g., human collagen/
alpha, tumor-specific human antibody) were successfully produced with
