Production of Avian Influenza
H1N1 Virus using TideCell
Bioreactor System
www.bioreactorsciences.com
A case study of Virus Prodcution
using MDCK cells
Comparison study
Due to significant difference in
characteristics of virus strain and host cell
line, the optimal process of virus
production can be significantly different.
In the following slides are requirement of
conditions for this specific case of study,
on which comparison of TideCell/BelloCell
system and other commonly used systems
are based.
High cell density is required to achieve
high virus titer.
TdeCell: High surface area provided
increase cell density. Cell density reach
around 4 x106 cells/ml.
Roller bottle: The surface area is limited.
Cell density reach around
0.5~1x106cells/ml
Microcarrier system: The bead density is
limited. Cell density reach around 1~2x106
cells/ml
Cell attachment efficiency is low due to
long term trypsinization.
 TideCell: Extremely low shear enviorment
enables high attachment rate even the cells
have been over-trypsinized.
 Roller bottle:A rolling culture status increases the
difficulties of cell attachment, especially in
serum-free culture medium.
 Microcarrier system: Agitated environment
increases the difficulties of cell attachment. The
cell attachment efficiency will become lower
when the scale is increased.
Cells tend to detach after infection
TideCell: Extremely low shear stress
environment enables cells not easy to
detach after infection and increase the
productivity.
Roller bottle: A rolling culture environment
enhances cell detach after infection.
Microcarrier system: Agitated environment
enhances cell detach after infection.
Low DNA and host cell protein are required
 TideCell: Low shear stress culture environment
enables cells retaining in the matrix without
being flushing out. DNA and host cell protein
residues are relatively low in the harvest.
 Roller bottle: A rolling agitated environment
causes cell disruption and release of DNA and
host cell protein directly into harvest.
 Microcarrier system: Agitated environment
causes cell disruption and release of DNA and
host cell protein directly into harvest.
Nutrient supply and medium exchange are
required to minimize cell interference and dilution
of virus titer.
 TideCell: Directly exchange culture medium from
the mixing tank without interfere cells in the
matrix vessel
 Roller bottle: Exchange culture medium directly
from the bottle causing detach of cells.
 Microcarrier system: Culture has to be stopped
temperarily and allow the microcarriers to settle
before medium exchange.
Cell Density before Infection
Summary of results
Production profile
Purification profile
Conclusion
TideCell: Virus HA titer: 512~1024
Roller Bottle: HA titer: 256
Microcarrier system: HA titer: 256~512
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