Case Study

"We use TideCell to produce rabies viruses for pet protection market. We are able to produce 1 log magnitude higher titer than from roller bottles.  Operate 15 L glass roller bottles are a heavy and tedious work. Thanks for TideCell that it reduces our burden on vaccine production not only on the cost saving."

Rabies Virus Production 

Rabies is a viral disease that causes acute inflammation of the brain in humans and other warm-bloodedanimals. Early symptoms can include fever and tingling at the site of exposure. These symptoms are followed by one or more of the following symptoms: violent movements, uncontrolled excitement, fear of water, an inability to move parts of the body, confusion, and loss of consciousness. Once symptoms appear, death nearly always results. The time period between contracting the disease and the start of symptoms is usually one to three months; however, this time period can vary from less than one week to more than one year. The time is dependent on the distance the virus must travel to reach the central nervous system. (cited from wikipedia)

Process Character
How TideCell supports the process requirement?
Can other systems do the same?
High cell density is required to achieve high titer, and reduce medium consumption.
High surface area provided in TideCell increase cell density. Cell density reach around 4 x106 cells/ml.
Roller bottle
No. low cell density due to limitation of surface area
Microcarrier stir tank
No. the bead density is limited
Fixed bed bioreactor,
Yes, but the scale is limited.
hollow fiber bioreactor
Yes, but the scale is limited.
Infection time and MOI is crucial. 
Capability of carrier sampling from the matrix vessel. Each carrier is with similar surface area and total number of carriers in a matrix vessel is fixed.  The total cell count is easy.
Roller bottle
Yes/No. Cell density and morphology could be observed under microscope. However, MOI is difficult to estimate.
Microcarrier stir tank
Yes. Carrier sampling is available.
Fixed bed bioreactor
No.  carrier sampling is not available.
CPE occurs slowly. A long term harvest is required.
Cells are immobilizd in a fixed-bed containing porous carriers.  Medium exchange is straight-forward and won’t damage or lost cells.
Roller bottle
Yes. Medium could be exchange directly.
Microcarrier stir tank
Yes/No, additional tool such as filter is required to stop microcarriers inside stir tank. Long term perfusion is difficult.
Fixed bed bioreactor
Yes, cells are immobilized. Medium could be exchange directly.
Require to reduce impurities to increase the recovery rate, reduce the host cell protein and DNA residues.
Cells, even lysis after virus infection, will be trapped inside the matrixes without flushing into the harvest medium. The host cell protein and DNA/RNA nucleic acid residues is several folds lower than conventional system.
Roller bottle
Yes, cells will retain on the bottle walls.
Microcarrier stir tank
No. Cells will be detached and milled by the microcarrier beads during agitation after infection and release high host cell protein and nucleic acids
Fixed bed bioreactor
No. Cells will be detached and milled by the microcarrier beads during agitation after infection and release high host cell protein and nucleic acids
Final Achievement
TCID50: Log 9.0
Roller bottle
Log 8.0
Microcarrier stir tank
Not available
Packed-bed bioreactor
Not available

Roller bottle
TideCell Bioreactor
Performance Analysis
15 L, 3000 cm2
10 L
550 g
Max. cell density
Culture days
Culture medium (cell culture)
1.5 L
290 L
Virus production days
Culture medium (virus production)
1.5 L
65 L
100 m2
3~6  m2
550 g
Culture medium
678 L
355 L
Virus concentration
Produce multivalent vaccine