Case Study

 "I feel this is a very easy to operate system.  I love its concept and it really works"

Bovine ephemeral fever also known as Three Day Sickness is an arthropod vector-borne disease of cattle and is caused by the Ephemerovirus virus of the Rhabdoviridae family of virus. The Rhabdoviridae are a class V virus according to the Baltimore classification of viruses. The BEF virus is a bullet or cone shaped virion which consists of a negative, single stranded RNA genome with a lipid envelope and 5 structural proteins. The envelope glycoprotein G contains type-specific and neutralizing antigenic sites. Theres has been recent evidence which demonstrated that the BEF virus induces apoptosis in several cell lines. It was however shown that apoptosis could be blocked by the caspaseinhibitor (Z-VAD-fmk), indicating that bovine ephemeral fever virus induces caspase-dependent apoptosis in cultured cells. (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 up to 10 folds.
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.
1.          2.
Cells tend to detach during post-infection period.
A gentle and relative static culture method enables a low shear stress culture environment. Cells will be not easy to detach after infection and increase the productivity.
Roller bottles
Yes. Shear stress is low.
Microcarrier stir tank
No. Shear stress is higher. Cells tend to detach during post-infection period
Fixed bed bioreactor
No. Shear stress is higher. Cells tend to detach during post-infection period
2.          3.
Infection time is crucial. 
Easy to take carrier sample for cell counting and MOI calculation.
Roller bottle
Yes. Can decide the infection time by observing the confluency from the bottles. But no exact cell density. MOI calcuation is rough.
Microcarrier stir tank
Yes. Carrier sample can be taken for cell counting.
Fixed bed bioreactor
No. Indirect estimation by DO or Glucose consumption rate. Difficult to calculate MOI.
3.          4.
Glucose consumption is not significant which make the adjustment of perfusion rate difficult. Batch run without exchange culture medium is determined.
Adjust matrix to culture medium ratio to 1:25 and make it a fed-batch to batch process.
Roller bottle
No. Not able to adjust culture medium volume.
Microcarrier stir tank
No. Not able to adjust matrix to medium volume ratio, unless to reduce microcarrier density. Fed-batch or batch procss is possible by reducing carrier density.
Fixed bed bioreactor
No. Not able to adjust matrix to medium volume ratio. Fed batch or batch process is not possible.
4.          5.
Linear scale-up to reduce process development time
BelloCell with 500 ml working volume and TideCell-020 with 500 L working volume reaches similar virus output (Log TCID50: 9.2 in BelloCell, 9.0 in TideCell -020)
Roller bottle
Yes, directly increase bottle number for scale up.
Microcarrier stir tank
No. process development is time consuming.
Fixed bed bioreactor
No. Not able to scale up.
5.          6.
Final Achievement
TCID50: log 9.0  with scale of 500 L
Log 9.2 (scale of 0.5 L)
Fixed bed bioreactor
Log 8.5  (scale of 2 L)