"We proved that TideCell could produce our viruses linearly from BelloCell up to TideCell-100 (1,000 folds scale increase). The productivity remains relatively constant with similar operation parameters. It increases our annual productivity to 5 folds and reduce labors and space to 50% compared with existed roller bottle system. I feel this is the best bioreactor in the world to produce our products."
Hepatitis A is an acute infectious disease of the liver caused by the hepatitis A virus (HAV). Many cases have few or no symptoms, especially in the young. The time between infection and symptoms, in those who develop them, is between two and six weeks. When symptoms occur, they typically last eight weeks and may include nausea, vomiting, diarrhea, jaundice, fever, and abdominal pain. Around 10–15% of people experience a recurrence of symptoms during the six months after the initial infection. Acute liver failure may rarely occur with this being more common in the elderly. (cited from wikipedia)
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No.
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Process Character
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How TideCell supports the process requirement?
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Can other systems do the same?
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1.
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Cells are highly sensitive to shear stress during post-infection period
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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.
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Roller bottles
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Yes. Shear stress is low.
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Microcarrier stir tank
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No, shear stress is higher. Cells tend to detach during post-infection period
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2.
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Virus doesn’t cause Cytopathic effect (CPE). Entire production process is long and requires exchanging culture medium continuously.
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Low shear stress and easy medium exchange allows a long cell culture cycle in TideCell.
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Roller bottles
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Yes. Medium exchange may cause temperature shock unless the medium is pre-warmed.
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Microcarrier stir tank
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Yes. Perfusion culture by continuous exchange culture medium is possible
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3.
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Virus is non-secreted and require cell harvest and disruption to harvest the cells
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TideCell concentrate cells in the matrix vessel reducing total working volume to 1/5~1/25. It scales down the cell harvest process and make the cell harvest easier and efficient.
Matrix vessel could be separated from mixing tank and placed in a freezer for direct freeze and thaw process, which make the cell harvest easier and efficient.
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Roller bottle
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Yes, but cell harvest has to be made by each bottle. Thousands of bottles are required to operated separated compared with a single TideCell system
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Microcarrier stir tank
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Yes, but cell harvest is done from entire stir tank. Operation is heavy and difficult. Difficult to do freeze and thaw.
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Packed-bed bioreactor
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No. Not possible to harvest cells or do freeze&thaw process.
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4.
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Virus productivity is sensitive to nutrient supply and cell growth rate. Higher cell growth rate result lower virus productivity.
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TideCell won’t cause cell over growth. Easy to control cell growth by reducing tidal frequency and limiting nutrient supply. A simple starving procedure enhances protein or virus expression.
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Roller bottle
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No. Difficult to do nutrient control.
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Microcarrier stir tank
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Yes/No. An over-growth is possible. Nutrient control is done by reducing perfusion rate.
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Packed-bed system
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Yes/No. An over-growth is possible. Nutrient control is done by reducing perfusion rate.
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5.
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Final Achievement
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0.5 mg/L bioreactor
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Roller bottle
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0.5 mg/L
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Microcarrier stir tank
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0 mg/L. Fail to culture cells during post-infection period due to serious cell detachment problems.
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Data confidential.