Adherent Cell Culture Scale-up: Transitioning to Larger Vessels
For many research groups, the first step in scaling up will involve transitioning from a typical T-150 flask to a larger vessel such as the Corning® CellSTACK®, HYPERFlask®, or HYPERStack® vessels. CellSTACK culture chambers are available in 1-, 2-, 5-, 10-, and 40-layer sizes with up to 25,440 cm² of growth area. All CellSTACKs can be converted to closed systems using a variety of closed system caps and tubing offered through Corning. Transitioning to a closed system will facilitate the transition to GMP (good manufacturing practice), which is essential for the production phase.
Corning HYPERFlask and HYPERStack use an innovative gas-permeable film to offer more compact solutions. These vessels have an outer layer of rigid polystyrene, but the growth surface is ultra-thin polystyrene that allows for gas exchange. The HYPERFlask is similar to a traditional T-175 flask in overall size and shape but has 10 layers of ultra-thin polystyrene for 1,720 cm² of growth area. HYPERFlask is available for manual or automated handling.
HYPERStack vessels come out of the box as a closed system and are available with 12 or 36 layers offering 6,000 or 18,000 cm² of growth surface respectively. The footprint of a HYPERStack vessel is similar to that of a CellSTACK chamber, but the HYPERStack-36 is just 28 cm tall compared to CellSTACK-40 at 72 cm tall. To reduce handling time, HYPERStack vessels can be joined together with single-use manifolds. A five-arm manifold can be used to join stacks of four HYPERStack-36 vessels.
To facilitate liquid handling and improve consistency, the Corning Automated Manipulator Platform can support six HYPERStack-36 vessels for a total of 108,000 cm² (or 10.8 m²) of growth area. Alternatively, it can support three CellSTACK-40 vessels for a total of 76,320 cm² (or 7.632 m²) of growth area.
Ensuring Compatibility in Early Adherent Cell Culture Scale-up
Using CellSTACK, HYPERFlask, and HYPERStack vessels requires relatively modest changes to traditional 2D cell culture techniques. While some verification and modification are necessary as the scale of production increases, the process tends to be fairly straightforward and thus a good choice when process development time is limited. In the research and development phase, cells are typically grown on a 2D polystyrene surface that has been treated for tissue culture and perhaps given an additional coating to promote cellular attachment. Early in the research process, check whether the surface coatings, cells, medium, and additional components (including medium, serum and supplements) being used are compatible with later steps in the process, including clinical trials. Also, consider how cells or cellular products are being harvested. If any changes need to be made, consider making them sooner rather than later.