A common solution for producing higher quantities of anchorage-dependent cells has been to use large numbers of roller bottles and multi-trays to simply multiply the number of static surface areas.
The main disadvantage of this approach is that the process requires large operational space, cost, and time. With growing demand for large-scale production of vaccines, stem cells, and personalized medicines, more efficient and scalable production methods for anchorage-dependent cells has become necessary.
The suspension-culture method using micro-carriers in large vessels has been used as a more efficient and cost-effective way to scale-up this process. However, this approach has limitations.
Anchorage-dependent cells on microcarriers in large volume in bioreactors are more sensitive to hydrodynamic shear stress than are suspension cells. To maintain constant mass transfer efficiency in traditionally designed stirred bioreactors, shear stress increases as the size of the vessel increases. This makes the scaleup of the shear-sensitive process challenging.
An ideal bioreactor for microcarrier-based cell-culture processes would provide high mass transfer and good mixing but without the attendant high hydrodynamic forces—regardless of the size of the reactor.
The initial seeding phase of anchorage-dependent cells onto microcarriers is particularly sensitive to hydrodynamic forces. Until the cells are securely anchored to the surface of micro-carriers with cell-attachment proteins, the cell attachments are relatively weak and susceptible to hydrodynamic shear damages.
In many cases, this attachment step is carried out in static conditions coupled with brief, intermittent agitations, because the shear stress caused by impeller agitation inhibits cell attachment.