Shear-sensitive cells

BIOREACTOR DESIGN FOR SHEAR SENSITIVE CELL CULTURES... 

Stirred- tank 1. Flexible and adaptable 2. Wide range of mixing intensity 3. Can handle high viscosity media 1. High power consumption 2. Damage shear sensitive cells 3. High equipment costs... 

CIB could have a promising future in its application in shear sensitive cell cultures [26]. 

Recently, Wang and Zhong successfully designed a novel centrifugation impeller bioreactor (Fig. 3) for shear-sensitive cell systems [35, 36]. They proved... 

Su WW, Caram HS Humphrey AE (1992) Optimal design of the tubular microporous membrane aerator for shear-sensitive cell cultures. Biotechnology Progress 8 19-24. 

The flat-bottomed design of the KLF 2000 bioreactor affords a higher stirrer speed to prevent sedimentation of cells compared with the round-bottomed NLF 22 bioreactor (see below). For cultivation of shear-sensitive cells, round-bottomed bioreactors may be necessary. To avoid high temperatures near the heat finger, a power control unit is used to restrict the power to the range 800-200 W but as low as possible to maintain a temperature of 37°C. In addition to this, heating is restricted to intervals of a few seconds only and the glass part of the bioreactor is insulated. 

Wide range of mixing intensity Damage shear sensitive cells... 

ITT systems have been used at aU process scales. With the appropriate cleaning validation to demonstrate removal of protein and debris from previous use, tangential flow Alters can be cleaned and used multiple times. ITT is usually not appropriate for clarihcation of a very shear-sensitive cell hne or a low viability process as the turbulent flow required to recirculate the cells in the system leads to more cell breakage, resulting in release of more impurities in the clarified product. 

A bioreactor must be designed for optimal heat, gas, and mass transfer as well as for short mixing times. At the same time, the fluid s dynamic environment in the bioreactor should not destroy shear-sensitive cells, such as mammalian cells, despite the required transfer and mixing conditions. 

Even though these special application examples demonstrate the scalability of the technology, and although airlift reactors have long been used for shear-sensitive cell-culture applications, the CSTR design has become the standard for microbial and mammalian cell suspension culture. Its design is versatile, and cultivations can be scaled from the laboratory to pilot scale and to up to 300 m in fully contained sterile fermenters. 

It can handle highly viscous fermentation broths and achieve high oxygen transfer and heat exchange rates and provides short mixing times. For shear-sensitive cells, turbines and flow breakers in the fermenter are replaced by impellers, resulting in lower fluid dynamic stress. 

Higher ceU densities maintained in a bioreactor Easier and lower-cost separation of ceUs from culture media Continuous ceU culture process at high dilution rates readily estabhshed Enhanced resistance to shear stress for shear-sensitive cells, for example, plant and mammahan ceUs Reduction of the lag phase of ceU growth Increased volumetric productivity Improved substrate utihzation... 

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