How to design a mammalian cell bioreactor? How to choose a suitable mixing tank?
In the past, reusable versions dominated, but in recent years, disposable stirred tank bioreactors have been widely used in mammalian cell culture processes due to improved design and monitoring capabilities. A working volume of 1000-2000L can basically meet commercial needs.
Design points of reusable stirred tank bioreactor
Structural parameters: mostly cylindrical glass or stainless steel tanks, with a height to diameter ratio of approximately 2:1, and a working volume accounting for about 70% of the total volume.
The diameter of the stirring blade, the gap between the blade and the tank bottom, and the distance between the blades have specific ratios.
Axial flow impellers are commonly used for stirring, such as "elephant ear" impellers, and combinations of axial and radial flow impellers are also used, with a lower rotational speed than microbial fermentation.
At the same time, a baffle with a width of 10% of the tank diameter is often set up to improve mixing.
Ventilation and parameter control
The supply of O ₂ and removal of CO ₂ are crucial for mammalian cell culture.
Reduce cell damage caused by bubbles by optimizing ventilation strategies and using protective agents. Tube or microbubble distributors are used for ventilation, and pure oxygen can be used instead of air if necessary.
In addition, suitable bioengineering parameters such as kLa and unit volume ventilation rate need to be determined, and a constant P/V is a commonly used scaling standard.
Design points of disposable stirred tank bioreactor
The cultivation container is made of plastic and contains pre assembled components that have been irradiated with gamma radiation. Its working volume range is wide, with a H/D ratio of 1.5:1 to 2.2:1, which can ensure a certain kLa value.
The cultivation bag is composed of multiple layers of thin films. However, there are issues with extractable and precipitable substances affecting cell growth and product quality, and due to material limitations, they are more commonly used for research and clinical sample production.
How to choose a bioreactor?
Disposable bioreactors are suitable for small and medium-sized projects with high flexibility requirements, strict pollution risk control, and tight time to market, but they have high costs and generate a lot of waste.
Reusable bioreactors are suitable for large-scale, long-term stable production. Although the initial investment is large, the long-term operating costs may be low. However, cleaning and sterilization are complex, and the risk of contamination is relatively high.
