The agitated bioreactor is the most widely used in the early development and research, pilot and production. It mainly composed of culture tanks, pipes, valves, pumps, motors and instruments. A reactor in which the motor drives the paddle to mix the culture solution, and uses the rotation of the agitator (Impeller) to drive the cell culture solution to flow and mix, so that the cells and nutrients are evenly distributed in the culture solution. Bioreactors type are divided into cage type aeration and stirring type, double-layer cage type aeration and stirring type, mechanical stirring type (stirred tank type), sea-going stirring type and centrifugal stirring type, etc. The tank of agitated bioreactor material is different. Small-scale bioreactor tanks are usually made of borosilicate glass, which can be sterilized in an autoclave for laboratory-scale research; large-scale bioreactor tanks are made of stainless steel through in situ sterilization with steam which is used in pilot and mass production. Different sensors installed on the tank body continuously detect the pH, temperature, dissolved oxygen, glucose consumption, ammonia accumulation and other parameters of the cell culture solution online.
Compared with other types of reactors, the stirring blades of agitated bioreactors provide the power for liquid phase agitation. The operating range of the agitated bioreactor allows it to have good mixing and concentration uniformity, so that the nutrients in the feed solution can be used sufficiently by the cells. And it can expand the gas-liquid contact surface, which is conducive to the transfer of oxygen; As for the shear force generated by mechanical agitation, it can be reduced by changing the shape and size of the blades or adding some protective agents to the cell culture medium which can reduce the influence caused by shearing force; In addition, another biggest advantage of the stirred bioreactor is that it can cultivate various types of animal cells, the cell density of the culture can reach 3×107 cells/ml, and the culture process is easy to scale up. So its product quality is stable and it is very suitable for industrial production which makes it a mainstream bioreactor for large-scale animal cell culture, and it is widely used in European and American countries in industrial production.
Now, the mainstream production process of biological products recommended by the FDA is to use suspension culture in a stirred bioreactor. The above also reflects the industry's common orientation towards suspension cell culture and adherent cell industrial culture platforms.
At present, the manufacturers of agitated bioreactors are mainly represented by KNIK BIO. And their products have a wide range of specifications, from laboratory scale to industrial scale. The large-volume bioreactor is designed and produced according to the user's requirements, and is applied to the production of industrial veterinary biological products. The agitated bioreactor produced is mainly adapted to industrialization and tends to be large-scale. The fully automatic 6000L bioreactor used in animal cell suspension culture. The development and design process of this reactor takes into account the characteristics of low shear tolerance of animal cells and high aerobic for high-density cells. It also has SIP and CIP functions to achieve "one key” operation performs automatic cleaning and automatic sterilization of tanks and pipelines, and has undergone a series of stability verification, CIP cleaning verification, sterility verification and multiple cell suspension culture verifications. The current design is based on the needs of users. Now, the 6000L bioreactor has been successfully applied to industrial production.