Why are there different types of Bioreactors
In upstream processing there are many different types and sizes of bioreactors. The reactors usually differ based on method of mixing. Each reactor type tends to have it’s own advantages and disadvantages, and some will be more suitable for a certain cell type than others. For example, for an extremely shear sensitive cell it may be better to grow it in a bioreactor that is mixed by bubbles instead of impellers. However, for cells that need a lot of oxygen, a stirred tank reactor would be more suitable since they have good air dispersion. These factors also affect bioreactor size, as explained below.
What does reactor size depend on?
Bioreactor size mainly depends on type of product, product potency and product demand. For example, antibiotics are in high demand as the majority of the population need them, and therefore large vessels are needed. For personalised gene therapy, such as CAR-T cell therapy, a large quantity of the product is not required since the cells are grown only for one individual. Vaccines are also in high demand, but since they are much more potent antibiotics, it does not require as big of a vessel.
Common types of reactors
Stirred Tank Reactor
A stirred tank reactor (STR) is probably the most common type of reactor found in industry. Mixing is achieved via stirring using an impeller, and aeration is done via a sparger (a pipe that pumps in air). Baffles are also used in STRs to reduce vortexing (mini whirlpools) of the fluid.
STRs are generally the most efficient at mixing large volumes of liquid and achieving liquid homogeneity (oxygen concentration, nutrient concentration, are more even throughout fluid). Also, STRs are well-characterised, which has made processes using STRs easily automated. This is why it is the most common reactor in the industry.
However, STRs generally have a higher power consumption (amount of power dissipated into the fluid) than other reactor types. Power consumption is related to the shear stress inflicted on the broth, which can cause damage to cells. Therefore STRs tend to be unsuitable for cells that are shear-sensitive, such as mammalian cells.
STRs are best suited for cells that are not shear-sensitive (such as bacterial cells).
Additionally, some cells are anchorage dependent (need to be attached to a substrate in order to proliferate), which is common for mammalian cell lines. These kinds of cells cannot be grown in a traditional STR. However, micro-carriers (basically porous balls that cells can anchor to in a fluid) have been increasingly popular, allowing anchorage-dependent cells to be grown in STRs.
Rocked bed bioreactor
A rocked bed bioreactor uses rocking (moving in a seesaw like pattern) to create mixing in the fluid. It generally consists of a pillow-shaped container attached to a rocking surface (look below). Aeration is achieved via surface aeration – air diffuses from the surface of the fluid into the bulk fluid.
Rocked bed bioreactors are good for cells that are shear sensitive, since power dissipation tends to be lower. However, surface aeration means that there is lower oxygen transfer than in a STR. Also, a rocked bed system is only effective at low volumes due to difficulty of rocking large volumes and inefficient mixing. Online monitoring and control is also difficult since probes will not be immersed in the fluid all the time (as the fluid is rocked back and forth).
Rocked bed bioreactors are commonly used to scale-up from a flask to a bioreactor, as they can raise cell numbers to higher cell numbers than a flask.
Packed bed bioreactor/Perfusion Culture
Packed bed reactors contain a solid substrate within the vessel for cells to attach to. Mixing and aeration are done by continuous flow of liquid through the vessel. The most common packed bed reactor is the Hollow fibre reactor. The hollow fibre reactor has numerous little pipes spanning the length of the vessel, on which cells can grow on the outside. The fibres contain perforations (holes) to allow liquid to flow through and to increase the surface area.
Packed bed reactors are good for anchorage-dependent cells as they provide a surface for the cells to attach and proliferate on. They also have better homogeneity than static (not mixed) cultures since there is constant fluid flowing through. As a tank is used, scalability and online monitoring and control is better than in a rocked bed or static culture, especially for anchorage-dependent cells.
However, sampling tends to be difficult and the sample is usually destroyed in the process, due to the complex design. This factor also makes cleaning the reactor very complicated. Cell distribution may also be uneven, which can cause cells to grow differently.
Packed bed reactors tend to be used for expansion of anchorage-dependent cells, though they are getting phased out by micro-carriers.
Shaken cultures
Shaken cultures are cell cultures mixed by shaking. This is done by placing a flask on a shaking system. Aeration is done via surface aeration. Shaken cultures are usually kept inside incubators in order to maintain constant temperature and oxygen levels.
Shaken cultures are well understood and characterised, making them easy to use. This also makes them easy to automate. However, they are not scalable, there is no online monitoring or control and cannot be used for large volumes of cell broth.
Shaken cultures are often used early in the process to grow cell numbers before cell expansion to a rocked bed reactor or small STR.
If you have any questions or want me to explain some other types of reactors, please leave a comment below and I will get onto it as soon as possible!
Bioprocessing Explained 