Synthetic biology has transformed biomanufacturing. Cells can be genetically engineered to produce proteins, including antibodies, for use in food, research, and clinical applications. However, to produce sufficient quantities of these proteins, a large number of cells has to be grown. Bioreactors are a key piece of equipment for scaling up cell culture. Here, we will introduce the various types of bioreactors and their distinguishing features.
The first bioreactor was created for compressed yeast production by George De Becze and A.J. Liebmann in 1944. This prototype consisted of stainless steel pipes that could introduce air containing oxygen for cells to grow. Subsequent designs included impellers for uniform mixing of nutrients and air bubble dispersal. Materials like plastics are replacing stainless steel in bioreactors, especially for smaller scale production like chimeric antigen receptor T cell manufacturing. This is because plastic bioreactors are designed to be single-use to minimize contamination and are also cheaper than stainless steel bioreactors to quickly optimize growth conditions for cells.
Stirred tank bioreactors
Stirred tank bioreactors, which can go up to tens of thousands of liters, are popular among major pharmaceutical companies and food manufacturers. Nevertheless, in stirred tank bioreactors, the vigorous motion of the impeller may damage delicate cells. For instance, turbulent flows and shear stresses can affect the differentiation and viability of primary stem cells
Rocking bed bioreactors
To maintain high cell quality, manufacturers have turned to an innovative type of bioreactor that uses wave-like motion. This rocking bed bioreactor minimizes shear stresses and allows nutrients to be evenly distributed. Rocking bed bioreactors can be classified as a form of benchtop bioreactor, which is generally more affordable and has a smaller physical footprint.
Bioreactors are a key piece of equipment for scaling up cell culture.
Packed bed bioreactors
Stirred tank and rocking bed bioreactors are most suitable for culturing non-adherent cells. For growing adherent cells such as muscle cells, a good option is the packed bed bioreactor. This bioreactor consists of a bed of microcarriers that cells adhere to, and it is coupled with uniform flow of gases and growth medium across immobilized cells. Researchers are also trying to replace the synthetic microcarriers with bioengineered (and biodegradable) scaffolds to improve tissue engineering projects like synthetic meat production.
Automation in bioreactor technology
Over the last few years, bioreactor manufacturers have turned to developing automated bioreactors, such as Miltenyi Biotec’s CliniMACS Prodigy and Lonza’s Cocoon. These automated platforms allow users to perform cell activation and expansion in a modular manner, and typically only for small scale processes like cell therapy. Automation in bioreactors can be helpful as they may reduce cell manufacturing failures and minimize contamination. It also improves compliance with good manufacturing practices and enables multiple batch production for autologous cell therapy.
The bioreactor is an invaluable piece of equipment for biological research and applications. Depending on the scale and routineness of production, users can choose from a range of products. Stirred tank bioreactors are most suitable for large scale manufacturing of cells with established recipes for cell growth. Packed bed bioreactors are an excellent option for culturing adherent cells. Benchtop bioreactors like rocking bed bioreactors are useful for small scale manufacturing of high-quality cells for use in therapies. Users can also expect to see more automation in bioreactor technology for performing cell expansion, monitoring cell growth, and harvesting cells.