Of nutrients and by-products—ways to control the culture environment
Despite the great variety of organisms, process parameters, and desired end-products, all bioprocesses have certain essential commonalities: The growth medium is inoculated with the desired cell line or microbial strain, which under favorable process conditions multiplies, consumes nutrients, and produces the desired end-product as well as by-products like lactate and ammonium.
In detail this looks different depending on the process mode.
Batch and fed-batch bioprocesses are well known and widely used. In a batch process the culture grows in the initially supplied batch of medium. The product accumulates in the culture. At some point the cells will stop growing and the proportion of viable cells will decline, because nutrients are consumed and toxic metabolites get concentrated. The fed-batch process is a variation of the batch process. Here the culture is fed to keep the concentration of nutrients constant.
High substrate concentrations can be achieved, resulting in higher cell densities and product titers, and prolonged cell viability, but toxic metabolites still accumulate over time. For a couple of years now, continuous cultivation has been discussed as a potential game changer in biopharma production. The idea is to keep the culture conditions constant by constantly adding fresh medium and harvesting ‘used’ medium.