High Density Microbial Culture

High density culture meets the need to produce the maximum quantity of product (usually a recombinant protein) in the minimum time/volume. INFORS HT has many year’s experience in designing systems to provide powerful mixing, good temperatuer control plus flexible oxygeneration and feeding strategies. This applies at the small scale e.g. 0.5 L to hundreds of litres.

The essential requirements are all met by INFORS HT bioreactors i.e.:

• Powerful motors to provide good mixing and meet the demand for high levels of dissolved oxygen as culture density increases.
• Temperature control which can cope with the increasing heat output as culture densities increase.
• A variety of strategies for maintaining dissolved oxygen levels appropriate to the culture density and substrate availability.
• Control of several feed pumps to allow for changes in substrates at different stages of the fermentation or automated addition of an induction agent.
• The ability to add external sensors to detect substrate concentration, the build-up of toxic by-products or the concentration of product

How automated process control can help:

High density culture is dependent upon high levels of available dissolved oxygen at times of maximum growth (using cascades of process parameter such as stirrer speed, gas flow and oxygen suplementation) or control of feed to match the quantity of substrate which is already present in the bulk culture. INFORS HT provides the ability to easily add on-line sensors for e.g. glucose or methanol, control feed based on microbial metabolism using e.g. respiratory quotient (RQ) or provide a range of options for feeding exponetially, in response to real-time measurement of substrate concentration or to match the available level of dissolved oxygen. Add features such as “Follow file” to easily repeat productive fermentations and flexible event-based sequence control provided by the Iris bioproces control software and reliable, reproducible optimisation strategies can be used combined with the ability to respond in case of unexpected variations in individual fermentations.

Typical microbes used for high density culture applications include:

• E. coli
• Pichia pastoris

Typical Working Volumes:

Multifors 2 0,5 - 1 l	Minifors 1 - 3 l	Labfors 5 1,2 - 10 l	Techfors-S 5 - 30 l	Techfors 20 - 750 l