TheFermentation Process发酵过程
Fermentation is widely used withinthe Pharmaceutical and Food industries. It requires the cultivation insubmerged culture of an identified micro-organism (mainly bacterial) as amonoculture under defined environmental conditions. The incubation regimeimposed is designed to maximize the productivity of the organism of interest byproviding optimal conditions for population growth (biomass). The product ofinterest might be a bioactive metabolite or recombinant protein.
During an incubation cycle anutrient energy source (e.g. glucose) is added and the biomass and end productwill increase as this is depleted.
Fermenter Design and Control
Incubation control necessitates theprecise control of a number of parameters.
Of primary importance are:
Temperature, pH, DO2 or Redox,agitation, pressure, foam control, auxiliary feed or a combination of thesecontrollers.
The control of these and any otherparameters is most usually carried out in fermenter vessels specificallydesigned for the purpose and accommodating various working volumes depending onthe yield and production requirements. Laboratory scale vessels could have acapacity of just 10 litres or less whereas production vessels may be as largeas several thousand liters.
The smallest units may incorporatean electrical heater and feed stocks (e.g. Nutrient and pH control agents) maybe fed from flasks via peristaltic pumps. Larger vessels have an integraljacket for controlling temperature via hot or cold water and allowing indirectsterilisation using injected steam. Where larger quantities of feed stock arerequired they may be held in separate pressurized tanks and fed via a ‘thrustpump’ arrangement of valves.
The actual fermentation process isknown as the Incubation Phase and is just part of the batch cycle. A completefermentation cycle can typically include the following steps (depending onvessel design):
§ Empty(Blank) Sterilisation of vessel & pipework using direct Steam
§ Injection
§ Chargingwith base medium
§ IndirectSterilisation via Steam Injected into the vessel jacket
§ Cooling& Jacket Drain
§ Pre-Inoculation– Vessel environment under control
§ Inoculation– Injection of a small sample of themonoculture
§ Incubation– The Fermentation process itself
§ Harvesting– Product removed ready for extractionprocesses
The R&D and Clinical Trialsenvironments in which many small scale fermenters operate are such that it isnot possible to predict the nature of any particular fermentation processeither in terms of culture or incubation conditions. Production facilities mustalso cater for a variety of products each having precisely defined incubationprofiles.
A control system must thereforeprovide flexibility in the way in which accurate and repeatable control of thefermentation environment is achieved and will include the following features:
§ Preciseloop control with Setpoint profile programming
§ RecipeManagement System for easy parameterization
§ Sequentialcontrol for vessel sterilisation and more complex control strategies
§ Securecollection of on-line data from the fermenter system for analysis and evidence
§ Localoperator display with clear graphics and controlled access to parameters