Operational modes of the bioreactor
Bioreactor cultivation operation and nutrient feeding has significant impact on the outcome of the bioreactor. Batch fermentation is initiated by inoculating a pre-sterilized and cooled medium. The reactor is a closed system and is highly dynamic in nature. Medium composition changes continuously with time to produce biomass and metabolites. The broth is harvested after the nutrients are consumed and products purified. The major problem of batch cultivation is high non production time and low productivity. In order to increase product formation and productivity substrate concentration in the batch could be taken higher, however sometimes it leads to substrate inhibition. This problem of high substrate concentration can be eliminated by gradual feeding of the substrate in the fed-batch cultivation.
A fed batch cultivation is identical to a batch operation, except that a feed is added to the broth continuously or intermittently. The volume of the broth increases with time. Feed rate and inlet substrate concentration in fed batch cultivation is decided in such a way that it improves the product formation and productivity of the fermentation. Also nutrient feeding in the fed – batch cultivation should be so designed that when the reactor is full it is having high product concentrations and no unconverted substrate. This is rather tricky and the mathematical model is usually very helpful in the design of the ideal nutrient feed strategy to optimize the product formation and productivity in fed-batch cultivation. The product formation and productivity will be adversely affected if the high concentration of the product inhibits biomass growth. For product inhibited cultivation Plug flow fermentation and continuous cultivations are particularly advantageous.
Plug flow bioreactor features cylindrical tubes in which substrate and microorganisms are continuously fed. The length and diameter of the tube is so selected that time required for the medium to travel from inlet to out let of the reactor is the total cultivation time. This type of reactor is severely limited by inadequate mixing problems. In terms of kinetics this reactor is equivalent to batch reactor. This mixing problem of plug flow reactor can be addressed by Continuous Stirred Tank Fermenter.
Continuous Stirred Tank Fermenter: This reactor is started as a batch and during the exponential growth of the microorganism fresh feed is initiated such that (D=Specific Growth Rate) the feed is continuously added and with drawn at the same rate, with the result constant volume is maintained in the reactor. Depending the supply of nutrients (and flow rate) the specific growth rate of the microorganism is automatically adjusted. This type of the reactor configuration is particularly suited for maintenance of right physiological state of the culture for sufficiently long time for high product formation. In this the productivity is high when both the product accumulation and dilution rates are high. In an attempt to increase high dilution rate sometimes the dilution rates equals to the maximum specific growth rate of microorganism. If this happens then the microorganisms are washed away from the bioreactor. To prevent this, sometimes the cells are recycled back (or retained in the bioreactor by spin filter device). This strategy significantly improves the productivity of fermentation. The productivity may also be improved by connecting either two CSTF’s in series. This arrangement is particularly useful when it is desirable to use different cultivation conditions for growth and product formation in the two different bioreactors.