dilution rate is specified. Solving equation 16 for X and substituting into equation 4 yields


where dS is the fractional substrate conversion. High substrate conversion leads to lower raw materials costs and reduces the burden of residual substrate on downstream purification and waste treatment operations. When operating near the maximum reactor productivity (i.e., maximum OTR), the dilution rate and the inlet substrate concentration can be adjusted independently to achieve target levels of cell concentration and/or substrate conversion, as shown in Figure 2.

For biomass production when O2 transfer is not limiting productivity, the CSTR is favored over batch operation when the specific growth rate is high and the batch turnaround time is long. However, most industrial processes will be operating at or near the oxygen or heat transfer limitation. The desirability of enhanced O2 transfer has motivated the development of novel bioreactor designs (e.g., bubble columns, loop or airlift reactors). For therapeutic products, however, the overwhelming majority of fermentations are batch or fed-batch processes. In these applications, the choice of operating mode is not based on biomass productivity. Performance metrics such as volumetric productivity of the product, product yield, and product concentration become more important in evaluating potential operating strategies than simply the biomass concentration.

Product Formation. When the goal of the fermentation is to produce a product other than biomass, the criteria used to evaluate alternative operational modes are less straightforward than biomass productivity. In order to evaluate process alternatives, a proper set of performance metrics must be identified that relate to overall process economics. When process economics are dominated by fer mentation costs (e.g., fuel alcohol or gluconic acid production), volumetric productivity and conversion yields are especially relevant criteria as they relate to the size and cost of the reactor system and the cost of raw materials. In processes where recovery costs dominate (e.g., antibiotics), however, the size and operational costs of the recovery system are proportional to the fluid volume processed and inversely proportional to the product concentration (8). As a result, the final product concentration, or titer, is more important than biomass productivity.

The material balance on the product can be written as shown below, in which product formation is expressed using a specific product formation rate qP (g product/g DCW X h), and product degradation by a specific rate constant

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