Factors for Computing Control Limits

R =(R-bar) average of the ranges of aU the subgroups A2, D3, D4, <4 =factors for computing control limits and process capability =multiplication symbol... 

For each parameter, the pH, DO (dissolved oxygen), ORP (oxidation-reduction potential), temperature, agitation speed, culture volume and pressure can be measured with sensors located in the fermenter. The output of the individual sensors is accepted by the computer for the on-line, continuous and real-time data analysis. Information stored in the computer control system then regulates the gas flow valves and the motors to the feed pumps. A model of a computer control system is shown in Fig. 11. The computer control systems, like the batch systems for mammalian cell culture, seem to level out at a maximum cell density of 10 cells/ml. It may be impossible for the batch culture method to solve the several limiting factors (Table 10) that set into high density culture where the levels are less than 10 cells/ml. 

Here again, the and values derived from Table 16-1 are the factors used to compute the control limits for the range chart. From this information we now can chart x and R values as shown in Figure 16-26. 

Park et al. [251, 252] used a mutant strain of R. eutropha capable of using alcohols as a carbon source for the production of PHB and PHBV in fed-batch fermentors. With phosphate limitation as inducing factor, ethanol was used for the production in 7 L of 46.6 g PHB L (74% of the CDM) in 50 h [251]. When 1-propanol was added to the medium, up to 15.1 mol% in 3HV units were incorporated to the polymer, and when propanol was the sole carbon source, the cells accumulated about 85% of their CDM in P(3HB-co-35.2-mol% 3HV). Both alcohols were completely consumed. In computer-controlled fermentations [252], switches between the alcohols or mixtures thereof led to improved copolymer yield from the substrates and production rates. 

Bourque and co-workers [255] used a new soil isolate of Methylobacterium extorquens in preliminary experiments to produce PHB from methanol and PHBV from methanol and valerate in 2-L, fed-batch fermentations. For PHB production, the addition rate of methanol was computer-controlled in an attempt to keep the alcohol s concentration at an optimal level, which the authors previously determined to be 1.7 g L for the new isolate. This only partially worked, and in spite of no growth-limiting factor, the CDM reached, after a long 160 h, 9 g L 30 to 33% of which as the homopolymer. The isolate was also able to accumulate a P(3HB-co-20-mol% 3HV) copolymer. The authors pointed out the advantages of using methanol as a carbon source besides being a non-food substrate, it is relatively inexpensive, easily manipulable, completely miscible with water and of low viscosity. 

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