Fermentation measurements

He does, in the same paper, express his optimism about fermentation measurements using NIR technology. 

In the process of the cultivation of recombinant E. coli, low yields are observed due to the formation and accumulation of acetic acid resulting from overflow metabolism. Thus, it is necessary to prevent and monitor the formation of acetic acid, which can be avoided by the introduction of glucose to the medium. However, the rate of glucose addition must be monitored in order to maintain the growth below a critical value. In this context, a flow injection system was developed for the determination of acetic acid in E. coli cultivations with electrochemical detection based on immobilized AK, PK, and LDH, with amperometric detection of NADH. A limitation associated with this system was that the enzyme AK lost 90% of its activity after only one fermentation. The authors thus suggested that, due to the low stability of immobilized AK in the fermentation measurements, alternative enzymes needed to be found (Tang et al., 1997). 

Temperature, pH, and feed rate are often measured and controlled. Dissolved oxygen (DO) can be controlled using aeration, agitation, pressure, and/or feed rate. Oxygen consumption and carbon dioxide formation can be measured in the outgoing air to provide insight into the metaboHc status of the microorganism. No rehable on-line measurement exists for biomass, substrate, or products. Most optimization is based on empirical methods simulation of quantitative models may provide more efficient optimization of fermentation. 

A suitable means of scale-up for aerobic processes is to measure the dissolved oxygen level that is adequate in small equipment and to adjust conditions in the plant until this level of dissolved oxygen is reached. However, some antibiotic fermentations and the production of fodder yeast from hydrocarbon substrates have very severe requirements, and designers are hard-pressed to supply enough oxygen. 

Bioprocess Control An industrial fermenter is a fairly sophisticated device with control of temperature, aeration rate, and perhaps pH, concentration of dissolved oxygen, or some nutrient concentration. There has been a strong trend to automated data collection and analysis. Analog control is stiU very common, but when a computer is available for on-line data collec tion, it makes sense to use it for control as well. More elaborate measurements are performed with research bioreactors, but each new electrode or assay adds more work, additional costs, and potential headaches. Most of the functional relationships in biotechnology are nonlinear, but this may not hinder control when bioprocess operate over a narrow range of conditions. Furthermore, process control is far advanced beyond the days when the main tools for designing control systems were intended for linear systems. 

Table 11-5 shows the mixing times for different sizes of reaetors used in penieillin fermentation with H/D = 2.5. The measured mixing time is eompared witli tlie ealeulated mixing time from Equation 11-102. The observed differenees in the measured and ealeulated t may be explained by the following ... 

The antibiotie Tylosin was produeed in a CSTR using Streptomyees fradiae in a 5 liter laboratory fermenter. For different substrate flow-rates the eoneentrations of produet and biomass were measured [23]. 

Fermenter An industrial microbiological reactor in which the addition of nutrients, removal of products, and insertion of measuring sensors and control devices are maintained while accessories like heating, aeration, agitation, and sterilization systems are provided. 

Where yield coefficients are constant for a particular cell cultivation system, knowledge of how one variable changes can be used to determine changes in the other. Such stoichiometric relationships can be useful in monitoring fermentations. For example, some product concentrations, such as CO2 leaving an aerobic bioreactor, are often the most convenient to measure in practice and give information on substrate consumption rates, biomass formation rates and product formation rates. 

Measurement of all these parameters provides suffident information to evaluate foe fermentation and leads to the economical production of foe amino add. We will now discuss several relevant parameters seperately with foe help of foe data obtained (see Figure 8.5). 

The concentration of dissolved oxygen in a fermenter is normally measured with a dissolved oxygen electrode, known as a DO probe. There are two types in common use galvanic... 

This is the most accurate method of measuring the mass transfer coefficient and it can be used in the actual fermentation system. It depends on accurate oxygen analyses and... 

Measurements and control of the fermentation conditions are very important for bioprocess control as they provide knowledge and hence a better understanding of the operation. 

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