Fermentation batch process

As you might have already gathered, the majority of industrial fermentations are batch processes. In closed batch systems, the growth medium is inoculated with cells and growth and product formation is allowed to proceed until the required amount of conversion has taken place. After harvesting the culture the vessel is cleaned, sterilised and filled with fresh medium prior to inoculation. For some processes, addition of all the feedstock prior to inoculation, as is done in closed batch fermentations, is undesirable and it is preferable to incrementally add the carbon source as the fermentation proceeds. Such a process is known as fed-batch culture and the approach is often used to extend the lifetime of batch cultures and thus product yields fed-batch cultures are considered further in Section 2.7.4. 

Figure 3.1 illustrates the main patterns for batch fermentation process kinetics for type 1,2 and 3 processes. 

Figure 3.7 shows the growth of R. rubrum in a batch fermentation process using a gaseous carbon source (CO). The data shown follow the logistic model as fitted by (3.14.2.11) with the solid lines, which also represent an unstructured rate model without any lag phase. The software Sigma Plot was used to fit model (3.14.2.11) to the experimental data. An increase in concentration of acetate in the prepared culture media did not improve the cell dry weight at values of 2.5 and 3 gT-1 acetate, as shown in Figure 3.7. However, the exponential growth rates were clearly observed with acetate concentrations of 0.5-2 g-F1 hi the culture media.

The actual fermentation process is known as the incubation phase and is just part of the batch cycle. A complete fermentation cycle can typically include the following steps, most likely depending on bioreactor design ... 

Batch fermentation means the cultivation of microorganisms, where the sterile growth medium in desired volume is inoculated with the microorganisms into the bioreactor and no additional growth medium is added during the fermentation. The product will be harvested at the end of the process. Typically, PHA s production is performed using batch fermentation because of low cost for investment and no special control. In addition, sterilization of the feed stock is easier than other fermentation processes, and operation is flexible. 

Fed-batch fermentation process is a production technique between batch and continuous fermentation. A proper medium feed rate is required to add sequentially into the fermentor during the process and the product is harvested at the end of fermentation just like a batch type. 

Fig. 21. Generalized description of fed-batch fermentation process data.

Bakshi and Stephanopoulos (1994b) have applied the above procedure to a fed-batch fermentation process. The problem involved 41 sets of batch records on 24 measured variables. Of these variables only very few were found by the decision tree to be relevant, and yield rules such as the following for guiding the diagnosis or control of a fermentor. 

J.F. van Impe and G. Bastin. Advanced Instrumentation, Data Interpretation, and Control of Biotechnological Processes, chapter Optimal Adaptive Control of Fed-Batch Fermentation Process, pages 401-435. Kluwer Academic Publishers,... 

H. Zhang and B. Lennox, Integrated condition monitoring and control of fed-batch fermentation processes, J. Process Control, 14, 41-50 (2004). 

Fermentation and alternative production techniques, such as roller bottles, can be carried out in four different ways. They are (1) batch process, (2) fed-batch process, (3) chemostat process, and (4) perfusion process. Batch and fed-batch processes require termination of cell growth while chemostat and perfusion processes allow continuous cell cultivation. 

In a batch fermentation process studied by Holmberg (ref. 3) the substrate is converted to biomass. The specific growth rate / ( 2) is described by the Michael is - Menten equation... 

There are several barriers to the successful control of bioprocesses due to particular circumstances that are related to their characteristics the complexities of microbial metabolisms, the nonlinearity of microbial reactions, the frequent use of batch and fed-batch operations, and the limited availability of sterihzable online sensors for important process variables such as cell and product concentrations. Furthermore, it is difficult to construct mathematical models that can predict the entire range of batch or fed-batch operations that many fermentation processes require. 

A software sensor for on-line determination of substrate was developed based on a model for fed-batch alcoholic fermentation process and on-line measured signals of ethanol, biomass, and feed flow. The ethanol and biomass signals were obtained using a colorimetric biosensor and an optical sensor developed in previous works that permitted determination of ethanol at a concentration of 0-40 g/L and biomass of 0-60 g/L. The volume in the fermentor could be continuously calculated using the total measured signal of the feed flow. The results obtained show that the model used is adequate for the proposed software sensor and determines continuously the substrate concentration with efficiency and security during the fermentation process. 

The control of a fed-batch alcoholic fermentation process can be obtained by controlling the substrate concentration in the medium by manipulation of the feed flow. The fermentation process presents complicated kinetic mechanisms. In addition, there is the absence of accurate and reliable mathematical models as well as the difficulty of obtaining direct measurements of the process variables owing to a lack of appropriate on-line analyzers and sensors. Control systems are formed by a set of instruments and control mechanisms connected through electrical signals in the... 

This article presents the design and implementation of a software sensor for the continuous determination of substrate concentration based on a simple model of a fed-batch fermentation process and the available signals of two other sensors—one for on-line biomass determination (7) and the other for on-line ethanol determination (8)—developed in previous works. The software sensor proposed provides a continuous signal that can be used in a control loop to manipulate the substrate feed flow in order to maintain almost constant substrate concentration and obtain an excellent level of productivity and yield during all of the process, as shown in experimental control strategy studies in previous works (9). 

A simple mathematical model is used for quantitative description of the process and consists of a set of equations relating inputs, outputs, and key parameters of the system. The model for an alcoholic fermentation fed-batch process developed by Mayer (10) and adapted with the Ghose and Tyagi (11) linear inhibition term by the product was used as the starting point for the development of a model-based substrate sensor with product (ethanol) and biomass on-line measurements. 

To simplify study of the fed-batch alcoholic fermentation process and with the purpose of regulating the substrate concentration in the fermentation medium, the following assumptions were made (1) the substrate concentration in the feed is constant and (2) the volume change in the fermentor is a function of feed flow. 

The fermentation process can be performed batch-wise or continuously at a given temperature and time. The broth is further processed to remove the desired chemical. Figure 11-11 shows a schematic and an abstracted physical model of a fermenter with the liquid phase as the control region. 

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