Repeated batch operation

Process steps include feed preparation, extraction, s >aration, and extxact finishing. Process parameters must be determirad for each raw material to achieve the optimum yield and quality of extract. The plant design must take into account hi pressure operation, food processing concerns, and repeated batch operation on lew bulk density solids. 

Devi, S. and Sridhar, P. (2000) Production of cephamycin C in repeated batch operations fi om immobilized Strepto-myces clavuligerus. Process Biochem.,... 

The cost-effective production of optically pure lactic acid from lignocellulose sugars is commercially attractive but challenging. Ca(OH)2 was found to be a better neutralizing agent than NaOH in terms of its giving higher lactic acid titer and productivity. From a kinetic point of view, SSF, a two-reactor fermentation system, and a one-reactor repeated batch operation increased lactic acid production. 

Much of the basic theory of reaction kinetics presented in Sec. 7 of this Handbook deals with homogeneous reaclions in batch and continuous equipment, and that material will not be repeated here. Material and energy balances and sizing procedures are developed for batch operations in ideal stirred tanks—during startup, continuation, and shutdown—and for continuous operation in ideal stirred tank batteries and plug flow tubulars and towers. 

All of the above processes are operated as batch fermentations, in which a volume of sterile medium in a vessel is inoculated. The broth is fermented for a defined period. The tank is then emptied and the products are separated to obtain the antibiotic. The vessel is then recharged for batch operation with medium and the sequence repeated, as often as required. Continuous fermentation is not common practice in the antibiotics industry. The antibiotic concentration will rarely exceed 20gT 1 and may be as low as 0.5g-l 1. 

Figure 1.8. Schematic frequency distributions for some independent (reaction input or control) resp. dependent (reaction output) variables to show how non-Gaussian distributions can obtain for a large population of reactions (i.e., all batches of one product in 5 years), while approximate normal distributions are found for repeat measurements on one single batch. For example, the gray areas correspond to the process parameters for a given run, while the histograms give the distribution of repeat determinations on one (several) sample(s) from this run. Because of the huge costs associated with individual production batches, the number of data points measured under closely controlled conditions, i.e., validation runs, is miniscule. Distributions must be estimated from historical data, which typically suffers from ever-changing parameter combinations, such as reagent batches, operators, impurity profiles, etc.

To accommodate completely batch operations, the procedure is easily modified by recognizing that water is required or available in discrete amounts, only at the beginning and end of both concentration and time intervals. The unknown concentrations (x) in the problem specification can be handled by repeating the calculations for a series of successively lower values for x, and selecting the lowest value that does not cause the overall water demand to increase. 

Solvent extraction of benzene works the same way. But instead of water, the various solvents used are sulfolane, liquid SO2, diethylene-glycol, and NMP (N-methyl pyrrolidone). The paint thinner/salt/water process described above might be called a batch solvent process, since it consists of sequential steps that can be repeated, batch after batch. Some low-volume commercial processes still operate that way. 

The bioreactor operation mode is normally defined at the outset of process configuration. Insect cells have been cultured in almost all known cultivation modes batch [10], repeated-batch [70], perfusion [71-74], fed-batch [75, 76], semi-continuous [77,78] and continuous [79]. In spite of this multitude of different strategies, the batch or, eventually, fed-batch mode is normally preferred due to the lytic infection cycle of the baculovirus. 

The low volumetric productivities that characterize batch cultivation processes are a disadvantage for the use of this operation mode for production. However, a variant known as repeated batches is an interesting alternative. It consists of initially carrying out a batch cultivation for the time needed to attain the desired product concentration. At that moment, just a part of the bioreactor contents is harvested. The remaining cell suspension inside the bioreactor is then used as inoculum for a new batch, by filling the vessel with fresh medium. This procedure can be repeated several times, until a decrease in cell growth or product formation is observed. The use of repeated batches allows a decrease of the time the bioreactor is non-productive. This eliminates the time periods that would be necessary for cleaning and sterilization between each batch. 

A disadvantage of the batch operation is that catalyst deactivation cannot be followed, unless the experiment can be repeated with the same catalyst sample. 

The operational modes for aqueous two-phase partitioning are similar to those used in solvent extraction. Single-stage partitioning, repeated batch... 

The system consists of a reactor vessel containing the carriers for cell growth and a reservoir vessel for medium (Figure 5.9.3). A recycle flow of medium from 40 ml, increasing with cell growth to 450 ml (per litre packed bed volume per minute), is pumped up through the bed and returned to the reservoir for oxygenation. The system can be operated in batch, repeated batch feed and harvest, or continuous mode. 

In a batch operation, substrates are placed in a reactor, and plasma polymerization coating is carried out as a unit operation. Repeating the same operation treats a large number of substrates. The batch processing is the primary mode for nearly all laboratory-scale operations. The batch processing can be done in a closed system or in a flow system. Because the number of molecules in a reactor under low pressure is small, it is often necessary to use a flow system to obtain a sufficient amount of coating. 

Next, the product is distilled as described in Chapter 5. Here also is a point at which lazy or unskilled operators err and thereby leave their product polluted with chlorephedrine. You see, it is next to impossible to completely convert the chlorephedrine into meth. The conversion can be encouraged by using plenty of catalyst, sufficient pressure, and ample reaction time in the bomb, but there will still be some left unreacted. As the catalyst wears out from doing repeated batches, the proportion of chlorephedrine in the product will increase. Only by doing careful fractional distillation, can the chlorephedrine be removed. 

The two-stage biocatalytic reaction can be performed in a single reactor [14], but the separation of the two reactions is preferred because of different reaction parameters (e.g., pH value, temperature, oxygen) and stability of the enzymes used. With water as the solvent and enzymes fixed on a carrier, the process runs in a repeated batch mode at room temperature (20-30°C). Higher temperatures lead to increased reaction rates, but also to higher byproduct formation and reduced stability of the biocatalysts. A pH value between 7.0 and 8.5 is recommended with respect to thermodynamics, enzyme activities and stability and formation of byproducts. The use of cells is not recommended with respect to operational stability and possible product contamination. Therefore purified enzymes covalently immobilized on a polymeric carrier are chosen for the industrial process for both steps. The particle diameter of the spherical biocatalyst is about 100-300 pm, to allow for acceptable mass transfer and filtration times. 

Culture techniques can be classified into batch, fed-batch, and continuous operation (Table 2). In batch processes, all the nutrients required for cell growth and product formation are present in the medium prior to cultivation. Oxygen is supplied by aeration. The cessation of growth reflects the exhaustion of the limiting substrate in the medium. For fed-batch processes, the usual fed-batch and the repeated fed-batch operations are listed in Table 2. 

In a batch operation, an ion exchange resin in the desired ionic form is placed into a stirred reaction vessel containing the solution to be treated. The mixture is stirred until equilibrium is reached (about 0.5 to 3 hours). Then the resin is separated from the liquid phase by rinsing with the eluting solution. An additional step may be required to reconvert the resin to the regenerated form if this is not done by the eluting solvent. The cycle may then be repeated. 

Production of L-carnitine by microbial hydroxylation of y-butyro-betaine (continuous process, yield > 130 g 1— 1 d 1, or repeated batch process) with amutant strain of Agrobac-terium/Rhizobium lacking L-carnitine dehydrogenase.This process (Fig. 17), developed by Lonza, operates on a 140 tons per year scale. L-Carnitine is used in pharmaceuticals as a thyroid inhibitor, as a slimming aid, and in sports foods and drinks [174,176,177]. 

L.R. Juneja, N. Hibi, T. Yamane, and S. Shimizu Repeated batch and continuous operations for phosphatidylglycerol synthesis from phosphatidylcholine with immobilized phospholipase U. Applied Microbiology and Biotechnology 27 (1987) 146-151. 

In addition, Jaworska and Szewczyk reported the production of chitosan from fungus Absidia orchids in batch, repeated batch, and continuous fermentation [60]. They reported that the batch process is better than other fermentation methods since it is easy to operate and gave higher amount of chitosan. 

To establish the operational stability over longer periods of operation, enzyme activity in the treated juice and wine was analysed. It was found that there is no enzyme desorption up to a monitoring period of 5 repeated batches and that 100% of activity is retained. In addition, after 6 months of storage at +4°C, the activity of the immobilized B-glucosidase was 100 % of the original activity. 

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