Bioreactor stirred-batch

Bioreactors a) batch stirred tank b) continuous stirred tank c) continuous packed-bed i) downward flow, ii) upward flow and iii) recycle d) continuous fluidised-bed e) continuous ultrafiltration. Redrawn from Katchalski - Katzir E. (1993) Trends in Biotechnology II, 471-477. 

Stimuli-responsive materials, shape-memory polymers as, 22 355-356 Stirling cycle, 8 43 Stirred autoclave, 14 89, 92t Stirred autoclave reactor, 20 216 Stirred batch RO unit, 21 644 Stirred mills, 16 615 Stirred tank bioreactors, 1 737-740 oxygen transfer driving force, 1 734 Stirred tank electrochemical reactor (STER), 9 660-662... 

In conventional shake-flask cultivation, D. discoideum cells can reach maximum cell densities of 1-2x10 cells mL in HL-5 and up to 3 X10 cells mL in FM medium. A small-scale industrial facility can easily increase this number to 5 x 10 cells (5 kg) per week. Improvement of the original FM medium to compensate Hmitations with respect to amino acids (SIH medium) increased the densities of D. discoideum cultures to 5-6x10 cells mL [105]. Growth of D. discoideum cells in bioreactors in batch and fed-batch mode in a stirred tank-type bioreactor is a convenient fermentation method [107]. Under these conditions, it is possible to accumulate 36 g cell material (dry weight) from 7 L of cell culture in about 4 days (E. Flaschel, personal communication). 

Membrane bioreactors have been modelled using approaches that have proven successful in the more conventional catalytic membrane reactor applications. The simplest membrane bioreactor system, as noted in Chapter 4, consists of two separate units, a bioreactor (typically a well-stirred batch reactor) coupled with an external hollow fiber or tubular or flat membrane module. These reactors have been modelled by coupling the classical equations of stirred tank reactors with the mathematical expressions describing membrane permeation. What makes this type of modelling unique is the complexity of the mecha-... 

The typical bioreactor is a two-phase stirred tank. It is a three-phase stirred tank if the cells are counted as a separate phase, but they are usually lumped with the aqueous phase that contains the microbes, dissolved nutrients, and soluble products. The gas phase supplies oxygen and removes by-product CO2. The most common operating mode is batch with respect to biomass, batch or fed-batch with respect to nutrients, and fed-batch with respect to oxygen. Reactor aeration is discussed in Chapter 11. This present section concentrates on reaction models for the liquid phase. 

Production of Lignin Peroxidase. Medium for the inoculum was rich in yeast extract (25 g/1) and glucose (25 g/l) to promote maximal growth of the mycelia. The inoculum of Phanerochaete chrysosporium ATCC 24725 was first cultivated for 3 days at 30°C in five litres of medium divided in five shake flasks. The shake flask batches were transferred to a 100 litre bioreactor and cultivated again for 3 days at 30°C. The batches were stirred and aerated to obtain maximal growth of mycelia. 

The bioreactor has been introduced in general terms in the previous section. In this section the basic bioreactor concepts, i.e., the batch, the fed-batch, the continuous-flow stirred-tank reactor (CSTR), the cascade of CSTRs and the plug-flow reactor, will be described. 

Several different bioreactor configurations have been described for use in cell culture and fermentation applications. These include stirred tanks, airlift, and hoUow-fiber systems. The majority of bioreactor systems in use for cell culture applications are still of the stirred-tank type. These systems have been used for batch, fed-batch, and perfusion operations. It would not be possible to adequately cover the field of stirred-tank scale-up in the space available here. Instead, this section will touch briefly on the important issues in bioreactor scale-up. For detailed methodologies on stirred-tank bioreactor scale-up, the reader is referred to several review papers on the topic [20,27,28]. 

Figure 20 shows a schematic of a novel membrane-integrated process for citric acid production from glucose syrups by Yarrowia lypolitica ATCC 20346, based on prolonged fed-batch fermentation carried out in a stirred bioreactor coupled to a MF unit equipped with tubular ceramic membranes, and disodium citrate recovery from MF permeates by ED (Moresi, 1995). 

The production of substances that preserve the food from contamination or from oxidation is another important field of membrane bioreactor. For example, the production of high amounts of propionic acid, commonly used as antifungal substance, was carried out by a continuous stirred-tank reactor associated with ultrafiltration cell recycle and a nanofiltration membrane [51] or the production of gluconic acid by the use of glucose oxidase in a bioreactor using P E S membranes [52]. Lactic acid is widely used as an acidulant, flavor additive, and preservative in the food, pharmaceutical, leather, and textile industries. As an intermediate product in mammalian metabolism, L( +) lactic acid is more important in the food industry than the D(—) isomer. The performance of an improved fermentation system, that is, a membrane cell-recycle bioreactors MCRB was studied [53, 54], the maximum productivity of 31.5 g/Lh was recorded, 10 times greater than the counterpart of the batch-fed fermentation [54]. 

Parameter Stirred-tank bioreactors operated in batch and fed-batch mode Stirred-tank bioreactors operated in perfusion mode Heterogeneous bioreactors (packed-bed or hollow-fiber) operated in perfusion mode... 

Considerations of Macromixing and Micromixing in Semi-Batch Stirred Bioreactors... 

The most common cell culture systems developed for pilot- and commercial-scale production of monoclonal antibodies (MAbs) are hollow-fibre and ceramic matrix modules, stirred bioreactors and airlift fermenters. These systems allow cultivation of cells in batch, fed-batch, continuous or perfusion mode. The selection of a culture system and culture mode for the large-scale production of a particular MAb should take into account the growth and antibody-production characteristics of the particular hybridoma line. This module therefore presents an overview of the important characteristics of these systems. Detailed descriptions with accompanying results and a large collection of cited literature are given elsewhere (Seaver, 1987 Mizrahi, 1989 sections 5.1 and 5.9). 

The optimization of culture parameters and the scale-up of a human hetero-hybridoma in a stirred bioreactor are described in this section. From the viewpoint of scale-up and handling, a stirred bioreactor is chosen as the most practical approach for industrial-scale production of monoclonal antibodies (MAbs). Furthermore, stirred bioreactors are very flexible with regard to the optimization of culture parameters, i.e. oxygen supply (bubble free, air sparging) and culture mode (e.g. batch, fed-batch, chemostat and perfusion). They also give easy access to cell samples at any time of culture, and keep cells homogeneously supplied with nutrients and oxygen. 

A third type of bioremediation involves the use of a bioreactor in a dedicated treatment area. The contaminated soil is excavated, slurried with water, and treated in the reactor. The horizontal drum and airlift-type reactors are usually operated in the batch mode but may also be operated in a continuous mode. Because there is considerable control over the operating conditions, treatment often is quick and effective. Contaminated groundwater and effluent also may be treated in either fixed-film or stirred-tank bioreactors. However, bioreactors are still in the developmental stages and further research is required to optimize their efficiency and cost effectiveness (Wilson and Jones 1993). 

An ideal stirred bioreactor is assumed to be well mixed so that the contents are uniform in composition at all times. The plug-flow bioreactor (PFB) is an ideal tubular-flow bioreactor without radial concentration variations. The nutrient concentration of an ideal batch bioreactor after time t will be the same as that of a steady-state PFB at the longitudinal location of the residence time. Therefore, the following analysis applies for both the ideal batch bioreactor and the steady-state PFB. 

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