Cell membrane bioreactor

Membrane Bioreactors with Membrane as Bio reactor 310 Enzyme Membrane Reactor 311 Whole-Cell Membrane Bioreactor 312 Membrane Bioreactors with Membrane as Separation... 

The modelling of enzymatic membrane reactors follows, in general, the same approach as described previously. In enzymatic membrane reactors the catalyst is a macromolecule (enzyme). It can be found either in a free form in the reactor or supported on the membrane surface, or inside the membrane porous structure by grafting it or in the form of a gel obtained by ultrafiltration. As in the case of the whole-cell membrane bioreactors discussed above, the proper calculation of the mass transfer characteristics is of great importance for the modelling of this type of reactor. One of the earliest models of enzymatic membrane bioreactors is by Salmon and Robertson [5.108]. These authors modelled an enzymatic membrane bioreactor, which was made of four coaxial compartments the enzyme is confined within one of the compartments, and one of the substrates is fed in a gaseous form. 

Loh, K. C., Chnng,T. S. and Ang, W. F. 1999. Immobilized-cell membrane bioreactor for high-strength phenol wastewater. Journal of Environmental Engineering, 126,75-79. 

Membrane-based separation, lactic acid production and, 14 120 Membrane biocompatibility, in hemodialysis, 26 823—824 Membrane bioreactors, 16 26 Membrane-bound enzymes, 10 338 Membrane cell process, 9 620 Membrane cells... 

In addition, the substrate and product should be transported through the cell membrane, either passively or actively, and necessary cofactors should be regenerated. Finally, the specific organism used should function well in an optimized bioreactor system. All of these requirements can be met by using strains that contain the desired enzyme in question. 

In the development of cell or enzyme-based processes, many process configurations exist, including batch, fed batch and continuous operation. In general, the conversion and the separation processes (downstream processing) are regarded as separate units, and most industrial processes are based on this approach. In the last decades, however, more attention is paid to the integration of conversion and separation, leading to the development of membrane bioreactors [49, 50], and some of these concepts have reached an industrial scale. The membranes used for this type of reactors are almost exclusively polymeric, as temperatures seldomly exceed 100 °C for obvious reasons. 

Generally, a distinction can be made between membrane bioreactors based on cells performing a desired conversion and processes based on enzymes. In ceU-based processes, bacteria, plant and mammalian cells are used for the production of (fine) chemicals, pharmaceuticals and food additives or for the treatment of waste streams. Enzyme-based membrane bioreactors are typically used for the degradation of natural polymeric materials Hke starch, cellulose or proteins or for the resolution of optically active components in the pharmaceutical, agrochemical, food and chemical industry [50, 51]. In general, only ultrafiltration (UF) or microfiltration (MF)-based processes have been reported and little is known on the application of reverse osmosis (RO) or nanofiltration (NF) in membrane bioreactors. Additionally, membrane contactor systems have been developed, based on micro-porous polyolefin or teflon membranes [52-55]. 

Keywords. Bioartificial liver, cell culture, hollow fiber bioreactor, flat membrane bioreactor, spheroids... 

Bader et al. [35] and De Bartolo et al. [36] developed the flat membrane bioreactor which consists of a multitude of stackable flat membrane modules as shown in Fig. 5. Each module has an oxygenating surface area of 1150 cm. Up to 50 modules can presently be run in parallel mode. Isolated hepatocytes are co-cultured with non-parenchymal cells. Liver cells are located of a distance of 20 pm of extracellular matrix from a supported polytetrafluorethylene (PTFE) film. Medium and cells in the modules are oxygenated in the incubator by molecular diffusion of air across the non-porous PTFE membrane. The design of the bioreactor is also the basis for its proven potential for cryostorage with fully differentiated adult primary human liver cells. 

Figure 11.9 Different arrangements and modes of operation for membrane bioreactors Continuous Stirred Tank Reactor (CSTR) with recirculation arrangement (a), dead-end cell (b), tubular with entrapped enzyme (c).

Another type of microbiological reactor is the hollow fiber membrane bioreactor shown in Figure 13.19. In this device, the microbial cells are trapped on... 

Applications of whole-cell biocatalytic membrane reactors, in the agro-food industry and in pharmaceutical and biomedical treatments are listed by Giorno and Drioli [3], Frazeres and Cabral [9] have reviewed the most important applications of enzyme membrane reactors such as hydrolysis of macromolecules, biotransformation of lipids, reactions with cofactors, synthesis of peptides, optical resolution of amino acids. Another widespread application of the membrane bioreactor is the wastewater treatment will be discussed in a separate section. 

Membrane bioreactors can be easily integrated with other systems, for example, with delivery of drugs or genes to individual cells achieved on the nanoscale using electroporation techniques. In one method developed in a recent patent, a flowthrough bioreactor having an inlet and an outlet connected by a flow chamber and a nanoporous membrane positioned in the flow chamber was used [28]. 

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]. 

FIGURE 47 Schematic representation of the complex multifunctions enabled in a dual membrane bioreactor for hydridoma cell culturing (Integra Biosciences AG, Wallisellen, Switzerland). 

Cantarella, M., Spera, A., Cantarella, L., and Alfani, F. 1998b. Acrylamide production in an ultrafiltration-membrane bioreactor using cells of Brevibacterium imperialis CBS 489-74. Journal of Membrane Science, 147 279-90. 

Figure 173 (a) Time course of reaction rate in UF-membrane bioreactor at different temperature. Appropriate substrate feed solution (benzonitrile or benzamide) lOmM, resting cell load 2mgocw, flow-rate 12mlh. Filled symbols for nitrile hydratase activity ... 

Figure 17.4 (a) Time course of product concentration in UF-membrane bioreactor at various substrate concentration (benzonitrile in 50mM sodium phosphate buffer, pFI 7.0). Cell load lOrngocw, temperature 10°C, flow-rate 12mlh. ... 

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