Ultrafiltration membrane reactor system

Jeon, Y. J. and Kim, S. K. 2002. Antitumor activity of chitosan ohgosaccharides produced in an ultrafiltration membrane reactor system. J. Microbiol. Biotechnol. 12 503-507. 

Cabral and coworkers [253] have investigated the batch mode synthesis of a dipeptide acetyl phenylalanine leucinamide (AcPhe-Leu-NH2) catalyzed by a-chymotrypsin in a ceramic ultrafiltration membrane reactor using a TTAB/oc-tanol/heptane reverse micellar system. Separation of the dipeptide was achieved by selective precipitation. Later on the same group successfully synthesized the same dipeptide in the same reactor system in a continuous mode [254] with high yields (70-80%) and recovery (75-90%). The volumetric production was as high as 4.3 mmol peptide/l/day with a purity of 92%. The reactor was operated for seven days continuously without any loss of enzyme activity. Hakoda et al. [255] proposed an electro-ultrafiltration bioreactor for separation of RMs containing enzyme from the product stream. A ceramic membrane module was used to separate AOT-RMs containing lipase from isooctane. Application of an electric field enhanced the ultrafiltration efficiency (flux) and it further improved when the anode and cathode were placed in the permeate and the reten-tate side respectively. 

Membrane reactor systems in which the enzyme is recovered by ultrafiltration of the reaction mixture after hydrolysis is complete have been developed. These systems have been pilot tested in Australia but have not been commercialized (Zadow 1984). 

To conclude, the nitrogen-containing ligands are easy to handle, to syndiesize and to support them on polymers, dius diis constitutes a crucial advantage for using them in various separation systems (precipitation, ultrafiltration, membrane reactor, biphasic solid/liquid or Uquid/liquid). 

Ultrafiltration has been used for the separation of dendritic polymeric supports in multi-step syntheses as well as for the separation of dendritic polymer-sup-ported reagents [4, 21]. However, this technique has most frequently been employed for the separation of polymer-supported catalysts (see Section 7.5) [18]. In the latter case, continuous flow UF-systems, so-called membrane reactors, were used for homogeneous catalysis, with catalysts complexed to dendritic ligands [23-27]. A critical issue for dendritic catalysts is the retention of the catalyst by the membrane (Fig. 7.2b, see also Section 7.5). 

Figure 13.18 Continuous recycle fermentor membrane reactor. An ultrafiltration module removes the liquid products of fermentation as a clean product. This system is being developed for production of ethanol, acetone and butanol by fermentation of food processing waste streams...

Fermentation is typically conducted in dilute suspension culture. The low concentration in such systems limits reaction efficiency, and the presence of particulate and colloidal solids poses problems for product recovery and purification. By circulating the fermentation broth through an ultrafiltration system, it is possible to recover product continuously as they are generated while minimizing loss of enzyme or cells and keeping product concentration in the bioreactor below the self-inhibition level for the biocatalyst. This process is referred to as perfusion. As the ultrafiltration unit is part of the production process, the entire system is often considered a membrane reactor. 

The enzymatic system used for the continuous production of Mn3+-malonate is presented in Fig. 10.3. It is composed by a stirred tank reactor (200-mL working volume) operated in continuous mode coupled to a 10 kDa cutoff ultrafiltration membrane (Prep/Scale-TFF Millipore), which permits the recycling of the enzyme to the reaction vessel. The enzyme was recycled in a recycling feed flow ratio of 12 1. 

Scaling up of the processes to large surface areas (i.e. to obtain asymmetric membrane systems with several layers) as is necessary for large-scale operations has been successfully demonstrated for micro/ultrafiltration and bioseparation processes, but not for other applications such as gas/vapour separation and membrane reactors, for which only small-scale laboratory equipment is available. 

The membrane reactor is an ultrafiltration system, in which a high concentration of hydrolytic enzyme is confined. High molecular weight substrate is fed continuously to the reactor, and the low molecular weight products are removed simultaneously as permeate. Ideally, a steady state is reached, in which the degradation of the substrate is carried out indefinitely with high efficiency and negligible loss of enzyme. 

The same reactors can be used for dealing with immobilized enzymes in organic solvents or with one-phase organic systems as for dealing with enzymes in aqueous solutions. For one-phase systems, the enzyme may be recovered from the solution by means of membrane filtration. Suspended enzyme particles may be retained in a slurry reactor (compare to Fig. 7-35) by microfiltration membranes or stainless steel sieves, whereas in other cases such as reverse micelles, ultrafiltration membranes have to be used 891. For some years ultrafiltration membranes have been available... 

In the previous examples the membranes have been considered generally as semiperineable barriers for the separation of small molecules from bigger ones. When in parallel to the separation a chemical reaction takes place in the bulk solution or in the membrane itself, the system may be identified as a true membrane reactor. A classical example is a stirred-tank enzymatic reactor connected by a continuous recirculation loop to an ultrafiltration or dialysis unit. Such a system, when well designed, permits the continuous removal of the reaction products from the bulk solution without loss of enzyme (or the insoluble or macromolecular substrate ). 

On the other hand, in nature a continuous uptake of substrate and release of product without loss of biocatalysts is not achieved by carrier fixation but by means of cellular membranes. Efficient immobilized enzyme reactor systems for technical applications can therefore be established replacing cellular membranes by ultrafiltration or reverse osmosis synthetic membranes, and the activated transport through the cellular wall by a forced flow across the membrane.7... 

Ultrafiltration of an enzyme solution through a UF membrane does not always result in gel layer formation. Unless a gel layer is formed, this immobilization technique cannot be used for flow systems lacking effective enzyme immobilization. In any event, soluble enzyme membrane reactors can be useful in order to perform kinetic analysis at high enzyme concentrations. Once steady state is attained, the theoretical model permits calculation of reaction rates in both regions. Once the layer is formed it behaves like a secondary membrane,34 capable of separating compounds of different molecular weight in the mixture as well as catalyzing a chemical reaction. 

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