Contained ultrafiltration systems

Ultrafiltration systems should never be taken off line without thorough flushing and cleaning. Because membrane modules are normally stored wet, the final rinse solutions should contain a bacteriostat such as 0.5% formaldehyde to inhibit bacterial growth. 

This brief overview describes some experiences using tangential-flow and dead-end ultrafiltration techniques for concentration of eukaryotic cells, proteins and virus. The data and conclusions presented here have been drawn from process development work employing available apparatus and should be considered preliminary, rather than definitive or exhaustive. Previous ultrafiltration systems have been described (1-14) for both bench and pilot scale separations of proteins and virus. This paper primarily summarizes work on cartridge and sheet filter systems and their application to processes requiring sterilizable and contained systems. 

Optimal fermentation parameters have been well established and air-lift, stirred tank, and hollow fibre systems have all been used. At commercial scale, fermentation volumes in excess of 1000 litres can be used, which can yield 100 g or more of final product. While hybridoma growth is straightforward, production levels of antibody can be quite low compared with ascites-based production systems. Typically, fermentation yields antibody concentrations of 0.1-0.5 mg/ml. Removal of cells from the antibody-containing media is achieved by centrifugation or filtration. An ultrafiltration step is then normally undertaken in order to concentrate the filtrate by up to 20-fold. 

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. 

Polymer-Assisted Ultrafiltration of Boric Acid. The Quickstand (AGT, Needham, MA) filtration apparatus is pictured schematically in Figure 3. The hollow fiber membrane module contained approximately 30 fibers with 0.5 mm internal diameter and had a nominal molecular weight cut-off of 10,000 and a surface area of 0.015 m2. A pinch clamp in the retentate recycle line was used to supply back pressure to the system. In a typical run, the transmembrane pressure was maintained at 25 psig and the retentate and permeate flow rates were 25 ml/min and 3 ml/min, respectively. Permeate flux remained constant throughout the experiments. 

Ultrafiltration is a French originated process that uses a membrane filtering system. In its raw form, whey contains protein, lactose, ash, and some minerals. This should not surprise anyone since whey is the bi-product of cheese or casein production from milk. The original ultrafiltration method separated the ash and lactose from the whey protein resulting in a product providing about 35-70% protein. As the process improved the protein, content was elevated to up to 80% -86.5% protein content. Ultrafiltration provides a decent product with... 

Figure 3.40 Typical tubular ultrafiltration module design. The membrane is usually cast on a porous fiberglass or paper support, which is then nested inside a plastic or steel support tube. In the past, each plastic housing contained a single 2- to 3-cm-diameter tube. More recently, several 0.5- to 1.0-cm-diameter tubes, nested inside single housings, have been introduced. (Courtesy of Koch Membrane Systems)...

For treating water containing VOCs with separation factors of more than 500, for which concentration polarization is a serious problem, feed-and-bleed systems similar to those described in the chapter on ultrafiltration can be used. For small feed volumes a batch process as illustrated in Figure 9.16 is more suitable. In a batch system, feed solution is accumulated in a surge tank. A portion of this solution is then transferred to the feed tank and circulated at high velocity through the pervaporation modules until the VOC concentration reaches the desired level. At this time, the treated water is removed from the feed tank, the tank is loaded with a new batch of untreated solution, and the cycle is repeated. 

Water supplied to industry has to meet stringent specifications. For example, process water for the chemical and biotechnology industries is routinely purified beyond potable water standards. Boiler feed water for steam generation must contain a minimum of silica. Reverse osmosis units designed specifically for these purposes are in widespread use today. For example, reverse osmosis/distillation hybrid systems have been designed to separate organic liquids. For semiconductor manufacture, reverse osmosis is combined with ultrafiltration, ion exchange, and activated carbon adsorption to produce the extremely clean water required. 

In this chapter, the impact of other membrane technologies on the operation of RO systems is discussed. Technologies considered include microfiltration (MF), ultrafiltration (UF), and nanofiltration (NF) as pretreatment to RO, and continuous electrodeionization (CEDI) as post-treatment to RO. This chapter also describes the HERO (high efficiency RO—Debasish Mukhopadhyay patent holder, 1999) process used to generate high purity water from water that is difficult to treat, such as water containing high concentrations of silica. 

Colloids are found in many systems, e.g. in natural waters and in the air. Traces of colloids formed by dust particles or by particles given olf from the walls of containers are practically omnipresent. They can only be removed by careful ultrafiltration. If a radionuclide or a labelled compound enters such a system, there is a high probability that it will be sorbed on the colloids, provided that the competition of other ions or molecules is not too strong. Only if the presence of colloids from other origins can be excluded and if the solubilities of relevant species are not exceeded, formation of radiocolloids by microamounts of radionuclides can be neglected. 

The choroid plexus are bags composed of epithelial cells that project into the ventricles and contain a capillary plexus (lohanson, 1988). The capillaries do not have barrier function and so produce an ultrafiltrate, w hich fills the bag. The epithelial cells have tight junctions and so prevent the ultrafiltrate fi om entering the ventricular space. Unlike the capillaries, the epithelial cells of the choroid plexus have a high rate of vesicular turnover, w hich is responsible for the production of the cerebrospinal fluid (CSF). How ever, the CSF is not an ultra-filfi ate, but a secreted substance. The choroid plexus also has many selective transport systems, some of w hich are specific to it or are enriched in comparison to the vascular BBB. 

A solution containing the metal ion to be extracted and a water-soluble polymer is delivered into an ultrafiltration unit (Figure 29.5). The feed stream, upstream of the UF system, is adequately stirred to enhance recovery of the radioactive ions. The metallic macromolecular complex is retained while low-molecular-weight solutes pass through the membrane. The efficiency of the process is mainly characterized by the passage of each species through the membrane. The transfer coefficient of a given solute, i, is defined by... 

Municipal water systems usually contain 5-50 EU/ml of endotoxin. Pharmaceutical waters are treated by ultrafiltration, distillation, or reverse osmosis to separate endotoxin from water.f The principal source of endotoxin is bacteria within a water system in the form of biofilm or colonies entrapped in resin beds, etc. A water system will be contaminated unless there is an ongoing sanitization program. The endotoxin limit for Water for Injection was set at 0.25 EU/ml because it is a critical vehicle and a major source of pyrogens. 

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