Scaling bioreactors

For large-scale bioreactors (21), especially those of the air lift type (22), the gas phase is best considered as being in plug dow, so that a log mean value of driving force is obtained ... 

Until recently most industrial scale, and even bench scale, bioreactors of this type were agitated by a set of Rushton turbines having about one-thind the diameter of the bioreactor (43) (Fig. 3). In this system, the air enters into the lower agitator and is dispersed from the back of the impeller blades by gas-fiUed or ventilated cavities (44). The presence of these cavities causes the power drawn by the agitator, ie, the power requited to drive it through the broth, to fall and this has important consequences for the performance of the bioreactor with respect to aeration (35). k a has been related to the power per unit volume, P/ U, in W/m and to the superficial air velocity, in m/s (20), where is the air flow rate per cross-sectional area of bioreactor. This relationship in water is... 

Alternatively, some subunit viral vaccines can be generated by rDNA techniques and expressed in a continuous ceU line or insect ceUs. Recent advances in bioreactor design and operation have improved the successful production of IPV in large-scale bioreactors. However, roUer bottles or flasks are stiU used for most current vaccine production. Development of insect ceU culture will allow for very large-scale Hquid suspension culture (143). Several vaccine candidates such as gpl60 for HIV and gD protein for herpes have been demonstrated in the insect ceU culture system. However, no vaccine has been approved for human use. 

Bubble behaviour was studied in the pilot-scale bioreactor so that a complete model of flow, OTR, mixing, cooling, energy requirement and disengagement could be developed for this system and larger production-scale vessels of similar type. 

The power per unit volume is constant. From power consumptions in a bench-scale bioreactor, the necessary agitation rate is calculated for the scale up ratio, using Equation (13.2.1). The choice of criterion is dependent on what type of fermentation process has been studied. The following equation expresses relations for the impeller size and agitation rate in small and large bioreactors. 

The bioreactor will be scaled up by a factor of 125. It is necessary to discuss the effect of operating variables resulting from constant power per unit volume, agitation rate, and speed tip velocity, NRe. The data for a small-scale bioreactor are a 100 litres fermenter with 187.5 rpm and... 

Factoring for scale-up, we make some assumptions and may use a few known correlations to progress our calculations. Let us say PaV=D-3, HID = 1 and D/Dt = 3. Also, use constant power per unit volume for the small- and large-scale bioreactor. 

The upstream processing element of the manufacture of a batch of biopharmaceutical product begins with the removal of a single ampoule of the working cell bank. This vial is used to inoculate a small volume of sterile media, with subsequent incubation under appropriate conditions. This describes the growth of laboratory-scale starter cultures of the producer cell line. This starter culture is, in turn, used to inoculate a production-scale starter culture that is used to inoculate the production-scale bioreactor (Figure 5.7). The media composition and fermentation conditions required to... 

Figure 5.7 Outline of the upstream processing stages involved in the production of a single batch of product. Initially, the contents of a single ampoule of the working cell bank (a) are used to inoculate a few hundred millilitres of media (b). After growth, this laboratory-scale starter culture is used to inoculate several litres/tens of litres of media present in a small bioreactor (c). This production-scale starter culture is used to inoculate the production-scale bioreactor (d), which often contains several thousands/tens of thousands litres of media. This process is equally applicable to prokaryotic or eukaryotic-based producer cell lines, although the bioreactor design, conditions of growth, etc., will differ in these two instances...

Lab-scale bioreactor integrated with active membrane system for hydrogen production experience and prospects. Ini../. Hydr. Energy., 27 1149-1155... 

Yabannavar et al. [81] used Eqs. (19) and (20) for scale-up purposes. Based on successful operation conditions determined for an existing 12-L bioreactor, they calculated the spin-filter dimensions and operation conditions for an existing 175-L bioreactor. Experiments with the spin-filter designed for the large-scale bioreactor resulted in an absence of filter clogging with cell retention efficiency similar to the 12-L bioreactor. This was considered as an evidence that the suggested scale-up strategy is adequate. 

By market volume the most important flavour molecule is L-glutamic acid. In 2004, the worldwide annual MSG production was estimated to be amount 1,500,0001 [21]. The amino acid is extensively used as taste enhancer, frequently in conjunction with nucleotides, a flavour impression which is also referred to as umamf, a term derived from the Japanese meaning deliciousness or a savoury or palatable taste. MSG is manufactured by aerobic cultivation of Coryne-bacterium glutamicum on starch hydrolysates or molasses media in large-scale bioreactors (up to 500 m ). Production strains with modified metabolic flux profiles and highly permeable cell walls for an improved product secretion are... 

In the field, o-xylene is also observed to degrade with nitrate in all but a few of the reported cases (Table 3.5). No o-xylene degradation was observed in either microcosms (Ball Reinhard, 1996) or in field-scale bioreactors by Ball et al. (1994). However, the removal of this substrate was apparent in a field injection experiment. Since the sediments were initially sulfate reducing, there may have been an adaptation period for substrate depletion with nitrate that was longer than the 40 and 60 day incubation periods associated with the microcosm and bioreactor study, respectively. As noted for the other alkylbenzenes, the second field study not showing anaerobic o-xylene degradation (Acton Barker, 1992) was compounded by the presence of acetylene in the experiment. 

Kang, G. Stevens, D. K. (1994). Degradation of pentachlorophenol in bench scale bioreactors using the white rot fungus Phanerochaete chrysosporium. Hazardous Waste Hazardous Materials, 11, 397-410. 

Characterization and optimization of treatment of organic wastes and toxic organic compounds by a lignolytic white rot fungus in bench-scale bioreactors. In On-Site Bioreclamation Processes for Xenobiotic Hydrocarbon Treatment, ed. R. E. Hinchee R. F. Olfenbuttel, pp. 341-65. Stoneham, MA Butterworth-Heinemann. 

The main advantages of continuous cell lines are (i) faster cell growth, achieving high cell densities in culture, particularly in bioreactors (ii) the possible use of defined culture media available in the market, mainly serum-free and protein-free media and (iii) the potential to be cultured in suspension, in large-scale bioreactors. 

Another material that is frequently employed is glass. It is used in small-scale vessels and also in sight glasses of large-scale bioreactors and tanks. A detailed review of the materials used in the manufacturing of bioreactors, as well as the surface treatments used, can be found in the literature (Krahe, 2003). 

Diaz C, Dieu P, Feuillerat C, Lelong P, Salome M (1996), Simultaneous adaptive predictive control of the partial pressures of dissolved oxygen (p02) and dissolved carbon dioxide (pC02) in a laboratory-scale bioreactor, J. Biotechnol. 52 135-150. 

Fixed-bed bioreactor (A) schematic representation including the external recirculation loop with an aeration tank (B) photograph of a small-scale bioreactor. 

The direct dependence of microorganisms on pressure changes is negligible provided they do not exceed many bars [18,186,211,474]. However, the partial pressure of dissolved gases and their solubility is indirectly affected and must, therefore, be at least considered if not controlled. A data sampling frequency in the range of a few 100 ms is appropriate for direct digital pressure control (DDC) in laboratory scale bioreactors. 

Because modulation of enzyme activities depends on metabolite concentrations, which in turn are determined by the entire metabolic network, the overall response time for these controls can be on the order of seconds. This is the same as the time scale for changes in environmental conditions (e.g., pH, dissolved oxygen concentration) encountered by cells as they circulate through the nonuniform contents of a large-scale bioreactor. Therefore, beyond the complexities of enzyme activity control in the steady state, dynamic properties of this control system are important. The circulation pattern in a bioreactor has major effects on product formation [28]. Lack of understanding of transient responses of cell metabolism is one central obstacle to systematic scale-up of laboratory results (obtained in idealized,... 

Ren, N., Li, I, Li, B., Wang, Y., and Liu, S. 2006. Biohydrogen production from molasses by anaerobic fermentation with a pilot-scale bioreactor system. Int. J. Hydrogen... 

Sivakumar, G. Bacchetta, L. Gatti, R. Zappa, G. 2005. FIPLC screening of natural vitamin E from mediterranean plant biofactories - a basic tool for pilot-scale bioreactors production of alpha-tocopherot. J. Plant Physiol. 162 1280-1283. 

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