Down-scale studies

Bubble columns and various modifications such as airlift reactors, impinging-jet-reactors, downflow bubble columns are frequently used in lab-scale ozonation experiments. Moderate /qa-values in the range of 0.005-0.01 s l can be achieved in simple bubble columns (Martin et al. 1994 Table 2-4 ). Due to the ease of operation they are mostly operated in a cocurrent mode. Countercurrent mode of operation, up-flow gas and down-flow liquid, has seldom been reported for lab-scale studies, but can easily be achieved by means of applying an internal recycle-flow of the liquid, pumping it from the bottom to the top of the reactor. The advantage is an increased level of the dissolved ozone concentration cL in the reactor (effluent), which is especially important in the case of low contaminant concentrations (c(M)) and/or low reaction rate constants, i. e. typical drinking water applications... 

The cognitive deficits seen in PD patients medicated with mild clinical disability can be less than those seen in PD patients earlier in the course of the disease who are yet to receive medication (Downes et ah, 1989 Owen et ah, 1995). Inferences can also be made on the basis of longitudinal studies. In one large-scale study, Growdon et ah (1998) reported that levodopa improves motor function without impairing cognition in mild, nondemented PD... 

Some Considerations In Scaling Up Or Scaling Down Alkylation Studies... 

A process step with many variables to control is equally difficult to scale down for bench scale studies. However, results from animal studies and human clinical trials have been consistent with the in vitro model virus clearance studies of the terminal freeze dry/dry heat treatment. 

Consistency of product quality is demonstrated by showing operating consistency and product quality from batch-to-batch, processing with only buffer (blank runs) with assays for contaminants, examination of cleaned surfaces and materials, and extended scale-down clearance studies on reused materials. Disposable processing components that eliminate the need for cleaning validation are increasingly used at small scale. 

Fractionation/Purification Process Lessons Learned from the Down-Scale Qualification Studies... 

Once enough process knowledge has been acquired, the next step involves the development and qualification of an appropriate down-scale model where the parameters of interest can be effectively studied. We normally qualify our down-scale models by processing a small portion of the input... 

The affinity chromatography process can be considered robust within the process parameter ranges studied using a qualified down-scale model. 

Purification of a therapeutic monoclonal antibody Scale-down characterization studies for various filtration and chromatography steps (including viral clearance) to predetermine acceptance criteria [87] (Biogen Idee)... 

Scale-down studies are a valuable tool in fermentation development [51]. If production is going to occur in a fermentor for which the KLa or other parameter is precisely defined [52], correct down-scaled reactors should be used to mimic such configurations. Scale-down studies are helpful in that restrictions due to scale up are known in advance, thus minimizing small-scale studies that do not satisfy the ultimate good. 

Nienow, A. W., Nordkvist, M., Boulton, C. A. (2011). Scale-down/scale-up studies leading to improved commercial beer fermentation. Biotechnology Journal, 6, 911-925. 

The down-scale factor was studied by Ryan in 1996 and it applies to all components and parameters of the system, such as flow rates, injection, detection volumes, and connecting capillaries. This factor is very important for the successful transfer of a conventional method to a microscale equivalent. The equation below shows that this factor is equal to the partition of the squares of both diameters ... 

Downing, L. S., Bibby, K. J., Esposito, K., Fascianella, T, Tsuchihashi, R. and Nerenberg, R. 2010. Nitrogen Removal from Wastewater Using a Hybrid Membrane-Bioflhn Process Pilot-Scale Studies. Water Environment Research, 82,195-201. 

The calculation of metabolic fluxes based on isotopomer distribution has gained importance as a quantitative and reliable tool for the study of cellular physiology. Metabolic fluxes are mainly calculated during steady-state conditions, which limits their applicability to scale-down dynamic studies. Nevertheless, research efforts with labeling experiments and mathematical models have allowed important advances in the dynamic C-based metabolic flux analysis [37-39], from which scale-down studies would be much benefited. An interesting example... 

Near critical points, special care must be taken, because the inequality L will almost certainly not be satisfied also, cridcal slowing down will be observed. In these circumstances a quantitative investigation of finite size effects and correlation times, with some consideration of the appropriate scaling laws, must be undertaken. Examples of this will be seen later one of the most encouraging developments of recent years has been the establishment of reliable and systematic methods of studying critical phenomena by simulation. 

Figure 1.3.2 gives another perspective for scale-down to recycle reactor studies. In this actual case, after preliminary studies in a recycle reactor, a 5-stage adiabatic reactor was envisioned (Betty 1979.) Scaling down the proposed commercial reactor, a 3 diameter tube was designed with elaborate temperature compensation (heating and insulation) for pilot-plant studies (Betty 1968, 1969.) Small squares in the proposed reactor represent side views of cylindrical catalyst cutouts for the recycle reactor... 

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