Multi-column process

Figure 12.11 Zone distribution of a multi-column continuous chromatography process.

The successful operation of an SMB process relies on the successful fulfillment of a number of separation conditions. To achieve a good separation, the flow rates in all four sections must be chosen in such a way that, at the end of each cycle, the fronts and rears of the bands of the two components of the feed are located within specific ranges in the proper column (or section, in a more complex, multi-column xmit). As we discussed earlier, an SMB separation can be studied as an equivalent TMB process, the solid-phase flow rate of which is related to the switching time of the SMB unit by... 

The principle of the Varicol process consists in a non-synchronous shift of the inlet and outlet ports of a multi-column system on a recycle loop [70]. The Varicol process is characterized by a even more efficient use of the stationary phase than the one achieved in the SMB process. 

While multi-product columns could be used to separate mixtures into products with distinct compositions, sharper separations usually require processing with multiple columns to achieve the desired splits and purities. A possible scheme would be to break down the separation process into a forward flowing series of single-feed, two-product distillation columns, each of which makes the separation between two key components. In a more complex multi-column approach, the process may include recycle streams, external separation-enhancing streams, stream splits, recombination of streams, energy integration, and so on, all aimed at achieving an economic optimum. 

Strohlein, G., Aumann, L., Mazzotti, M., and Morbidelli, M. (2006) A continuous, counter-current multi-column chromatographic process incorporating modifier gradients for ternary separations. /. Chromatogr. A, 1126, 338-346. 

Chan, S., Titchener-Hooker, N., and S0rensen, F. (2008) Optimal economic design and operation of single- and multi-column chromatographic processes. Biotechnol Prog., 24, 389-401. 

Most literature data on HETP are determined this way. Another possibility is the HTUINTU method. As an example, both methods have been applied to the separation of the fatty acid ethyl esters (Fig. 19). Both methods lead to results comparable to multi-component process simulation. Calculations were carried out for two different columns. 

Chambuso, M., Kovar, K. -A., and Zimmermann, W. (1994). The systematic separation of unknown mixtures of drugs by multi-column solid-phase extractions analogous to the Stas-Otto extraction process. Pharmazie 49 142-148. 

Distillation The fermented mash, now called "beer," will contain about 10% alcohol, as well as all the non-fermentable solids from the corn and the yeast cells. The mash will then be pumped to the continuous flow, multi-column distillation system where the alcohol will be removed from the solids and the water. The alcohol will leave the top of the final column at about 96% strength, and the residue mash, called stillage, will be transferred from the base of the column to the co-product processing area. 

Higher-order responses are the result of multi-capacitance processes that contain vessels in series, fluid or mechanical components of a process that are subjected to accelerations causing inertial effects to become important, or tbe addition of controllers to a system. In a chemical plant, higher-order systems that result from a combination of capacities and controllers are very common. Typical examples are reactors in series, heat exchangers and distillation columns. In the case of distillation columns, when controllers are attached to the column, very high-order, nonlinear differential equations result when the system is mathematically modelled. Mechanical conqtonent time constant and natural frequencies are very small relative to the process time constants and frequencies, and, as such, the resultant effects are typically minor. 

The dispersion of a solute band in a packed column was originally treated comprehensively by Van Deemter et al. [4] who postulated that there were four first-order effect, spreading processes that were responsible for peak dispersion. These the authors designated as multi-path dispersion, longitudinal diffusion, resistance to mass transfer in the mobile phase and resistance to mass transfer in the stationary phase. Van Deemter derived an expression for the variance contribution of each dispersion process to the overall variance per unit length of the column. Consequently, as the individual dispersion processes can be assumed to be random and non-interacting, the total variance per unit length of the column was obtained from a sum of the individual variance contributions. 

Figure 5 shows that using average velocity data the extracted value for the multi-path term is negative, which is physically impossible, and, furthermore, for a capillary column should be zero or close to zero. In contrast, the extracted values for the different dispersion processes obtained from data involving the exit velocity give small positive, but realistic values for the multi-path term. 

In a similar manner to the design process for packed columns, the physical characteristics and the performance specifications can be calculated theoretically for open tubular columns. The same protocol will be observed and again, the procedure involves the use of a number of equations that have been previously derived and/or discussed. However, it will be seen that as a result of the geometric simplicity of the open tubular column, there are no packing factors and no multi-path term and so the equations that result are far less complex and easier to manipulate and to understand. 

We found that the optimal reaction protocol was to add a solution of a-bromo ketone in THF to the amidine in aqueous THF in the presence of potassium bicarbonate under vigorous reflux. Using this procedure, 2,4-disubstituted imidazoles were isolated in excellent yields with >95% purity without column chromatography. Aromatic and aliphatic a-halo ketones participate in this reaction with a variety of aromatic amidines, as indicated in Table 1. Particularly noteworthy is that reactions involving pyridylamidines or chloroacetone are substantially more robust using this process (entries 3 and 4). We have successfully used this protocol on a multi-kilogram scale. 

Van Deemter considered peak dispersion results from four spreading processes that take place in a column, namely, the Multi-Path Effect, Longitudinal Diffusion, Resistance to Mass Transfer in the Mobile Phase and Resistance to Mass Transfer in the Stationary Phase. Each one of these dispersion processes will now be considered separately... 

For toluene fluorination, the impact of micro-reactor processing on the ratio of ortho-, meta- and para-isomers for monofluorinated toluene could be deduced and explained by a change in the type of reaction mechanism. The ortho-, meta- and para-isomer ratio was 5 1 3 for fluorination in a falling film micro reactor and a micro bubble column at a temperature of-16 °C [164,167]. This ratio is in accordance with an electrophilic substitution pathway. In contrast, radical mechanisms are strongly favored for conventional laboratory-scale processing, resulting in much more meta-substitution accompanied by imcontroUed multi-fluorination, addition and polymerization reactions. 

ICP is intolerant to the solvents commonly used in LC development. Consequently, most LC-ICP-AES systems have been employed with ion-exchange columns, as this separation process largely involves aqueous mobile phases that are amenable to the ICP-AES instrument. Use of acetonitrile or THF in the mobile phase has usually evoked a change in interface design to accommodate the different solvents. The advantages of LC-ICP-AES include multi-element detection and the ability to obtain real-time chromatograms. LC-ICP-AES... 

Product manufacture entails viral vector propagation in a suitable animal packing cell line (known as HEK 293). After cell recovery and lysis, the crude product is clarified by filtration and concentrated by ultrafiltration. The product is then treated with a nuclease preparation in order to degrade contaminant DNA and further downstream processing entails multi-step high-resolution column chromatography (see also Figure 14.7). 

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