Parameters computer-assisted optimization

Computer-assisted optimization of parameters has not been universally accepted, primarily due to a lack of ease of use. All compounds must be tracked across all experiments, and all retention times must be introduced to the system for each component. This is sometimes difficult because significant variations in the retention and elution order could be observed for certain analytes. With diode array detection, even if the different analytes have distinct... 

In this section a short overview is given of preparative chromatography and the determination of adsorption isotherm parameters - single and competitive - to be used for computer-assisted optimization of separations. 

To operate SMB chromatography a lot of parameters (column diameter, column length, total column number and number of columns per section, eluent, feed, raffinate, extract and recycle fluid flow and switch time interval) have to be chosen correctly. Therefore, design and process optimization should be done by computer simulations. It is much more difficult to optimize SMB during nonlinear conditions as compared to linear conditions. In fact, empirical approaches for optimization during overloaded and non-linear conditions are in most cases even impossible [96, 97], Computer-assisted optimization is therefore especially important for chiral separations since these CSPs have in general lower saturation capacities compared to non-chiral columns (see paper III). 

The accurate determination of the adsorption isotherm parameters of the two enantiomers on a CSP is of fundamental importance to do computer-assisted optimization to scale up the process. Such determinations are usually done with an analytical column and the most traditional method to determine the parameters and saturation capacity is by frontal analysis (see section 3.4.2). The aim of paper III was to investigate the adsorption behavior and the chiral capacity of the newly developed Kromasil CHI-TBB column using a typical model compound. Many of the previous studies from the group have been made on low-capacity protein columns which has revealed interesting information about the separation mechanism [103, 110, 111], For this reason a column really aimed for preparative chiral separations was chosen for investigation [134], As solute the enantiomers of 2-phenylbutyric acid was chosen. 

Preparative chromatography is widely used for the purification of different compounds, but this procedure needs to be optimized to achieve the minimum production costs. This can be done by computer-assisted modeling. However, this approach requires a priori determination of accurate competitive adsorption isotherm parameters. The methods to determine this competitive information are poorly developed and hence often a time limiting step or even the reason why the computer-assisted optimization is still seldom used. In this thesis in papers IV-VI, a new injection method was developed that makes it possible to determine these competitive adsorption isotherm parameters more easily and faster than before. The use of this new... 

SPE processes may be subjected to computer assisted optimization. As an example, an orthogonal array design was employed for the optimization of an SPE process applied to atrazine, diazinon, ame-tryn, and fenthion in surface water. Seven parameters (type of desorption solvent, type of sorbent, flow rate of the elution solvent, sample pH, sample volume, elution volume, organic modifier addition, and flow rate of the water sample) were studied and optimized. 

I hope that my thesis can be used as a contribution in the future for analysis and validation in biotechnology, and also for the rapid determination of competitive adsorption isotherm parameters so that computer-assisted simulations may be used more extensively, in scaling-up and optimization of large scale chromatography. 

When a detailed time course can be determined, intracellular pharmacokinetic modeling can be achieved. To optimize intracellular trafficking, the complete process must be balanced. For example, it is generally accepted that the tight condensation of pDNA, which permits a small size of complex, is desirable for cellular uptake, whereas excess condensation inhibits transcription. Considering that the intracellular disposition of DNA is ruled out by so many processes, a computer-assisted intracellular kinetic model (Fig. 8.6) integrating the kinetic parameters (i.e., first-order rate... 

The above-mentioned guideline describes practical procedures based on the migration behavior [9]. Computer-assisted modeling, predictions, and multifactor optimization strategy are proposed based on physicochemical models describing the migration behavior for ionizable analytes [69-71]. Other than the factors mentioned above, several experimental parameters that include temperature, applied voltage, buffer concentration, pH, and so forth affect resolution and many parameters can... 

Simplex optimization has become very popular and has been widely used in chromatography, but there are three major disadvantages (1) the relationship between the factor to be optimized and the parameters involved is seldomly revealed in detail, and the procedure therefore does not lead to a better understanding of the separation process, (2) a local optimum may be found and the optimization process stops there, and (3) a larger number of experiments are required. In order to overcome these drawbacks, recently a computer-assisted mixture design simplex method has been introduced by Wang and co-workers [18]. 

An efficient support from LFERs to speed-up method development and optimization is not yet conceivable. Besides the huge effort needed to determine solute parameters of new compoimds, even the most powerful LFER strategies do not yet offer the required accuracy in the prediction of selectivities. This vision, however, has been a focus of interest of HPLC experts for a long time. The future will show whether an LEER strategy is capable of bringing HPLC closer to the goal of computer-assisted precise prediction of retention on a physico-chemical basis. 

The kind of energy terms, their functional form, and how carefully (number, quality, and kind of reference data) the parameters were derived determine the quality of a force field. Accurate force fields exist for organic molecules (e.g., MM2, MM3), but more approximate force fields (e.g., with fixed bond distances) optimized for computational speed rather than accuracy [e.g., AMBER (assisted model building with energy refinement), CHARMM (chemistry at Harvard molecular mechanics), GROMOS (Groningen molecular simulation)] are the only practical choice for the treatment of large biomolecules. The type of molecular system to be smdied determines the choice of the force field. 

We discuss (1) the theoretical analysis of the spheromak, (recent theoretical studies are summarized and a comparison is made with other approaches), and (2) a spheromak plasma formation scheme. One of the difficult aspects of spheromak research is to produce a toroidal plasma in the absence of coils down the axis of rotational symmetry. A novel plasma formation scheme has been developed at PPPL to create a toroidal plasma by using a flux generating core technique. This formation scheme has been optimized with the assistance of resistive MHD computer codes. The parameters of the S-1 device, now under construction, were determined with various theoretical aids. 

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