Automation optimization experiments

Automated parallel experiments were carried out to rapidly screen and optimize the reaction conditions for ATRP of methyl methacrylate (MMA) [34]. A set of 108 different reactions was designed for this purpose. Different initiators and different metal salts have been used, namely ethyl-2-bromo-tTo-butyrate (EBIB), methyl bromo propionate (MBP), (1-bromo ethyl) benzene (BEB), and p-toluene sulfonyl chloride (TsCl), and CuBr, CuCl, CuSCN, FeBr2, and FeCl2, respectively. 2,2 -Bipyridine and its derivatives were used as ligands. The overall reaction scheme and the structure of the used reagents are shown in Scheme 2. 

TaUe 9. Optimization experiments in HPLC using the Simplex procedure. Adapted from J. Berridge T hniques for the automated optimization of HPLC j rations , p. 150 (1984), Wi% Sons, En and. Copyri t 1984, John Wiley Sons, Inc. Reprinted by permission of J. Wiley Sons Ltd. England... 

The first results of optimization in chromatography were published in 1975 Since then a growing number of optimization experiments in HPLC using the Simplex procedure has been reported (table 9). The examples are mainly reversed-phase separations, in which the composition of the ternary or binary mobile phase composition is optimized. The factors optimized are usually a selection from flow rate, column temperature and length, the eluents constitution (e.g. organic modifier content, buffer concentration and pH), the gradient shape. Seven years after the first applications of Simplex optimization had appeared, the first fully automated optimization of HPLC separations was published by Berridge in 1982. This development coincid-... 

Robotics and automated process development are emerging as efficient tools for optimization [28, 29]. The ease of running large numbers of experiments will allow more investigators to take advantage of DOE to optimize experiments efficiently [30],... 

In addition to aspects of early small-scale production, the development process itself can take advantage of MRT. It is interesting to note that already standardized microreaction systems are commercially available that allow sequential operations and, moreover, coupling to in-Hne analytical facilities [24]. Obviously, these devices are high-throughput tools for the combinatorial optimization of continuous reactions, e.g. the fully automated optimization of a reaction by the aid of DoE (Design of Experiments) can be reahzed within a few hours. 

If selectivity tuning of certain separations is possible by changing pH or changing temperature, the question arises what is the preferred way. It is obviously more convenient to change the temperature. This can be easily set at the instrument and does not require further mobile phase preparation work. Moreover, there is limited flexibility for pH changes with a given buffer type, especially if the buffer capacity has to be maintained. These considerations clearly promote the temperature as the first choice, and this optimization experiment can easily be automated. 

For many years, flow injection analysis has been used for automated spectrophotometric determination of anionics. Although UV absorbance at 224 nm has been reported for FLA of LAS (68), FIA is normally based upon the more robust methylene blue visible spectrophotometric method (69-71). Other cationic dyes may be used in place of methylene blue (72,73). The methylene blue method requires a two-phase system, a feature which is a continuing target of optimization experiments. Most commercial systems rely on gravity... 

The Optimization Xpert Automated design of experiments that builds on the foundation established in Setup Xpert and allows users to further optimize the combination of processing parameters to determine a robust good parts processing window. 

The Production Xpert A comprehensive production monitoring and control system that will maintain the optimized processing conditions determined with MPX s automated design of experiments. 

In the second experiment, we carried out an optimal control experiment on the production of highly charged ions [11]. The optimal control technique [12] consists of varying a large number of parameters that characterize the laser pulse shape in an automated way in order to... 

---