High workflow

From the time when it was shovm that micro flow reactors can provide valuable contributions to organic chemistry, it was obvious to develop them further and their workflow towards modern screening techniques [20]. It was especially the finding of high reaction rates, the capability to transport and transform minute sample volumes and the first integration of analytics that paved the way to a parallelization of micro flow processing. These benefits were combined with the ease of automation of a micro flow system. By this means, the potential of on-line analysis of the reactions can be fully exploited. 

Two different microwave reactors for scale-up have been tested with special focus on handling, automation, workflow, and typical scale-up issues. The Synthos 3000 as a batch mode reactor provides a relatively large reaction volume (16 x 70 ml), allows high temperature and pressure (240°C/40 bar), and proved to be very robust. Handling of suspen-... 

In our laboratories, a cycle time of 90 sec can be achieved with a dilution factor of 1 25 for a given sample concentration, allowing the purity and identity control of two and a half 384-well microtiter plates per day. The online dilution eliminated an external step in the workflow and reduced the risks of decomposition of samples in the solvent mixture (weakly acidic aqueous solvent) required for analysis. Mao et al.23 described an example in which parallel sample preparation reduced steps in the workflow. They described a 2-min cycle time for the analysis of nefazodone and its metabolites for pharmacokinetic studies. The cycle time included complete solid phase extraction of neat samples, chromatographic separation, and LC/MS/MS analysis. The method was fully validated and proved rugged for high-throughput analysis of more than 5000 human plasma samples. Many papers published about this topic describe different methods of sample preparation. Hyotylainen24 has written a recent review. 

LC/MS analyses requiring high resolving power to separate all compounds present in a sample may be optimized as well to increase throughput. Optimizing in the LC dimension utilizes smaller particles as well more radical approaches may involve a change in workflow toward extremely high column efficiencies and peak capacities in contrast to the present common work flow of many individual runs with modified selectivities. 

Fig. 16.5 Computer-aided drug discovery workflow based on combination of QSAR modeling and consensus database mining as applied to the discovery of novel anticonvulsants [10]. The workflow emphasizes the importance of model validation and applicability domain in ensuring high hit rates as a result of database mining with predictive QSAR models.

Walter, T. S., et al. (2005). A procedure for setting up high throughput nanolitre crystallization experiments. III. Crystalhzation workflow for initial screening. 

Once the robotic system and procedure passed the optimization and reproducibility tests for a certain type of reaction, the researcher has the chance to move on to the most delightful part of a high-throughput experimentation workflow that is to follow the reaction kinetics of the reaction by withdrawing several samples under comparable conditions. The characterization of these samples allows the determination of the apparent rate constants and activation energies in a very reproducible way. As an example, the anionic polymerization of St in cyclohexane initiated by i-BuLi under different reaction conditions was investigated. Several samples were withdrawn during the reaction into small vials which were prefllled with 25 pL of... 

Meier MAR, Schubert US (2005) Integration of MALDl-TOEMS as high-throughput screening tool into the workflow of combinatorial polymer research. Rev Sci Instrum 76 062211... 

Bray M-A, Fraser AN, Hasaka TP et al (2011) Workflow and metrics for image quality control in large-scale high-content screens. J Biomol Screen 17 135-143... 

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