High-throughput screening quality control

Gunter, B., Brideau, C., Pikounis, B., and Liaw, A., Statistical and graphical methods for quality control determination of high-throughput screening data, J. Biomol. Screen., 8, 624, 2003. 

Zhang X. D, (2007) A pair of new statistical parameters for quality control in RNA interference high-throughput screening assays. Genomics 89 552-561... 

Dalvit, C., et al., NMR-based quality control approach for the identification of false positives and false negatives in high throughput screening. Curr Drug Discov Technol, 2006, 3, 115-124. 

Padmanabha, R., Cook, L., and Gill, J. 2005. HTS quality control and data analysis a process to maximize information from a high-throughput screen. Comb. Chem. High-Throughput Screen. 8, 521-527. 

In addition to the limited range of cellulose-compatible synthesis protocols, two further drawbacks remain that are inherent to on-array approaches. Because synthesis takes place directly on the surface that is subsequently used for screening, quality control of the synthesis products is restricted to the surface-bound molecules. Standard cleave-and-characterize procedures involving LC-MS analytical techniques are not practical. This is a severe problem even for the synthesis of peptides where well-established protocols are available and becomes more pronounced when novel chemistries have to be employed. Secondly, each array produced is unique, which renders the production rather costly and prevents the generation of numerous copies of the same array for high-throughput applications. 

The dispensed liquid volume is one of the key parameters that need to be properly controlled in order for experiments and tests to be well conducted. In fact, experiments may fail simply because an erroneous liquid volume has been introduced, resulting mainly from an operator s poor technique or the use of uncaUbrated instrument. For applicatirms such as high-throughput screening, making sme that the liquid volume delivered is well controlled becomes even more important, since a small difference leads to a relatively large deviation, and the accuracy of the dispensed volume can substantially affect the analysis results. Therefore, measurement of the dispensed liquid volume is indispensable for satisfactory quality control of related products. 

In the pharmaceutical field, PFE has also been used for two primary purposes, namely to extract pharmacologically active substances from plants and, especially, for quality control of tablets and medical foods. In this field, PFE clearly surpasses classical extraction methods such as those endorsed by pharmacopeias (which use as official standards techniques such as Soxhlet extraction, percolation, maceration, digestion, extraction under reflux, and steam distillation) and others based on ultrasonica-tion or turboextraction. PFE is a firm candidate for use in high-throughput screening programs for natural product discovery, where large numbers of small-scale extractions have to be performed in an efficient, reproducible manner. 

Studies and optimization of chemical formulations for polymerization reactions in MF reactors require on-chip characterization of reagents and products. Implementation of in situ characterization enables (i) exploration of the reaction variable space for high-throughput screening, (ii) opportunity for feedback control of the reaction variables, (iii) quality control of reaction products, (iv) detection of transient species, which may not exist upon their removal from the MF reactor, and (v) kinetic studies with good time resolution. 

In general, standard methods applicable to a vast majority of compounds of interest to ensure throughput capabilities are critical for LC/MS screens. Although not optimized for specificity, standard conditions provide a systemic measure of control. This control results in data that has high quality, reliability, and comparability. With a strategic selection of compounds that have similar molecular weights, structural features, and chromatographic properties, the detection selectivity and precision are satisfactory for this particular type of analysis. 

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