Parallel analysis systems

High-Throughput Screening (HTS) and Parallel Analysis Systems 99... 

Another generic approach in HTS is parallel analysis, which enjoyed prominent success in the rapid decoding of the Human Genome by capillary electrophoresis with multiple capillaries in 2000. Figure 4.16a-c shows some available HPLC equipment used for parallel analysis. Systems might include... 

In the cyclobutylfluoro system, the excited diazirine, 21-F, is considerably less involved. A parallel analysis indicates that only about 12% of 22-F and 23-F arise from excited diazirine, while 88% of those products descend from carbene 17-F.28 The increased carbene involvement in the photolysis of 21-F presumably reflects the greater stability of fluorocarbene 17-F over its chloro analogue 17-C1 and, consequently, a more favorable partition (ki/k3) of excited diazirine 21-F to the carbene. 

We developed a staggered parallel HPLC system with a CTC HTS PAL autosampler equipped with trio valves. The system consists of four (six if gradient is needed) independent HPLC pumps. Parallel analysis is achieved by an offset dual-stream system with a time delay that allows efficient staggering of MS acquisition times. 

One drawback of this approach is the relatively low sample throughput of traditional HPLC systems. The primary reason for this low throughput is that each standard and sample must be assayed under a minimum of three different isocratic conditions. Assuming a run time (injection to injection) of 10 min, it would take 50 hr to analyze 4 standards and 96 unknowns. /./PLC is ideally suited for determination of log P since it facilitates parallel analysis of a large number of compounds under identical chromatographic conditions (Table 6.4). 

FIGURE 8.2 Staggered parallel analysis scheme showing two systems run with staggered start times. 

Reduce complexity and design modular systems As far as possible, use proven techniques and combine them in new ways, but let them be independent from each other, e.g., allow different synthesis methods that are independent from your reactor configuration. Furthermore, allow different sequential or parallel analysis methods. This is not a contradiction to the aforementioned integration because workflow integration does not necessarily mean technology integration. 

Several successful attempts were done to transfer classical CEIA to a microchip-based format. This kind of miniaturization is a trend that can overcome the limitations of CE in high-throughput systems. On-chip CE offers both parallel analysis of samples and short separation times. Koutny et al. showed the use of an immunoassay on-chip (32). In this competitive approach fluorescein-labeled cortisol was used to detect unlabeled cortisol spiked to serum (Fig. 8). The system showed good reproducibility and robustness even in this problematic kind of sample matrix. Using serum cortisol standards calibration and quantification is possible in a working range of clinical interest. This example demonstrated that microchip electrophoretic systems are analytical devices suitable for immunological assays that can compete with common techniques. 

Optical gene chips dense arrays of oligonucleotides have been successfully applied to detect transcriptional profiling and SNP discovery, where massively parallel analysis is required. However, the fluorescence-based readout of these chips involves not only highly precise and expensive instrumentation but also sophisticated numerical algorithms to interpret the data, and therefore these methods have been commonly limited to use in research laboratories. In this way, thin-film arrays of 14, 20, 25, 48 and 64 electrodes have already been fabricated [12,15,39,40,44,48], using lithographic techniques. Readout systems for these arrays based on electrical detection have also been developed. 

Workstations are perhaps a more flexible complement to a robotics method. These systems are capable of in-series or parallel analysis. Methods are developed with very specific and specialized functions that allow higher throughput and operation in a batch mode. These dedicated approaches would seem to be a popular choice in the drug discovery and preclinical development stages. Workstations could be... 

Branebjerg, J., Larsen, U. D., Biankenstein, G., Fast mixing by parallel multilayer lamination, in Widmer, E., Verpoorte, E., Banard, S. (Eds.), Proceedings of the 2nd International Symposium on Miniaturized Total Analysis Systems, Analytical Methods and Instrumentation, Special Issue pTAS 96, Basel, 1996, 228—230. 

Performing parallel analysis of compound libraries offers many potential advantages over serial-based LC/MS analytical methods, the most obvious of which is dramatically increased compound analysis throughput. Using singlechannel HPLC-based purification systems, routine sample throughput of up to 192 reaction mixtures per 24-hour day was reported [64]. With parallel HPLC systems, it has been reported that the theoretical throughput increases to 384 samples per day for a two-channel system and to 768 samples per day for a four-channel system. 

---