Parallel cycle time

Introducing parallel operations to the steps which limit the batch cycle time. 

Whether parallel operations, larger or smaller items of equipment, and intermediate storage should be used can only be judged on the basis of economic tradeoffs. However, this is still not the complete picture as far as the batch process tradeoffs are concerned. So far the batch size has not been varied. Batch size can be varied as a function of cycle time. Overall, the variables are... 

The volume of the closest standard stirred tanks are 1.6 and 2.5 m while a tray drier of 0.5 m can be assumed standard. The total volume of the equipment is 4.6 m . Since the bottleneck is in stage 1 two units in parallel out-of-phase operation may be considered. The cycle time then becomes ... 

In Figure 14.24, the reactor limits the batch cycle time, that is, it has no dead time. On the other hand, the evaporator and stripper both have significant dead time. Figure 14.26 shows the schedule for an arrangement with two reactors operating in parallel. With parallel operation, the reaction operations can... 

Figure 14.26 Placing units in parallel for the limiting step reduces the batch cycle time.

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. 

FIGURE 3.11 Different cycle time optimization possibilities achieved by parallelizing individual steps of LCMS-analysis. 

Such columns are excellent filters and require more sample preparation to ensure the removal of all solids. To benefit from the full power of LC optimization, the detectors must be optimized as well. Data rates and duty times must match the narrower peaks in very fast (and well resolving) separations. Careful consideration and optimization of all instrument components and software can produce significant cycle time improvements of fast LC separations and further increase throughput. An important aspect of cycle time improvement is parallelization of components of individual analyses. 

In 1995, when HPLC/MS/MS was becoming the premier tool for PK assays, chromatographic sample cycle times were typically 10 to 12 min. At 10 min per sample, 16 hr were required to process 96 samples. By 2000, scientists used shorter HPLC columns and per-sample cycle times decreased to 5 to 6 min. At 5 min per sample, it takes about 8 hr to assay one 96-well plate of samples. As a result, parallel HPLC became popular Korfmacher et al.154 described a two-column system and an MS vendor produced a triple quadrupole system designed to work with four HPLC columns.16155-158 Advances in fast chromatography continued and by 2005, sample cycle times of 1 to 2 min became common.21 87 159-161 At 2 min per sample, 3 hr are required to assay one 96-well plate of samples. 

The duration of the injection is a substantial fraction of the cycle time. An effective technique, therefore, is to run the feed vaporiser continuously and to direct the vapour/carrier mixture to one of, say, 2-5 parallel columns in sequencc(24 26). 

The HTP is a batch process the volume treated per unit time is a function of the cycle-time (that is the sum of the times of each step sealing, pressurization, maintenance at the operating pressure, depressurization, opening, and unloading times), of the batch volume, and of the number of cells used simultaneously in parallel in the same cycle. 

---