Implementation of medium- and high-throughput screening for chemical process development is developing rapidly. Several commercial systems have been introduced and publications are beginning to demonstrate the value and return on investment for such systems. The cases cited here demonstrate that medium throughput (ten-at-a-time approach) in conjunction with statistical DOE has taken hold. At the screening/optimization stages, process chemists generally have significant insights into the mechanism of the reaction, thus rendering this approach especially powerful and dramatically accelerating the process development.
In the case that an entirely novel process has to be developed, where only a minimal level of chemical knowledge exists, the true combinatorial high-throughput methodology (hundred-at-a-time or thousand-at-a-time approach) needs to be implemented. There will be, however, significant technical hurdles between the ten-at-a-time technology and the hundred-at-a-time technology, and it will take considerable efforts to develop these systems . Not only will the close collaboration between process chemists and combinatorial chemists be necessary, but the involvement of engineers and computer scientists will be likewise indispensable for full implementation. Nevertheless, the truly high-throughput systems will fundamentally change the way chemical process development is carried out in the future.
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