Microreactors and NeSSI: Straight Talk from CPAC Director Mel Koch

By Paul Thomas, Managing EditorThe Center for Process Analytical Chemistry at the University of Washington is a hub of the process analytical technology movement. The Center has collaborated extensively with FDA to formulate and shape PAT concepts and training programs. CPAC is also spearheading NeSSI, an initiative intended to further modular and miniature process analyzer sample system components. The man behind it all is Center director Mel Koch. Pharmaceutical Manufacturing spoke with Koch to get the skinny on this year’s CPAC Summer Institute.The Institute started in 1996 as a forum for “vigorous discussion” and brainstorming related to process analysis and control. It hasn’t disappointed, each year providing progressive thought on a variety of topics. This year’s theme was “Micro Instrumentation for High Throughput Experimentation and Process Intensification: A Valuable Tool for PAT.”Koch is in the process of assembling his summative report on SI 2005. For more information, visit www.cpac.washington.edu.P.M.: What topic seemed to generate a "buzz" at this summer's institute?M.K.: There were several examples of microreactors being used in commercial operations. The growing number of examples was impressive and shows the value of miniaturizing production unit operations. These examples stimulated discussion on what would be required to better utilize this equipment for process intensification. The conclusion was that the high-throughput experimental approach using microreaction equipment, but interfaced to real-time analysis instrumentation, could determine how best to scale a reaction.The basic premise was that it would be possible to characterize liquid-phase reactions fully in a high-throughput mode. This approach would enable better processes to be developed faster for both production evaluation and process intensification activities.P.M.: What are the enabling factors inherent in microinstrumentation?M.K.: One key advantage is that its laminar flow characteristics facilitate modeling so that a greater understanding of what is occurring in the flow channels is possible compared to traditional lab-scale equipment. Also, the equipment comes to equilibrium rapidly, so that more operating conditions can be explored per unit time. Finally, the uniform nature of the physical variables such as temperature and mixing in the flow path tends to give cleaner chemistries and more reproducible results for easier trend detection.P.M.: What were the skeptics saying about the viability of microinstrumentation for high-throughput experimentation?M.K.: There were both technical and emotional issues raised. The technical included concerns with handling physical characteristics such as viscosity and multiphase chemistries in the reactor systems, the time and cost of developing system capabilities, and the difficulty with analytical method development. The key emotional barrier was the conservative nature of the chemical industry coupled with the need for researchers to do their work in a very different way.P.M.: What else had people at the Summer Institute talking?M.K.: Other discussion dealt with the vast amounts of data that can be generated in high throughput experimentation. Many attendees already face a high-throughput data problem. It’s a broad-based problem that will require much R&D to solve. There are also challenges with data fusion, assimilating the various data types, such as video with spectroscopic, particularly when data come from multiple computer systems.The consensus was that more and improved microanalytical instrumentation is needed to gather the desired data and to monitor the micro-scale equipment.P.M.: What is the natural tie-in between NeSSI and microinstrumentation?M.K.: The NeSSI platform for analytical devices has significantly improved the ability to monitor microreactors. The NeSSI platform can be readily plumbed to most microreactor systems, thus allowing for an array of measurement technologies to be deployed. Many of the Summer Institute talks involving microanalytical developments were aimed at the new technology being NeSSI compatible.P.M.: Measurement was also a key theme at the SI. What was said?M.K.: A key issue for lab operation is the need for better ways to evaluate, quantitatively, the rapidly changing chemistries. Also, we discussed the need to develop instrumentation that is truly, rather than potentially, NeSSI-operable. Many details need to be resolved such as data system links and power for intrinsically safe operation, especially in plant situations. More interdisciplinary discussion is needed.