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Process monitoring of an intensified continuous production unit with compact NMR spectroscopy
(2016)
Monitoring chemical reactions is the key to chemical process control. Today, mainly optical online methods are applied. NMR spectroscopy has a high potential for direct loop process control. Compact NMR instruments based on permanent magnets are robust and relatively inexpensive analyzers, which feature advantages like low cost, low maintenance, ease of use, and cryogen-free operation. Instruments for online NMR measurements equipped with a flow-through cell, possessing a good signal-to-noise-ratio, sufficient robustness, and meeting the requirements for integration into industrial plants (i.e., explosion safety and fully automated data analysis) are currently not available off the rack. Recently, promising benchtop NMR instruments with acceptable performance came to market and process integrated sensors developed on basis of such laboratory instruments are on their way.
Intensified continuous processes are in focus of current research. Compared to traditional batch processes, these are giving admittance to new and difficult to produce compounds, leading to better product uniformity, and dras-tically reducing the consumption of raw materials and energy. Flexible (modular) chemical plants can produce different products using the same equipment with short down-times between campaigns, and quick introduction of new products to the market. Typically, such plants have smaller scale than big size facilities for production of basic chemicals but are still capable to produce kilograms to tons of specialty products each day. Such flexible (modular) plants can be provided in the size of 20 ft freight containers and represent a promising approach by their ability of easy transfer to production sites as well as the possibility of increasing production capacity by a simple numbering-up-approach.
However, full automation is a prerequisite to realize such benefits of intensified continuous production. In continu-ous flow processes steady automated measurements and tight closed-loop control of the product quality are mandatory. If these are not available, there is a huge risk of producing large amounts of out-of-spec (OOS) prod-ucts. This is addressed in the European Union’s Research Project CONSENS (Integrated Control and Sensing) by development and integration of smart sensor modules for process monitoring and control within such modular plant setups.
Process monitoring of an intensified continuous production unit with compact NMR spectroscopy
(2017)
Monitoring chemical reactions is the key to chemical process control. Today, mainly optical online methods are applied. NMR spectroscopy has a high potential for direct loop process control. Compact NMR instruments based on permanent magnets are robust and inexpensive analysers, which feature advantages like low maintenance, ease of use, and cryogen-free operation. Instruments for online NMR measurements equipped with a flow-through cell, possessing a good signal-to-noise-ratio, robustness, and meeting the requirements for integration into industrial plants (i.e., explosion safety and fully automated data analysis) are currently not available off the rack.
Intensified continuous processes are in focus of current research. Flexible (modular) chemical plants can produce different products using the same equipment with short down-times between campaigns and quick introduction of new products to the market. In continuous flow processes online sensor data and tight closed-loop control of the product quality are mandatory. Otherwise there is a huge risk of producing large amounts of out-of-spec (OOS) products. This is addressed in the European Union’s Research Project CONSENS by development and integration of smart sensor modules for process monitoring and control within such modular plant setups.
The presented NMR module is provided in an explosion proof housing with a module size of 57 x 57 x 85 cm and involves a compact 43.5 MHz NMR spectrometer together with an acquisition unit and a programmable logic controller for automated data preparation (phasing, baseline correction) and evaluation. Indirect Hard Modeling (IHM) was selected for data analysis of the low-field NMR spectra. A set-up for monitoring continuous reactions in a thermostated 1/8” tubular reactor using automated syringe pumps was used to validate the IHM models by using high-field NMR spectroscopy as analytical reference method.
Process monitoring of an intensified continuous production unit with compact NMR spectroscopy
(2016)
Monitoring chemical reactions is the key to chemical process control. Today, mainly optical online methods are applied. NMR spectroscopy has a high potential for direct loop process control. Compact NMR instruments based on permanent magnets are robust and relatively inexpensive analyzers, which feature advantages like low cost, low maintenance, ease of use, and cryogen-free operation. Instruments for online NMR measurements equipped with a flow-through cell, possessing a good signal-to-noise-ratio, sufficient robustness, and meeting the requirements for integration into industrial plants (i.e., explosion safety and fully automated data analysis) are cur-rently not available off the rack. Recently, promising benchtop NMR instruments with acceptable performance came to market and process integrated sensors developed on basis of such laboratory instruments are on their way.
Monitoring chemical reactions is the key to chemical process control. Today, mainly optical online methods are applied, which require excessive calibration effort. NMR spectroscopy has a high potential for direct loop process control while exhibiting short set-up times. Compact NMR instruments make NMR spectroscopy accessible in industrial and harsh environments for advanced process Monitoring and control, as demonstrated within the European Union’s Horizon 2020 project CONSENS.
We present a range of approaches for the automated spectra analysis moving from conventional multivariate statistical approach, (i.e., Partial Least Squares Regression) to physically motivated spectral models (i.e., Indirect Hard Modelling and Quantum Mechanical calculations). By using the benefits of traditional qNMR experiments data analysis models can meet the demands of the PAT community (Process Analytical Technology) regarding low calibration effort/calibration free methods, fast adaptions for new reactants or derivatives and robust automation schemes.
Monitoring specific chemical properties is the key to chemical process control. Today, mainly optical online methods are applied, which require time- and cost-intensive calibration effort. NMR spectroscopy, with its advantage being a direct comparison method without need for calibration, has a high potential for closed-loop process control while exhibiting short set-up times. Compact NMR instruments make NMR spectroscopy accessible in industrial and rough environments for process monitoring and advanced process control strategies.
We present a fully automated data analysis approach which is completely based on physically motivated spectral models as first principles information (Indirect Hard Modelling – IHM) and applied it to a given pharmaceutical lithiation reaction in the framework of the European Union’s Horizon 2020 project CONSENS. Online low-field NMR (LF NMR) data was analysed by IHM with low calibration effort, compared to a multivariate PLS-R (Partial Least Squares Regression) approach, and both validated using online high-field NMR (HF NMR) spectroscopy.