TY - CONF A1 - Meyer, Klas T1 - NMR Spectroscopy as a PAT tool: Field integration of a laboratory instrument N2 - Companies of chemical industry find themselves more often in a rapidly changing environment, e.g., due to variability of raw material quality or energy costs and efficiency. Process optimization and new process concepts become more and more important. Flexible and modular chemical plants can produce various high-quality products using multi-purpose equipment with short downtimes between campaigns and reduce time to market for new products. Intensified continuous production plants allow for difficult to produce compounds like exothermic reactions with high heat dissipation. Highly automated chemical process monitoring along with real-time quality control are prerequisites to such concepts and, thus, should be based on chemical information. A commercially available benchtop NMR spectrometer was integrated to the full requirements of an automated chemical production environment such as explosion safety, field communication, and robust evaluation of sensor data. Field studies in modular and conventional production plant setups show promising results gaining process knowledge for further optimization. NMR spectroscopy appeared as preeminent online analytical method and allows using a modular data analysis approach, which can even serve as reliable reference method for further calibration-dependent PAT applications (e.g., NIR or Raman spectroscopy). Based on experiences from earlier field studies an improved field enclosure setup was developed and built, including the option of a secondary analytical method (e.g., optical spectroscopy). Integrated control systems allow for a flexible implementation based on the available automation infrastructure at the chemical plant or pilot plant setup. In the future, modular interconnecting “smart” PAT systems and process equipment have the potential speed up the setup of production equipment for chemicals and pharmaceuticals and therefore help to reduce the time-to-market. T2 - ANAKON 2025 CY - Leipzig, Germany DA - 10.03.2025 KW - NMR Spectroscopy KW - Process Analytical Technology KW - Field Integration KW - Benchtop-NMR PY - 2025 AN - OPUS4-62744 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas T1 - Deconvolution in High-Field- and Benchtop-NMR applications N2 - Numerical "sum integration" is the typical way to extract signal area from NMR spectra for quantitative evaluation, however, in complex situations of peak overlaps or crowded spectra this can be impractical. Deconvolution methods based on linefitting and optimization allow for a more accurate extraction of signal features from the spectrum in these cases. The increasing number of benchtop NMR applications showing lower signal dispersion and therefore more often complex spectral patterns foster the development and application of model-based spectra evaluation methods. This includes techniques like Indirect Hard Modeling (IHM), Quantum-Mechanical Spectra Analysis (QMSA), Chemometric modeling like PLS-R or MCR, as well as Machine-learning approaches using Neural Networks. This presentation gives an overview and introduction into deconvolution methods in the context of high-field and benchtop-NMR applications in complex spectra and process monitoring. T2 - CCQM OAWG/PAWG Advances in qNMR Workshop CY - Sèvres, France DA - 08.04.2025 KW - NMR Spectroscopy KW - Process Analytical Technology KW - Deconvolution KW - Benchtop-NMR PY - 2025 AN - OPUS4-62956 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas T1 - NMR Spectroscopy as a PAT tool: Field integration of a laboratory instrument N2 - Companies of chemical industry find themselves more often in a rapidly changing environment, e.g., due to variability of raw material quality or energy costs and efficiency. Process optimization and new process concepts become more and more important. Flexible and modular chemical plants can produce various high-quality products using multi-purpose equipment with short downtimes between campaigns and reduce time to market for new products. Intensified continuous production plants allow for difficult to produce compounds like exothermic reactions with high heat dissipation. Highly automated chemical process monitoring along with real-time quality control are prerequisites to such concepts and, thus, should be based on chemical information. A commercially available benchtop NMR spectrometer was integrated to the full requirements of an automated chemical production environment such as explosion safety, field communication, and robust evaluation of sensor data. Field studies in modular and conventional production plant setups show promising results gaining process knowledge for further optimization. NMR spectroscopy appeared as preeminent online analytical method and allows using a modular data analysis approach, which can even serve as reliable reference method for further calibration-dependent PAT applications (e.g., NIR or Raman spectroscopy). Based on experiences from earlier field studies an improved field enclosure setup was developed and built, including the option of a secondary analytical method (e.g., optical spectroscopy). Integrated control systems allow for a flexible implementation based on the available automation infrastructure at the chemical plant or pilot plant setup. In the future, modular interconnecting “smart” PAT systems and process equipment have the potential speed up the setup of production equipment for chemicals and pharmaceuticals and therefore help to reduce the time-to-market. T2 - Practical Applications of NMR in Industry Conference (PANIC) CY - Rockville, MD, USA DA - 19.05.2025 KW - Compact NMR spectroscopy KW - Process Analytical Technology KW - Field Integration KW - qNMR PY - 2025 AN - OPUS4-63193 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas T1 - On-line monitoring of polyhydroxyalkanoate extraction process using compact NMR spectroscopy N2 - Portable benchtop NMR spectrometers enable real-time process and reaction monitoring in contrast to conventional laboratory based off-line gas chromatography or high-field NMR measurements. In this study, benchtop NMR spectroscopy is demonstrated as a process analytical technology (PAT) tool for the application of the solvent extraction step in downstream processing of polyhydroxyalkanoate (PHA) biopolymers. These are one of the few thermoplastic polymers synthesized 100 % via biotechnological routes which fully biodegrade in common natural environments. This makes them excellent candidate materials for sustainable replacement of conventional plastic materials. Online NMR experiments were conducted using a fully automated setup, employing commercially available PTFE tubing as a flow-cell assembly. Extraction was carried out in a thermostated stirred batch reactor in lab-scale. Single-scan NMR spectra allowed continuous monitoring of the extraction of the PHA copolymer poly-(hydroxybutyrate-co-hydroxyhexanoate) containing 13.5 mol-% hydroxyhexanoate from Ralstonia eutropha biomass. Extractions were performed in chloroform and acetone across ground lyophilized cell loadings ranging from 20 to 120 g/L. The reproducibility and reliability of compact NMR spectroscopy closely matched with high-field NMR measurements. A strong correlation was observed between online low-field NMR data and offline gas chromatography (GC) analysis. The study highlights the versatility of compact NMR for process monitoring, facilitating endpoint determination and enhancing extraction efficiency by optimizing process parameters. Steady-state conditions were achieved within 6 to 10 minutes for chloroform and acetone, respectively, underscoring the method’s value in supporting downstream process development and optimization for PHA recovery. T2 - 20. Herbstkolloquium Arbeitskreis Prozessanalytik CY - Frankfurt am Main, Germany DA - 03.12.2025 KW - Polyhydroxyalkanoate KW - Process Analytical Technology KW - Downstream processing KW - Benchtop-NMR PY - 2025 AN - OPUS4-65065 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas T1 - Low-Field NMR Spectroscopy on Solid Dispersions – A Flow Injection Method for End-Point Control of Azo Couplings for Industrial Pigment Production N2 - Global demand for pigments is expected to increase to around 13.4 million tons per year by 2030, representing approximately $22 billion – 5 % of which will be azo pigments as the main organic pigments. Azo pigments, i.e., especially the azo bridge required for them, are almost exclusively produced in technology by azo coupling reactions in large-scale approaches on the scale of 50–100 cubic meters. Among other things, one of the reasons why large-scale production itself is still essentially discontinuous is the lack of analytical methods for a continuous process control. In an azo coupling process, an aromatic amine is diazotized to form the diazonium compound (diazo compound), which reacts with a coupling component, i.e., "couples". A slight excess of the coupler is desired for the end of the reaction, which stoichiometrically consumes the remaining (harmful) diazo compound, i.e., below 500 ppm. This is carried out with a manual spotting reaction of a fast-binding reagent. To carry out continuous azo coupling, care must be taken to ensure that the actual coupling reaction proceeds as rapidly as possible, i.e., preferentially, compared with possible side reactions. Reliable measuring methods are thus a decisive criterion for the useful performance of a continuous azo pigment synthesis. An analytical online procedure is difficult due to several limitations at once: solid dispersions extremely limit the range of reproducible analytical procedures. In addition, the appearance of a signal (e.g., excess of a starting material) in the ppm range must be reliably detected within the matrix background. A proposal based on a back-titration method and benchtop NMR spectroscopy were used to overcome these problems. We present a feasibility study for a suitable process analysis with benchtop NMR spectroscopy on disperse systems for equimolar dosing of the "diazotization" or "coupling" sub-step in azo coupling. This could potentially replace tedious manual spotting reactions in conventional discontinuous production and paves the way for continuous production. T2 - 19. Kolloquium AK Prozessanalytik CY - Darmstadt, Germany DA - 04.12.2024 KW - NMR Spectroscopy KW - Process Analytical Technology KW - Azo-Pigments KW - Benchtop-NMR PY - 2024 AN - OPUS4-62176 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas T1 - Benchtop NMR spectroscopy in chemical manufacturing: From hardware field integration to data modeling N2 - The use of benchtop-NMR instruments is constantly increasing during the recent years. Advantages of being affordable, portable and easy-to-operate without the need for trained staff make them especially interesting for industrial applications in quality control. However, applications of NMR spectroscopy as an online PAT tool are still very rare but offer a huge potential for process optimization and control. A key task to exploit this potential is hardware field integration of the lab-instruments in a rough environment of a chemical plant. Additionally, developments in automation and data evaluation are mandatory to ensure a robust unattended operation with low maintenance requirements. Here, we show an approach of a fully automated analyzer enclosure considering explosion safety, field communication, as well as environmental conditions in the field. Temperature sensitivity is still a limitation of benchtop-NMR instruments in flow applications. Recent developments of manufacturers allow for limited operation at static temperature levels, however, a dynamic system for continuous operation is still not available. Using a prototype system offering a larger bore, active temperature shielding studies with thermostated air were performed evaluating the performance. Automated data evaluation of NMR spectra using a modular indirect hard modeling (IHM) approach showed good results and flexibility. A second data analysis approach based on artificial neural networks (ANN) was evaluated.Therefore, amount of data was augmented to be sufficient for training. The results show comparable performance, while improving the calculation time tremendously, offering new ways to simultaneously evaluating large numbers of different models. T2 - Quantitative NMR Methods for Reaction and Process Monitoring (NMRPM) CY - Kaiserslautern, Germany DA - 24.05.2023 KW - Field integration KW - Benchtop-NMR KW - Process Analytical Technology PY - 2023 AN - OPUS4-57560 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas T1 - Low-Field NMR Spectroscopy on Solid Dispersions A Flow Injection Method for End-Point Control of Azo Couplings for Industrial Pigment Production N2 - Global demand for pigments is expected to increase to around 13.4 million tons per year by 2030, representing approximately $22 billion – 5% of which will be azo pigments as the main organic pigments. Azo pigments, i.e., especially the azo bridge required for them, are almost exclusively produced in technology by the so-called azo coupling reaction in large-scale approaches on the scale of 50–100 cubic meters. Among other things, one of the reasons why large-scale production itself is still essentially discontinuous is the lack of analytical methods for a continuous azo pigment synthesis. In an azo coupling process, an aromatic amine is diazotized to form the diazonium compound (diazo compound), which then reacts with a coupling component, i.e., "couples". A slight excess of the coupler is desired for the end of the reaction, which stoichiometrically consumes the remaining (harmful) diazo compound, i.e., below 500 ppm. This is carried out with a manual spotting reaction of a fast-binding coupler. To carry out continuous azo coupling, care must be taken to ensure that the actual coupling reaction proceeds as rapidly as possible, i.e., preferentially, compared with possible side reactions. Reliable measuring methods are thus a decisive criterion for the useful performance of a continuous azo pigment synthesis. An analytical online procedure is difficult due to several limitations at once: solid dispersions extremely limit the range of reproducible analytical procedures. In addition, the appearance of a signal (e.g., excess of a starting material) in the ppm range must be reliably detected against the matrix background. The back-titration method and benchtop NMR spectroscopy were used to overcome these problems. We present a feasibility study for a suitable process analysis with benchtop NMR spectroscopy on disperse systems for equimolar dosing of the "diazotization" or "coupling" sub-step in azo coupling, which was carried out in cooperation with a chemical company. This could replace tedious manual spotting T2 - SMASH Small molecule NMR conference 2023 CY - Baveno, Italy DA - 17.09.2023 KW - Benchtop NMR KW - Dispersions KW - Process Analytical Technology KW - Process monitoring PY - 2023 AN - OPUS4-58399 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas T1 - Compact NMR Spectroscopy in the field: A Versatile PAT Tool for Production of Specialty Chemicals N2 - Companies of chemical industry find themselves more often in a rapidly changing environment, e.g., due to variability of raw material quality or energy costs and efficiency. Process optimization and new process concepts become more and more important. For example, flexible and modular chemical plants can produce various high-quality products using multi-purpose equipment with short downtimes between campaigns and reduce time to market for new products. Intensified continuous production plants allow for difficult to produce compounds like exothermic reactions with high heat dissipation. Highly automated “chemical” process control along with real-time quality control are prerequisites to such concepts and thus should be based on “chemical” information. A commercially available benchtop NMR spectrometer was integrated to the full requirements of an automated chemical production environment such as explosion safety, field communication, and robust evaluation of sensor data. Field studies in modular and conventional production plant setups show promising results gaining process knowledge for further optimization. NMR appeared as preeminent online analytical method and allow using a modular data analysis approach, which can even serve as reliable reference method for further calibration-dependent PAT applications (e.g., NIR or Raman spectroscopy). Based on experiences from earlier field studies an improved NMR analyzer enclosure setup was developed and built, including the option of a secondary method (e.g., optical spectroscopy). Integrated control systems allow for a flexible implementation based on the available automation infrastructure at the chemical plant or pilot plant setup. In the future, fully integrated and intelligently interconnecting “smart” PAT systems and processes have the potential speed up the setup of production equipment for chemicals and pharmaceuticals and therefore help to reduce the time-to-market. T2 - SMASH Small molecule NMR conference 2023 CY - Baveno, Italy DA - 17.09.2023 KW - Benchtop-NMR KW - Process Analytical Technology KW - Chemical Production KW - NMR spetroscopy PY - 2023 AN - OPUS4-58398 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas T1 - Contributions Towards Variable Temperature Shielding for Compact NMR Instruments N2 - The application of compact NMR instruments to hot flowing samples or exothermically reacting mixtures is limited by the temperature sensitivity of permanent magnets. Typically, such temperature effects directly influence the achievable magnetic field homogeneity and hence measurement quality. The internal-temperature control loop of the magnet and instruments is not designed for such temperature compensation. Passive insulation is restricted by the small dimensions within the magnet borehole. Here, we present a design approach for active heat shielding with the aim of variable temperature control of NMR samples for benchtop NMR instruments using a compressed airstream which is variable in flow and temperature. Based on the system identification and surface temperature measurements through thermography, a model predictive control was set up to minimise any disturbance effect on the permanent magnet from the probe or sample temperature. This methodology will facilitate the application of variable-temperature shielding and, therefore, extend the application of compact NMR instruments to flowing sample temperatures that differ from the magnet temperature. T2 - SMASH Small molecule NMR conference 2023 CY - Baveno, Italy DA - 17.09.2023 KW - Benchtop NMR KW - Temperature Control KW - Process Analytical Technology KW - Flow NMR PY - 2023 AN - OPUS4-58400 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas T1 - Contributions Towards Variable Temperature Shielding for Compact NMR Instruments N2 - The application of compact NMR instruments to continuously flowing samples at higher temperatures or exothermically reacting mixtures is limited by the temperature sensitivity of permanent magnets. Typically, such temperature effects directly influence the achievable magnetic field homogeneity and hence measurement quality. The internal-temperature control loop of the magnet and instruments is typically not designed for compensation of such effects. Passive insulation is restricted by the small dimensions within the magnet borehole. Here, we present a design approach for active heat shielding with the aim of variable temperature control of NMR samples for benchtop NMR instruments using a compressed airstream which is variable in flow and temperature. Based on the system identification and surface temperature measurements using an optical thermo-graphy setup, a model predictive control was set up to minimize any disturbance effect on the permanent magnet from the probe or sample temperature. This methodology will facilitate the application of variable-temperature shielding and, therefore, potentially extend the application of compact NMR instruments to flowing samples at higher temperature than the permanent magnet. T2 - 18. Kolloquium AK Prozessanalytik CY - Krefeld, Germany DA - 27.11.2023 KW - Thermostating KW - Benchtop-NMR KW - NMR spectroscopy KW - Process Analytical Technology PY - 2023 AN - OPUS4-58970 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -