TY - GEN A1 - Kern, Simon A1 - Liehr, Sascha A1 - Wander, Lukas A1 - Bornemann-Pfeiffer, Martin A1 - Müller, S. A1 - Maiwald, Michael A1 - Kowarik, Stefan T1 - Training data of quantitative online NMR spectroscopy for artificial neural networks N2 - Data set of low-field NMR spectra of continuous synthesis of nitro-4’-methyldiphenylamine (MNDPA). 1H spectra (43 MHz) were recorded as single scans. Two different approaches for the generation of artificial neural networks training data for the prediction of reactant concentrations were used: (i) Training data based on combinations of measured pure component spectra and (ii) Training data based on a spectral model. Synthetic low-field NMR spectra First 4 columns in MAT-files represent component areas of each reactant within the synthetic mixture spectrum. Xi (“pure component spectra dataset”) Xii (“spectral model dataset”) Experimental low-field NMR spectra from MNDPA-Synthesis This data set represents low-field NMR-spectra recorded during continuous synthesis of nitro-4’-methyldiphenylamine (MNDPA). Reference values from high-field NMR results are included. KW - NMR spectroscopy KW - Real-time process monitoring KW - Artificial neural networks KW - Online NMR spectroscopy KW - Automation KW - Process industry PY - 2020 DO - https://doi.org/10.5281/zenodo.3677139 PB - Zenodo CY - Geneva AN - OPUS4-50456 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Kern, Simon A1 - Guhl, Svetlana A1 - Meyer, Klas A1 - Wander, Lukas A1 - Paul, Andrea A1 - Maiwald, Michael T1 - Mathematical and statistical tools for online NMR spectroscopy in chemical processes T2 - Tagungsband 13. Dresdner Sensor-Symposium N2 - 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. T2 - 13. Dresdner Sensor Symposium CY - Dresden, Germany DA - 04.12.2017 KW - Online NMR spectroscopy KW - Process control KW - Partial least squares regression KW - Indirect hard modeling KW - Quantum mechanics KW - First principles PY - 2017 UR - https://www.ama-science.org/proceedings/details/2748 SN - 978-3-9816876-5-1 DO - https://doi.org/10.5162/13dss2017/P2.07 SP - P2, 209 EP - 212 PB - AMA Service GmbH CY - Berlin AN - OPUS4-43254 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Kern, Simon A1 - Guhl, Svetlana A1 - Meyer, Klas A1 - Paul, Andrea A1 - Wander, Lukas A1 - Gräßer, Patrick A1 - Maiwald, Michael T1 - Design and Validation of a Compact NMR Analyser T2 - Processdings of 4th European Conference on Process Analytics and Control Technology (EuroPACT 2017) N2 - 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 analysers, 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. 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. If these are not available, there is a huge risk of producing large amounts of out-of-spec (OOS) products. This is addressed in the European Unionʼs 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. The presented NMR module is provided in an explosion proof housing of 57 x 57 x 85 cm module size 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. T2 - 4th European Conference on Process Analytics and Control Technology (EuroPACT 2017) CY - Potsdam, Germany DA - 10.05.2017 KW - Prozessanalytik KW - Reaction Monitoring KW - Online NMR Spectrsocopy KW - Process Analytical Technology KW - Industrie 4.0 KW - EuroPACT PY - 2017 SP - 72 EP - 73 CY - Frankfurt a. M. AN - OPUS4-40229 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - RPRT A1 - Kern, Simon A1 - Guhl, Svetlana A1 - Meyer, Klas A1 - Maiwald, Michael ED - Maiwald, Michael T1 - Validation report on NMR N2 - The departure from the current automation landscape to next generation automation concepts for the process industry has already begun. Smart functions of sensors simplify their use and enable plug and play integration, even though they may appear to be more complex at first sight. Smart sensors enable concepts like self-diagnostics, self-calibration, and self-configuration/ parameterization whenever our current automation landscape allows it. Here we summarize the currently discussed general requirements for process sensors 4.0 and introduce a smart online NMR sensor module as example, which was developed for an intensified industrial process funded by the EU’s Horizon 2020 research and innovation programme (www.consensspire.eu). KW - Process Monitoring KW - Online NMR Spectroscopy KW - Indirect Hard Modeling KW - Process Control KW - Process Analytical Technology KW - CONSENS PY - 2017 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-435521 SP - 1 EP - 31 AN - OPUS4-43552 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Kern, Simon A1 - Gräßer, Patrick A1 - Zientek, Nicolai A1 - Maiwald, Michael T1 - First steps towards field integration of benchtop NMR spectroscopy for online monitoring and process control T2 - Tagungsband - 11. Kolloquium Arbeitskreis Prozessanalytik N2 - Online monitoring and process control requires fast and noninvasive analytical methods, which are able to monitor the concentration of reactants in multicomponent mixtures with parts-per-million resolution. Online NMR spectros-copy can meet these demands when flow probes are directly coupled to reactors, since this method features a high linearity between absolute signal area and sample concentration, which makes it an absolute analytical com-parison method being independent on the matrix. Due to improved magnet design and field shimming strategies portable and robust instruments have been introduced to the market by several manufacturers during the last few years. First studies with this technology showed promising results to monitor chemical reaction in the laboratory. T2 - 11. Kolloquium Arbeitskreis Prozessanalytik CY - Wien, Austria DA - 30.11.2015 KW - Online NMR Spectroscopy KW - Smart Sensors KW - Prozess-Spektroskopie KW - Process Analytical Technology KW - Process control PY - 2015 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-388411 SP - 43 EP - 44 AN - OPUS4-38841 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Kern, Simon A1 - Meyer, Klas A1 - Gräßer, Patrick A1 - Guhl, Svetlana A1 - Paul, Andrea A1 - Maiwald, Michael T1 - Ugly spectra and lousy interfaces – challenges for compact NMR spectroscopy in process control N2 - With the introduction of advanced process analytical technology, the closeness of key process variables to their limits can be directly controlled and the product can be classified or even released in real time. Compact NMR instruments can make NMR spectroscopy accessible in industrial and harsh environments for process control. T2 - ProcessNet-Jahrestagung und 32. DECHEMA-Jahrestagung der Biotechnologen 2016 CY - Aachen, Germany DA - 12.09.2016 KW - Industrie 4.0 KW - Online NMR spectroscopy KW - Reaction monitoring KW - Smart sensors PY - 2016 AN - OPUS4-37405 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Kern, Simon A1 - Wander, Lukas A1 - Bornemann-Pfeiffer, Martin A1 - Guhl, Svetlana A1 - Meyer, Klas A1 - Maiwald, Michael T1 - Novel Flow Cell Designs for Process Monitoring with Compact NMR Spectroscopy N2 - Compact nuclear magnetic resonance (NMR) instruments make NMR spectroscopy and relaxometry accessible in industrial and harsh environments for reaction characterization and process control. Robust field integration of NMR systems have to face explosion protection or integration into process control systems with short set-up times. This paves the way for industrial automation in real process environments. The design of failsafe, temperature and pressure resistant flow through cells along with their NMR-specific requirements is an essential cornerstone to enter industrial production plants and fulfill explosion safety requirements. Additionally, if fast reactions are monitored, suitable mixing devices need to be placed in close vicinity to the measuring volume to mix the reactants properly. NMR-specific requirements aim at full quantitative pre-magnetization and acquisition with maximum sensitivity while reducing sample transfer times and dwell-times. All parameters are individually dependent on the applied NMR instrument. Luckily, an increasing number of applications are reported together with an increasing variety of commercial equipment. However, these contributions have to be reviewed thoroughly. The performance of sample flow cells commonly used in online analytics and especially for low-field NMR spectroscopy was experimentally and theoretically investigated by 1H-NMR experiments and numerical simulations. Especially, the applicability of 3D printed zirconium dioxide for innovative flow cell designs was of interest. Here, we demonstrate and discuss an automated test method to determine the critical parameters of flow through cells for quantitative online NMR spectroscopy. The setup is based on randomized setpoints of flow rates in order to reduce temperature related effects. Five flow cells and tubing were assessed and compared for high-field as well as low-field NMR spectrometers. T2 - Practical Applications of NMR in Industry Conference ​(PANIC) 2018 CY - La Jolla, California, USA DA - 04.03.2018 KW - Process Monitoring KW - Process Control KW - Flow Cell KW - Online NMR Spectroscopy KW - Additive Manufacturing KW - CONSENS PY - 2018 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-444364 N1 - Geburtsname von Bornemann-Pfeiffer, Martin: Bornemann, M. - Birth name of Bornemann-Pfeiffer, Martin: Bornemann, M. AN - OPUS4-44436 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Kern, Simon A1 - Meyer, Klas A1 - Wander, Lukas A1 - Guhl, Svetlana A1 - Paul, Andrea A1 - Maiwald, Michael T1 - Process monitoring of intensified continuous production units with compact NMR spectroscopy N2 - 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 (www.consens-spire.eu) 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. T2 - Seminar, Institute of Technical Biocatalysis, Hamburg University of Technology CY - Hamburg, Germany DA - 13.01.2017 KW - Process monitoring KW - Online NMR spectroscopy KW - Indirect hard modeling KW - Process control KW - Process analytical technology KW - CONSENS PY - 2017 AN - OPUS4-43551 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Kern, Simon A1 - Guhl, Svetlana A1 - Meyer, Klas A1 - Paul, Andrea A1 - Maiwald, Michael T1 - Reading between the lines – Automated data analysis for low field NMR spectra N2 - For reaction monitoring and process control using NMR instruments, in particular, after acquisition of the FID the data needs to be corrected in real-time for common effects using fast interfaces and automated methods. When it comes to NMR data evaluation under industrial process conditions, the shape of signals can change drastically due to nonlinear effects. Additionally, the multiplet structure becomes more dominant because of the comparably low-field strengths which results in overlapping of multiple signals. However, the structural and quantitative information is still present but needs to be extracted by applying predictive models. We present a range of approaches for the automated spectra analysis moving from statistical approach, (i.e., Partial Least Squares Regression) to physically motivated spectral models (i.e., Indirect Hard Modeling). 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. T2 - Small Molecule NMR Conference (SMASH) CY - Baveno, Italy DA - 17.09.2017 KW - Online NMR spectroscopy KW - Data analysis KW - Chemometrics KW - Indirect hard modeling KW - Spectral modeling KW - Line prediction KW - CONSENS KW - SMASH PY - 2017 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-419498 UR - http://www.smashnmr.org/conference/program AN - OPUS4-41949 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - THES A1 - Kern, Simon T1 - Prozessüberwachung mittels Niederfeld-NMR-Spektroskopie als Online-Methode N2 - Die Geräteentwicklungen im Bereich der Niederfeld-NMR-Spektroskopie im vergangenen Jahrzehnt ermöglichen den Einsatz kompakter, portabler Magnete mit geringen Streufeldern in Laborumgebungen und industriellen Produktionsanlagen. Somit werden neue Möglichkeiten für hochauflösende NMR-Experimente zur Reaktionsüberwachung eröffnet. Im Rahmen des EU-Projekts CONSENS wurden die Möglichkeiten dieser Methode umfassend anhand einer technisch bedeutenden Reaktion (elektrophile aromatische Substitutionsreaktionen) evaluiert. Um die Flexibilität einer kontinuierlichen und modularen Pilotanlage durch Echtzeit- Qualitätskontrolle zu fördern, wurde ein vollständig automatisiertes Online- NMR-Modul entwickelt. Der Einsatz eines kommerziellen Niederfeld-NMR-Geräts im industriellen Umfeld wurde durch die entwickelten Lösungen der automatisierten Datenanlyse sowie durch ein zertifiziertes Sicherheitskonzept für den Betrieb in explosionsgefährdeten Zonen ermöglicht. Neben der Überwachung der Produktqualität wurden Online-NMR-Daten in einem neuen iterativen Optimierungsansatz zur Maximierung des Anlagenertrags eingesetzt und dienten als zuverlässige Referenz für die Kalibrierung eines Nahinfrarot-Spektrometers. Für die Entwicklung einer robusten Datenauswertung der NMR-Spektren, die dem Anspruch der Flexibilität bei Produktwechseln genügt, wurden zunächst Versuche im Labormaßstab durchgeführt, um eine Datenbasis zu schaffen. In diesen Versuchen wurden die aromatischen Amine Anilin, p-Toluidin und p-Fluoranilin mit o-Fluornitrobenzol gekoppelt. Durch Zugabe einer Organolithium-Verbindung (Li- HMDS) findet ein Protonenaustausch zwischen dem primären Amin und Li-HMDS statt. Dies führt zu einer hohen Reaktionsenthalpie und instabilen Aryllithium-Verbindungen. Die Reaktionen wurden hinsichtlich anfallender Zwischenprodukte mittels Hochfeld-NMR-Spektroskopie analysiert. Nachfolgend wurden die Reaktionen sowohl im Semi-Batch-Verfahren als auch im kontinuierlichen Laborbetrieb mit Online-Niederfeld-NMR-Spektroskopie und Online- Hochfeld-NMR-Spektroskopie untersucht. Da die gemessenen NMR-Spektren besonders im aromatischen Spektralbereich hohe Signalüberlappungen der Reaktanden aufweisen, wurden chemometrische Modelle entwickelt und anhand der Hochfeld-NMR-Methode validiert. Die verwendeten Durchflusszellen für die Niederfeld-NMR-Spektroskopie wurden hinsichtlich ihrer Anwendbarkeit für quantitative Messungen im kontinuierlichen Durchfluss untersucht. Es konnte gezeigt werden, dass Messungen mit einer additiv gefertigten Keramikdurchflusszelle prinzipiell möglich sind. KW - NMR-Spektroskopie KW - Niederfeld-NMR-Spektroskopie KW - Prozessanalytik KW - Industrie 4.0 KW - Indirect Hard Modeling KW - CONSENS PY - 2019 UR - https://nbn-resolving.org/10.14279/depositonce-9404 DO - https://doi.org/10.14279/depositonce-9404 SP - 1 EP - 112 CY - Berlin AN - OPUS4-50196 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -