TY - CONF A1 - Gottu Mukkula, A. R. A1 - Engell, S. A1 - Kern, Simon A1 - Guhl, Svetlana A1 - Meyer, Klas A1 - Maiwald, Michael T1 - PAT-basierte iterative Optimierung der Fahrweise eines kontinuierlichen organischen Syntheseprozesses T2 - Chemie Ingenieur Technik N2 - Im Zuge der Digitalisierung der Prozessindustrie werden zunehmend modellbasiere Echtzeitoptimierungsverfahren eingesetzt, sog. „Advanced Process Control“. Mithilfe der sogenannten Modifier-Adaptation ist eine iterative Betriebspunktoptimierung auch mit ungenauen Modellen möglich, sofern zuverlässige Prozessdaten zur Verfügung stehen. Am Beispiel eines smarten Online-NMR-Sensors, der in einem EU-Projekt von der BAM entwickelt wurde, konnte das Konzept in einer modularen Produktionsanlage zur Herstellung eines pharmazeutischen Wirkstoffs erfolgreich getestet werden. T2 - ProcessNet-Jahrestagung und 33. DECHEMA-Jahrestagung der Biotechnologen CY - Aachen, Germany DA - 10.09.2018 KW - Prozessanalytik KW - Echtzeitoptimierungsverfahren KW - Modifier-Adaptation KW - Prozess-Steuerung KW - Betriebspunktoptimierung KW - CONSENS PY - 2018 UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/cite.201855233 DO - https://doi.org/10.1002/cite.201855233 SN - 0009-286X VL - 90 SP - 1237 EP - 1237 PB - Wiley-VCH Verlag GmbH & Co. KGaA CY - Weinheim AN - OPUS4-45902 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Gottu Mukkula, A. R. A1 - Kern, Simon A1 - Salge, M. A1 - Holtkamp, M. A1 - Guhl, Svetlana A1 - Fleischer, C. A1 - Meyer, Klas A1 - Remelhe, M. A1 - Maiwald, Michael A1 - Engell, S. T1 - An Application of Modifier Adaptation with Quadratic Approximation on a Pilot Scale Plant in Industrial Environment JF - IFAC-PapersOnLine N2 - The goal of this work is to identify the optimal operating input for a lithiation reaction that is performed in a highly innovative pilot scale continuous flow chemical plant in an industrial environment, taking into account the process and safety constraints. The main challenge is to identify the optimum operation in the absence of information about the reaction mechanism and the reaction kinetics. We employ an iterative real-time optimization scheme called modifier adaptation with quadratic approximation (MAWQA) to identify the plant optimum in the presence of plant-model mismatch and measurement noise. A novel NMR PAT-sensor is used to measure the concentration of the reactants and of the product at the reactor outlet. The experiment results demonstrate the capabilities of the iterative optimization using the MAWQA algorithm in driving a complex real plant to an economically optimal operating point in the presence of plant-model mismatch and of process and measurement uncertainties. KW - Process Analytical Technology KW - Online NMR Spectroscopy KW - Process Industry KW - Iterative real-time optimization KW - Modifier adaptation KW - Plant-model mismatch KW - Reactor control KW - CONSENS PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-524531 DO - https://doi.org/10.1016/j.ifacol.2020.12.685 SN - 1522-2640 VL - 53 IS - 2 SP - 11773 EP - 11779 PB - Elsevier CY - Amsterdam AN - OPUS4-52453 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Guhl, Svetlana A1 - Kern, Simon A1 - Meyer, Klas A1 - Gräßer, Patrick A1 - Wander, Lukas A1 - Maiwald, Michael T1 - Online NMR Spectroscopy for Process Monitoring in Intensified Continuous Production Plants T2 - Processdings of 4th European Conference on Process Analytics and Control Technology (EuroPACT 2017) N2 - Process analytical techniques are extremely useful tools for chemical production and manufacture and are of particular interest to the pharmaceutical, food and (petro-) chemical industries. 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. A major advantage of NMR spectroscopy is that the method features a high linearity between absolute signal area and sample concentration, which makes it an absolute analytical comparison method which is independent of the matrix. This is an important prerequisite for robust data evaluation strategies within a control concept and reduces the need for extensive maintenance of the evaluation model over the time of operation. Additionally, NMR spectroscopy provides orthogonal, but complimentary physical information to conventional, e.g., optical spectroscopy. It increases the accessible information for technical processes, where aromatic-toaliphatic conversions or isomerizations occur and conventional methods fail due to only minor changes in functional groups. As a technically relevant example, the catalytic hydrogenation of 2-butyne-1,4-diol and further pharmaceutical reactions were studied using an online NMR sensor based on a commercially available low-field NMR spectrometer within the framework of the EU project CONSENS (Integrated Control and Sensing). T2 - 4th European Conference on Process Analytics and Control Technology (EuroPACT 2017) CY - Potsdam, Germany DA - 10.05.2017 KW - Process Monitoring KW - CONSENS KW - Online NMR Spectroscopy KW - Process Analytical Technology KW - Process control KW - Hydration KW - EuroPACT PY - 2017 SP - 103 EP - 103 CY - Frankfurt a. M. AN - OPUS4-40231 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Guhl, Svetlana A1 - Kern, Simon A1 - Meyer, Klas A1 - Wander, Lukas A1 - Bornemann-Pfeiffer, Martin A1 - Maiwald, Michael T1 - Produzieren Sie schon oder kalibrieren Sie noch? – Online-NMR-Spektrometer als Smarte Feldgeräte T2 - Chemie Ingenieur Technik N2 - Der Vortrag zeigt allgemeine Anforderungen an "smarte Feldgeräte" und deren Entwicklung in den vergangenen Jahren. Am Beispiel eines smarten Online-NMR-Sensors, der in einem EU-Projekt von der BAM entwickelt wurde, wird die Umsetzung der Anforderung aufgezeigt. Schließlich werden weitere Technologieanforderungen und Lösungsansätze vorgestellt. T2 - ProcessNet-Jahrestagung und 33. DECHEMA-Jahrestagung der Biotechnologen CY - Aachen, Germany DA - 10.09.2018 KW - Prozessanalytik KW - Prozessindustrie KW - Online-NMR-Spektroskopie KW - Datenkonzepte KW - Datenanalyse KW - CONSENS PY - 2018 UR - https://onlinelibrary.wiley.com/doi/abs/10.1002/cite.201855229 DO - https://doi.org/10.1002/cite.201855229 SN - 0009-286X N1 - Geburtsname von Bornemann-Pfeiffer, Martin: Bornemann, M. - Birth name of Bornemann-Pfeiffer, Martin: Bornemann, M. VL - 90 IS - 9 SP - 1236 EP - 1236 PB - Wiley-VCH Verlag GmbH & Co. KGaA CY - Weinheim AN - OPUS4-45901 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Guhl, Svetlana A1 - Meyer, Klas A1 - Kern, Simon A1 - Gräßer, Patrick A1 - Maiwald, Michael T1 - Process monitoring of an intensified continuous production unit 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 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 - Workshop for Process Industry - Tackling the Future of Plant Operation CY - Frankfurt am Main, Germany DA - 25.01.2017 KW - Online NMR spectroscopy KW - Process analytical technology KW - Prozessanalytik KW - Process control KW - CONSENS PY - 2017 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-391386 AN - OPUS4-39138 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 - TY - CONF A1 - Kern, Simon A1 - Guhl, Svetlana A1 - Meyer, Klas A1 - Paul, Andrea A1 - Maiwald, Michael T1 - Mathematical and statistical tools for online NMR spectroscopy in chemical processes N2 - Monitoring chemical reactions is the key to chemical process control. Today, mainly optical online methods are applied, which are calibration intensive. 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. Within the European Union’s Research Project CONSENS (Integrated CONtrol and SENsing, www.consens-spire.eu) by development and integration of a smart NMR module for process monitoring was designed and delivers online spectra of various reactions. The presented NMR module is provided in an explosion proof housing of 57 x 57 x 85 cm module size and involves a compact spectrometer together with an acquisition unit and a programmable logic controller for automated data preparation (phasing, baseline correction), and evaluation. For reaction monitoring and process control using NMR instruments 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 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 - Process Monitoring KW - Process sensors KW - Process analytical technology KW - Online NMR spectroscopy KW - Direct loop control KW - Numerical methods KW - Spectral modeling KW - Indirect hard modeling KW - CONSENS PY - 2017 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-432085 AN - OPUS4-43208 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -