TY - CONF A1 - Meyer, Klas A1 - Kraemer, B. A1 - Zientek, Nicolai A1 - Esche, E. A1 - Müller, D. A1 - Wozny, G. A1 - Maiwald, Michael T1 - Vom Labor zum Prozess- Eine robuste Prozessanalytik für die Reaktivabsorption von CO2 aus in industriellen Gasströmen basierend auf Onlin-NMR- und Raman-Spektroskopie T2 - Anakon 2015 T2 - Anakon 2015 CY - Graz, Östereich DA - 2015-03-23 PY - 2015 AN - OPUS4-33132 LA - deu 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 - Zientek, Nicolai A1 - Meyer, Klas A1 - Panne, Ulrich A1 - Kraume, M. A1 - Maiwald, Michael T1 - Untersuchung der Auflösungskinetik von pharmazeutischen Cokristallen mittels Onlilne-NMR-Spektroskopie T2 - 7. Interdisziplinäres Doktorandenseminar N2 - Bei der Entwicklung pharmazeutischer Wirkstoffe werfen Substanzen mit einer geringen Löslichkeit, Auflösungsrate und damit einhergehend schlechten Bioverfügbarkeit immer größere Probleme auf. Diese Eigenschaften und nicht etwa toxikologische Eigenschaften oder schlechte Wirksamkeit sorgen dafür, dass es weniger als 1 % aller Wirkstoffe bis in die Markteinführung schaffen. Eine Reihe von Ansätzen zur Verbesserung der schlechten Wasserlöslichkeit konnten bereits etabliert werden. Hierunter zählen die gezielte Salzbildung bzw. Salzscreening, Solubilisierung mit Cosolventien oder die Nutzung von Polymeren als mögliche Transportwege. Eine weitere Möglichkeit bietet die Bildung verschiedener polymorpher Formen, sowohl der Einzelkomponente als auch von den verschiedenen Mehrkomponentenverbindungen. T2 - 7. Interdisziplinäres Doktorandenseminar CY - Berlin, Germany DA - 24.02.2013 KW - Quantitative Online-NMR-Spektroskopie KW - Pharmazeutische Cokristalle PY - 2013 SN - 978-3-9815360-9-6 SP - 9 EP - 11 PB - Bundesanstalt für Materialforschung und -prüfung (BAM) AN - OPUS4-28266 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Kern, Simon A1 - Meyer, Klas A1 - Paul, Andrea A1 - Maiwald, Michael T1 - Ugly Spectra and Lousy interfaces – Challenges for Compact NMR Spectroscopy in Process Control T2 - Chemie Ingenieur Technik 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 - Online NMR Spectroscopy KW - Smart Sensors KW - Industrie 4.0 KW - Reaction Monitoring PY - 2016 UR - http://onlinelibrary.wiley.com/doi/10.1002/cite.201650243/full DO - https://doi.org/10.1002/cite.201650243 SN - 1522-2640 VL - 88 SP - 1304 EP - 1317 PB - Wiley-VCH Verlag GmbH & Co. KGaA CY - Weinheim AN - OPUS4-37317 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maiwald, Michael A1 - Meyer, Klas A1 - Zientek, Nicolai T1 - Towards online reaction monitoring with fully automated NMR data evaluation and modelling - Current results from simultaneous 19F-1H medium resolution NMR experiments N2 - NMR Process Monitoring Towards an automated field integration T2 - 3rd Practical Applications of NMR in Industry Conference (PANIC) - Mestrelab users' meeting CY - La Jolla, CA, USA DA - 08.02.2015 KW - Online NMR spectroscopy KW - Reaction monitoring KW - Prozessanalytik KW - Process analytical technology PY - 2015 AN - OPUS4-36145 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maiwald, Michael A1 - Gräßer, Patrick A1 - Wander, Lukas A1 - Zientek, Nicolai A1 - Guhl, Svetlana A1 - Meyer, Klas A1 - Kern, Simon T1 - Strangers in the Night—Smart Process Sensors in Our Current Automation Landscape T2 - Proceedings 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.consens-spire.eu). T2 - Eurosensors 2017 Conference CY - Paris, France DA - 03.09.2017 KW - Process Monitoring KW - Smart Sensors KW - CONSENS KW - Online NMR Spectroscopy KW - Mini-plant PY - 2017 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-415772 UR - http://www.mdpi.com/2504-3900/1/4/628 DO - https://doi.org/10.3390/proceedings1040628 VL - 1 SP - 628 EP - 631 PB - MDPI CY - Basel AN - OPUS4-41577 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Bornemann-Pfeiffer, Martin A1 - Wolf, Jakob A1 - Meyer, Klas A1 - Kern, S. A1 - Angelone, D. A1 - Leonov, A. A1 - Cronin, L. A1 - Emmerling, Franziska T1 - Standardization and control of Grignard reactions in a universal chemical synthesis machine using online NMR T1 - Standardisierung und Kontrolle von Grignard-Reaktionen mittels Online-NMR in einer universellen chemischen Syntheseplattform JF - Angewandte Chemie - International Edition N2 - A big problem with the chemistry literature is that it is not standardized with respect to precise operational parameters, and real time corrections are hard to make without expert knowledge. This lack of context means difficult reproducibility because many steps are ambiguous, and hence depend on tacit knowledge. Here we present the integration of online NMR into an automated chemical synthesis machine (CSM aka. “Chemputer” which is capable of small-molecule synthesis using a universal programming language) to allow automated analysis and adjustment of reactions on the fly. The system was validated and benchmarked by using Grignard reactions which were chosen due to their importance in synthesis. The system was monitored in real time using online-NMR, and spectra were measured continuously during the reactions. This shows that the synthesis being done in the Chemputer can be dynamically controlled in response to feedback optimizing the reaction conditions according to the user requirements. N2 - Ein Problem der chemischen Literatur ist die fehlende Standardisierung bezüglich genauer Bedingungen, auch Echtzeit-Korrekturen sind ohne Expertenwissen nur schwer möglich. Dieser Mangel an Details erschwert experimentelle Reproduzierbarkeit, da Schritte oft mehrdeutig sind und daher von implizitem Wissen abhängen. Hier präsentieren wir die Integration von Online-NMR Spektroskopie in eine automatisierte chemische Syntheseplattform (CSM aka. “Chemputer”, unter Verwendung einer universellen Programmiersprache zur Synthese kleiner Moleküle fähig), um eine automatisierte Analyse und Anpassung von Reaktionen im laufenden Betrieb zu ermöglichen. Das System wurde anhand von Grignard-Reaktionen, die aufgrund ihrer Bedeutung für die Synthese ausgewählt wurden, validiert und einem Härtetest unterzogen. Synthesen wurden in Echtzeit mit Online-NMR überwacht, und die Spektren wurden während der Reaktionen kontinuierlich aufgenommen und analysiert. Dies zeigt, dass der Chemputer dynamisch mittels einer Regelung kontrolliert werden kann, um die Reaktionsbedingungen entsprechend den Anforderungen des Benutzers zu optimieren. KW - Grignard reaction KW - NMR spectroscopy KW - Process analytical technology KW - Process control KW - Grignard-Reaktion KW - NMR-Spektroskopie KW - Prozessanalytik KW - Prozesskontrolle PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-531260 DO - https://doi.org/10.1002/anie.202106323 SN - 1521-3773 SN - 1433-7851 N1 - Bibliografische Angaben für die deutsche Version: Angewandte Chemie 2021, Jg. 133, S. 1–7, ISSN 0044-8249, ISSN 1521-3757, https://doi.org/10.1002/ange.202106323 - Bibliographic information for the German version: Angewandte Chemie 2021, vol. 133, p. 1–7, ISSN 0044-8249, ISSN 1521-3757, https://doi.org/10.1002/ange.202106323 VL - 60 IS - 43 SP - 1 EP - 6 PB - Wiley-VCH CY - Weinheim AN - OPUS4-53126 LA - mul AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Zientek, Nicolai A1 - Laurain, Clement A1 - Meyer, Klas A1 - Kraume, M. A1 - Guthausen, G. A1 - Maiwald, Michael T1 - Simultaneous 19F-1H medium resolution NMR spectroscopy for online reaction monitoring JF - Journal of magnetic resonance N2 - Medium resolution nuclear magnetic resonance (MR-NMR) spectroscopy is currently a fast developing field, which has an enormous potential to become an important analytical tool for reaction monitoring, in hyphenated techniques, and for systematic investigations of complex mixtures. The recent developments of innovative MR-NMR spectrometers are therefore remarkable due to their possible applications in quality control, education, and process monitoring. MR-NMR spectroscopy can beneficially be applied for fast, non-invasive, and volume integrating analyses under rough environmental conditions. Within this study, a simple 1/16'' fluorinated ethylene propylene (FEP) tube with an ID of 0.04'' (1.02 mm) was used as a flow cell in combination with a 5 mm glass Dewar tube inserted into a benchtop MR-NMR spectrometer with a 1H Larmor frequency of 43.32 MHz and 40.68 MHz for 19F. For the first time, quasi-simultaneous proton and fluorine NMR spectra were recorded with a series of alternating 19F and 1H single scan spectra along the reaction time coordinate of a homogeneously catalysed esterification model reaction containing fluorinated compounds. The results were compared to quantitative NMR spectra from a hyphenated 500 MHz online NMR instrument for validation. Automation of handling, pre-processing, and analysis of NMR data becomes increasingly important for process monitoring applications of online NMR spectroscopy and for its technical and practical acceptance. Thus, NMR spectra were automatically baseline corrected and phased using the minimum entropy method. Data analysis schemes were designed such that they are based on simple direct integration or first principle line fitting, with the aim that the analysis directly revealed molar concentrations from the spectra. Finally, the performance of 1/16'' FEP tube set-up with an ID of 1.02 mm was characterised regarding the limit of detection (LOQ (1H) = 0.335 mol L-1 and LOQ (19F) = 0.130 mol L-1 for trifluoroethanol in D2O (single scan)) and maximum quantitative flow rates up to 0.3 mL min-1. Thus, a series of single scan 19F and 1H NMR spectra acquired with this simple set-up already presents a valuable basis for quantitative reaction monitoring. KW - NMR KW - 1H KW - 19F KW - Medium-resolution NMR KW - Online NMR KW - Quantitative NMR KW - Reaction monitoring KW - Data processing KW - Process analytical technology PY - 2014 DO - https://doi.org/10.1016/j.jmr.2014.10.007 SN - 1090-7807 SN - 0022-2364 VL - 249 SP - 53 EP - 62 PB - Elsevier CY - San Diego, Calif. AN - OPUS4-32008 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - GEN A1 - Kern, Simon A1 - Wander, Lukas A1 - Meyer, Klas A1 - Guhl, Svetlana A1 - Gottu Mukkula, A. R. A1 - Holtkamp, M. A1 - Salge, M. A1 - Fleischer, C. A1 - Weber, N. A1 - Engell, S. A1 - Paul, Andrea A1 - King, R. A1 - Maiwald, Michael T1 - Raw data of pilot plant runs for CONSENS project (Case study 1) N2 - In case study one of the CONSENS project, two aromatic substances were coupled by a lithiation reaction, which is a prominent example in pharmaceutical industry. The two aromatic reactants (Aniline and o-FNB) were mixed with Lithium-base (LiHMDS) in a continuous modular plant to produce the desired product (Li-NDPA) and a salt (LiF). The salt precipitates which leads to the formation of particles. The feed streams were subject to variation to drive the plant to its optimum. The uploaded data comprises the results from four days during continuous plant operation time. Each day is denoted from day 1-4 and represents the dates 2017-09-26, 2017-09-28, 2017-10-10, 2017-10-17. In the following the contents of the files are explained. KW - Process Analytical Technology KW - Multivariate Data Analysis KW - Nuclear Magnetic Resonance KW - Near Infrared Spectroscopy KW - Continuous Manufacturing KW - CONSENS PY - 2018 DO - https://doi.org/10.5281/zenodo.1438233 PB - Zenodo CY - Geneva AN - OPUS4-48063 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas A1 - Zientek, Nicolai A1 - Kraemer, B. A1 - Maiwald, Michael T1 - Quantitative Online NMR Spectroscopy of Technical Mixtures and Gases T2 - Agilent NMR-Seminar T2 - Agilent NMR-Seminar CY - Waldbronn DA - 2014-05-20 PY - 2014 AN - OPUS4-31888 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -