TY - JOUR A1 - Wander, Lukas A1 - Lommel, Lukas A1 - Braun, Ulrike A1 - Meyer, Klas A1 - Paul, Andrea T1 - Development of a Low-Cost Method for Quantifying Microplastics in Soils and Compost Using Near-Infrared Spectroscopy JF - Meas. Sci. Technol. N2 - Near-infrared (NIR) spectroscopy is a promising candidate for low-cost, nondestructive, and highthroughput mass quantification of microplastics in environmental samples. Widespread application of the technique is currently hampered mainly by the low sensitivity of NIR spectroscopy compared to thermoanalytical approaches commonly used for this type of analysis. This study shows how the application of NIR spectroscopy for mass quantification of microplastics can be extended to smaller analyte levels by combining it with a simple and rapid microplastic enrichment protocol. For this purpose, the widely used flotation of microplastics in a NaCl solution, accelerated by centrifugation, was chosen which allowed to remove up to 99 % of the matrix at recovery rates of 83–104 %. The spectroscopic measurements took place directly on the stainless-steel filters used to collect the extracted particles to reduce sample handling to a minimum. Partial least squares regression (PLSR) models were used to identify and quantify the extracted microplastics in the mass range of 1–10 mg. The simple and fast extraction procedure was systematically optimized to meet the requirements for the quantification of microplastics from common PE-, PP-, and PS-based packaging materials with a particle size < 1 mm found in compost or soils with high natural organic matter content (> 10 % determined by loss on ignition). Microplastics could be detected in model samples at a mass fraction of 1 mg g-1. The detectable microplastic mass fraction is about an order of magnitude lower compared to previous studies using NIR spectroscopy without additional enrichment. To emphasize the cost-effectiveness of the method, it was implemented using some of the cheapest and most compact NIR spectrometers available. KW - Mikroplastik KW - NIR KW - Sensor KW - Kompost KW - Multivariat PY - 2022 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-552605 DO - https://doi.org/10.1088/1361-6501/ac5e5f VL - 33 IS - 7 SP - 1 EP - 13 PB - IOP Publishing Ltd. CY - Bristol AN - OPUS4-55260 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 - 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 - 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 - Kern, Simon A1 - Guhl, Svetlana A1 - Wander, Lukas A1 - Paul, Andrea A1 - Maiwald, Michael T1 - Already Producing or Still Calibrating? – Advances of Model-Based Automation for Online NMR Spectroscopy N2 - The transition 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. Monitoring specific information (i.e., “chemical” such as physico-chemical properties, chemical reactions, etc.) is the key to “chemical” process control. Here we introduce our smart online NMR sensor module provided in an explosion proof housing as example. Due to NMR spectroscopy as an “absolute comparison method”, independent of the matrix, it runs with very short set-up times in combination with “modular” spectral models. These are based on pure component NMR spectra without the need for tedious calibrations runs. We present approaches from statistical, (i.e., Partial Least Squares Regression) to physically motivated models (i.e., Indirect Hard Modelling). Based on concentration measurements of reagents and products by the NMR analyser a continuous production and direct loop process control were successfully realized for several validation runs in a modular industrial pilot plant and compared to conventional analytical methods (HPLC, near infrared spectroscopy). The NMR analyser was developed for an intensified industrial process funded by the EU’s Horizon 2020 research and innovation programme (“Integrated CONtrol and SENsing”, www.consens-spire.eu). T2 - 2nd Reaction Monitoring Symposium CY - Bath, UK DA - 28.01.2019 KW - Process Analytical Technology KW - NMR Spectroscopy KW - Modular Production PY - 2019 AN - OPUS4-47309 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas A1 - Abele, M. A1 - Falkenstein, S. A1 - Friedrich, Y. A1 - Kern, S. A1 - Korth, K. A1 - Maiwald, Michael T1 - Industrial Applications of benchtop NMR Spectroscopy for Quality Control of Silanes N2 - The combination of different silanes as starting materials and as a product of hydrolysis by several alcohols or water creates a range of hundreds of technical products for a wide range of applications. In recent years, functional trialkoxysilanes have proven to be multi-purpose organosilanes. Applications range from weather protection of buildings to additives for glass fiber industry, sealants, adhesives, coatings and paints to the modification of polymers. Commercial benchtop NMR spectrometers have the potential to be used in silane chemistry as an online method for reaction monitoring and quality control. NMR nuclei of interest for silane products are 1H and 29Si. In a joint research cooperation between EVONIK and BAM, the applicability of low-field NMR spectroscopy for the chemical analysis of silanes was evaluated. It was shown how it can extend the application range where existing technologies like NIR, Raman, UV/VIS, etc. cannot be used quantitatively due to a lack of reference data. In a first case study the process of hydrolysis and condensation was observed using online NMR analysis. For this purpose, the substituents of a trialkoxysilane are first hydrolyzed by adding water and corresponding silanols are formed, which can then bind to materials via SiOH functions and crosslink to form siloxane units. Another case study was dealing with the kinetics of the cleavage of a cyclic silane compound. Online NMR analysis was used both in the laboratory and in the manufacturing plant. For this purpose, a fully automated containment system was used, which enables the use of a commercial NMR spectrometer in ATEX-environments. In the third case study presented, quantitative 1H-NMR spectra were acquired on product mixtures of a trialkoxysilane and other components such as organic stabilizers, organotin compounds, an aromatic amine and organic peroxides. An automatic evaluation method based on Indirect Hard Modeling (IHM) was developed. T2 - Magritek's Spinsolve NMR Users Meeting 2021 CY - Online meeting DA - 20.04.2021 KW - NMR spectroscopy KW - Silanes KW - Process Analytical Technology KW - Quality Control PY - 2021 AN - OPUS4-52557 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas A1 - Guhl, Svetlana A1 - Kern, Simon A1 - Wander, Lukas A1 - Gräßer, Patrick A1 - Acker, J. A1 - Maiwald, Michael T1 - Online NMR and Raman Spectroscopy – Combination of PAT tools for Process Monitoring N2 - Improvement in deep process understanding is a mandatory prerequisite for the application of modern concepts like Industrial Internet of Things (IIoT) or “Industrie 4.0”. The direct hyphenation with online methods of process analytical technology (PAT) allows profound insights into the actual reactions within chemical and pharmaceutical production steps and provides necessary information for associated advanced control strategies. While the industrial application of online Raman spectroscopy has already been successfully demonstrated, low-field NMR spectroscopy is not yet adequately developed as a robust online method for use in process industry. The high information content combined with the low calibration effort makes NMR spectroscopy a highly promising method for modern process automation with a high flexibility due to short set-up times and novel calibration concepts. This is a major advantage compared to other analytical methods, especially regarding multi-purpose plant strategies, as well as processes suffering from fluctuating quality of raw materials. The work presented here focusses on the heterogeneous catalyzed hydrogenation of 2-butyne-1,4-diol, as a step of the synthesis of industrially important solvent tetrahydrofuran. This reaction is proceeding via an intermediate product and suffers from competitive reaction paths. In this application, online NMR and Raman spectroscopy were combined with data from classical process sensors, e.g., pressure, temperature, and flow transducers in a highly automated setup for the development of innovative control concepts. T2 - Quantitative NMR Methods for Reaction and Process Monitoring (NMRPM) CY - Kaiserslautern, Germany DA - 31.01.2019 KW - Process Analytical Technology KW - Hydrogenation KW - Compact NMR Spectroscopy KW - Online-NMR spectroscopy PY - 2019 AN - OPUS4-47310 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas A1 - Bornemannn-Pfeiffer, Martin A1 - Kern, S. A1 - Abele, M. A1 - Falkenstein, S. A1 - Döring, T. A1 - Friedrich, Y. A1 - Maiwald, Michael T1 - Online-NMR Spektroskopie in der PAT - Entwicklungen zwischen Labor- und Feldeinsatz N2 - Die NMR-Spektroskopie ist eine der zentralen nicht-invasiven Analysenmethoden in der organischen Chemie und aus dem Laboralltag nicht mehr wegzudenken. Die direkte Proportionalität zwischen der Anzahl der Atomkerne im Messvolumen und der Signalfläche im Spektrum ist vergleichbar mit einem „Zählen der Kernspins“. Der Kalibrieraufwand für die Quantifizierung ist minimal und aus dem NMR-Spektrum sind Informationen zu Struktur und Identität zugänglich. Online-NMR-Spektroskopie wird unter Zuhilfenahme von speziellen Durchflussproben-köpfen und Messzellen bereits seit Jahrzehnten erforscht und eingesetzt. Durch die hohen Anforderungen an die Aufstellung und den Betrieb von klassischen Hochfeld-NMR-Spektrometern konnte sie allerdings nie den Sprung vom Labor in den Prozess schaffen. Dies hat sich durch die Entwicklungen im Bereich mobil einsetzbarer Benchtop-NMR-Spektrometer grundlegend verändert. Geringere Investitions- und Betriebskosten, sowie die Robustheit und einfache Bedienbarkeit dieser Systeme sind entscheidende Faktoren. Damit rückt eine Anwendung als Online-PAT-Methode technisch in greifbare Nähe. Designierte Prozess-NMR-Spektrometer sucht man heutzutage allerdings auf dem Markt meist noch vergebens. Die Reaktionsverfolgung im Labormaßstab konnte an unterschiedlichen Systemen erfolgreich demonstriert werden. Dabei zeigten sich allerdings Limitierungen in Hinblick auf einen möglichen Prozesseinsatz. Insbesondere die Temperaturempfindlichkeit der Magnetsysteme ist hier zu nennen. Anhand eines Prototyps wurde eine aktive Temperaturisolation mittels temperierter Luftströmungen entwickelt und erprobt. Eine Feldintegration von Laborsystemen geht sowohl technisch als auch regulatorisch mit zahlreichen Herausforderungen einher. Das raue Umfeld von Produktionsanlagen, sowie die Anforderungen an Explosionsschutz erfordern eine zugelassene Einhausung. Auf Basis von Erfahrungen mit einem ersten Prototyp erfolgte die gemeinsame Entwicklung eines möglichst flexibel einsetzbaren Analysenschranks. Neben der Hardware-Integration sind die automatisierte modellbasierte Auswertung der NMR-Spektren, sowie die Einbindung in die Prozessleittechnik essenziell für einen zuverlässigen Betrieb als PAT-Analysengerät. T2 - 18. Kolloquium AK Prozessanalytik CY - Krefeld, Germany DA - 27.11.2023 KW - Prozessanalytik KW - Online-NMR-Spektroskopie KW - NMR-Spektroskopie KW - Benchtop-NMR KW - Feldintegration PY - 2023 AN - OPUS4-58969 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - GEN A1 - Bernstein, Michael A1 - Diehl, Bernd W. K. A1 - Holzgrabe, Ulrike A1 - Maiwald, Michael A1 - Meyer, Klas A1 - Monakhova, Yulia A1 - Schönberger, Torsten T1 - qNMR - The handbook N2 - Quantitative NMR (qNMR) has been around for a long time, but also has great potential to solve future problems in any quantitative analysis. As a primary method, it differs fundamentally from chromatographic methods: it is better described as a quantum mechanical balance. Succesful implementation of qNMR requires certain attention to detail. "qNMR - the handbook" is intended to be a guide for analysts to help understand the fundamental principles of NMR and the significant points relating to its implementation for quantitation. Regulatory considerations of qNMR adoption are explained. NMR fundamentals are explained to provide understanding. Together with many useful examples, the book is a compelling addition to the laboratory's reference library, providing all the tools that any practitioner should know to successfully implement qNMR. The authors are qNMR pioneers and come from a variety of backgrounds including business, government and academia. KW - Quantitative NMR spectroscopy KW - NMR spectroscopy KW - Handbook KW - qNMR PY - 2023 SN - 978-3-7568-7891-8 SN - 978-3-7583-8050-1 SP - 1 EP - 302 PB - BoD – Books on Demand CY - Norderstedt AN - OPUS4-59839 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - GEN A1 - Tchipilov, Teodor A1 - Meyer, Klas A1 - Weller, Michael G. T1 - Quantitative 1H Nuclear Magnetic Resonance (qNMR) of Aromatic Amino Acids for Protein Quantification T2 - Preprints N2 - qNMR is a valuable technique for metrological studies due to the uniformity of its signal response for all chemical species of an isotope of interest, which enables compound-independent calibration. However, protein quantification remained challenging as large molecules produce wide, low-intensity signals that reduce the already low sensitivity. Combining qNMR with the hydrolysis of protein samples into amino acids circumvents many of these issues and facilitates the use of NMR spectroscopy for absolute protein and peptide quantification.In this work, different conditions have been tested for quantifying aromatic amino acids and proteins. First, we examined the pH-based signal shifts in the aromatic region. The preferable pH depends on the selection of the amino acids for quantification and which internal standard substance should be used to avoid peak overlap. Several aromatic compounds, such as terephthalic acid, sulfoisophthalic acid, and benzene tricarboxylic acid, have been applied as internal standards. The quantification of amino acids from an amino acid standard, as well as from a certified reference material (bovine serum albumin), was performed. Using the first two suggested internal standards, recovery was ~ 97 % for histidine, phenylalanine, and tyrosine at a concentration of approximately 1 mM in solution. Acidic hydrolysis of a certified reference material (CRM) of bovine serum albumin (BSA) and subsequent quantification of Phe and Tyr yielded recoveries of 98 ± 2 and 88 ± 4 %, respectively, at a protein concentration of 16 g/L or 250 µM. KW - Amino acid analysis KW - AAA KW - Protein hydrolysis KW - Metrology KW - Traceability KW - Reference materials KW - Internal standards KW - Calibration PY - 2022 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-564520 DO - https://doi.org/10.20944/preprints202211.0569.v1 SP - 1 EP - 13 PB - MDPI CY - Basel AN - OPUS4-56452 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -