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 - TY - CONF A1 - Meyer, Klas T1 - Compact NMR Spectroscopy: A Versatile Tool for Automated Continuous-Flow Production of Chemicals and Pharmaceuticals N2 - Chemical companies must find new paths to successfully survive in a changing environment. The potential of digital technologies belongs to these. 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. Therefore, fully automated “chemical” process control along with real-time quality control are prerequisites to such concepts and thus should be based on “chemical” information. The advances of a fully automated NMR sensor were exploited, using a given pharmaceutical lithiation reaction as an example process within a modular pilot plant. A commercially available benchtop NMR spectrometer was integrated to the full requirements of an automated chemical production environment such as, e.g., explosion safety, field communication, and robust evaluation of sensor data. It was thereof used for direct loop advanced process control and real-time optimization of the process. NMR appeared as preeminent online analytical tool and allowed using a modular data analysis tool, which even served as reliable reference method for further PAT applications. In future, such fully integrated and intelligently interconnecting “smart” systems and processes can speed up the high-quality production of specialty chemicals and pharmaceuticals. T2 - USP qNMR Emerging Technologies Workshop & Roundtable CY - Online meeting DA - 17.11.2020 KW - Quantitative NMR spectroscopy KW - Benchtop-NMR KW - Process Analytical Technology PY - 2020 AN - OPUS4-51595 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas T1 - BAM quality toolbox framework for qNMR N2 - Accreditation of analytical methods, either according to GxP or ISO regulations, requires a comprehensive quality management system. General quality documents are often already in place, which need to be extended by method-specific documentation. In this presentation we like to show an idea of a modular set of standard operating procedures (SOP) specifically developed meeting the requirements for quantitative NMR. The future goal is to collaborate with different accreditated NMR laboratories to compile a universal set of SOP and other quality documents that can be modified and used as a starting point for developing your own quality system for applications of qNMR in a regulated environment. T2 - ValidNMR Workshop at Practical Applications of NMR in Industry Conference (PANIC) CY - Online meeting DA - 22.10.2020 KW - ValidNMR KW - Validation KW - NMR spectroscopy KW - ISO 17025 KW - GxP PY - 2020 AN - OPUS4-51466 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Meyer, Klas T1 - Atomkerne zählen - Quantitative NMR-Spektroskopie als vielseitige Methode in Labor und Prozess N2 - Meist präsentieren sich Laboratorien für NMR-Spektroskopie auf den ersten Blick von außen nur wenig einladend. Es lohnt sich aber einen Blick hinein zu riskieren, denn die Methode ist heute unverzichtbar für die analytische Chemie. Die quantitativen Möglichkeiten werden häufig unterschätzt, erfahren allerdings durch den aufstrebenden Markt kompakter Benchtop-NMR-Spektrometer verstärktes Interesse für Anwendungen von der Laborbank bis hin zum Industrieprozess. KW - NMR-Spektroskopie KW - Benchtop-NMR KW - qNMR PY - 2020 UR - https://analyticalscience.wiley.com/do/10.1002/was.000600052 SN - 0016-3538 VL - 64 IS - 10 SP - 28 EP - 30 PB - Wiley-VCH GmbH CY - Weinheim AN - OPUS4-51464 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Maiwald, Michael A1 - Meyer, Klas T1 - Laboratory accreditation as a reliable indicator of technical competence for testing, calibration and measurement organizations – An introduction to ISO/IEC 17025 using the example of qNMR spectroscopy N2 - ISO/IEC 17025 is the worldwide quality standard for testing and calibration laboratories. It is the basis for accreditation by an accreditation body. The current version was published in 2018. Implementing ISO/IEC 17025 as part of laboratory quality initiatives offers both laboratory and business benefits, such as expanding the potential customer base for testing and/or calibration, increasing the reputation and image of the laboratory at national and international level, continuous improvement of the data quality and the effectiveness of the laboratory or creation of a good basis for most other quality systems in the laboratory sector, such as GxP. The main difference between a proper approach to analysis and a formal accreditation is shown in a targeted documentation, especially on the qualification of the personnel, the test equipment and the validation of the analytical methods. Using quantitative NMR spectroscopy as an example, it is shown how accreditation can be carried out and what documentation is required. In our case, we have described the procedure in an SOP ("Determination of the quantitative composition of simple mixtures of structurally known compounds with 1H-NMR spectroscopy") and supported it with a modular system of organizational and equipment SOPs. The special feature is that the accredited method is independent for the choice of the analyte and the matrix and therefore it is possible to operate with a single validated method. In our case, we have proposed three quality levels ("leagues") with different levels of analytical effort, which differ in their measurement uncertainty, in order to simplify the workflow and analysis design. T2 - 9th Annual Practical Applications of NMR in Industry Conference (PANIC) CY - Online meeting DA - 17.10.2021 KW - Quantitative NMR Spectroscopy KW - qNMR KW - Accreditation KW - ISO 17025 KW - ISO/IEC 17025 KW - PANIC PY - 2021 AN - OPUS4-53564 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Meyer, Klas T1 - Compact NMR Spectroscopy: A Versatile Tool for Automated Continuous-Flow Production of Chemicals and Pharmaceuticals N2 - Chemical companies must find new paths to successfully survive in a changing environment. The potential of digital technologies belongs to these. 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. Therefore, fully automated “chemical” process control along with real-time quality control are prerequisites to such concepts and thus should be based on “chemical” information. The advances of a fully automated NMR sensor were exploited, using a given pharmaceutical lithiation reaction as an example process within a modular pilot plant. A commercially available benchtop NMR spectrometer was integrated to the full requirements of an automated chemical production environment such as, e.g., explosion safety, field communication, and robust evaluation of sensor data. It was thereof used for direct loop advanced process control and real-time optimization of the process. NMR appeared as preeminent online analytical tool and allowed using a modular data analysis tool, which even served as reliable reference method for further PAT applications. In future, such fully integrated and intelligently interconnecting “smart” systems and processes can speed up the high-quality production of specialty chemicals and pharmaceuticals. T2 - ACHEMA Pulse 2021 CY - Online meeting DA - 15.06.2021 KW - Process Analytical Technology KW - NMR spectroscopy KW - Benchtop-NMR PY - 2021 AN - OPUS4-52822 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Fricke, F. A1 - Mahmood, S. A1 - Hoffmann, J. A1 - Brandalero, M. A1 - Liehr, Sascha A1 - Kern, Simon A1 - Meyer, Klas A1 - Kowarik, Stefan A1 - Westerdicky, S. A1 - Maiwald, Michael A1 - Hübner, M. T1 - Artificial Intelligence for Mass Spectrometry and Nuclear Magnetic Resonance Spectroscopy N2 - Mass Spectrometry (MS) and Nuclear Magnetic Resonance Spectroscopy (NMR) are critical components of every industrial chemical process as they provide information on the concentrations of individual compounds and by-products. These processes are carried out manually and by a specialist, which takes a substantial amount of time and prevents their utilization for real-time closed-loop process control. This paper presents recent advances from two projects that use Artificial Neural Networks (ANNs) to address the challenges of automation and performance-efficient realizations of MS and NMR. In the first part, a complete toolchain has been developed to develop simulated spectra and train ANNs to identify compounds in MS. In the second part, a limited number of experimental NMR spectra have been augmented by simulated spectra to train an ANN with better prediction performance and speed than state-of-theart analysis. These results suggest that, in the context of the digital transformation of the process industry, we are now on the threshold of a possible strongly simplified use of MS and MRS and the accompanying data evaluation by machine-supported procedures, and can utilize both methods much wider for reaction and process monitoring or quality control. T2 - 2021 Design, Automation & Test in Europe Conference & Exhibition (DATE) CY - Online meeting DA - 01.02.2021 KW - Industry 4.0 KW - Cyber-Physical Systems KW - Artificial Neural Networks KW - Mass Spectrometry KW - Nuclear Magnetic Resonance Spectroscopy PY - 2021 UR - www.date-conference.com SN - 978-3-9819263-5-4 SP - 615 EP - 620 PB - Research Publishing AN - OPUS4-52180 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kuner, Maximilian A1 - Kühn, S. A1 - Haase, H. A1 - Meyer, Klas A1 - Koch, Matthias T1 - Cleaving Ergot Alkaloids by Hydrazinolysis - A Promising Approach for a Sum Parameter Screening Method N2 - Ergot alkaloids are mycotoxins formed by fungi of the Claviceps genus, which are some of the most common contaminants of food and feed worldwide. These toxins are a structurally heterogeneous group of compounds, sharing an ergoline backbone. Six structures and their corresponding stereoisomers are typically quantified by either HPLC-FLD or HPLC-MS/MS and the values subsequently summed up to determine the total ergot alkaloid content. For the development of a screening method targeting all ergot alkaloids simultaneously, the alkaloids need to be transferred to one homogeneous structure: a lysergic acid derivative. In this study, two promising cleaving methods—acidic esterification and hydrazinolysis—are compared, using dihydroergocristine as a model compound. While the acidic esterification proved to be unsuitable, due to long reaction times and oxidation sensitivity, hydrazinolysis reached a quantitative yield in 40-60 min. Parallel workup of several samples is possible. An increasing effect on the reaction rate by the addition of ammonium iodide was demonstrated. Application of hydrazinolysis to a major ergot alkaloid mix solution showed that all ergopeptines were cleaved, but ergometrine/-inine was barely affected. Still, hydrazinolysis is a suitable tool for the development of a sum parameter screening method for ergot alkaloids in food and feed. KW - Ergot alkaloids KW - Sum parameter method KW - Hydrazinolysis KW - Esterification PY - 2021 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-527508 DO - https://doi.org/10.3390/toxins13050342 VL - 13 IS - 5 SP - 342 PB - MDPI CY - Basel, Switzerland AN - OPUS4-52750 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 lyophilized cell loadings ranging from 20 to 120 g/L. The reproducibility and reliability of compact NMR spectroscopy closely matched that of parallel 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 - qNMR Summit Europe 2025 CY - Bari, Italy DA - 19.11.2025 KW - NMR Spectroscopy KW - Extraction KW - Downstream processing KW - Benchtop-NMR PY - 2025 AN - OPUS4-64920 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 - JOUR A1 - Srivastava, Priyanka A1 - Tavernaro, Isabella A1 - Scholtz, Lena A1 - Genger, C. A1 - Welker, P. A1 - Schreiber, Frank A1 - Meyer, Klas A1 - Resch-Genger, Ute T1 - Dual color pH probes made from silica and polystyrene nanoparticles and their performance in cell studies N2 - Ratiometric green–red fluorescent nanosensors for fluorometrically monitoring pH in the acidic range were designed from 80 nm-sized polystyrene (PS) and silica (SiO2) nanoparticles (NPs), red emissive reference dyes, and a green emissive naphthalimide pH probe, analytically and spectroscopically characterized, and compared regarding their sensing performance in aqueous dispersion and in cellular uptake studies. Preparation of these optical probes, which are excitable by 405 nm laser or LED light sources, involved the encapsulation of the pH-inert red-fuorescent dye Nile Red (NR) in the core of self-made carboxylated PSNPs by a simple swelling procedure and the fabrication of rhodamine B (RhB)-stained SiO2-NPs from a silane derivative of pH-insensitive RhB. Subsequently, the custom-made naphthalimide pH probe, that utilizes a protonation-controlled photoinduced electron transfer process, was covalently attached to the carboxylic acid groups at the surface of both types of NPs. Fluorescence microscopy studies with the molecular and nanoscale optical probes and A549 lung cancer cells confirmed the cellular uptake of all probes and their penetration into acidic cell compartments, i.e., the lysosomes, indicated by the switching ON of the green naphthalimide fluorescence. This underlines their suitability for intracellular pH sensing, with the SiO2-based nanosensor revealing the best performance regarding uptake speed and stability. KW - Sensors KW - Silica and polystyrene nanoparticles KW - pH probe KW - Fluorescence spectroscopy KW - Cell studies KW - Dye KW - Particle synthesis PY - 2023 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-569198 DO - https://doi.org/10.1038/s41598-023-28203-0 SN - 2045-2322 VL - 13 IS - 1 SP - 1321 EP - 1336 PB - Nature CY - London AN - OPUS4-56919 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 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 - Völzke, Jule L. A1 - Hodjat Shamami, Parya A1 - Gawlitza, Kornelia A1 - Feldmann, Ines A1 - Zimathies, Annett A1 - Meyer, Klas A1 - Weller, Michael G. T1 - High-purity corundum as support for affinity extractions from complex samples N2 - Nonporous corundum powder, known as an abrasive material in the industry, was functionalized covalently with protein binders to isolate and enrich specific proteins from complex matrices. The materials based on corundum were characterized by TEM, ESEM, BET, DLS, EDS, and zeta potential measurements. The strong Al-O-P bonds between the corundum surface and amino phosphonic acids were used to introduce functional groups for further conjugations. The common crosslinker glutaraldehyde was compared with a hyperbranched polyglycerol (PG) of around 10 kDa. The latter was oxidized with periodate to generate aldehyde groups that can covalently react with the amines of the surface and the amino groups from the protein via a reductive amination process. The amount of bound protein was quantified via aromatic amino acid analysis (AAAA). This work shows that oxidized polyglycerol can be used as an alternative to glutaraldehyde. With polyglycerol, more of the model protein bovine serum albumin (BSA) could be attached to the surface under the same conditions, and lower non-specific binding (NSB) was observed. As a proof of concept, IgG was extracted with protein A from crude human plasma. The purity of the product was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). A binding capacity of 1.8 mg IgG per gram of corundum powder was achieved. The advantages of corundum include the very low price, extremely high physical and chemical stability, pressure resistance, favorable binding kinetics, convenient handling, and flexible application. KW - Corundum KW - Sapphire KW - Affinity chromatography KW - Antibodies KW - Self-assembled monolayers (SAM) KW - Polyglycerol KW - Dendrimer KW - Nonspecific binding (NSB) KW - Purification KW - Solid-phase extraction (SPE) PY - 2022 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-559342 DO - https://doi.org/10.3390/separations9090252 VL - 9 IS - 9 SP - 1 EP - 13 PB - MDPI CY - Basel AN - OPUS4-55934 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - INPR A1 - Tchipilov, Teodor A1 - Meyer, Klas A1 - Weller, Michael G. T1 - Quantitative 1H nuclear magnetic resonance (qNMR) of aromatic amino acids for protein quantification 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 - TY - JOUR A1 - Gugin, Nikita A1 - Yusenko, Kirill A1 - King, Andrew A1 - Meyer, Klas A1 - Al-Sabbagh, Dominik A1 - Villajos Collado, José Antonio A1 - Emmerling, Franziska T1 - Lighting up industrial mechanochemistry: Real-time in situ monitoring of reactive extrusion using energy-dispersive X-ray diffraction N2 - Mechanochemistry is an environmentally friendly synthetic approach that enables the sustainable production of a wide range of chemicals while reducing or eliminating the need for solvents. Reactive extrusion aims to move mechanochemistry from its conventional gram-scale batch reactions, typically performed in laboratory ball mills, to a continuous, large-scale process. Meeting this challenge requires in situ monitoring techniques to gain insights into reactive extrusion and its underlying processes. While the effectiveness of in situ Raman spectroscopy in providing molecular-level information has been demonstrated, our study uses energy-dispersive X-ray diffraction to monitor reactive extrusion in real time at the crystalline level. Our results provide previously unavailable control over the reactive extrusion process, promoting its perception as an industrially feasible green alternative to traditional solvent-based syntheses. KW - Mechanochemistry KW - Reactive extrusion KW - Green chemistry KW - In situ studies KW - Time-resolved in situ KW - TRIS KW - Synchrotron radiation KW - Scalable synthesis KW - Solid-state reactions KW - Reaction mechanisms PY - 2024 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-613969 DO - https://doi.org/10.1016/j.chempr.2024.07.033 VL - 10 IS - 11 SP - 1 EP - 16 PB - Elsevier B.V. AN - OPUS4-61396 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Tchipilov, Teodor A1 - Meyer, Klas A1 - Weller, Michael G. T1 - Quantitative 1H nuclear magnetic resonance (qNMR) of aromatic amino acids for protein quantification N2 - Hydrolysis of protein samples into amino acids facilitates the use of NMR spectroscopy for protein and peptide quantification. Different conditions have been tested for quantifying aromatic amino acids and proteins. The pH-dependent signal shifts in the aromatic region of amino acid samples were examined. A pH of 12 was found to minimize signal overlap of the four aromatic amino acids. Several aromatic compounds, such as terephthalic acid, sulfoisophthalic acid, and benzene tricarboxylic acid, were applied as internal standards. The quantification of amino acids from an amino acid standard 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 - Aromatic amino acid analysis KW - AAA KW - AAAA KW - Protein hydrolysis KW - Hydrochloric acid KW - Metrology KW - Traceability KW - NIST KW - Reference materials KW - Internal standard KW - Calibration KW - Compound-independent calibration KW - Histidine KW - Tyrosine KW - Tryptophan KW - Phenylalanine KW - Terephthalic acid KW - Benzene-1,3,5-tricarboxylic acid KW - Bovine serum albumin (BSA) KW - Quantitative protein analysis KW - Phenylketonuria PY - 2023 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-570943 DO - https://doi.org/10.3390/mps6010011 VL - 6 IS - 1 SP - 1 EP - 13 PB - MDPI CY - Basel, Schweiz AN - OPUS4-57094 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -