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Chemical and pharmaceutical companies need to find new ways to survive successfully in a changing environment, while finding more flexible ways of product and process development to bring their products to market faster - especially high-value, high-end products such as fine chemicals or pharmaceuticals. This is complicated by changes in value chains along a potential circular economy.
One current approach is flexible and modular chemical production units that use multi-purpose equipment to produce various high-value products with short downtimes between campaigns and can shorten time-to-market for new products. Online NMR spectroscopy will play an important role for plant automation and quality control, as the method brings very high linearity, matrix independence and thus works almost calibration-free. Moreover, these properties ideally enable automated and machine-aided data analysis for the above-mentioned applications.
Using examples, this presentation will outline a possible more holistic approach to digitalization and the use of machine-based processes in the production of specialty chemicals and pharmaceuticals through the introduction of integrated and networked systems and processes.
Die BAM ist nahezu über die gesamte Wertschöpfungskette hinweg wissenschaftlich tätig. Von der sicheren und effizienten Wasserstofferzeugung (POWER-to-GAS), über die (Zwischen-)Speicherung von Wasserstoff in Druckgasspeichern bis hin zum Transport bspw. mittels Trailerfahrzeug zum Endverbraucher.
Komplettiert werden die Aktivitäten der BAM durch die sicherheitstechnische Beurteilung von wasserstoffhaltigen Gasgemischen, die Verträglichkeitsbewertung von Werkstoffen bis hin zur Detektion von Wasserstoffkonzentrationen über geeignete Sensorik, auch mittels ferngesteuerter Messdrohnen (sog. UAV-Drohnen).
Zudem untersucht die BAM proaktiv Schadensrisiken und Unfallszenarien für die Sicherheitsbetrachtung, um mögliche Schwachstellen aufzeigen und potenzielle Gefährdungen erkennen zu können.
What is the future of Analytical Sciences? The talk starts with a definition, comparing the current view with that from 1968. How do wie set trends? How do we get Analytics inside? Some examples of "Big Science" are given and discussed in relation to a definition of AS. How does AS face the current Grand Challenges?
As exaples for something significant, several exaples are presented, such as Climate Change of Hydrogen Storage. Another important trand are eScience and automation concepts for AS, which are highlighted.
But (Analytical) Science has to be politcal in our times to face Fake News and to breake barriers!
There have been an increasing number of publications on flow chemistry applications of compact NMR. Despite this, there is so far no comprehensive workflow for the technical design of flow cells. Here, we present an approach that is suitable for the design of an NMR flow cell with an integrated static mixing unit. This design moves the mixing of reactants to the active NMR detection region within the NMR instrument, presenting a feature that analyses chemical reactions faster (5–120 s region) than other common setups. During the design phase, the targeted mixing homogeneity of the components was evaluated for different types of mixing units based on CFD simulation. Subsequently, the flow cell was additively manufactured from ceramic material and metal tubing. Within the targeted working mass flow range, excellent mixing properties as well as narrow line widths were confirmed in validation experiments, comparable to common glass tubes.
Um in einem veränderten Umfeld erfolgreich bestehen zu können, müssen Chemieunternehmen neue Pfade beschreiten. Dazu gehört insbesondere das Potential digitaler Technologien. Mit flexiblen, modularen chemischen Vielzweck-Produktionsanlagen lassen sich häufig wechselnde Produkte mit kürzeren Vorlauf- und Stillstandzeiten zwischen den Kampagnen und dennoch hoher Qualität realisieren. Intensivierte, kontinuierliche Produktionsanlagen erlauben auch den Umgang mit schwierig zu handhabenden Substanzen.
Grundvoraussetzung für solche Konzepte ist eine hochautomatisierte "chemische" Prozesskontrolle zusammen mit Echtzeit-Qualitätskotrolle, die "chemische" Informationen über den Prozess bereitstellt. In einem Anwendungsbeispiel wurde eine pharmazeutische Lithiierungsreaktion aus einer modularen Pilot-Anlage betrachtet und dabei die Vorzüge eines vollautomatischen NMR-Sensors untersucht. Dazu wurde ein kommerziell erhältliches Benchtop-NMR-Spektrometer mit Permanentmagnet auf die industriellen Anforderungen, wie Explosionsschutz, Feldkommunikation und vollautomatischer, robuster Datenauswertung angepasst. Der NMR-Sensor konnte schließlich erfolgreich im vollautomatischen Betrieb nach fortschrittlichen Regelkonzepten und für die Echtzeitoptimierung der Anlage getestet werden. Die NMR-Spektroskopie erwies sich als hervorragende Online-Methode und konnte zusammen mit einer modularen Datenauswertung sehr flexibel genutzt werden. Die Methode konnte überdies als zuverlässige Referenzmethode zur Kalibrierung konventioneller Online-Analytik eingesetzt werden.
Zukünftig werden voll integrierte und intelligent vernetzte "smarte" Sensoren und Prozesse eine kontinuierliche Produktion von Chemikalien und Pharmazeutika mit vertretbaren Qualitätskosten möglich machen.
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 down-times 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.
Um in einem veränderten Umfeld erfolgreich bestehen zu können, müssen Chemieunternehmen neue Pfade beschreiten. Dazu gehört insbesondere das Potential digitaler Technologien. Mit flexiblen, modularen chemischen Vielzweck-Produktionsanlagen lassen sich häufig wechselnde Produkte mit kürzeren Vorlauf- und Stillstandzeiten zwischen den Kampagnen und dennoch hoher Qualität realisieren. Intensivierte, kontinuierliche Produktionsanlagen erlauben auch den Umgang mit schwierig zu handhabenden Substanzen.
Grundvoraussetzung für solche Konzepte ist eine hochautomatisierte "chemische" Prozesskontrolle zusammen mit Echtzeit-Qualitätskotrolle, die "chemische" Informationen über den Prozess bereitstellt. In einem Anwendungsbeispiel wurde eine pharmazeutische Lithiierungsreaktion aus einer modularen Pilot-Anlage betrachtet und dabei die Vorzüge eines vollautomatischen NMR-Sensors untersucht. Dazu wurde ein kommerziell erhältliches Benchtop-NMR-Spektrometer mit Permanentmagnet auf die industriellen Anforderungen, wie Explosionsschutz, Feldkommunikation und vollautomatischer, robuster Datenauswertung angepasst. Der NMR-Sensor konnte schließlich erfolgreich im vollautomatischen Betrieb nach fortschrittlichen Regelkonzepten und für die Echtzeitoptimierung der Anlage getestet werden. Die NMR-Spektroskopie erwies sich als hervorragende Online-Methode und konnte zusammen mit einer modularen Datenauswertung sehr flexibel genutzt werden. Die Methode konnte überdies als zuverlässige Referenzmethode zur Kalibrierung konventioneller Online-Analytik eingesetzt werden.
Zukünftig werden voll integrierte und intelligent vernetzte "smarte" Sensoren und Prozesse eine kontinuierliche Produktion von Chemikalien und Pharmazeutika mit vertretbaren Qualitätskosten möglich machen.
Analysis of dynamic systems
(2019)
Monitoring specific information (i.e., physico-chemical properties, chemical reactions, etc.) is the key to chemical process control when looking at dynamic systems, and quantitative online NMR spectroscopy is the method of choice for the investigation and understanding of dynamic multi-component systems. NMR provides rapid and non-invasive information, and due to the inherent linearity between sample concentration and signal intensity, peak areas can be directly used for quantification of multiple components in a mixture (without the need for any further calibration). This is one of the most attractive features of quantitative NMR spectroscopy. With the launch of devices covering magnetic field strengths from 40 to 90 MHz, so called compact or benchtop NMR systems, this analytical method is now reaching a sufficient degree of compactness and operability for an application outside of very specialized laboratories.
Whilst there are also many other tools available to examine various analytical parameters from dynamic processes, such as mass spectrometry, (near) infrared or Raman spectroscopy, each of these tools can only really be used independently. How can we examine and compare all data describing a particular chemical reaction? How can we visualize information rich, specific, or direct methods together with less specific but established analytical methods? And how can we transfer calibration information to the most appropriate process analytical method or method combination? Quantitative NMR spectroscopy (qNMR) has the potential to substitute offline laboratory analysis for calibration purposes by delivering quantitative reference data as an online method.
The workshop briefly presents the current state of the art of the analysis of dynamic systems by online NMR spectroscopy and analytical data fusion, with the remaining time being used for questions and open discussion with the attendees.
In 2018, BAM (Federal Institute for Materials Research and Testing) and the young analysts of the department Analytical Chemistry at the Gesellschaft Deutscher Chemiker (German Chemical Society, GDCh) jointly organized the second summer school on quality assurance in analytical chemistry in Berlin, Germany. Over fifty doctoral students that are still in the initial stages of work participated in the week-long event and the participants were confronted with the most important basic concepts of internal and external systems of quality assurance in analytical chemistry.
Especially young scientists and scholars deal with the development of analysis methods and often generate an increasingly growing wealth of data. Results are mostly evaluated under quantitative aspects and need to be assessed subject-specifically. In addition to the purely scientific requirements these results also should meet the requirements of analytical quality assurance. For this purpose, the development of analytical methods is accompanied by a process of validation – the documented proof that a method is suitable for the intended purpose and the defined requirements.
This talk summarizes the didactic concept, which was used by the organizers to span an arc from the handling of process characteristics, such as accuracy, precision, linearity, recovery, up to measurement uncertainty and modern multivariate analysis techniques. In an open space workshop, the participants discussed their idea of quality management and worked out requirements after common sense. Interestingly, many participants had already implemented important quality assurance without professionally knowing it.
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 down-times 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 while being based on “chemical” information.
As an example, a fully automated NMR sensor is introduced, using a given pharmaceutical lithiation reaction as an example process within a modular pilot plant. Therefore, a commercially available benchtop NMR spectrometer was adapted 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.
A full integration and intelligent interconnection of such systems and processes progresses only hesitantly. The talk should encourage to re-think digitization of process industry based on smart sensors, actuators, and communication more comprehensively and informs about current technical perspectives such as the “one-network paradigm”, edge computing, or virtual machines. These give smart sensors, actuators, and communication a new perspective.
Modular plants using intensified continuous processes represent an appealing concept to produce pharmaceuticals. It can improve quality, safety, sustainability, and profitability compared to batch processes, and it enables plug-and-produce reconfiguration for fast product changes. To facilitate this flexibility by real-time quality control, we developed a solution that can be adapted quickly to new processes and includes a compact Nuclear Magnetic Resonance (NMR) spectrometer for online quality monitoring as well as a new model-based control approach. The NMR sensor is a benchtop device enhanced to the requirements of automated chemical production including ro-bust evaluation of sensor data.
Here, we present alternatives for the quantitative determination of the analytes using modular, physically motivated models. These models can be adapted to new substances solely by the use of their corresponding pure component spectra, which can either be derived from experimental spectra as well as from quantum mechanical models or NMR predictors. Modular means that spec-tral models can simply be exchanged together with alternate reagents and products. Beyond that, we comprehensively calibrated an NIR spectrometer based on online NMR process data for the first time within an industrial plant. The integrated solution was developed for a metal organic reac-tion running on a commercial-scale modular pilot plant and it was tested under industrial conditions.
Im Vortrag werden Anforderungen und Lösungsvorschläge für das Labor der Zukunft diskutiert. Industrie 4.0 bzw. das Labor 4.0 hilft uns, komplexere Prozesse schneller umzusetzen. Entwicklung von Anlagen und Prozessen beginnt im Labor 4.0. Dazu werden offene, nicht proprietäre Schnittstellen und Standards bei Laborgeräten und Feldgeräten dringend benötigt.
Gas adsorption is based on physical properties between gases and solid materials, enriching the surface with packed gas molecules with a higher density than in the bulk phase. For using this mechanism as a gas storage strategy, highly porous materials are necessary since large surfaces in small volumes can provide the storage system with a higher density than the gas phase. In the case of hydrogen gas, the interaction forces with solid surfaces are generally low at room temperature but can increase considerably at low operating temperatures. As a counterpart, the storage pressure is considerably lower than that necessary by traditional gas compression.
Amongst ultra-porous adsorbent materials for hydrogen cryoadsorption, metal-organic frameworks (MOFs) are a group of remarkable solids made from metallic nodes linked by organic molecules exhibiting a wide variety of composition, geometry, porous properties, and chemical functionality. The scientific community focused in the last years on enhancing both the specific area of materials and the interaction energy to extend the storage properties of cryoadsorption to ambient-temperature and use it as hydrogen storage mechanisms in vehicles. However, the found difficulty in achieving ultra-porous structures with high-enough interaction energies decreased this research interest in the last years.
However, for a stationary application like hydrogen refueling stations, where space and weight are not such limits as in vehicles, cryoadsorption can still be considered a feasible candidate for hydrogen storage. Cryoadsorption is the only fast and fully reversible approach to store hydrogen at similar density values as compressed gas. Cryogenic operation is a technological challenge, but first, liquid nitrogen is cheap, and second, it is less energy-demanding than hydrogen liquefaction, which is indeed considered as feasible for transportation and storage. Cryoadsorption involves lower pressure
than compressed gas, increasing safety in the storage facilities, but additional research on the construction materials properties is necessary to better understand their behavior in contact with hydrogen at cryogenic temperatures. However, the knowledge of all these mechanisms is important to identify the improvement opportunities based on, probably, the interphase between different solutions.
To achieve the set project goals, this internal research report describes the work packages realised within the framework of the project.
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.
Companies in the chemical industry have to tread new paths in order to survive successfully in a changed environment. This includes, in particular, the potential of digital technologies. The full integration and intelligent networking of systems and processes is making slow progress.
This talk is a tribute to the field level. It wants to encourage a more holistic approach to the digitalisation of the process industry based on smart sensors, actuators and communication and provides information on current technical perspectives, such as the "one-network paradigm", ad-hoc networking, edge computing, FPGAs, virtual machines or blockchain. These give smart sensors, actuators and communication a completely new perspective.
Process analytical technology (PAT) is a cross-sectional technology and thus essential for future smart production. While in the past decades, the focus of process optimization strategies was on increasing efficiency, in the future, the focus will be on the sustainability of a production and its products. In addition, products will be increasingly personalized in order to match the property profile exactly to the intended use. PAT is able to provide context-sensitive information at the molecular level for process control. Spectroscopic sensors can determine inline and simultaneously both the chemical composition and its sub-microscopic morphology. The article will focus on the optical spectroscopy and therefore starts with a brief introduction on the basic concepts of molecular spectroscopy. In addition, the particularities of measuring liquids, surfaces, or particulate systems in PAT applications are described. This should enable the reader to select the appropriate method for the specific problem. Many examples from everyday industrial practice illustrate the applications. The areas covered are the manufacturing industry, process and pharmaceutical industry, food industry, as well as biotechnology and medical technology. Future will show that PAT is especially important for applications in the field of medicine (point of care) circular economy (recycling, water–wastewater, etc.). It is important to emphasize that sustainability in industrial production can only be successful with an inter- and transdisciplinary close exchange between the different disciplines.
The European project MefHySto addresses the need of large-scale energy storage, which is required for a shift to renewable energy supply. The project is funded by the European Metrology Programme on Innovation and Research (EMPIR) and consists of 14 consortium partners from all over Europe (www.mefhysto.eu). It is demonstrated, how MefHySto is contributing to the EMN for Energy Gases aiming at prioritisation of the measurement gaps and challenges interacting with the EMN stakeholders.
Unternehmen der Prozessindustrie müssen neue Wege finden, um in einem sich wandelnden Umfeld erfolgreich zu überleben, und gleichzeitig flexiblere Wege der Produkt- und Prozessentwicklung finden, um ihre Produkte schneller auf den Markt zu bringen – insbesondere hochwertige, hochwertige Produkte wie Feinchemikalien oder Arzneimittel. Dies wird zukünftig durch Veränderungen in den Wertschöpfungsketten entlang einer potenziellen Kreislaufwirtschaft erschwert.
Anhand von Beispielen wird in diesem Vortrag ein möglicher ganzheitlicher Ansatz zur Digitalisierung und zum Einsatz maschineller Verfahren in der Produktion von Spezialchemikalien durch die Einführung integrierter und vernetzter Systeme und Prozesse skizziert.
Es wird auch auf die aktuelle Technologie-Roadmap „Prozess-Sensoren 2027+“ eingegangen, die Ende 2021 erschienen ist. Im Zentrum dieser Roadmaps stehen Sensoren zur Erfassung von physikalischen und chemischen Messgrößen mittels spezifischer und unspezifischer Messverfahren, die zur Steuerung und dem besseren Verständnis von Prozessen dienen. Die Roadmap fasst die gemeinsame Technologie- und Marktsicht von Anwendern, Herstellern und Forschungs¬einrichtungen im Bereich Prozess-Sensorik in der verfahrenstechnischen Industrie zusammen. Digitalisierung und Nachhaltigkeit sind übergreifende Kernthemen der künftigen Entwicklung.
Die BAM setzt in ihren analytischen Labors zunehmend Labor-Robotik ein, um gefähliche oder zeitraubende Routineaufgaben zu automatisieren. Durch Automation kann auch die Reproduzierbarkeit solcher Anwendungen erhöht werden.
Im Beitrag werden einige aktuelle Beispiele aus den Analytiklabors diskutiert, wie z. B. die Anwendung für die Herstellung und RFA-Analytik von Gläsern, eine Feinwäge-Robotik für 10-L-Gaszylinder im Rahmen der Herstellung von Primärnormalen oder die Automatisierung von Probenpräsentationen für optische Spektroskopie und chemical Imaging. Auch wird kurz auf den Einsatz von Speicherprogrammierbaren Steuerungen in der modularen Laborautomation und die Virtualisierung von analytischen Laborrechnern eingengangen.
Zusätzlich zu Methodenentwicklung, Miniaturisierung und Kopplungsverfahren zeigen sich die Hyperspektroskopie zusammen mit Imaging‐Verfahren, der Einzelmolekülnachweis und der Einsatz von 3‐D‐Druckern als neue Schwerpunkte. Hinzu kommen künstliche Intelligenz bei Sensoren, Bildgebungsverfahren und Prozesssteuerung sowie die Vernetzung von Analyse‐ und Laborgeräten. Trends und Forschungsthemen aus der analytischen Chemie, zusammengestellt von elf Autoren, koordiniert von Günter Gauglitz.
Prozess-Sensoren 4.0 vereinfachen ihre Einbindung über Plug and Play, obwohl sie komplexer werden. Sie bieten Selbstdiagnose, Selbstkalibrierung und erleichterte Parametrierung. Über die Konnektivität ermöglichen die Prozess-Sensoren den Austausch ihrer Informationen als Cyber-physische Systeme mit anderen Prozess-Sensoren und im Netzwerk. Der Aufbruch von der aktuellen Automation zum smarten Sensor hat bereits begonnen. Automatisierungstechnik und Informations- und Kommunikationstechnik (IKT) verschmelzen zunehmend. Wenn die Prozessindustrie dieses nicht definiert, tun es andere.
Für die weitere Entwicklung von der Ist‐Situation zu einer Industrie-4.0-Welt in der Prozessindustrie werden mehrere Szenarien diskutiert. Diese reichen vom erleichterten Abruf sensorbezogener Daten über zusätzliche Kommunikationskanäle zwischen Sensor und mobilen Endgeräten über vollständig bidirektionale Kommunikation bis hin zur Einbindung der Cloud und des Internets in virtualisierte Umgebungen.
Um zu einer störungsfreien Kommunikation aller Sensoren untereinander zu kommen, muss mindestens ein einheitliches Protokoll her, das alle Sensoren sprechen und verstehen. Der derzeit greifbarste offengelegte Standard, der moderne Kommunikationsanforderungen erfüllt, ist OPC Unified Architecture (OPC-UA). Viele halten das Sortieren der Kommunikationsstandards für eines der wesentlichen Errungenschaften von Industrie 4.0.
Eine Topologie für smarte Sensoren, das Zusammenwirken mit daten- und modellbasierte Steuerungen bis hin zur Softsensorik sowie weitere Anforderungen an Sensoren sind jedoch heute noch nicht angemessen beschrieben. Wir müssen jetzt schnell die Weichen für eine smarte und sichere Kommunikationsarchitektur stellen, um zu einer störungsfreien Kommunikation aller Sensoren auf Basis eines einheitlichen Protokolls zu kommen, welches alle Sensoren ausgeben und verstehen.
Aktuelle und zukünftige öffentliche Förderung von Industrie 4.0-Projekten sind eine gute Investition. Wegen der hohen Komplexität und Interdisziplinarität gelingt die Umsetzung nur gemeinsam zwischen Anwendern aus der Prozessindustrie, Software- und Geräteherstellern und Forschungsgruppen. Anwender sind gefragt, diese neue Technologie durch eine beschleunigte Validierung und Akzeptanz umzusetzen. Sie erhalten die einzigartige Chance, ihre Prozesse und Anlagen wettbewerbsfähig zu halten. Kooperativ betriebenen F&E-Zentren und gemeinsam anerkannten Applikationslaboren kommt dafür eine hohe Bedeutung zu.
For absorption processes with fluctuating feed gas compositions it is vital to continuously adjust
the operation point to achieve energy efficiency. In this contribution a Raman-based advanced
process control (APC) is introduced for the absorption of carbon dioxide (CO2) using an aqueous
solution of monoethanolamine (MEA). The APC is based on a Raman spectroscopic analysis of
the composition and CO2 load of the scrubbing liquid and a non-linear model predictive control
(NMPC) to adjust the scrubbing liquid cycle. In addition, an outer real-time optimization loop is
set in place to update the set points for the absorption process depending on the current feed gas composition minimizing the energy consumption of the process. Implementation and testing of the APC have been carried out in a mini-plant at TU Berlin. During a plant operation of more than 160 hours robustness and stability of the APC were shown.
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.
Die Technologie-Roadmap „Prozess-Sensoren 2027+“ ist eine Weiterentwicklung vorgängiger Technologie-Roadmaps. Im Zentrum dieser Roadmaps stehen Sensoren zur Erfassung von physikalischen und chemischen Messgrößen mittels spezifischer und unspezifischer Messverfahren, die zur Steuerung und dem besseren Verständnis von Prozessen dienen.
Die Roadmap fasst die gemeinsame Technologie- und Marktsicht von Anwendern, Herstellern und Forschungseinrichtungen im Bereich Prozess-Sensorik in der verfahrenstechnischen Industrie zusammen. Sie beschreibt die wesentlichen Trends im Bereich Prozess-Sensorik und künftige Handlungsbedarfe für Hersteller, Anwender sowie für Einrichtungen der Forschung und Lehre.
Für die aktuellen und zukünftigen Anforderungen an Prozess-Sensoren werden 19 Thesen formuliert. Die Thesen basieren auf den Thesen der vorangegangenen Roadmaps, wobei die aus heutiger Sicht erforderlichen Anpassungen, Ergänzungen und teilweise auch Streichungen vorgenommen wurden. Die Thesen sind in 5 Themencluster eingeordnet. Digitalisierung und Nachhaltigkeit sind übergreifende Kernthemen der künftigen Entwicklung.
Optimizing the Green Synthesis of ZIF-8 by Reactive Extrusion Using In Situ Raman Spectroscopy
(2023)
We report the scale-up of a batch solid synthesis of zeolitic imidazolate framework-8 (ZIF-8) for reactive extrusion. The crystalline product forms in the extruder directly under the mixture of solid 2-methylimidazole and basic zinc carbonate in the presence of a catalytic amount of liquid. The process parameters such as temperature, liquid type, feeding rate, and linker excess were optimized using the setup specifically designed for in situ Raman spectroscopy. Highly crystalline ZIF-8 with a Brunauer–Emmett–Teller (BET) surface area of 1816 m2 g–1 was quantitatively prepared at mild temperature using a catalytic amount of ethanol and a small excess of the linker. Finally, we developed a simple and comprehensive approach to evaluating the environmental friendliness and scalability of metal–organic framework (MOF) syntheses in view of their large-scale production.
Der Wandel von der aktuellen Automation zum smarten Sensor ist im vollen Gange. Automatisierungstechnik, sowie die Informations- und Kommunikationstechnik (IKT) verschmelzen zunehmend. Eine Topologie für smarte Sensoren, die das Zusammenwirken mit daten- und modellbasierten Steuerungen bis hin zur Softsensorik beschreibt gibt es bis heute jedoch noch nicht. Um zu einer störungsfreien Kommunikation aller Komponenten auf Basis eines einheitlichen Protokolls zu kommen sollte die Prozessindustrie die Weichen für eine smarte und sichere Kommunikationsarchitektur stellen. Sie verwehrt stattdessen die Entwicklungen ihrer Zulieferer und wartet lieber ab. Der Beitrag greift die Anforderungen der Technologie-Roadmap „Prozess-Sensoren 4.0“ auf und zeigt Möglichkeiten zu ihrer Realisierung am Beispiel eines Online-NMR-Analysators, der im Rahmen eines EU-Projekts entwickelt wurde.
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.
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.
Introduction
NMR spectroscopy is one of the most important analytical methods in organic chemistry. While most analyses are carried out qualitatively with the aim of substance identification and structure elucidation, quantitative NMR spectroscopy (qNMR) is increasingly gaining importance in research and industry. qNMR provides the most universally applicable form of direct purity determination without need for reference materials of impurities or the calculation of response factors but only exhibiting suitable NMR properties.
Methods
One of the most attractive features of quantitative NMR spectroscopy is that the NMR peak areas can be used directly for concentration quantification without further calibration. Another advantage of NMR spectroscopy is that the method has a high linearity between absolute signal area and sample concentration, which makes it an absolute analytical comparison method that is independent of the matrix. This enables automated robust data evaluation strategies that can be used for online applications of qNMR spectroscopy.
Jancke et al. proposed NMR spectroscopy as a relative primary analytical method because it can be fully described by mathematical equations from which a complete uncertainty budget can be derived, allowing it to be used at the highest metrological level. Weber et al. discussed in detail important aspects of the procedure that enable the realisation of low measurement uncertainties in qNMR measurements. Since certification of CRM requires expanded mea¬sure¬ment uncertainties of less than 0.5 % (relative), the work of Weber et al. demonstrated for the first time that qNMR can fulfil this criterion.
Results
To date, further comparative studies have been carried out in metrology and industry, demonstrating the performance of quantitative NMR spectroscopy and further reducing measurement uncertainties. The development of validation concepts and the commercial availability of suitable certified reference materials facilitate the application, especially in the usually highly regulated industrial environment. Users can thus accelerate the development of analytical methods. The talk will cover a wide range of topics from current metrological activities to new challenges for qNMR spectroscopy and also deals with aspects such as validation and accreditation.
Innovative aspects
• qNMR provides the most universally applicable form of direct purity determination
• Expanded measurement uncertainties lower than 0.15 % (relative) possible
• Benchtop NMR instruments increasingly used for qNMR spectroscopy
Intelligent sensor systems, certified reference materials and instrumental analytical-chemical methods contribute to safety and functionality in hydrogen technologies.
This article gives a brief overview of SensRef activities in the Competence Centre H2Safety@BAM on the issues: Analytical methods for the determination of hydrogen purity, certified reference materials as measurement standards with regard to gas quality (primary calibrators) of BAM, test methods for gas sensor systems to detect hydrogen in air as well as the application of fibre-optic sensor systems to monitor the expansion and ageing behaviour of composite containers in hydrogen technologies.
Reaction monitoring in disperse systems, such as emulsions, is of significant technical importance in various disciplines like biotechnological engineering, chemical industry, food science, and a growing number other technical fields. These systems pose several challenges when it comes to process analytics, such as heterogeneity of mixtures, changes in optical behavior, and low optical activity. Concerning this, online nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for process monitoring in complex reaction mixtures due to its unique direct comparison abilities, while at the same time being non-invasive and independent of optical properties of the sample. In this study the applicability of online-spectroscopic methods on the homogeneously catalyzed hydroformylation system of 1-dodecene to tridecanal is investigated, which is operated in a mini-plant scale at Technische Universität Berlin. The design of a laboratory setup for process-like calibration experiments is presented, including a 500 MHz online NMR spectrometer, a benchtop NMR device with 43 MHz proton frequency as well as two Raman probes and a flow cell assembly for an ultraviolet and visible light (UV/VIS) spectrometer. Results of high-resolution online NMR spectroscopy are shown and technical as well as process-specific problems observed during the measurements are discussed.
A major industrial reaction based on homogeneous catalysis is hydroformylation for the production of aldehydes from alkenes and syngas. Hydroformylation in microemulsions, which is currently under investigation at Technische Universität Berlin on a mini-plant scale, was identified as a cost efficient approach which also enhances product selectivity. Herein, we present the application of online Raman spectroscopy on the reaction of 1-dodecene to 1-tridecanal within a microemulsion. To achieve a good representation of the operation range in the mini-plant with regard to concentrations of the reactants a design of experiments was used. Based on initial Raman spectra partial least squares regression (PLSR) models were calibrated for the prediction of 1-dodecene and 1-tridecanal. Limits of predictions arise from nonlinear correlations between Raman intensity and mass fractions of compounds in the microemulsion system. Furthermore, the prediction power of PLSR models becomes limited due to unexpected by-product formation. Application of the lab-scale derived calibration spectra and PLSR models on online spectra from a mini-plant operation yielded promising estimations of 1-tridecanal and acceptable predictions of 1-dodecene mass fractions suggesting Raman spectroscopy as a suitable technique for process analytics in microemulsions.
The project InPROMPT aims to establish a robust hydroformylation reaction process of the alkene n-dodecene to the aldehyde n-tridecanal using a rhodium complex as catalyst in the presence of syngas. This industrial relevant production process demands further research for optimization and expansion. For that purpose, the fiber optic coupled probe of a process Raman spectrometer is directly introduced in the product stream, which enables the recording of spectra within short control intervals.
The Collaborative Research Center InPROMPT aims to establish a novel process concept for the hydroformylation of long-chained olefins, using a rhodium complex as catalyst in the presence of syngas. Recently, the hydroformylation in micro-emulsions, which allows for the efficient recycling of the expensive rhodium catalyst, was found to be feasible. However, the temperature and concentration sensitive multi-phase system demands a continuous observation of the reaction to achieve an operational and economically feasible plant operation. For that purpose, we tested the potential of both NMR and Raman spectroscopy for process control assistance. The lab-scale experiments were supported by sampling for off-line GC-analysis as reference analytics. The results of the NMR experiments will be part of another contribution.
Der Artikel ist ein Editorial, der für die Herstellung eines grundlegenden Vertrauens in medizinische Produkte - insbesondere Impfstoffe - wirbt, um Skeptiker zu Unterstützern zu machen. Er wirbt nicht nur für die Impfstoffe, sondern auch für die Kultur der Pharmazie und Chemie und die Wissenschaft ganz allgemein und regt an, mehr erklärende Formate wie z. B. im Stil der Sendung mit der Maus für diese Dinge zu werben. Der Artikel geht auch auf den ungeheuren Reiz der seit gut zwanzig Jahren diskutierten risikobasierten Ansätze für pharmazeutische Entwicklung und Herstellung von Arzneimitteln auf Basis der Quality Guidelines ein.
Die Abtrennung von CO2 aus industriellen Gasströmen ist eine großtechnisch wichtige Trennaufgabe. Neben der Aufarbeitung von Erdgas werden diese Verfahren zur Verminderung der CO2-Emission durch industrielle Rauchgase, insbesondere für alternativlose Prozesse wie die Stahl- und Zementproduktion diskutiert.
Hydroformylation represents an important homogeneous catalyzed process, which is widely used within chemical industry. Usually applied with simple alkenes like Propene and Butene aldehydes obtained from alkenes >C6 are relevant intermediates in production of plasticizers, surfactants and polymers. Today the active catalyst species is often based on valuable Rhodium complexes in aqueous solution. This implies the problem of limited water solubility of the reactands, which is acceptable for short chain lengths, but states a problem in case of higher alkenes. Along with that efficient separation and recycling of the catalyst becomes more complicated. There are different approaches tackling this problem, e.g., by using of salt formation in the BASF process or downstream distillation within the Shell process
Compact nuclear magnetic resonance (NMR) instruments make NMR spectroscopy and relaxometry accessible in industrial and harsh environments for reaction and process control. An increasing number of applications are reported. To build an interdisciplinary bridge between “process control” and “compact NMR”,we give a short overviewon current developments in the field of process Engineering such as modern process design, integrated processes, intensified processes along with requirements to process control, model based control, or soft sensing. Finally, robust field integration of NMR systems into processes environments, facing explosion protection or Integration into process control systems, are briefly discussed.
Compact nuclear magnetic resonance (NMR) instruments make NMR spectroscopy and relaxometry accessible in industrial and harsh environments for reaction and process control. An increasing number of applications are reported. Robust field integration of NMR systems have to face explosion protection or integration into process control systems with short set-up times. Tis paves the way for industrial automation in real process environments.
Automated data preparation and analysis are cornerstones for a breakthrough of NMR techniques for process control. Particularly, robust chemometrics as well as automated signal processing methods have to be (further) developed especially for NMR spectroscopy in process control. This becomes even more important for so called “smart sensors” providing the basis for the future project “Industrie 4.0”, and Industrial Internet of Things (IIoT), along with current requirements to process control, model based control, or soft sensing. Data analysis techniques are available but currently mostly used for off-line data analysis to detect the causes of variations in the product quality.
The talk presents current research activities towards process control with compact NMR and reflects “cultural differences” between the interdisciplinary parties involved.
Die auf der NAMUR HS 2015 vorgestellte Technologie-Roadmap „Prozess-Sensoren 4.0“ zeigt die nötigen Anforderungen an Prozess-Sensoren sowie an deren Kommunikations-fähigkeiten auf. Wir berichten über den Stand der Diskussionen im Trialog zwischen Anwendern, Software- und Geräteherstellern sowie der Forschung.
Ein wichtiger Schlüssel ist die Definition einer bedarfsgerechten und einheitlichen Topologie für solche smarten Sensoren, die in einem Arbeitskreis „Smarte-Sensorik“ ohne im wechselseitigen Austausch mit Geräte- und Softwareherstellern und Forschungseinrichtungen vorangetrieben werden soll.
Process monitoring of an intensified continuous production unit with compact NMR spectroscopy
(2016)
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 analyzers, 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 cur-rently not available off the rack. Recently, promising benchtop NMR instruments with acceptable performance came to market and process integrated sensors developed on basis of such laboratory instruments are on their way.
The Royal Society of Chemistry NMR Discussion Group and Molecular Spectroscopy Group would like to invite you to the 2017 Spring Meeting, which will be held at GlaxoSmithKline (GSK), Stevenage. The theme for the meeting is “Low level detection and quantification by NMR” and different NMR technologies, including solution state NMR, solid state NMR and benchtop/low field NMR will be discussed. The presentations will cover a range of NMR related disciplines, including conventional low level detection and quantification, the use of cryoprobes, quantification of polymorphism using ssNMR and also methods for spectral simplification. Recent developments and applications of hyperpolarisation techniques, within both solution state and solid state NMR, will be presented in conjunction with the effect these sensitivity enhancements have with respect to quantification and limits of detection.
Berichtet wird über die automatisierte und spektral-modellgestützte Datenauswertung quantitativer Online-NMR-Spektren von technischen Systemen, die einen grundlegenden Beitrag zum Thematik Smart Sensors im Sinne kalibrierarmer bzw. kalibrierfreier Verfahren liefern.
Die quantitative Online-NMR-Spektroskopie ist besonders reizvoll für diese Thematik: Sie kommt durch den direkten Nachweis der Kernspins ohne Kalibrierung aus und arbeitet auch in Konzentrationsrandbereichen äußerst linear. Als „absolute Vergleichsmethode“ (direkte Proportionalität der Signale zu den Stoffmengen innerhalb eines Spektrums) ist die NMR-Spektroskopie für die durchgeführten Grundlagenuntersuchungen im Zusammenhang mit spektralen Modellen prädestiniert.
Smart functions of sensors simplify their use and enable plug-and-play, even though they are more complex. This is particularly important for, self-diagnostics, self-calibration and self-configuration/parameterization. Intelligent field devices, digital field networks, Internet Protocol (IP)-enabled connectivity and web services, historians, and advanced data analysis software are providing the basis for the future project “Industrie 4.0” and Industrial Internet of Things (IIoT).
Important smart features include connectivity and communication ability according to a unified protocol (OPC-UA currently most widely discussed), maintenance and operating functions, traceability and compliance, virtual description to support a continuous engineering, and well as interaction capabilities between sensors. This is a prerequisite for the realization of Cyber Physical Systems (CPS) within these future automation concepts for the process industry. Therefore, smart process sensors enable new business models for users, device manufacturers, and service providers.
The departure from current automation to smart sensor has already begun. Further development is based on the actual situation over several steps. Possible perspectives will be via additional communication channels to mobile devices, bidirectional communication, integration of the cloud and virtualization. The integration of virtual runtime environments can provide a more flexible topology for process control environments.
The talk summarizes the currently discussed requirements to process sensors 4.0 and introduces an online NMR sensor as an example, which was developed in the EU project CONSENS.
The talk reflects how PAT could be applied in future developments ofpharma manufacturing. It shows the benefits, increase quality, size and increasing speed of production with significant reduction of quality costs, which are possible. Using Smart Sensors and model based data evaluation methods are the key to reduce set-up times and costs. Industry 4.0 will help shape the Pharmaceutical industry of tomorrow. This is demonstrated by an example using modular production units for Continuous Manufacturing. The development of a smart online NMR analyser is shown.
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).
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.