Hochauflösende Online-NMR-Spektroskopie für das Reaktions- und Prozeßmonitoring - Beispiele zur Anwendung in der Verfahrenstechnik

Die moderne Reaktions- und Trenntechnik in der chemischen Industrie ist eine Hochtechnologie. Die dort eingesetzten Verfahren zur Reaktionsführung und Auftrennung der Produkte sind weitestgehend optimiert. Zu diesem Stand hat die instrumentelle Analytik – speziell die Prozeßanalytik – wesentlich beigetragen. Das Reaktions- und Prozeßmonitoring ist eine wichtige Hilfe zum Verständnis der komplexen Zusammenhänge. In der vorliegenden Arbeit wird der Einsatz der NMR-Spektroskopie in verfahrenstechnischen Anwendungen wie dem Reaktions- und Prozeß-Monitoring diskutiert und alle dazu notwendigen Grundlagen erläutert. Solche Anwendungen erfordern häufig Techniken, mit denen hochaufgelöste Spektren zerstörungsfrei aufgenommen werden können, oft bei erhöhtem Druck und erhöhter Temperatur. Neben der quantitativen Bestimmung der Zusammensetzung komplexer reagierender Mischungen besteht gleichzeitig die Möglichkeit zur Identifikation von Nebenprodukten. Dieses gelingt insbesondere durch die Nutzung der NMR-Spektroskopie als Online-Methode, die in der Literatur bislang nur in wenigen Einzelfällen beschrieben und trotz ihrer enormen Möglichkeiten noch nicht konsequent angewendet wird. Durch die fortschreitende Entwicklung auf dem Gebiet der NMR-Spektroskopie kann eine Online-Anbindung heute durchgehend mit Hilfe kommerziell erhältlicher Komponenten erfolgen – wie die vorliegende Arbeit zeigt. Fallende Kosten in der Beschaffung und dem Betrieb leistungsfähiger NMR-Spektrometer machen die Methode auch im verfahrenstechnischen Umfeld mittlerweile sehr attraktiv. Die Attraktivität der Methode gewinnt neuerdings insbesondere durch die erweiterten Einsatzmöglichkeiten kompakterer NMR-Magneten mit geringen Streufeldern. Obwohl sich in den Ingenieurwissenschaften damit vielfältige Einsatzmöglichkeiten ergeben, wird die NMR-Spektroskopie dort bislang noch leider kaum genutzt. Besondere Herausforderungen stellen sich u. a. dadurch, daß sich weder deuterierten Komponenten einsetzen lassen noch die Probe in einer geeigneten Weise in einer Probenvorbereitung verändert werden kann. Damit kommen hochkonzentrierte Mischungen zur direkten Untersuchung. Dieses hat signifikante Rückwirkungen auf die einzusetzende NMR-Methodik, die im Rahmen der Arbeit umfassend untersucht wurde. In der Regel lassen sich die Probleme bei entsprechender experimenteller Vorgehensweise umgehen. Zur Garantie quantitativer Meßwerte wurden alle eingesetzten Meß- und Auswertungsstrategien ausführlich untersucht und teilweise erweitert. Um quantitativ aussagekräftige Online-NMR-Spektren mit Hilfe der 1H- und 13C-NMRSpektroskopie von technischen Mischungen zu erhalten, wurden folgende Aufgaben gelöst: Entwicklung und Validierung von Vorgehensweisen zur Messung hochkonzentrierter, technischer Mischungen ohne Probenvorbereitung und ohne Zusatz deuterierter Komponenten; Konstruktion geeigneter Apparaturen zur Untersuchung von Reaktionsgleichgewichten und -kinetiken für verschiedene Druck- und Temperaturbereiche, die sich optimal für die Online-NMR-Spektroskopie einsetzen lassen; Ankopplung der NMR-Spektrometers an die unterschiedlichen Apparate mit Hilfe von NMR-Durchflußzellen; Schaffung einer möglichst noninvasiven Untersuchungsmethode hinsichtlich aller Probenparameter (z. B. Druck, Temperatur); Schaffung und Erprobung von Meß- und Auswertungsstrategien im Hinblick auf quantitative Parameter, Erweiterung des zugänglichen Druck- und Temperaturbereiches der Messungen sowie Verkürzung des Zeitfensters für Messungen durch geeignete Peripherie und konstruktiven Veränderungen am NMR-Probenkopf. Als Beispiel werden Messungen an binären und ternären flüssigen Mischungen aus Formaldehyd, Wasser und Methanol diskutiert. In diesen Systemen ist Formaldehyd fast ausschließlich in Poly(oxymethylen)Glykolen und -hemiformalen chemisch gebunden. Die chemischen Reaktionen in formaldehydhaltigen Mischungen bestimmen deren thermodynamisches Verhalten sowie ihre Trennung mit thermischen Verfahren. Die NMR-Spektroskopie ist das zentrale analytische Verfahren, mit dem sich diese Vorgänge aufklären und quantifizieren lassen. Für die hier vorgestellten Untersuchungen zum Prozeßmonitoring kamen u. a. eine Online-NMRKopplung mit einem Dünnschichtverdampfer sowie mit einem Rührreaktor zum Einsatz. In weiteren Anwendungsbeispielen zum Thema Formaldehyd wird aufgezeigt, daß sich die Online-NMR-Spektroskopie auch zum Studium komplexer Reaktionsnetzwerke, zur Messung von Gaslöslichkeiten oder zur Quantifizierung kleinster Produktmengen unter schwierigen, technischen Reaktionsbedingungen eignet. Ferner werden Arbeiten zur Aufklärung und Quantifizierung der chemischen Prozesse bei der Absorption von Kohlendioxid in wässrigen Aminlösungen bei Drücken bis zu 30 bar und reaktionskinetische Untersuchungen von Veresterungen vorgestellt, bei denen auch ein Vergleich mit einer GC-Analytik durchgeführt wurde. Ebenso wird gezeigt, daß sich die Online-NMR-Spektroskopie zur Beobachtung von Reaktionen in Ionischen Flüssigkeiten eignet. Ein Teil der Arbeit beschäftigt sich mit der Untersuchung fluider Mischungen bei hohen Drücken. Beispielhaft werden Arbeiten zu H-Brückengleichgewichten von Methanol in überkritischem Kohlendioxid vorgestellt, die eine wertvolle, experimentelle Datenbasis zur Überprüfung molekulardynamischer Modelle in der molekularen Simulation liefern. Für die meisten Anwendungsbeispiele werden neue Reaktoren und Meßapparaturen vorgestellt, die sich besonders für den Einsatz in der Durchfluß-NMR-Spektroskopie eignen. Schließlich wird kurz auf die Anwendung der NMR-Spektroskopie zur Bestimmung physikalisch chemischer Größen eingegangen, wie z. B. zur Bestimmung von Diffusuionskoeffizienten in technischen Mischungen. Erstmals wird der Einsatz der Methode in der Taylor-Dispersionstechnik beschrieben und experimentell belegt

CASIMIR: a high resolution far-IR/submm spectrometer for airborne astronomy

CASIMIR, the Caltech Airborne Submillimeter Interstellar Medium Investigations Receiver, is a far-infrared and submillimeter heterodyne spectrometer, being developed for the Stratospheric Observatory For Infrared Astronomy, SOFIA. CASIMIR will use newly developed superconducting-insulating-superconducting (SIS) mixers. Combined with the 2.5 m mirror of SOFIA, these detectors will allow observations with high sensitivity to be made in the frequency range from 500 GHz up to 1.4 THz. Initially, at least 5 frequency bands in this range are planned, each with a 4-8 GHz IF passband. Up to 4 frequency bands will be available on each flight and bands may be swapped readily between flights. The local oscillators for all bands are synthesized and tuner-less, using solid state multipliers. CASIMIR also uses a novel, commercial, field-programmable gate array (FPGA) based, fast Fourier transform spectrometer, with extremely high resolution, 22000 (268 kHz at 6 GHz), yielding a system resolution > 10^6. CASIMIR is extremely well suited to observe the warm, ≈ 100K, interstellar medium, particularly hydrides and water lines, in both galactic and extragalactic sources. We present an overview of the instrument, its capabilities and systems. We also describe recent progress in development of the local oscillators and present our first astronomical observations obtained with the new type of spectrometer

Modeling time delay in the NFκB signaling pathway following low dose IL-1 stimulation

Stimulation of human epithelial cells with IL-1 (10 ng/ml) + UVB radiation results in sustained NFκB activation caused by continuous IKKβ phosphorylation. We have recently published a strictly reduced ordinary differential equation model elucidating the involved mechanisms. Here, we compare model extensions for low IL-1 doses (0.5 ng/ml), where delayed IKKβ phosphorylation is observed. The extended model including a positive regulatory element, most likely auto-ubiquitination of TRAF6, reproduces the observed experimental data most convincingly. The extension is shown to be consistent with the original model and contains very sensitive processes which may serve as potential intervention targets

Ultrasensitive force and displacement detection using trapped ions

The ability to detect extremely small forces is vital for a variety of disciplines including precision spin-resonance imaging, microscopy, and tests of fundamental physical phenomena. Current force-detection sensitivity limits have surpassed 1 $aN/\sqrt{Hz}$ (atto $=10^{-18}$) through coupling of micro or nanofabricated mechanical resonators to a variety of physical systems including single-electron transistors, superconducting microwave cavities, and individual spins. These experiments have allowed for probing studies of a variety of phenomena, but sensitivity requirements are ever-increasing as new regimes of physical interactions are considered. Here we show that trapped atomic ions are exquisitely sensitive force detectors, with a measured sensitivity more than three orders of magnitude better than existing reports. We demonstrate detection of forces as small as 174 $yN$ (yocto $=10^{-24}$), with a sensitivity 390$\pm150$ $yN/\sqrt{Hz}$ using crystals of $n=60$ $^{9}$Be$^{+}$ ions in a Penning trap. Our technique is based on the excitation of normal motional modes in an ion trap by externally applied electric fields, detection via and phase-coherent Doppler velocimetry, which allows for the discrimination of ion motion with amplitudes on the scale of nanometers. These experimental results and extracted force-detection sensitivities in the single-ion limit validate proposals suggesting that trapped atomic ions are capable of detecting of forces with sensitivity approaching 1 $yN/\sqrt{Hz}$. We anticipate that this demonstration will be strongly motivational for the development of a new class of deployable trapped-ion-based sensors, and will permit scientists to access new regimes in materials science.Comment: Expanded introduction and analysis. Methods section added. Subject to press embarg

Establishing ZIF-8 as a reference material for hydrogen cryoadsorption: An interlaboratory study

Hydrogen storage by cryoadsorption on porous materials has the advantages of low material cost, safety, fast kinetics, and high cyclic stability. The further development of this technology requires reliable data on the H2 uptake of the adsorbents, however, even for activated carbons the values between different laboratories show sometimes large discrepancies. So far no reference material for hydrogen cryoadsorption is available. The metal-organic framework ZIF-8 is an ideal material possessing high thermal, chemical, and mechanical stability that reduces degradation during handling and activation. Here, we distributed ZIF-8 pellets synthesized by extrusion to 9 laboratories equipped with 15 different experimental setups including gravimetric and volumetric analyzers. The gravimetric H2 uptake of the pellets was measured at 77 K and up to 100 bar showing a high reproducibility between the different laboratories, with a small relative standard deviation of 3–4 % between pressures of 10–100 bar. The effect of operating variables like the amount of sample or analysis temperature was evaluated, remarking the calibration of devices and other correction procedures as the most significant deviation sources. Overall, the reproducible hydrogen cryoadsorption measurements indicate the robustness of the ZIF-8 pellets, which we want to propose as a reference material.M. Maiwald, J. A. Villajos, R. Balderas and M. Hirscher acknowledge the EMPIR programme from the European Union's Horizon 2020 research and innovation programme for funding. F. Cuevas and F. Couturas acknowledge support from France 2030 program under project ANR-22-PEHY-0007. D. Cazorla and A. Berenguer-Murcia thank the support by PID2021-123079OB-I00 project funded by MCIN/AEI/10.13039/501100011033, and “ERDF A way of making Europe”. K. N. Heinselman, S. Shulda and P. A. Parilla acknowledge the support from the National Renewable Energy Laboratory, operated by Alliance for Sustainable Energy, LLC, for the U.S. Department of Energy (DOE) under Contract No. DE-AC36-08GO28308. Funding provided by U.S. Department of Energy Office of Energy Efficiency and Renewable Energy Hydrogen and Fuel Cell Technology Office through the HyMARC Energy Materials Network

Capabilities of Gossamer-1 derived small spacecraft solar sails carrying MASCOT-derived nanolanders for in-situ surveying of NEAs

Any effort which intends to physically interact with specific asteroids requires understanding at least of the composition and multi-scale structure of the surface layers, sometimes also of the interior. Therefore, it is necessary first to characterize each target object sufficiently by a precursor mission to design the mission which then interacts with the object. In small solar system body (SSSB) science missions, this trend towards landing and sample-return missions is most apparent. It also has led to much interest in MASCOT-like landing modules and instrument carriers. They integrate at the instrument level to their mothership and by their size are compatible even with small interplanetary missions. The DLR-ESTEC Gossamer Roadmap NEA Science Working Groups‘ studies identified Multiple NEA Rendezvous (MNR) as one of the space science missions only feasible with solar sail propulsion. Parallel studies of Solar Polar Orbiter (SPO) and Displaced L1 (DL1) space weather early warning missions studies outlined very lightweight sailcraft and the use of separable payload modules for operations close to Earth as well as the ability to access any inclination and a wide range of heliocentric distances. These and many other studies outline the unique capability of solar sails to provide access to all SSSB, at least within the orbit of Jupiter. Since the original MNR study, significant progress has been made to explore the performance envelope of near-term solar sails for multiple NEA rendezvous. However, although it is comparatively easy for solar sails to reach and rendezvous with objects in any inclination and in the complete range of semi-major axis and eccentricity relevant to NEOs and PHOs, it remains notoriously difficult for sailcraft to interact physically with a SSSB target object as e.g. the Hayabusa missions do. The German Aerospace Center, DLR, recently brought the Gossamer solar sail deployment technology to qualification status in the Gossamer-1 project. Development of closely related technologies is continued for very large deployable membrane-based photovoltaic arrays in the GoSolAr project. We expand the philosophy of the Gossamer solar sail concept of efficient multiple sub-spacecraft integration to also include landers for one-way in-situ investigations and sample-return missions. These are equally useful for planetary defence scenarios, SSSB science and NEO utilization. We outline the technological concept used to complete such missions and the synergetic integration and operation of sail and lander. We similarly extend the philosophy of MASCOT and use its characteristic features as well as the concept of Constraints-Driven Engineering for a wider range of operations

Small Spacecraft Based Multiple Near-Earth Asteroid Rendezvous and Landing with Near-Term Solar Sails and ‘Now-Term‘ Technologies

Physical interaction with small solar system bodies (SSSB) is the next step in planetary science, planetary in-situ resource utilization (ISRU), and planetary defense (PD). It requires a broader understanding of the surface properties of the target objects, with particular interest focused on those near Earth. Knowledge of composition, multi-scale surface structure, thermal response, and interior structure is required to design, validate and operate missions addressing these three fields. The current level of understanding is occasionally simplified into the phrase, ”If you’ve seen one asteroid, you’ve seen one asteroid”, meaning that the in-situ characterization of SSSBs has yet to cross the threshold towards a robust and stable scheme of classification. This would enable generic features in spacecraft design, particularly for ISRU and science missions. Currently, it is necessary to characterize any potential target object sufficiently by a dedicated pre-cursor mission to design the mission which then interacts with the object in a complex fashion. To open up strategic approaches, much broader in-depth characterization of potential target objects would be highly desirable. In SSSB science missions, MASCOT-like nano-landers and instrument carriers which integrate at the instrument level to their mothership have met interest. By its size, MASCOT is compatible with small interplanetary missions. The DLR-ESTEC Gossamer Roadmap Science Working Groups‘ studies identified Multiple Near-Earth asteroid (NEA) Rendezvous (MNR) as one of the space science missions only feasible with solar sail propulsion. The Solar Polar Orbiter (SPO) study showed the ability to access any inclination, theDisplaced-L1 (DL1) mission operates close to Earth, where objects of interest to PD and for ISRU reside. Other studies outline the unique capability of solar sails to provide access to all SSSB, at least within the orbit of Jupiter, and significant progress has been made to explore the performance envelope of near-term solar sails for MNR. However, it is difficult for sailcraft to interact physically with a SSSB. We expand and extend the philosophy of the recently qualified DLR Gossamer solar sail deployment technology using efficient multiple sub-spacecraft integration to also include landers for one-way in-situ investigations and sample-return missions by synergetic integration and operation of sail and lander. The MASCOT design concept and its characteristic features have created an ideal counterpart for thisand has already been adapted to the needs of the AIM spacecraft, former part of the NASA-ESA AIDA mission. Designing the combined spacecraft for piggy-back launch accommodation enables low-cost massively parallel access to the NEA population

Solar Sails for Planetary Defense and High-Energy Missions

20 years after the successful ground deployment test of a (20 m)² solar sail at DLR Cologne, and in the light of the upcoming U.S. NEAscout mission, we provide an overview of the progress made since in our mission and hardware design studies as well as the hardware built in the course of our solar sail technology development. We outline the most likely and most efficient routes to develop solar sails for useful missions in science and applications, based on our developed ‘now-term’ and near-term hardware as well as the many practical and managerial lessons learned from the DLR-ESTEC GOSSAMER Roadmap. Mission types directly applicable to planetary defense include single and Multiple NEA Rendezvous ((M)NR) for precursor, monitoring and follow-up scenarios as well as sail-propelled head-on retrograde kinetic impactors (RKI) for mitigation. Other mission types such as the Displaced L1 (DL1) space weather advance warning and monitoring or Solar Polar Orbiter (SPO) types demonstrate the capability of near-term solar sails to achieve asteroid rendezvous in any kind of orbit, from Earth-coorbital to extremely inclined and even retrograde orbits. Some of these mission types such as SPO, (M)NR and RKI include separable payloads. For one-way access to the asteroid surface, nanolanders like MASCOT are an ideal match for solar sails in micro-spacecraft format, i.e. in launch configurations compatible with ESPA and ASAP secondary payload platforms. Larger landers similar to the JAXA-DLR study of a Jupiter Trojan asteroid lander for the OKEANOS mission can shuttle from the sail to the asteroids visited and enable multiple NEA sample-return missions. The high impact velocities and re-try capability achieved by the RKI mission type on a final orbit identical to the target asteroid‘s but retrograde to its motion enables small spacecraft size impactors to carry sufficient kinetic energy for deflection

A gain-of-function variant in <i>DIAPH1 </i>causes dominant macrothrombocytopenia and hearing loss

Macrothrombocytopenia (MTP) is a heterogeneous group of disorders characterized by enlarged and reduced numbers of circulating platelets, sometimes resulting in abnormal bleeding. In most MTP, this phenotype arises because of altered regulation of platelet formation from megakaryocytes (MK). We report the identification of DIAPH1, which encodes the Rho-effector diaphanous-related formin 1 (DIAPH1), as a candidate gene for MTP using exome sequencing, ontological phenotyping and similarity regression. We describe two unrelated pedigrees with MTP and sensorineural hearing loss that segregate with a DIAPH1 p.R1213* variant predicting partial truncation of the DIAPH1 diaphanous autoregulatory domain. The R1213* variant was associated with reduced proplatelet formation from cultured MKs, cell clustering and abnormal cortical filamentous actin. Similarly, in platelets there was increased filamentous actin and stable microtubules, indicating constitutive activation of DIAPH1. Over-expression of DIAPH1 R1213* in cells reproduced the cytoskeletal alterations found in platelets. Our description of a novel disorder of platelet formation and hearing loss extends the repertoire of DIAPH1-related disease and provides new insights into the autoregulation of DIAPH1 activity