TY - JOUR A1 - Maiwald, Michael T1 - Integrated and Networked Systems and Processes—A Perspective for Digital Transformation in Thermal Process Engineering N2 - Separation technology as a sub-discipline of thermal process engineering is one of the most critical steps in the production of chemicals, essential for the quality of intermediate and end products. The discipline comprises the construction of facilities that convert raw materials into value-added products along the value chain. Conversions typically take place in repeated reaction and separation steps—either in batch or continuous processes. The end products are the result of several production and separation steps that are not only sequentially linked, but also include the treatment of unused raw materials, by-products and wastes. Production processes in the process industry are particularly susceptible to fluctuations in raw materials and other influences affecting product quality. This is a challenge, despite increasing fluctuations, to deliver targeted quality and simultaneously meet the increasing dynamics of the market, at least for high value fine chemicals. In order to survive successfully in a changed environment, chemical companies must tread new paths. This includes the potential of digital technologies. The full integration and intelligent networking of systems and processes is progressing hesitantly. This contribution aims to encourage a more holistic approach to the digitalization in thermal process engineering by introduction of integrated and networked systems and processes. KW - Smarter Sensor KW - Digitalisation KW - Digital transformation KW - Process Industry KW - Thermal Process Engineering KW - Digital Twins PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-504964 DO - https://doi.org/10.3390/chemengineering4010015 SN - 2305-7084 VL - 4 IS - 15 SP - 1 EP - 9 PB - MDPI CY - Basel AN - OPUS4-50496 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Gottu Mukkula, A. R. A1 - Kern, Simon A1 - Salge, M. A1 - Holtkamp, M. A1 - Guhl, Svetlana A1 - Fleischer, C. A1 - Meyer, Klas A1 - Remelhe, M. A1 - Maiwald, Michael A1 - Engell, S. T1 - An Application of Modifier Adaptation with Quadratic Approximation on a Pilot Scale Plant in Industrial Environment N2 - The goal of this work is to identify the optimal operating input for a lithiation reaction that is performed in a highly innovative pilot scale continuous flow chemical plant in an industrial environment, taking into account the process and safety constraints. The main challenge is to identify the optimum operation in the absence of information about the reaction mechanism and the reaction kinetics. We employ an iterative real-time optimization scheme called modifier adaptation with quadratic approximation (MAWQA) to identify the plant optimum in the presence of plant-model mismatch and measurement noise. A novel NMR PAT-sensor is used to measure the concentration of the reactants and of the product at the reactor outlet. The experiment results demonstrate the capabilities of the iterative optimization using the MAWQA algorithm in driving a complex real plant to an economically optimal operating point in the presence of plant-model mismatch and of process and measurement uncertainties. KW - Process Analytical Technology KW - Online NMR Spectroscopy KW - Process Industry KW - Iterative real-time optimization KW - Modifier adaptation KW - Plant-model mismatch KW - Reactor control KW - CONSENS PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-524531 DO - https://doi.org/10.1016/j.ifacol.2020.12.685 SN - 1522-2640 VL - 53 IS - 2 SP - 11773 EP - 11779 PB - Elsevier CY - Amsterdam AN - OPUS4-52453 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Rosenkranz, D. A1 - Kriegel, F. L. A1 - Mavrakis, E. A1 - Pergantis, S. A. A1 - Reichardt, P. A1 - Tentschert, J. A1 - Jakubowski, N. A1 - Laux, P. A1 - Panne, Ulrich A1 - Luch, A. T1 - Versatile dual-inlet sample introduction system for multi-mode single particle inductively coupled plasma mass spectrometry N2 - Metal-containing nanoparticles (NP) can be characterized with inductively coupled plasma mass spectrometers (ICP-MS) in terms of their size and number concentration by using the single-particle mode of the instrument (spICP-MS). The accuracy of measurement depends on the setup, operational conditions of the instrument and specific parameters that are set by the user. The transport efficiency of the ICP-MS is crucial for the quantification of the NP and usually requires a reference material with homogenous size distribution and a known particle number concentration. Currently, NP reference materials are available for only a few metals and in limited sizes. If particles are characterized without a reference standard, the results of both size and particle number may be biased. Therefore, a dual-inlet Setup for characterizing nanoparticles with spICP-MS was developed to overcome this problem. This setup is based on a conventional introduction system consisting of a pneumatic nebulizer (PN) for nanoparticle solutions and a microdroplet Generator (μDG) for ionic calibration solutions. A new and flexible interface was developed to facilitate the coupling of μDG, PN and the ICP-MS system. The interface consists of available laboratory components and allows for the calibration, nanoparticle (NP) characterization and cleaning of the arrangement, while the ICP-MS instrument is still running. Three independent analysis modes are available for determining particle size and number concentration. Each mode is based on a different calibration principle. While mode I (counting) and mode III (μDG) are known from the literature, mode II (sensitivity), is used to determine the transport efficiency by inorganic ionic Standard solutions only. It is independent of NP reference materials. The μDG based inlet system described here guarantees superior analyte sensitivities and, therefore, lower detection limits (LOD). The size dependent LODs achieved are less than 15 nm for all NP (Au, Ag, CeO2) investigated. KW - Spectrometer KW - Reference KW - Calibration PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-536121 DO - https://doi.org/10.3791/61653 SN - 1940-087X IS - 163 SP - 1 EP - 19 PB - MyJoVE Corporation CY - Cambridge, MA, USA AN - OPUS4-53612 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Santos, C.I.L. A1 - Machado, W.S. A1 - Wegner, Karl David A1 - Gontijo, L.A.P. A1 - Bettini, J. A1 - Schiavon, M.A. A1 - Reiss, P. A1 - Aldakov, D. T1 - Hydrothermal Synthesis of Aqueous-Soluble Copper Indium Sulfide Nanocrystals and Their Use in Quantum Dot Sensitized Solar Cells N2 - facile hydrothermal method to synthesize water-soluble copper indium sulfide (CIS) nanocrystals (NCs) at 150 degrees C is presented. The obtained samples exhibited three distinct photoluminescence peaks in the red, green and blue spectral regions, corresponding to three size fractions, which could be separated by means of size-selective precipitation. While the red and green emitting fractions consist of 4.5 and 2.5 nm CIS NCs, the blue fraction was identified as in situ formed carbon nanodots showing excitation wavelength dependent emission. When used as light absorbers in quantum dot sensitized solar cells, the individual green and red fractions yielded power conversion efficiencies of 2.9% and 2.6%, respectively. With the unfractionated samples, the efficiency values approaching 5% were obtained. This improvement was mainly due to a significantly enhanced photocurrent arising from complementary panchromatic absorption. KW - Aqueous quantum dot KW - Solar cells KW - CUINS2 nanocrystals KW - Colloidal semiconductor nanocrystals PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-517983 DO - https://doi.org/10.3390/nano10071252 VL - 10 IS - 7 SP - 1252 PB - MDPI AN - OPUS4-51798 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Bhuckory, S. A1 - Wegner, Karl David A1 - Qiu, X. A1 - Wu, Y.T. A1 - Jennings, T. L. A1 - Incamps, A. A1 - Hildebrandt, N. T1 - Triplexed CEA-NSE-PSA Immunoassay Using Time-Gated Terbium-to-Quantum Dot FRET N2 - Time-gated Förster resonance energy transfer (TG-FRET) between Tb complexes and luminescent semiconductor quantum dots (QDs) provides highly advantageous photophysical properties for multiplexed biosensing. Multiplexed Tb-to-QD FRET immunoassays possess a large potential for in vitro diagnostics, but their performance is often insufficient for their application under clinical conditions. Here, we developed a homogeneous TG-FRET immunoassay for the quantification of carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and prostatespecific antigen (PSA) from a single serum sample by multiplexed Tb-to-QD FRET. Tb–IgG antibody donor conjugates were combined with compact QD-F(ab’)2 antibody acceptor conjugates with three different QDs emitting at 605, 650, and 705 nm. Upon antibody–antigen–antibody Sandwich complex formation, the QD acceptors were sensitized via FRET from Tb, and the FRET ratios of QD and Tb TG luminescence intensities increased specifically with increasing antigen concentrations. Although limits of detection (LoDs: 3.6 ng/mL CEA, 3.5 ng/mL NSE, and 0.3 ng/mL PSA) for the triplexed assay were slightly higher compared to the single-antigen assays, they were still in a clinically relevant concentration range and could be quantified in 50 μL serum samples on a B·R·A·H·M·S KRYPTOR Compact PLUS clinical immunoassay plate reader. The simultaneous quantification of CEA, NSE, and PSA at different concentrations from the same serum sample demonstrated actual multiplexing Tb-to-QD FRET immunoassays and the potential of this technology for translation into clinical diagnostics. KW - Lanthanides KW - Nanoparticles KW - Biosensing KW - Multiplexing KW - FRET KW - Fluorescence KW - PSA KW - NSE KW - CEA PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-512290 DO - https://doi.org/10.3390/molecules25163679 VL - 25 IS - 16 SP - 3679 PB - MDPI AN - OPUS4-51229 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Kalot, G. A1 - Godard, A. A1 - Busser, B. A1 - Pliquett, J. A1 - Broekgaarden, M. A1 - Motto-Ros, V. A1 - Wegner, Karl David A1 - Resch-Genger, Ute A1 - Köster, U. A1 - Denat, F. A1 - Coll, J.-L. A1 - Bodio, E. A1 - Goze, C. A1 - Sancey, L. T1 - Aza-BODIPY: A New Vector for Enhanced Theranostic Boron Neutron Capture Therapy Applications N2 - Boron neutron capture therapy (BNCT) is a radiotherapeutic modality based on the nuclear capture of slow neutrons by stable 10B atoms followed by charged particle Emission that inducing extensive damage on a very localized level (<10 um). To be effcient, a suffcient amount of 10B should accumulate in the tumor area while being almost cleared from the normal surroundings. A water-soluble aza-boron-dipyrromethene dyes (BODIPY) fluorophore was reported to strongly accumulate in the tumor area with high and BNCT compatible Tumor/Healthy Tissue ratios. The clinically used 10B-BSH (sodium borocaptate) was coupled to the water-soluble aza-BODIPY platform for enhanced 10B-BSH tumor vectorization. We demonstrated a strong uptake of the compound in tumor cells and determined its biodistribution in mice-bearing tumors. A model of chorioallantoic membrane-bearing glioblastoma xenograft was developed to evidence the BNCT potential of such compound, by subjecting it to slow neutrons. We demonstrated the Tumor accumulation of the compound in real-time using optical imaging and ex vivo using elemental imaging based on laser-induced breakdown spectroscopy. The tumor growth was significantly reduced as compared to BNCT with 10B-BSH. Altogether, the fluorescent aza-BODIPY/10B-BSH compound is able to vectorize and image the 10B-BSH in the tumor area, increasing its theranostic potential for effcient approach of BNCT. KW - Aza-BODIPY KW - SWIR KW - NIR-I KW - Theranostic KW - Boron compound KW - Optical imaging PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-512280 DO - https://doi.org/10.3390/cells9091953 VL - 9 IS - 9 SP - 1953 PB - MDPI AN - OPUS4-51228 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Soares, J. X. A1 - Wegner, Karl David A1 - Ribeiro, D. S. M. A1 - Melo, A. A1 - Häusler, I. A1 - Santos, J. L. M. A1 - Resch-Genger, Ute T1 - Rationally designed synthesis of bright AgInS2/ZnS quantum dots with emission control N2 - In the blossoming field of Cd-free semiconductor quantum dots (QDs), ternary I–III–VI QDs have received increasing attention due to the ease of the environmentally friendly synthesis of high-quality materials in water, their high photoluminescence (PL) Quantum yields (QYs) in the red and near infrared (NIR) region, and their inherently low toxicity. Moreover, their oxygen-insensitive long PL lifetimes of up to several hundreds of nanoseconds close a gap for applications exploiting the compound-specific parameter PL lifetime. To overcome the lack of reproducible synthetic methodologies and to enable a design-based control of their PL properties, we assessed and modelled the synthesis of high-quality MPA-capped AgInS2/ZnS (AIS/ZnS) QDs. Systematically refined Parameters included reaction time, temperature, Ag:In ratio, S:In ratio, Zn:In ratio, MPA:In ratio, and pH using a design-of-experiment approach. Guidance for the optimization was provided by mathematical models developed for the application-relevant PL parameters, maximum PL wavelength, QY, and PL lifetime as well as the elemental composition in terms of Ag:In:Zn ratio. With these experimental data-based models, MPA:In and Ag:In ratios and pH values were identified as the most important synthesis parameters for PL Control and an insight into the connection of these parameters could be gained. Subsequently, the experimental conditions to synthetize QDs with tunable emission and high QY were predicted. The excellent agreement between the predicted and experimentally found PL features confirmed the reliability of our methodology for the rational design of high quality AIS/ZnS QDs with defined PL features. This approach can be straightforwardly extended to other ternary and quaternary QDs and to doped QDs. KW - Modelling KW - Nanoparticle KW - AIS KW - Semiconductor quantum dot KW - Design of experiment KW - Photoluminescence KW - Quantum yield KW - Surface chemistry KW - Synthesis KW - Lifetime PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-510075 DO - https://doi.org/10.1007/s12274-020-2876-8 VL - 13 IS - 9 SP - 2438 EP - 2450 PB - Springer AN - OPUS4-51007 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Raysyan, Anna A1 - Moerer, R. A1 - Coesfeld, Bianca A1 - Eremin, S. A1 - Schneider, Rudolf T1 - Fluorescence polarization immunoassay for the determination of diclofenac in wastewater N2 - Pharmacologically active compounds are often detected in wastewater and surface waters. The nonsteroidal anti-inflammatory drug diclofenac (DCF) was included in the European watch list of substances that requires its environmental monitoring in the member states. DCF may harmfully influence the ecosystem already at concentrations ≤ 1 μg L−1. The fast and easy quantification of DCF is becoming a subject of global importance. Fluorescence polarization immunoassay (FPIA) is a homogeneous mix-and-read method which does not require the immobilization of reagents. FPIA can be performed in one phase within 20–30 min, making it possible to analyse wastewater without any complicated pre-treatment. In this study, new tracermolecules with different structures, linking fluorophores to derivatives of the analyte, were synthesized, three homologous tracers based on DCF, two including a C6 spacer, and one heterologous tracer derived from 5-hydroxy-DCF. The tracer molecules were thoroughly assessed for performance. Regarding sensitivity of the FPIA, the lowest limit of detection reached was 2.0 μg L−1 with a working range up to 870 μg L−1. The method was validated for real wastewater samples against LC-MS/MS as reference method with good agreement of both methods. KW - Abwasser KW - Umweltschadstoffe KW - Antikörper KW - Antibody PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-518398 DO - https://doi.org/10.1007/s00216-020-03058-w SN - 1618-2642 VL - 413 IS - 4 SP - 999 EP - 107 PB - Springer CY - Heidelberg AN - OPUS4-51839 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Paul, Martin A1 - Weller, Michael G. T1 - Antibody Screening by Microarray Technology - Direct Identification of Selective High-Affinity Clones N2 - The primary screening of hybridoma cells is a time-critical and laborious step during the development of monoclonal antibodies. Often, critical errors occur in this phase, which supports the notion that the generation of monoclonal antibodies with hybridoma technology is difficult to control and hence, a risky venture. We think that it is crucial to improve the screening process to eliminate most of the critical deficits of the conventional approach. With this new microarray-based procedure, several advances could be achieved: Selectivity for excellent binders, high-throughput, reproducible signals, avoidance of misleading avidity (multivalency) effects, and performance of simultaneous competition experiments. The latter can also be used to select clones of desired cross-reactivity properties. In this paper, a model system with two excellent clones against carbamazepine, two weak clones, and blank supernatant containing fetal bovine serum was designed to examine the effectiveness of the new system. The excellent clones could be detected largely independent of the immunoglobulin G (IgG) concentration, which is usually unknown during the clone screening since the determination and subsequent adjustment of the antibody concentration are not feasible in most cases. Furthermore, in this approach, the enrichment, isolation, and purification of IgG for characterization is not necessary. Raw cell culture supernatant can be used directly, even when fetal calf serum (FCS) or other complex media is used. In addition, an improved method for the oriented antibody-immobilization on epoxy-silanized slides is presented. Based on the results of this model system with simulated hybridoma supernatants, we conclude that this approach should be preferable to most other protocols leading to many false positives, causing expensive and lengthy elimination steps to weed out the poor clones. KW - ELISA KW - Immunoassay KW - Microarray KW - Lab-on-a-chip KW - Miniaturization KW - Aautomatisation KW - HTS KW - High-throughput KW - Screening KW - Fluorescence KW - Label KW - Hybridoma KW - Inhibition PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-503361 DO - https://doi.org/10.3390/antib9010001 SN - 2073-4468 VL - 9 IS - 1 SP - 1 EP - 16 PB - MDPI CY - Basel AN - OPUS4-50336 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Paul, Martin A1 - Tscheuschner, Georg A1 - Herrmann, Stefan A1 - Weller, Michael G. T1 - Fast Detection of 2,4,6-Trinitrotoluene (TNT) at ppt Level by a Laser-Induced Immunofluorometric Biosensor N2 - The illegal use of explosives by terrorists and other criminals is an increasing issue in public spaces, such as airports, railway stations, highways, sports venues, theaters, and other large buildings. Security in these environments can be achieved by different means, including the installation of scanners and other analytical devices to detect ultra-small traces of explosives in a very short time-frame to be able to take action as early as possible to prevent the detonation of such devices. Unfortunately, an ideal explosive detection system still does not exist, which means that a compromise is needed in practice. Most detection devices lack the extreme analytical sensitivity, which is nevertheless necessary due to the low vapor pressure of nearly all explosives. In addition, the rate of false positives needs to be virtually zero, which is also very difficult to achieve. Here we present an immunosensor system based on kinetic competition, which is known to be very fast and may even overcome affinity limitation, which impairs the performance of many traditional competitive assays. This immunosensor consists of a monolithic glass column with a vast excess of immobilized hapten, which traps the fluorescently labeled antibody as long as no explosive is present. In the case of the explosive 2,4,6-trinitrotoluene (TNT), some binding sites of the antibody will be blocked, which leads to an immediate breakthrough of the labeled protein, detectable by highly sensitive laser-induced fluorescence with the help of a Peltier-cooled complementary metal-oxide-semiconductor (CMOS) camera. Liquid handling is performed with high-precision syringe pumps and chip-based mixing-devices and flow-cells. The system achieved limits of detection of 1 pM (1 ppt) of the fluorescent label and around 100 pM (20 ppt) of TNT. The total assay time is less than 8 min. A cross-reactivity test with 5000 pM solutions showed no signal by pentaerythritol tetranitrate (PETN), 1,3,5-trinitroperhydro-1,3,5-triazine (RDX), and octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX). This immunosensor belongs to the most sensitive and fastest detectors for TNT with no significant cross-reactivity by non-related compounds. The consumption of the labeled antibody is surprisingly low: 1 mg of the reagent would be sufficient for more than one year of continuous biosensor operation. KW - Airport KW - Aviation KW - Bombs KW - Terrorism KW - Biosensing KW - Continuous Sensor KW - High-Speed KW - Ultrasensitive PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-511245 DO - https://doi.org/10.3390/bios10080089 VL - 10 IS - 8 SP - 89 PB - MDPI CY - Basel AN - OPUS4-51124 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Tscheuschner, Georg A1 - Schwaar, Timm A1 - Weller, Michael G. T1 - Fast Confirmation of Antibody Identity by MALDI-TOF MS Fingerprints N2 - Thousands of antibodies for diagnostic and other analytical purposes are on the market. However, it is often difficult to identify duplicates, reagent changes, and to assign the correct original publications to an antibody. This slows down scientific progress and might even be a cause of irreproducible research and a waste of resources. Recently, activities were started to suggest the sole use of recombinant antibodies in combination with the open communication of their sequence. In this case, such uncertainties should be eliminated. Unfortunately, this approach seems to be rather a long-term vision since the development and manufacturing of recombinant antibodies remain quite expensive in the foreseeable future. Nearly all commercial antibody suppliers also may be reluctant to publish the sequence of their antibodies, since they fear counterfeiting. De novo sequencing of antibodies is also not feasible today for a reagent user without access to the hybridoma clone. Nevertheless, it seems to be crucial for any scientist to have the opportunity to identify an antibody undoubtedly to guarantee the traceability of any research activity using antibodies from a third party as a tool. For this purpose, we developed a method for the identification of antibodies based on a MALDI-TOF MS fingerprint. To circumvent lengthy denaturation, reduction, alkylation, and enzymatic digestion steps, the fragmentation was performed with a simple formic acid hydrolysis step. Eighty-nine unknown monoclonal antibodies were used for this study to examine the feasibility of this approach. Although the molecular assignment of peaks was rarely possible, antibodies could be easily recognized in a blinded test, simply from their mass-spectral fingerprint. A general protocol is given, which could be used without any optimization to generate fingerprints for a database. We want to propose that, in most scientific projects relying critically on antibody reagents, such a fingerprint should be established to prove and document the identity of the used antibodies, as well as to assign a specific reagent to a datasheet of a commercial supplier, public database record, or antibody ID. KW - Reproducibility KW - Quality Control KW - Traceability KW - Diagnostics KW - Hybridoma KW - Monoclonal Antibody KW - Recombinant Antibody PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-506611 DO - https://doi.org/10.3390/antib9020008 SN - 2310-287X VL - 9 IS - 2 SP - 1 EP - 17 PB - MDPI CY - Basel AN - OPUS4-50661 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Brangsch, J. A1 - Reimann, C. A1 - Kaufmann, Jan Ole A1 - Adams, L. C. A1 - Onthank, D. A1 - Thöne-Reineke, C. A1 - Robinson, S. A1 - Wilke, Marco A1 - Weller, Michael G. A1 - Buchholz, R. A1 - Karst, U. A1 - Botnar, R. A1 - Hamm, B. A1 - Makowski, M. R. T1 - Molecular MR-Imaging for Noninvasive Quantification of the Anti-Inflammatory Effect of Targeting Interleukin-1β in a Mouse Model of Aortic Aneurysm N2 - Background: Molecular-MRI is a promising imaging modality for the assessment of abdominal aortic aneurysms (AAAs). Interleukin-1β (IL-1β) represents a new therapeutic tool for AAA-treatment, since pro-inflammatory cytokines are key-mediators of inflammation. This study investigates the potential of molecular-MRI to evaluate therapeutic effects of an anti-IL-1β-therapy on AAA-formation in a mouse-model. Methods: Osmotic-minipumps were implanted in apolipoprotein-deficient-mice (N = 27). One group (Ang-II+01BSUR group, n = 9) was infused with angiotensin-II (Ang-II) for 4 weeks and received an anti-murine IL-1β-antibody (01BSUR) 3 times. One group (Ang-II-group, n = 9) was infused with Ang-II for 4 weeks but received no treatment. Control-group (n = 9) was infused with saline and received no treatment. MR-imaging was performed using an elastin-specific gadolinium-based-probe (0.2 mmol/kg). Results: Mice of the Ang-II+01BSUR-group showed a lower aortic-diameter compared to mice of the Ang-II-group and control mice (p < 0.05). Using the elastin-specific-probe, a significant decrease in elastin-destruction was observed in mice of the Ang-II+01BSUR-group. In vivo MR-measurements correlated well with histopathology (y = 0.34x-13.81, R2 = 0.84, p < 0.05), ICP-MS (y = 0.02x+2.39; R2 = 0.81, p < 0.05) and LA-ICP-MS. Immunofluorescence and western-blotting confirmed a reduced IL-1β-expression. Conclusions: Molecular-MRI enables the early visualization and quantification of the anti-inflammatory-effects of an IL-1β-inhibitor in a mouse-model of AAAs. Responders and non-responders could be identified early after the initiation of the therapy using molecular-MRI. KW - Cardiovascular KW - Molecular-MRI KW - Magnetic resonance imaging KW - Gadolinium-based contrast agent KW - Elastin-specific contrast agent ESMA KW - Gadovist KW - Gadofosveset KW - MR Angiography KW - Inductively Coupled Mass Spectroscopy KW - Element Specific Bioimaging Using Laser Ablation KW - Visualization PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-517150 DO - https://doi.org/10.1177/1536012120961875 VL - 19 SP - 61875 PB - SAGE AN - OPUS4-51715 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - GEN A1 - Tscheuschner, Georg A1 - Schwaar, Timm A1 - Weller, Michael G. T1 - Fast Confirmation of Antibody Identity by MALDI-TOF-MS Fingerprints N2 - Thousands of antibodies for diagnostic and other analytical purposes are on the market. However, it is often difficult to identify duplicates, reagent changes, and to assign the correct original publications to an antibody. This slows down scientific progress and might even be a cause of irreproducible research and a waste of resources. Recently, activities were started to suggest the sole use of recombinant antibodies in combination with the open communication of their sequence. In this case, such uncertainties should be eliminated. Unfortunately, this approach seems to be rather a long-term vision since the development and manufacturing of recombinant antibodies remain quite expensive in the foreseeable future. Also, nearly all commercial antibody suppliers may be reluctant to publish the sequence of their antibodies, since they fear counterfeiting. De-novo sequencing of antibodies is also not feasible today for a reagent user without access to the hybridoma clone. Nevertheless, it seems to be crucial for any scientist to have the opportunity to identify an antibody undoubtedly to guarantee the traceability of any research activity using antibodies from a third party as a tool. For this purpose, we developed a method for the identification of antibodies based on a MALDI-TOF-MS fingerprint. To circumvent lengthy denaturation, reduction, alkylation, and enzymatic digestion steps, the fragmentation was performed with a simple formic acid hydrolysis step. Eighty-nine unknown monoclonal antibodies were used for this study to examine the feasibility of this approach. Although the molecular assignment of peaks was rarely possible, antibodies could be easily recognized in a blinded test, simply from their mass-spectral fingerprint. A general protocol is given, which could be used without any optimization to generate fingerprints for a database. We want to propose that in most scientific projects relying critically on antibody reagents, such a fingerprint should be established to prove and document the identity of the used antibodies and to assign a specific reagent to a datasheet of a commercial supplier, a public database record or an antibody ID. KW - Reproducibility KW - Quality Control KW - Traceability KW - Diagnostics KW - ELISA KW - Immunoassay PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-506590 DO - https://doi.org/10.20944/preprints202002.0207.v1 SN - 2310-287X SP - 1 EP - 17 PB - MDPI CY - Basel AN - OPUS4-50659 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Steglich, P. A1 - Bondarenko, S. A1 - Mai, C. A1 - Paul, Martin A1 - Weller, Michael G. A1 - Mai, A. T1 - CMOS-Compatible Silicon Photonic Sensor for Refractive Index Sensing Using Local Back-Side Release N2 - Silicon photonic sensors are promising candidates for lab-on-a-chip solutions with versatile applications and scalable production prospects using complementary metal-oxide semiconductor (CMOS) fabrication methods. However, the widespread use has been hindered because the sensing area adjoins optical and electrical components making packaging and sensor handling challenging. In this work, a local back-side release of the photonic sensor is employed, enabling a separation of the sensing area from the rest of the chip. This approach allows preserving the compatibility of photonic integrated circuits in the front-end of line and metal interconnects in the back-end of line. The sensor is based on a micro-ring resonator and is fabricated on wafer-level using a CMOS technology. We revealed a ring resonator sensitivity for homogeneous sensing of 106 nm/RIU. KW - Photonic biosensor KW - Lab-on-a-chip KW - Ring resonator KW - Resonance wavelength shift KW - PIC technology KW - Back-side integration PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-517139 DO - https://doi.org/10.1109/LPT.2020.3019114 VL - 32 IS - 19 SP - 1241 EP - 1244 PB - IEEE AN - OPUS4-51713 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Adams, L. C. A1 - Brangsch, J. A1 - Reimann, C. A1 - Kaufmann, Jan Ole A1 - Buchholz, R. A1 - Karst, U. A1 - Botnar, R. M. A1 - Hamm, B. A1 - Makowski, M. R. T1 - Simultaneous molecular MRI of extracellular matrix collagen and inflammatory activity to predict abdominal aortic aneurysm rupture N2 - Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with an up to 80% mortality in case of rupture. Current biomarkers fail to account for size-independent risk of rupture. By combining the information of different molecular probes, multi-target molecular MRI holds the potential to enable individual characterization of AAA. In this experimental study, we aimed to examine the feasibility of simultaneous imaging of extracellular collagen and inflammation for size-independent prediction of risk of rupture in murine AAA. The study design consisted of: (1) A outcome-based longitudinal study with imaging performed once after one week with follow-up and death as the end-point for assessment of rupture risk. (2) A week-by-week study for the characterization of AAA development with imaging after 1, 2, 3 and 4 weeks. For both studies, the animals were administered a type 1 collagen-targeted gadolinium-based probe (surrogate marker for extracellular matrix (ECM) remodeling) and an iron oxide-based probe (surrogate marker for inflammatory activity), in one imaging session. In vivo measurements of collagen and iron oxide probes showed a significant correlation with ex vivo histology (p < 0.001) and also corresponded well to inductively-coupled plasma-mass spectrometry and laser-ablation inductively-coupled plasma mass spectrometry. Combined evaluation of collagen-related ECM remodeling and inflammatory activity was the most accurate predictor for AAA rupture (sensitivity 80%, specificity 100%, area under the curve 0.85), being superior to information from the individual probes alone. Our study supports the feasibility of a simultaneous assessment of collagen-related extracellular matrix remodeling and inflammatory activity in a murine model of AAA. KW - Atherosclerosis KW - Specific probe KW - Magnetic resonance imaging KW - Gadolinium KW - Iron oxide KW - Ferumoxytol KW - Inductively‑coupled mass spectrometry KW - ICP-MS KW - LA-ICP-MS KW - Laser ablation PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-525864 UR - https://www.nature.com/articles/s41598-020-71817-x DO - https://doi.org/10.1038/s41598-020-71817-x VL - 10 IS - 1 SP - 15206 PB - Springer Nature Limited CY - London, New York, Berlin, Shanghai and Tokyo AN - OPUS4-52586 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Adams, L. C. A1 - Brangsch, J. A1 - Reimann, C. A1 - Kaufmann, Jan Ole A1 - Nowak, K. A1 - Buchholz, R. A1 - Karst, U. A1 - Botnar, R. M. A1 - Hamm, B. A1 - Makowski, M. R. T1 - Noninvasive imaging of vascular permeability to predict the risk of rupture in abdominal aortic aneurysms using an albumin binding probe N2 - Abdominal aortic aneurysm (AAA) remains a fatal disease. Its development encompasses a complex interplay between hemodynamic stimuli on and changes in the arterial wall. Currently available biomarkers fail to predict the risk of AAA rupture independent of aneurysm size. Therefore, novel biomarkers for AAA characterization are needed. In this study, we used a mouse model of AAA to investigate the potential of magnetic resonance imaging (MRI) with an albumin-binding probe to assess changes in vascular permeability at different stages of aneurysm growth. Two imaging studies were performed: a longitudinal study with follow-up and death as endpoint to predict rupture risk and a week-by-week study to characterize AAA development. AAAs, which eventually ruptured, demonstrated a significantly higher in vivo MR signal enhancement from the albumin-binding probe (p = 0.047) and a smaller non-enhancing thrombus area compared to intact AAAs (p = 0.001). The ratio of albumin-binding-probe enhancement of the aneurysm wall to size of non-enhancing-thrombus-area predicted AAA rupture with high sensitivity/specificity (100%/86%). More advanced aneurysms with higher vascular permeability demonstrated an increased uptake of the albumin-binding-probe. These results indicate that MRI with an albumin-binding probe may enable noninvasive assessment of vascular permeability in murine AAAs and prediction of rupture risk. KW - Magnetic resonance imaging KW - Imaging KW - Tomography KW - Gadolinium KW - Contrast agent KW - Atherosclerosis KW - ICP-MS KW - Gadofosveset KW - Angiography KW - LA-ICP-MS PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-525541 DO - https://doi.org/10.1038/s41598-020-59842-2 VL - 10 SP - Article number: 3231 PB - Springer Nature Limited CY - London, New York, Berlin, Shanghai and Tokyo AN - OPUS4-52554 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Keller, S. A1 - Borde, T. A1 - Brangsch, J. A1 - Reimann, C. A1 - Kader, A. A1 - Schulze, D. A1 - Buchholz, R. A1 - Kaufmann, Jan Ole A1 - Karst, U. A1 - Schellenberger, E. A1 - Hamm, B. A1 - Makowski, M. R. T1 - Assessment of the hepatic tumor extracellular matrix using elastin‑specific molecular magnetic resonance imaging in an experimental rabbit cancer model N2 - To investigate the imaging performance of an elastin-specific molecular magnetic resonance imaging (MRI) probe with respect to the extracellular matrix (ECM) in an experimental hepatic cancer model. Twelve rabbits with hepatic VX2 tumors were examined using 3 T MRI 14, 21, and 28 days after tumor implantation for two subsequent days (gadobutrol, day 1; elastin-specific probe, day 2). The relative enhancement (RE) of segmented tumor regions (central and margin) and the peritumoral matrix was calculated using pre-contrast and delayed-phase T1w sequences. MRI measurements were correlated to histopathology and element-specific and spatially resolved mass spectrometry (MS). Mixed-model analysis was performed to assess the performance of the elastin-specific probe. In comparison to gadobutrol, the elastin probe showed significantly stronger RE, which was pronounced in the tumor margin (day 14–28: P ≤ 0.007). In addition, the elastin probe was superior in discriminating between tumor regions (χ2(4) = 65.87; P < 0.001). MRI-based measurements of the elastin probe significantly correlated with the ex vivo elastinstain (R = .84; P <0 .001) and absolute gadolinium concentrations (ICP-MS: R = .73, P <0 .01). LA-ICP-MS imaging confirmed the colocalization of the elastin-specific probe with elastic fibers. Elastin-specific molecular MRI is superior to non-specific gadolinium-based contrast agents in imaging the ECM of hepatic tumors and the peritumoral tissue. KW - Elastin-specific molecular agent KW - Extracellular matrix KW - Hepatocellular carcinoma KW - Inductively coupled plasma mass spectroscopy KW - Laser ablation-inductively coupled plasma-mass spectrometry KW - Magnetic resonance imaging KW - MR imaging KW - ESMA KW - Gadolinium PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-517360 DO - https://doi.org/10.1038/s41598-020-77624-8 VL - 10 IS - 1 SP - 20785 PB - Nature AN - OPUS4-51736 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Climent Terol, Estela A1 - Biyikal, Mustafa A1 - Gröninger, Delia A1 - Weller, Michael G. A1 - Martínez Mánez, R. A1 - Rurack, Knut ED - Climent Terol, Estela T1 - Multiplexed Detection of Analytes on Single Test Strips with Antibody-Gated Indicator-Releasing Mesoporous Nanoparticles N2 - Rapid testing methods for the use directly at apointof need are expected to unfold their true potential especiallywhen offering adequate capabilities for the simultaneousmeasurement of multiple analytes of interest. Considering theunique modularity,high sensitivity,and selectivity of antibody-gated indicator delivery (gAID) systems,amultiplexed assayfor three small-molecule explosives (TATP, TNT,PETN) wasthus developed, allowing to detect the analytes simultaneouslywith asingle test strip at lower ppb concentrations in the liquidphase in < 5min using afluorescence reader or asmartphonefor readout. While the TNT and PETN systems were newlydeveloped here,all the three systems also tolerated harshermatrices than buffered aqueous model solutions.Besidesasingle-track strip,the outstanding modularity of the hybridbiosensor materials in combination with strip-patterningtechnologies allowed us to obtain amultichannel strip inastraightforwardmanner,offering comparable analyticalperformance while allowing to be tailored even more to theusersneed. KW - Multiplexing KW - Explosives detection KW - Gated materials KW - Fluorescence PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-518424 DO - https://doi.org/10.1002/anie.202009000 SN - 1433-7851 SN - 1521-3773 VL - 59 IS - 52 SP - 23862 EP - 23869 PB - Wiley-VCH CY - Weinheim AN - OPUS4-51842 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Ziegler, K. A1 - Kunert, A. T. A1 - Reinmuth-Selzle, K. A1 - Leifke, A. L. A1 - Widera, D. A1 - Weller, Michael G. A1 - Schuppan, D. A1 - Fröhlich-Nowoisky, J. A1 - Lucas, K. A1 - Pöschl, U. T1 - Chemical modification of pro-inflammatory proteins by peroxynitrite increases activation of TLR4 and NF-κB: Implications for the health effects of air pollution and oxidative stress N2 - Environmental pollutants like fine particulate matter can cause adverse health effects through oxidative stress and inflammation. Reactive oxygen and nitrogen species (ROS/RNS) such as peroxynitrite can chemically modify proteins, but the effects of such modifications on the immune system and human health are not well understood. In the course of inflammatory processes, the Toll-like receptor 4 (TLR4) can sense damage-associated molecular patterns (DAMPs). Here, we investigate how the TLR4 response and pro-inflammatory potential of the proteinous DAMPs α-Synuclein (α-Syn), heat shock protein 60 (HSP60), and high-mobility-group box 1 protein (HMGB1), which are relevant in neurodegenerative and cardiovascular diseases, changes upon chemical modification with peroxynitrite. For the peroxynitrite-modified proteins, we found a strongly enhanced activation of TLR4 and the pro-inflammatory transcription factor NF-κB in stable reporter cell lines as well as increased mRNA expression and secretion of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-8 in human monocytes (THP-1). This enhanced activation of innate immunity via TLR4 is mediated by covalent chemical modifications of the studied DAMPs. Our results show that proteinous DAMPs modified by peroxynitrite more potently amplify inflammation via TLR4 activation than the native DAMPs, and provide first evidence that such modifications can directly enhance innate immune responses via a defined receptor. These findings suggest that environmental pollutants and related ROS/RNS may play a role in promoting acute and chronic inflammatory disorders by structurally modifying the body's own DAMPs. This may have important consequences for chronic neurodegenerative, cardiovascular or gastrointestinal diseases that are prevalent in modern societies, and calls for action, to improve air quality and climate in the Anthropocene. KW - Protein nitration KW - Protein oligomerization KW - Damage-associated molecular patterns (DAMPs) KW - Pattern recognition receptor KW - Anthropocene KW - Environmental pollutants PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-517128 DO - https://doi.org/10.1016/j.redox.2020.101581 VL - 37 SP - 101581 PB - Elsevier B.V. AN - OPUS4-51712 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Hachenberger, Y. U. A1 - Rosenkranz, D. A1 - Kriegel, Fabian L. A1 - Krause, B. A1 - Matschaß, René A1 - Reichardt, P. A1 - Tentschert, J. A1 - Laux, P. A1 - Jakubowski, Norbert A1 - Panne, Ulrich A1 - Luch, A. T1 - Tackling Complex Analytical Tasks: An ISO/TS-Based Validation Approach for Hydrodynamic Chromatography Single Particle Inductively Coupled Plasma Mass Spectrometry N2 - Nano-carrier systems such as liposomes have promising biomedical applications. Nevertheless, characterization of these complex samples is a challenging analytical task. In this study a coupled hydrodynamic chromatography-single particle-inductively coupled plasma mass spectrometry (HDC-spICP-MS) approach was validated based on the technical specification (TS) 19590:2017 of the international organization for standardization (ISO). The TS has been adapted to the hyphenated setup. The quality criteria (QC), e.g., linearity of the calibration, transport efficiency, were investigated. Furthermore, a cross calibration of the particle size was performed with values from dynamic light scattering (DLS) and transmission electron microscopy (TEM). Due to an additional Y-piece, an online-calibration routine was implemented. This approach allows the calibration of the ICP-MS during the dead time of the chromatography run, to reduce the required time and enhance the robustness of the results. The optimized method was tested with different gold nanoparticle (Au-NP) mixtures to investigate the characterization properties of HDC separations for samples with increasing complexity. Additionally, the technique was successfully applied to simultaneously determine both the hydrodynamic radius and the Au-NP content in liposomes. With the established hyphenated setup, it was possible to distinguish between different subpopulations with various NP loads and different hydrodynamic diameters inside the liposome carriers. KW - Single particle ICP-MS KW - Nanoparticle characterization KW - Nano-carrier KW - Iposomes KW - Hydrodynamic chromatography (HDC) KW - Validation PY - 2020 UR - https://nbn-resolving.org/urn:nbn:de:kobv:b43-506609 DO - https://doi.org/10.3390/ma13061447 VL - 13 IS - 6 SP - 1 EP - 14 CY - Basel, Switzerland AN - OPUS4-50660 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -