Chemische Charakterisierung und Spurenanalytik
Filtern
Dokumenttyp
- Vortrag (367)
- Posterpräsentation (155)
- Zeitschriftenartikel (53)
- Sonstiges (16)
- Beitrag zu einem Tagungsband (13)
- Forschungsdatensatz (7)
- Buchkapitel (6)
- Dissertation (5)
- Forschungsbericht (3)
- Beitrag zu einem Sammelband (1)
Sprache
- Englisch (473)
- Deutsch (152)
- Mehrsprachig (3)
Referierte Publikation
- nein (628) (entfernen)
Schlagworte
- Process Analytical Technology (31)
- Mikroplastik (28)
- ICP-MS (27)
- Synchrotron (27)
- BAMline (23)
- HR-CS-GFMAS (21)
- Laser ablation (21)
- PFAS (20)
- Prozessanalytik (20)
- TED-GC/MS (19)
- Nanoparticle (18)
- XRF (18)
- Metrology (17)
- Benchtop-NMR (15)
- Fluorine (15)
- LIBS (15)
- Online NMR Spectroscopy (15)
- Prozessindustrie (15)
- CONSENS (14)
- HR-CS-MAS (14)
- LA-ICP-MS (14)
- Machine learning (14)
- Traceability (12)
- qNMR (12)
- Automation (11)
- Bioimaging (11)
- Isotope analysis (11)
- Microplastic (11)
- Microplastics (11)
- NMR spectroscopy (11)
- Digitalisierung (10)
- Fluorescence (10)
- Immunoassay (10)
- Soil (10)
- Absolute isotope ratio (9)
- Online NMR spectroscopy (9)
- Online-NMR-Spektroskopie (9)
- XANES (9)
- ELISA (8)
- Imaging (8)
- Isotope (8)
- Isotope ratio (8)
- Magnesium (8)
- Modular Production (8)
- NMR-Spektroskopie (8)
- Optical spectroscopy (8)
- Plasma modeling (8)
- Process Industry (8)
- Reference material (8)
- TED-GC-MS (8)
- Analytik (7)
- Benchtop NMR (7)
- CRM (7)
- Cell (7)
- Datenanalyse (7)
- Isotope dilution (7)
- Lithium (7)
- Mycotoxins (7)
- Per- and Polyfluoroalkyl substances (PFAS) (7)
- Reaction Monitoring (7)
- Reference materials (7)
- Referenzmaterialien (7)
- Single cell analysis (7)
- Uncertainty (7)
- Data Analysis (6)
- Electrochemistry (6)
- GD-OES (6)
- Gold (6)
- HR-CS-AAS (6)
- Industrie 4.0 (6)
- Industry 4.0 (6)
- Isotopes (6)
- Laser induced plasma (6)
- Lithium Ion Batteries (6)
- Mass spectrometry (6)
- Nanoparticles (6)
- Quantitative NMR Spectroscopy (6)
- Speciation analysis (6)
- Transformationsprodukte (6)
- Amperometry (5)
- Capillary electrophoresis (5)
- Copper (5)
- Estrogens (5)
- Extractable organically bound fluorine (EOF) (5)
- GC-MS (5)
- High resolution-continuum source-graphite furnace molecular absorption spectrometry (HR-CS-GFMAS) (5)
- Hydrogen (5)
- ISO-Guide 35 (5)
- Measurement uncertainty (5)
- Per- and polyfluorinated alkyl substances (PFASs) (5)
- Plasma diagnostics (5)
- Process analytical technology (5)
- Surface chemistry (5)
- Umweltsimulation (5)
- VOC (5)
- Analysis (4)
- Antibody (4)
- Antikörper (4)
- Battery (4)
- Bayesian Statistics (4)
- Certification (4)
- Chemometrics (4)
- Comparability (4)
- Hyphenated techniques (4)
- Indirect hard modeling (4)
- Interlaboratory Comparison (4)
- Isotope dilution mass spectrometry (4)
- Isotope fractionation (4)
- Isotope reference material (4)
- Isotopic analysis (4)
- Lanthanide (4)
- Mass Spectrometry (4)
- Messunsicherheit (4)
- Microbiologically influenced corrosion (4)
- Modular production (4)
- Plasma (4)
- Process industry (4)
- Process monitoring (4)
- Provenance (4)
- Quantification (4)
- SC-ICP-ToF-MS (4)
- SI traceability (4)
- Sc-ICP-ToF-MS (4)
- Single cell (4)
- Single cell-ICP-ToF-MS (4)
- Smarte Sensoren (4)
- Spectrometry (4)
- Spectroscopy (4)
- TXRF (4)
- Trichodiene (4)
- UFP (4)
- Warfarin (4)
- Absolute fluorometry (3)
- Amoxicillin (3)
- Antibodies (3)
- Archaea (3)
- BFR (3)
- Benchtop NMR spectroscopy (3)
- Boron (3)
- Böden (3)
- CCQM (3)
- CIC (3)
- Calibration (3)
- Chemical characterization (3)
- Coded Aperture (3)
- Combustion Ion Chromatography (3)
- DNA (3)
- Datenkonzepte (3)
- Delta value (3)
- Digital Transformatioin (3)
- Digitalisation (3)
- Digitization (3)
- Dosimetry (3)
- EN 16516 (3)
- EOF (3)
- Effect based Method (3)
- Elektrochemie (3)
- Elektrolyseverfahren (3)
- Emission reference materials (3)
- Environmental analysis (3)
- FIB (3)
- Gaussian process (3)
- ISO 16000-6 (3)
- Indirect Hard Modeling (3)
- Indoor air quality (3)
- Isotopenanalyse (3)
- LC-MS/MS (3)
- Labeling (3)
- Lithium isotope (3)
- Lithium-ion batteries (3)
- MC-ICP-MS (3)
- MS based method (3)
- Machine Learning (3)
- Mass-Spectrometry (3)
- Massenspektrometrie (3)
- Materials emissions test (3)
- Mechanochemistry (3)
- Method development (3)
- Microwave inductively coupled atmospheric pressure mass spectrometry (MICAP-MS) (3)
- Mikroplastik-Analytik (3)
- Molecularly imprinted polymers (3)
- Multi-element analysis (3)
- Multicollector-ICP-MS (3)
- Mycotoxin Biomarker (3)
- Mykotoxine (3)
- Nanocrystal (3)
- Nanomaterial (3)
- Nanoparticles separation capillary electrophoresis asymmetrcial flow field flow fractionation (3)
- Neural network (3)
- Nitrogen plasma (3)
- Probennahme (3)
- Process Monitoring (3)
- Quality Control (3)
- Quantum dot (3)
- RFA (3)
- Referenzmaterial (3)
- Reliable measurements (3)
- Risk assessment (3)
- SARS-CoV-2 (3)
- SPE HR-CS GF MAS (3)
- SPM (3)
- Sewage sludge (3)
- Silane (3)
- Size (3)
- Software (3)
- Solid-liquid extraction (3)
- Standardisation (3)
- Sulfur (3)
- Trinkwasser (3)
- Triple isotope fractionation (3)
- VVOCs (3)
- Validation (3)
- Water (3)
- X-ray fluorescence (3)
- ZRM (3)
- Zinc (3)
- Accurate mass (2)
- Adsorbable organically bound fluorine (AOF) (2)
- Aktivkohle (2)
- Analytic (2)
- Analytical Sciences (2)
- Analytical method (2)
- Archaeometry (2)
- Artificial Inelligence (2)
- Artificial intelligence (2)
- Artificial neural networks (2)
- Assay (2)
- Atomic absorption spectrometry (2)
- Batteries (2)
- Bayesian Optimization (2)
- Betriebspunktoptimierung (2)
- Biosensor (2)
- Biotechnology (2)
- Borosilicate glass (2)
- COVID-19 (2)
- Cascade impactor (2)
- Cells (2)
- Cement (2)
- Certified reference material (2)
- Combustion ion chromatography (CIC) (2)
- Compact NMR Spectroscopy (2)
- Compound annotation (2)
- Conventional isotope ratio (2)
- Corona (2)
- Coulometric sensors (2)
- Cyanide in soil (2)
- Cyclic voltammetry (2)
- Datenauswertung (2)
- Datenvorbehandlung (2)
- Delta values (2)
- Depth-profiling (2)
- Diatomic molecule (2)
- Diatoms (2)
- Digitale Transformation (2)
- Dynamische Lichtstreuung (2)
- Düngemittel (2)
- E. coli (2)
- EDX (2)
- Electrospray ionization (2)
- Environmental simulation (2)
- Ergot (2)
- Ergot alkaloids (2)
- Extrahierbar organisch gebundenes Fluor (EOF) (2)
- FFF-3D-Printer (2)
- Fluor (2)
- Food (2)
- GDMS (2)
- Gas pressure influence (2)
- Gaschromatography-Mass Spectrometry (2)
- Glasmalfarben (2)
- Glow Discharge Mass Spectrometry (2)
- Graphite (2)
- Graphite furnace (2)
- Halogene (2)
- Halogens (2)
- Hapten Immunoassay (2)
- Harmonisation (2)
- Herkunftsbestimmung (2)
- High-resolution MS (2)
- History of the research work of Norbert Jakubowski (2)
- Homogeneity (2)
- Humboldt Codices (2)
- Hydrolytic resistance (2)
- ICP-ToF-MS (2)
- ILC (2)
- IR (2)
- ISO 17025 (2)
- ISO Guide 35 (2)
- Immuno-assay (2)
- Immunohistochemistry (2)
- In situ (2)
- Inductively Coupled Plasma Mass Spectrometry (2)
- Interferences (2)
- Internal Standard (2)
- Ionische Flüssigkeiten (2)
- Ionophore Antibiotika (2)
- Isotope amount ratio (2)
- Isotope delta value (2)
- Isotopic shift (2)
- Klärschlamm (2)
- LA-ICP-MS with cellular resolution (2)
- LFIA (2)
- Lab of the Future (2)
- Laser Ablation (2)
- Laser-induced XUV spectroscopy (2)
- Lithium batteries (2)
- Low-field NMR Spectroscopy (2)
- Low-field NMR spectroscopy (2)
- MALDI (2)
- MALDI-TOF-MS (2)
- MDG (2)
- MOSES (2)
- Mass cytometry (2)
- Metabolomics (2)
- Metrologie (2)
- Microbiological influenced corrosion MIC (2)
- Modulare Produktion (2)
- Molecular absorption spectrometry (2)
- Mono-hydride (2)
- Multicellular spheroid (2)
- Multivariate data analysis (2)
- NIR (2)
- NMR Spectroscopy (2)
- NMR Validation (2)
- Nanopartikel (2)
- Network (2)
- Nitrogen (2)
- Non-metals (2)
- Nontarget analysis (2)
- Oberflächengewässer (2)
- Ochratoxin A (2)
- Optischer Spektroskopie (2)
- PANIC (2)
- PBFSM (2)
- PEG (2)
- Passive sampling (2)
- Pharmaceuticals (2)
- Pollen (2)
- Pollutants (2)
- Polyethylene glycole (2)
- Polymer (2)
- Polymer 3R (2)
- Polymere (2)
- Polymers (2)
- Polypropylen (2)
- Polystyrol (2)
- Probenahme (2)
- Process Control (2)
- Proteins (2)
- Prozesskontrolle (2)
- Purity (2)
- Quality Assurance (2)
- Quality testing (2)
- Quantitative NMR spectroscopy (2)
- RBD (2)
- Real-time process monitoring (2)
- Referenzmaterial-Herstellung (2)
- Remediation (2)
- Retrospective analysis (2)
- Ringversuch (2)
- SEM (2)
- SHS (2)
- SPE (2)
- Safety (2)
- Sampling (2)
- Sampling techniques (2)
- Schadstoffaustrag (2)
- Schadstoffe (2)
- Schwebstoffe (2)
- Screening (2)
- Semiconductor (2)
- Sensorbeschichtung (2)
- Silanes (2)
- Single cell ICP-MS (2)
- Specialty Chemicals (2)
- Speciation Analysis (2)
- Spike-Protein (2)
- Spurenfeuchtemessung (2)
- Stability (2)
- Standards (2)
- Standarisierung (2)
- Steel (2)
- Structural Health Monitoring (2)
- Temperature (2)
- Thermal extraction (2)
- Thermogravimetrie (2)
- Total cyanide (2)
- Trace analysis (2)
- Trace elements (2)
- Trace humidity measurement (2)
- Transformation product (2)
- Tumor metabolism (2)
- Ultraschall (2)
- Ultrasound (2)
- Umwelt (2)
- Umweltverhalten (2)
- Virus (2)
- Volatile organic compounds (2)
- WFD (2)
- WWTP (2)
- Wasseraufbereitung (2)
- Wasserstoff (2)
- Wastewater (2)
- Water analysis (2)
- Welding (2)
- Whole water samples (2)
- XAFS (2)
- 3D printing (1)
- AAAA (1)
- ACE2 (1)
- ACE2-Rezeptor (1)
- AF4 (1)
- AFM (1)
- AKR (1)
- ANAKON (1)
- AOF (1)
- Accreditation (1)
- Acoustic levitation (1)
- Additive (1)
- Advanced nanomaterials (1)
- Affinity (1)
- Affinity Chromatography (1)
- Affinitätschromatographie (1)
- Affinitätskonstante (1)
- Africa (1)
- Aging (1)
- Aging Mechanisms (1)
- Aging mechanisms (1)
- Air traffic (1)
- Albumin (1)
- Algen (1)
- Alkylierung (1)
- Alteration (1)
- Aluminiumoxid (1)
- Alzheimer disease (1)
- Amino acid analysis (1)
- Analyse (1)
- Analyseverfahren (1)
- Analytical Chemistry (1)
- Analytical science (1)
- Analytical standards (1)
- Analytics (1)
- Analytische Methode (1)
- Anion recognition (1)
- Anode (1)
- Antagonists (1)
- Anti-cancer (1)
- Antibiotics (1)
- Antibody Quantification (1)
- Antibody quantification (1)
- Antifouling-Biozide (1)
- Antikörpermarkierung (1)
- Anwendungsmöglichkeiten (1)
- Application properties (1)
- Applied optical spectroscopy (1)
- Arbeitsanleitung (1)
- Archean ocean (1)
- Archäometrie (1)
- Aromatische Aminosäureanalytik (1)
- Artificial Intelligence (1)
- Artificial Neural Networks (1)
- Arzneimittel (1)
- Asymmetrical flow field flow fractionation (AF4) (1)
- Atomabsorptionsspektrometrie (1)
- Atomic absorption spectroscopy (1)
- Atomic spectrometry (1)
- Atomic spectroscopy (1)
- Atomic weights (1)
- Aufbereitung (1)
- Automated single cell-ICP-ToF-MS (1)
- Automatisierung (1)
- Autonomous chemistry (1)
- BAM Data Store (1)
- BBodSchV (1)
- BCA (1)
- BLE Bluetooth low energy (1)
- BPA (1)
- BSA (1)
- Bakterien (1)
- Basic Statistics (1)
- Battery aging (1)
- Baustoffe (1)
- Bauwerksdiagnostik (1)
- Bayes (1)
- Beamline (1)
- Benchtop NMR Spectroscopy (1)
- Benz[a]anthracene (BaA) (1)
- Benzo[a]pyrene (BaP) (1)
- Bernstorf (1)
- Beton (1)
- Betonfahrbahndecken (1)
- Betonschwellen (1)
- Bewitterung (1)
- Bias (1)
- Big Data (1)
- Big science (1)
- Bio engineering (1)
- Bio-apatite (1)
- BioProScale (1)
- Bioconjugates (1)
- Bioconjugation (1)
- Biomarkers (1)
- Biotransformation (1)
- Bisphenols (1)
- Bitumen und bitumenhaltige Bindemittel (1)
- Bivalves (1)
- Boden (1)
- Bone matrix (1)
- Border surveillance (1)
- Boron monohydride (1)
- Bradford-Assay (1)
- Bunsen-Kirchhoff-Preis (1)
- CCMV (1)
- CE (1)
- CE-ICP-MS (1)
- CE/MC-ICP-MS (1)
- CF LIBS algorithms (1)
- CMC (1)
- CMOS (1)
- CaF (1)
- Cadmium (1)
- Caenorhabditis elegans (1)
- Calcium (1)
- Calcium monofluoride (1)
- Calibration standards (1)
- Calibration-free LIBS (1)
- Cancer (1)
- Capecitabine (1)
- Capillary electrophoresis (CE) (1)
- Carbon (1)
- Carbon cycle (1)
- Carbon steel corrosion (1)
- Carrier gas hot extraction (1)
- Cascade filtration (1)
- Catalysis (1)
- Cathode (1)
- Causes leading to scientific misconduct (1)
- CellenONE (1)
- Certified reference materials (1)
- Ceruloplasmin (1)
- Chamber measurement (1)
- Channel access (1)
- Cheese (1)
- Chemical Production (1)
- Chemical and material safety (1)
- Chemical composition (1)
- Chemical coverage (1)
- Chemical reactors (1)
- Chemiluminescence (1)
- Chemische Prozesskontrolle (1)
- Chemometric (1)
- Chemometrie (1)
- Chemometrik (1)
- Chemometry (1)
- Chip (1)
- Chip-Screening (1)
- Chlor (1)
- Chlorid (1)
- Circular economy (1)
- Cispaltin (1)
- Civil engineering (1)
- Cleaning (1)
- Cleavable probe (1)
- Climate Changes (1)
- Climate change (1)
- Clinical samples (1)
- Clones (1)
- Cobalt deposition (1)
- Cocaine (1)
- Cocoa (1)
- Cocrystal (1)
- Cocrystals (1)
- Color X-ray Camera (1)
- Coltan (1)
- Combinatorial library (1)
- Combinatorial screening (1)
- Compact NMR (1)
- Compact NMR spectroscopy (1)
- Comparative test (1)
- Competitive Immunoassay (1)
- Compost (1)
- Concrete (1)
- Conductometry (1)
- Confiscation (1)
- Construction Products (1)
- Consumer products (1)
- Continuous Manufacturing (1)
- Continuum source atomic absorption spectrometry (1)
- Conventional isotope ratios (1)
- Cooper (1)
- Core-shell nanoparticles (1)
- Core/shell nanoparticle (1)
- Coronavirus (1)
- Corrosion (1)
- Corundum (1)
- Counting detector (1)
- Crossreactivity (1)
- Crude oil (1)
- Cultural heritage (1)
- Curse tablets (1)
- Customs (1)
- Cyber-physical Lab (1)
- Cyclisierung (1)
- Cylic Voltammetry (1)
- D2XRF (1)
- DCF (1)
- DLS (1)
- DNA strand break (1)
- Data Analyses (1)
- Data conversion (1)
- Data manipulation (1)
- Datenerfassung (1)
- Dating (1)
- Deactivation pathways (1)
- Dead Sea Scrolls (1)
- Deep work (1)
- Degradation (1)
- Delivery system (1)
- Dementia (1)
- Depth profiles (1)
- Desorption (1)
- Detection (1)
- Detector deadtime (1)
- Detektion (1)
- Detektion von Mikroplastik (1)
- Diagenesis (1)
- Diagnostics (1)
- Diatom (1)
- Diatom, Bacteria (1)
- Diatomeenanalytik (1)
- Diatomic (1)
- Diatomic molecules (1)
- Diclofenac (1)
- Digital Radiology (1)
- Digital laboratory (1)
- Digital transformation (1)
- Digitaler Zwilling (1)
- Digitalization (1)
- Direct loop control (1)
- Dispersions (1)
- Dissolution (1)
- Doppler effect (1)
- Dose (1)
- Drawings (1)
- Druckfeuchte (1)
- Drug search (1)
- Drug trafficking (1)
- Drugs (1)
- Dual mode detector (1)
- Duftstoffe (1)
- Duplex stainless steels (1)
- Durchflusszytometrie (1)
- EC/LC/MS (1)
- EDC (1)
- EDX Analysis (1)
- EMN (1)
- EMPIR (1)
- EPICS (1)
- EQS (1)
- ESEM (1)
- ESI-MS (1)
- ETV/ICP-MS (1)
- EU-WFD (1)
- EXAFS (1)
- Easy-use device (1)
- Echtzeitoptimierungsverfahren (1)
- Ecotoxicological Assessment (1)
- Ectoine (1)
- Ectoine radiation protection (1)
- Egypt (1)
- Electrochemical (1)
- Electrochemical oxidation (1)
- Electrohpresis (1)
- Electron number density (1)
- Electronic Lab Notebook (ELN) (1)
- Electronic lab notebook (ELN) (1)
- Elektronisches Laborbuch (1)
- Elemental Impurities (1)
- Elementspezies & Isotope (1)
- Elutionsverfahren (1)
- Emerging Contaminants (1)
- Emerging pollutants (1)
- Emission (1)
- Emission Test Chamber (1)
- Emission Testing (1)
- Emission line profiles (1)
- Emission spectroscopy (1)
- Emission test chamber (1)
- Emissions (1)
- Energy Gases (1)
- Energy input (1)
- Environment (1)
- Environment-material interactions (1)
- Environmental & life science application (1)
- Environmental pollutants (1)
- Enzyme Immobilisation (1)
- Equilibrium isotope fractionation (1)
- Explosives (1)
- Expression (1)
- Extraktion (1)
- FPLC (1)
- FTIR (1)
- FTIR-Spektroskopie (1)
- Fab Fragment (1)
- Faecal contamination (1)
- Fake news (1)
- False Positives (1)
- Farbenlehre (1)
- Faseroptische Sensoren (1)
- Faseroptische Sensorik (1)
- Fatty acid metabolism (1)
- Feldintegration (1)
- Fertilizer (1)
- Fibre-optic sensors (1)
- Field integration (1)
- Field test (1)
- Filtration (1)
- Fingerprint (1)
- Finow Canal (1)
- Flame retardants (1)
- Flammschutzmittel (1)
- Flow NMR (1)
- Fluoreszenz (1)
- Fluorine Detection (1)
- Fluorine sum parameter (1)
- Fluorouracil (1)
- Flux Analysis (1)
- Fluxomics (1)
- Food analysis (1)
- Food safety (1)
- Food web (1)
- Formaldehyd (1)
- Formaldehyde (1)
- Forschungsbedarf (1)
- Forschungsdatenmanagement (1)
- Fraktionierte Filtration (1)
- Framework (1)
- Fresenius (1)
- Fresenius Lecture (1)
- Fresenius lecture (1)
- Functional group (1)
- Fundamental science (1)
- GC/ICP-ToF-MS (1)
- GDOES (1)
- GMAW (1)
- GUI (1)
- Gadolinium (1)
- Gas Analysis (1)
- Gas Reference Material (1)
- Gas analysis (1)
- Gas chromatography (1)
- Gas chromatography (GC) (1)
- Gas purity (1)
- Gaschromatographie-Massenspektrometrie (1)
- Gassensoren (1)
- Gassensorik (1)
- Gaussian Process (1)
- Geführte Ultraschallwellen (1)
- Geological Storage (1)
- Geological thermometer (1)
- Geothermal engineering (1)
- Germanium chlorides (1)
- Gerätekommunikation (1)
- Glas (1)
- Glass (1)
- Glass paints (1)
- Gleisoberbau (1)
- Glow Discharge (1)
- Glow-discharge (1)
- Goethe (1)
- Gold nanocluster (1)
- Gold-Nanopartikel (1)
- Grand challenges (1)
- Gravimetric preparation (1)
- Gravimtric isotope mixtures (1)
- Ground water (1)
- Größenausschlusschromatographie (1)
- Gutachten (1)
- GxP (1)
- Gypsum (1)
- H/D-Austausch (1)
- H/D-Exchange (1)
- H2020 (1)
- H2Safety@BAM (1)
- HDF5 (1)
- HLA (1)
- HPLC (1)
- HPLC-MS (1)
- HRMS (1)
- Halomonas elongata (1)
- Hamonisierung (1)
- Handbook (1)
- Handheld (1)
- Harmonisierung (1)
- Heißgasextraktion (1)
- High purity material (1)
- High repetition-rate (1)
- High throughput (1)
- High-entropy alloy (1)
- High-frequency arc discharge (1)
- High-resolution (1)
- High-resolution absorption isotopic spectrometry (1)
- High-resolution continuum source atomic absorption spectrometer (1)
- High-resolution synchrotron XRF (1)
- Histology (1)
- Hochauflösende Massenspektrometrie (1)
- Hochdurchsatzscreening (1)
- Holistic science (1)
- Holographic microscopy (1)
- Hybridoma (1)
- Hydrazin (1)
- Hydrodynamic model (1)
- Hydrogen Metrology (1)
- Hydrogen Purity (1)
- Hydrogen Storage (1)
- Hydrogen Storage Materials (1)
- Hydrogen analysis (1)
- Hydrogen reduction (1)
- Hydrogenation (1)
- Hydrogenierung (1)
- Hydrolysis (1)
- IAQ (1)
- IC (1)
- IC50 (1)
- ICH guideline Q3D (1)
- ICP-AES (1)
- ICP-MS & HR-CS-GFMAS (1)
- ICP-TOF-MS (1)
- IDMS (1)
- IIoT (1)
- ISO/IEC 17025 (1)
- IUTA (1)
- Iisotopic signature (1)
- Illicit drug (1)
- Image manipulation (1)
- Image unsharpness (1)
- Imaging Mass Cytometry (1)
- Imaging condition (1)
- Imaging mass cytometry (1)
- Immuno assay (1)
- Immuno-Assays (1)
- Immunosensor (1)
- Immunpräzipitation (1)
- Implant material (1)
- In situ measurement (1)
- Indirect Hard Modelling (1)
- Indoor Air Quality (1)
- Indoor Products (1)
- Industrielle Analytik (1)
- Infrastruktur (1)
- Inhalation exposure (1)
- Ink fingerprint (1)
- Inorganic Reference Materials (1)
- Instrument Communication (1)
- Instrument control (1)
- Instrumentation (1)
- Instrumentation utilization (1)
- Integrating sphere spectroscopy (1)
- Integrating sphere spectroscopy, (1)
- Inter-laboratory comparison (1)
- International drug trade (1)
- Interner Standard (1)
- Ionische Flüssigkeit (1)
- Ionization (1)
- Ionizing radiation (1)
- Ionophore Antibiotics (1)
- Ionophore antibiotic (1)
- Ir DNA staining approach (1)
- Iron (1)
- Iron isotopes (1)
- Isotope Dilution (1)
- Isotope anaylsis (1)
- Isotope delta (1)
- Isotope dilution (ID) (1)
- Isotope dilution analysis (1)
- Isotope mixtures (1)
- Isotope purification (1)
- Isotopic fingerprints (1)
- Java GUI (1)
- Kalibriertransfer (1)
- Kapillarelektrophorese-Massenspektrometrie (1)
- Kinetic isotope fractionation (1)
- Klassifizierung (1)
- Klimawechsellagerung (1)
- Klon A1.1.1 (1)
- Klon EW75C (1)
- Komplementäre Massenspektrometrie (1)
- Kopplungstechniken (1)
- Kreuzreaktion (1)
- Kristallolgraphie (1)
- Kupferazid (1)
- Künstlicher Intelligenz (1)
- LAMIS (1)
- LC-HRMS (1)
- LC-MS/MS peptide quantification (1)
- LIP-AAS (1)
- LIP-LIF (1)
- Lab-on-a-chip (1)
- Lab-on-chip (1)
- Labor 4.0 (1)
- Labor der Zukunft (1)
- Laboratory 4.0 (1)
- Laboratory automation (1)
- Laboratory management (1)
- Lanthanoid (1)
- Lapis lazuli (1)
- Laser Ablation Molecular Absorption spectrometry (1)
- Laser Ablation/Imaging (1)
- Laser induced XUV spectroscopy (1)
- Laser induced plasma deposition (1)
- Laser spectroscopy (1)
- Laser-induced Breakdown Spectroscopy (1)
- Lastwechsel (1)
- Leckdetektion (1)
- Legacy pollution (1)
- Leonardo da Vinci (1)
- Levitation (1)
- Lightning talk (1)
- Lignin (1)
- Linear Regression (1)
- Linear dynamic range (1)
- Lipidomic profile (1)
- Liquid chromatography (LC) (1)
- Liquid chromatography-mass spectrometry (1)
- MALDI Imaging (1)
- MALDI-TOF MS (1)
- MALDI-TOF Massenspektrometrie (1)
- MALDI-ToF MS (1)
- MDG ICP-ToF-MS (1)
- MIPs (1)
- MOUSE (1)
- MRFA (1)
- MS-ICP-MS (1)
- MST (1)
- MYCN (1)
- Machine-Assisted Workflows (1)
- Machining (1)
- Macrophages (1)
- Magnesium delta values (1)
- Magnesium monofluoride (1)
- Magnetpartikel (1)
- Mammals (1)
- Mangesium (1)
- Manufacturing (1)
- Mass Isotopomer Distribution (1)
- Mass Spectroscopy (1)
- Mass contents (1)
- Mass spectrometry (MS) (1)
- Mass spectroscopy (MS) (1)
- Mass-spectrometry (1)
- Material - Environment interaction (1)
- Material Science (1)
- Material analysis (1)
- Material characterization (1)
- Material science (1)
- Materialfeuchte (1)
- Materialuntersuchungen (1)
- Mathematics and Statistics (1)
- Matrix separation (1)
- Measurement (1)
- Measurement data conversion (1)
- Measurement space (1)
- Medieval glasses (1)
- MefHySto (1)
- Mercury (1)
- Mercury solution (1)
- Meta-study (1)
- Metabolic stress (1)
- Metabolismus (1)
- Metabolites (1)
- Metal complexes (1)
- Metal sublimation (1)
- Metal-Tag (1)
- Metal-tag (1)
- Metals (1)
- Metformin (1)
- Methoden (1)
- Methodenentwicklung Böden (1)
- Methodology (1)
- Methylmercury (1)
- Metrics (1)
- Metrologie zur Wasserstoffspeicherung (1)
- Micro Reactor (1)
- Micro-XRF (1)
- Micro-chamber (1)
- Microbe interactions (1)
- Microdosimetry (1)
- Microdroplet generator (1)
- Microfluidic (1)
- Microfluidics (1)
- Microplastic analysis (1)
- Microplastic mass (1)
- Microplastic particles (1)
- Microplastic pathways (1)
- Microplastics analytic (1)
- Microplastics sampling (1)
- Microplastics standardisation (1)
- Microscopy (1)
- Microwave plasma (1)
- Migration (1)
- Mikroplastik Böden (1)
- Mikroplastik Massegehalt (1)
- Mikroplastik in Luft (1)
- Mikroplastikreferenzmaterial (1)
- Mining (1)
- Mobile device (1)
- Modeling (1)
- Modellbasierte Optimierung (1)
- Modifier-Adaptation (1)
- Moisture measurements (1)
- Molecular imprinted polymers (1)
- Molecular spectrum (1)
- Monitoring (1)
- Monoamine oxidase B (1)
- Monoclonal Antibodies (1)
- Monoelemental solutions (1)
- Motor controller (1)
- Multielemental analysis (1)
- Multielementanalytik (1)
- Multielementanalytik in kurzen transienten Signalen (1)
- Multimodal (1)
- Multimodale Analytik (1)
- Multivariate Analyse (1)
- Multivariate Data Analysis (1)
- Multivariate Datenanalyse (1)
- Multivariate Datenauswertung (1)
- Multivariate analysis (1)
- Muon tomography (1)
- Mutationen (1)
- Mycotoxin (1)
- Mycotoxin Analysis (1)
- Mycotoxin-Biomarker (1)
- Mykotoxin-Biomarker (1)
- Müllverbrennung (1)
- N-capsid (1)
- NAMUR (1)
- NIR Spektroskopie (1)
- NMR (1)
- NMR Accreditation (1)
- NMR Method Validation (1)
- NMR Spektroskopie (1)
- NMR spetroscopy (1)
- NMR validation (1)
- NSO-Heterozyklen (1)
- NXsas (1)
- NaCl-Methode (1)
- Nahinfrarotspektroskopie (1)
- NanoPlattform (1)
- Nanobody (1)
- Nanocarrier (1)
- Nanocluster (1)
- Nanodiamant (1)
- Nanomaterialien (1)
- Nanomaterials (1)
- Nanoparticles with same nominal diameter; surface coating; two-dimensional off-line coupling (1)
- Nanoplastic (1)
- Nanoplastics (1)
- Nanotoxicity (1)
- Naphthalene (Nap) (1)
- Narcotics (1)
- Nasschemie (1)
- Natural language processing (1)
- NeXus (1)
- Near Infrared Spectroscopy (1)
- Nebra (1)
- Neodymium (1)
- Neural Network (1)
- Neural networks (1)
- Neutralisierende Antikörper (1)
- New ecotoxicological testing tools (1)
- Nichtmetall-Analytik (1)
- Nichtmetalle (1)
- Nickel (1)
- Niederfeld-NMR-Spektroskopie (1)
- Niobcarbid (1)
- Nitroaromaten (1)
- Nitromoschus (1)
- Noise (1)
- Non metals (1)
- Non-invasive analysis (1)
- Non-metal analysis (1)
- Non-metals analysis (1)
- Non-target (1)
- Nontargeted approach (1)
- Normen (1)
- Normung (1)
- Nuclear Magnetic Resonance (1)
- Nucleocapsid-Protein (1)
- OBOC (1)
- Oberflächenwasser (1)
- Oberflächenwasser und Boden (1)
- Oil analysis (1)
- Online-NMR spectroscopy (1)
- Online-RFA-Spektroskopie (1)
- OpenBIS (1)
- Optical isotopic spectrometry (1)
- Optical spectrometry (1)
- Optimierung (1)
- Optimization (1)
- Optimum magnification (1)
- Ordinary Portland cement (1)
- Organic calibration solution (1)
- Organically bound fluorine (1)
- Organophosphate esters (1)
- Outreach (1)
- Oxygen (1)
- PAK (1)
- PARCI-MS (1)
- PEGomics (1)
- PEM-Wasserelektrolyse (1)
- PFAS TOP Assay soil contamination (1)
- PGAA (1)
- PIXE (1)
- PP (1)
- PRORA (1)
- PS (1)
- Paper mills (1)
- Papier (1)
- Parkinsons's disease (1)
- Partikel (1)
- Peptid-Aptamer (1)
- Peptid-Synthese (1)
- Peptidbibliothek (1)
- Peptidbibliotheken (1)
- Peptide analysis (1)
- Peptide library (1)
- Peptidsequenzierung (1)
- Periplasma (1)
- Peristaltic pumps (1)
- Pesticide (1)
- Pflanzenvirus (1)
- Pharmaceutical Drugs (1)
- Pharmacopoeial Reference Standards (1)
- Pharmacy (1)
- Phosphonates (1)
- Phosphor (1)
- Phosphorus (1)
- Photocatalysis (1)
- Photodynamische Inaktivierung (1)
- Photokatalyse (1)
- Photoluminescence (1)
- Photonic Integrated Circuits (1)
- Photonic Sensor (1)
- Photosensibilisator (1)
- Phthalocyanin (1)
- Pigment analyses (1)
- Planetary science (1)
- Plants (1)
- Plasma chemistry (1)
- Plasma fundamentals (1)
- Plasma processes (1)
- Plasmaspectrochemistry (1)
- Point-Of-Care-Diagnostics (1)
- Pollenkörner (1)
- Polycapillaries (1)
- Polycyclic aromatic hydrocarbon (PAH) (1)
- Polyethyleneglycol (1)
- Polymere Eigenschaften (1)
- Polymorph (1)
- Pomodore (1)
- Porphyrin (1)
- Poster presentation (1)
- Pouch cell (1)
- Pozessindustrie (1)
- Precision Profile (1)
- Primary standard (1)
- Primäre Kalibriersubstanzen (1)
- Prisma (1)
- Probenpräparation (1)
- Probenvorbereitung (1)
- Procee Analytical Technology (1)
- Process-NMR (1)
- Protein (1)
- Protein G (1)
- Protein analysis (1)
- Provenance studies (1)
- Prozess-Sensoren 4.0 (1)
- Prozess-Steuerung (1)
- Prozessanalysentechnik (1)
- Prozesslabor (1)
- Prussian blue (1)
- Präzision (1)
- Präzisionsprofil (1)
- Purification (1)
- Purity determination (1)
- Pyrethroids (1)
- Python (1)
- QI-Digital (1)
- QNMR (1)
- Quadratic approximation (MAWQA) (1)
- Quality (1)
- Quality Infrastructure (1)
- Quality assurance (1)
- Qualitätskontrolle (1)
- Qualitätssicherung (1)
- Quantum dots (1)
- Quantum yield (1)
- Qumranrollen (1)
- R package (1)
- RAMAN (1)
- RSSI Received Signal Strength Indicator (1)
- RUSEKU (1)
- Radiation (1)
- Radiation damage (1)
- Raid test (1)
- Raman spectroscopy (1)
- Raman-Spektroskopie (1)
- Rapid test (1)
- Real-time Process Monitoring (1)
- Reference Material (1)
- Reference procedure (1)
- Reifenabrieb (1)
- Reinstmetalle (1)
- Reinststoffe (1)
- Rekombinante Antikörper (1)
- Release kinetics (1)
- Reliabiilty (1)
- Renal disease (1)
- Reproducibility (1)
- Research (1)
- Research Agenda (1)
- Research Data Infrastructure (1)
- Research Data Management (1)
- Research data management (1)
- Reverse time migration (1)
- Ring resonator (1)
- Round robin test (1)
- Röntgenfluoreszenz (1)
- Rückverstromung (1)
- SAFIA (1)
- SAXS (1)
- SC-ICP-MS (1)
- SDS-PAGE (1)
- SI Traceability (1)
- SI-traceable (1)
- SMASH (1)
- Salt (1)
- Sample preparation (1)
- Sata corrections (1)
- Scattering (1)
- Schadensanalyse (1)
- Schadstofftransfer (1)
- Schieneninfrastruktur (1)
- Science (1)
- Scientific misconduct (1)
- Screen-printed electrodes (1)
- Sediment (1)
- Sedimentationskasten (1)
- Sedimenttaionskasten (1)
- SensRef (1)
- Sensor (1)
- Sensor network (1)
- Sensor response (1)
- Sensorik (1)
- Sensors (1)
- Separation (1)
- Sequenzierung (1)
- Shiny-App (1)
- Shortwave infrared (1)
- Si isotope fractionation (1)
- Si wafer filter (1)
- Sialic acid (1)
- Silicon Photonics (1)
- Silicon chlorides (1)
- Silver artefacts (1)
- Silver nanoparticles (1)
- Simultaneous determination (1)
- Single Cell (1)
- Single Particle (1)
- Single particle spectroscopy (1)
- Single particle-ICP-ToF-MS (1)
- Size exclusion chromatography (1)
- Slags (1)
- Small-angle scattering (1)
- Smart Laboratoy (1)
- Smart Sensors (1)
- Smarte Aktoren (1)
- Smarte Laborgeräte (1)
- Smartphone (1)
- Solid microanalysis (1)
- Solid phase extraction (SPE) (1)
- Solid support (1)
- Spannbetonschwelle (1)
- Spatial Heterodyne Spectrometer (1)
- Spatial heterodyne spectrometer (1)
- Spatial information (1)
- Species-specific Isotope Analysis (1)
- Species-specific Isotope ratios (1)
- Spectrochemical analysis (1)
- Spectrocube (1)
- Speiseöle (1)
- Spielzeug (1)
- Sportböden (1)
- Spurenfeuchte in Gasen (1)
- Stable-Isotope-Dilution-Analysis (1)
- Stained glass windows (1)
- Stained glasses (1)
- Stakeholders (1)
- Standard (1)
- Standardization (1)
- Statistics (1)
- Storage Technologies (1)
- Strontium (1)
- Structural Health Monitoring (SHM) (1)
- Sub-doppler spectroscopy (1)
- Sulfur species conversion (1)
- Sulfur-copper-sepration (1)
- Sulfur-matrix separation (1)
- Sum Parameter (1)
- Sum parameter (1)
- Surface coating (1)
- Surface water (1)
- Surfacewaters (1)
- Sustainable Food Safety (1)
- Synthesis (1)
- TCE (1)
- TEM (1)
- TMB (1)
- TNT (1)
- Tau protein (1)
- Tausalzeintrag (1)
- Temperature Control (1)
- Temperatures (1)
- Terbutryne (1)
- Terminology (1)
- Test strip (1)
- Testbed (1)
- Textile fibres (1)
- Thermal Desorption (1)
- Thermal Extraction (1)
- Thermal equilibrium (1)
- Thermal treatment (1)
- Thermoanalyse (1)
- Thermoanalysis (1)
- Thermoanalytic (1)
- Thermoanalytical methods (1)
- Thermoanalytics (1)
- Thermoanalytik (1)
- Thermoplastic filaments (1)
- Thermostating (1)
- Thin metal alloy layers (1)
- Time-gated Raman-Spektroskpie (1)
- Tire wear (1)
- Tissue (1)
- Titanium dioxide (1)
- Tools to combat scientific misconduct (1)
- Toxicity (1)
- Toxicity testing (1)
- Trace Analysis (1)
- Transcriptomic (1)
- Transformation Product (1)
- Transformation Products (1)
- Transformation products (1)
- Transformations products (1)
- Trialkoxysilane (1)
- Triazine herbicide (1)
- Trichodien (1)
- Trinitrotoluol (1)
- Truffles (1)
- Tutzing-Symposion (1)
- Umlaufkühler (1)
- Umwelt-Speziation (1)
- Uncertainty Evaluation (1)
- Underwater LIBS (1)
- Unsicherheit (1)
- Upconversion (1)
- Uptake rate (1)
- VAMAS (1)
- VIS (1)
- VIS- Spektroskopie (1)
- VOC Emission (1)
- VRF (1)
- ValidNMR (1)
- Vanadium redox flow battery (1)
- Vanadiumcarbid (1)
- Vergleichuntersuchung (1)
- Verwertung Bodenmaterial (1)
- Vhh (1)
- Vibrational Sum-Frequency Generation Spectroscopy (1)
- WAXS (1)
- Wasser (1)
- Wasserproben (1)
- Wasserstoff-Qualität (1)
- Wasserstoffspeicher (1)
- Wasserzeichen (1)
- Weathering (1)
- Weighing Uncertainty (1)
- Wolframcarbid (1)
- Wooden toys (1)
- Writing inks (1)
- X-ray and electron diffraction (1)
- X-ray photoelectron spectroscopy (1)
- X-ray scattering (1)
- X-ray spectroscopy (1)
- XANES spectroscopy (1)
- XRD (1)
- ZVEI (1)
- Zerstörungsfreie Prüfung (1)
- Zertifizierung (1)
- ZfP (1)
- Zr-Modifier (1)
- electrocatalysis (1)
- microplastics, sampling, sampling techniques, water (1)
- nanostructured (1)
- openBIS (1)
- sc-ICP-ToF-MS (1)
- single cell-ICP-ToF-MS (1)
- single particle-ICP-ToF-MS (1)
- µJ-DPSS laser (1)
Organisationseinheit der BAM
- 1 Analytische Chemie; Referenzmaterialien (454)
- 1.1 Anorganische Spurenanalytik (158)
- 6 Materialchemie (129)
- 1.4 Prozessanalytik (116)
- 1.6 Anorganische Referenzmaterialien (82)
- 1.8 Umweltanalytik (61)
- 4 Material und Umwelt (59)
- 6.6 Physik und chemische Analytik der Polymere (58)
- 6.3 Strukturanalytik (57)
- 1.7 Organische Spuren- und Lebensmittelanalytik (52)
In dieser Arbeit wurden drei verschiedene Nanomaterialien auf ihre Bindungsfähigkeit zu Proteinen untersucht. Zu Beginn standen dabei die Herstellung stabiler Dispersionen der einzelnen Nanopartikel und die Stabilität der gebildeten Konjugate im Vordergrund. Der Nachweis einer erfolgreichen Konjugatbildung, sprich der Beschichtung von Nanopartikel mit Proteinen, wurde sowohl qualitativ mittels DLS-Messungen als auch über quantitative Protein-Bestimmungen erbracht. Für die Quantifizierung konnten verschiedene Methoden eingesetzt werden. Neben der klassischen Vorgehensweise, welche indirekt über die Quantifizierung von ungebundenem Protein im Überstand erfolgt, konnten ihm Rahmen dieser Arbeit verschiedene direkte Bestimmungsmethoden entwickelt werden. So wurden mittels kolorimetrischer Tests, wie dem BCA-Assay und dem Bradford-Assay, Nanodiamantdispersionen mit Hilfe einer Korrekturwellenlänge vermessen und quantifiziert. Ebenso zum Einsatz kam die Methode der Aminosäureanalytik, welche aufgrund ihrer guten Rückführbarkeit auf Aminosäurestandards Ergebnisse mit hoher Richtigkeit generieren kann und ebenso die Detektion kleiner Proteinmengen möglich macht.
Nach den erfolgten quantitativen Betrachtungen wurden die Protein-beschichteten Nanopartikel auf ihre Anwendbarkeit als Analoga von Virus-like Particles (VLP) bei einer Immunisierung zur Gewinnung von polyklonalen Antikörpern gegen humanes Ceruloplasmin in Kaninchen überprüft. Es konnte mittels ELISA gezeigt werden, dass die Konjugate erfolgreich für die Herstellung von Antikörpern eingesetzt werden können und im zeitlichen Verlauf einer Immunisierung eine Steigerung des Antikörper-Titers zu erreichen ist.
Quantifizierung der Schädigung von DNA in wässriger Lösung unter direkter Elektronenbestrahlung
(2018)
To cure cancer radiation therapy is used to kill tumor cells.
It is based on radiation induced damage to biomolecules.
Especially DNA damage is of key interest due to its central role in apoptosis and mutation.
Because of the high amount of water in biological tissue, most of the damage is caused by the secondary particles produced by the inelastic scattering of ionizing radiation and water.
A detailed understanding of the underlying molecular processes under physiological conditions is the prerequisite to develop more efficient therapies.
Goal of this work is to quantify the DNA damage caused by ionizing radiation in dependence of the inelastic scattering events and the energy deposit within the microscopic target volume of biological relevance.
The irradiations have to be performed in liquid, under consideration of the chemical environment.
Therefore, a new combination of experiment and Monte-Carlo simulations was developed and tested.
To make it possible to irradiate liquids with electrons within scanning electron microscopes a new sample holder was constructed incorporating an electron transparent nanomembrane.
It makes it possible to irradiate DNA, proteins or cells at different pH, salinity and in the presence of cosolutes.
%The most important results of this work are as follows:
The median lethal dose for a model system of plasmid DNA and water was determined by the combination of experimental data, particle scattering simulations (Geant4-DNA) and diffusion calculations as D0.5=(1.7+-0.3) Gy.
From the convolution of plasmid positions and the spatially resolved energy deposit, as determined by electron scattering simulations, the histogram of the energy deposit within the target volume of the plasmids and the microscopic median lethal energy deposit was calculated as E0.5=6+-4eV.
It could be deduced that on average less than two ionization events are sufficient to cause a single-strand-break.
The relation of single-strand-breaks (SSB) to double-strand-breaks (DSB), which is of importance for microdosimetric modeling, was determined as SSB:DSB = 12:1.
The presented method for the determination of microscopic dose-damage relations was further extended to be applicable for general irradiation experiments.
It becomes independent of the type of primary radiation used, the experimental geometry, and the diffusional properties of the molecules under investigation.
This way different experimental systems with varying, inhomogeneous energy deposit characteristics become comparable with each other, which is not possible when only macroscopic averaged values are taken into account.
In addition, the radiation protection properties of the compatible solute ectoine, as well as its influence on the water properties and biomolecules were investigated.
%In addition, the influence of the compatible solute ectoine on water, biomolecules and its radiation protection properties were investigated.
Raman spectroscopy revealed a concentration dependent increase of the collective water modes in the OH-stretching region, which was found to be independent of the sodium chloride concentration.
Molecular dynamic simulations showed that the zwitterionic properties of ectoine lead to its half-chair conformation.
The hydrogen bonds in the first hydration shell are more stable and have an increased lifetime compared to the bulk water.
Irradiation experiments with DNA in the presence of 1M ectoine revealed an increase of the survival rate by a factor of 1.41 as compared to the absence of ectoine.
The protective properties of ectoine result from the increase of the inelastic scattering probabilities of low energy electrons at the acoustic vibrational modes of water and its properties as OH-radical scavenger.
This was shown by Raman spectroscopy and electron paramagnetic resonance measurements (EPR).
The overall interest in nanotoxicity, triggered by the increasing use of nanomaterials in the material and life sciences, and the synthesis of an ever increasing number of new functional nanoparticles calls for standardized test procedures1,2 and for efficient approaches to screen the potential genotoxicity of these materials. Aiming at the development of fast and easy to use, automated microscopic methods for the determination of the genotoxicity of different types of nanoparticles, we assess the potential of the fluorometric γH2AX assay for this purpose. This assay, which can be run on an automated microscopic detection system, relies on the detection of DNA double strand breaks as a sign for genotoxicity3. Here, we provide first results obtained with broadly used nanomaterials like CdSe/CdS and InP/ZnS quantum dots as well as iron oxide, gold, and polymer particles of different surface chemistry with previously tested colloidal stability and different cell lines like Hep-2 and 8E11 cells, which reveal a dependence of the genotoxicity on the chemical composition as well as the surface chemistry of these nanomaterials. These studies will be also used to establish nanomaterials as positive and negative genotoxicity controls or standards for assay performance validation for users of this fluorometric genotoxicity assay. In the future, after proper validation, this microscopic platform technology will be expanded to other typical toxicity assays.
In der Berliner Sammlung "Manuscripta Americana" befinden sich Fragmente von Bilderhandschriften, die Alexander von Humboldt 1804 in Mexiko erwarb und der Königlichen Bibliothek schenkte. Die in der frühen Kolonialzeit hergestellten verschiedenartigen Codices waren damals schon nicht mehr an den Orten ihrer ursprünglichen Verwendung. Entsprechend ihres Seltenheitswertes gelangten einzelne Schriftstücke seit der Conquista in die Bestände bedeutender Persönlichkeiten. Hierzu fertigte man auch Abschriften oder Kopien an, oder zerstückelte sogar einzelne Blätter, so dass die Darstellungen auf den abgetrennten Fragmenten oft nur zum Teil abgebildet vorliegen.
Um herauszufinden, ob einige Schriftstücke der "Humboldt Codices" in Bezug zu einander stehen, werden die Dokumente, ihre Symbole und Schriftzeichen und das zur Herstellung verwendete Material miteinander verglichen.
Mit den für die Analyse von Manuskripten bewährten Untersuchungsmethoden werden Papier und Farbmittel identifiziert. Hierzu zählen Raman-, FTIR-, Röntgenfluoreszenz- und VIS- Spektroskopie. Charakteristisch für die Herstellung von schriftlichen Dokumenten in der Kolonialzeit von Amerika ist die Verwendung von indigenem Material wie Papier aus Baumrinde und Pflanzenfarben zusammen mit den aus Europa bekannten Materialien. Geklärt wird, inwieweit neben den bekanntesten Farbstoffen wie Cochenille, Mayablau oder Mischungen mit Tonmineralen auch mineralische Pigmente zum Einsatz kamen.
Vorgestellt werden die auf Tafel 36 in den "Vues des Cordillères et Monuments des Peuples Indigènes de l`Amerique, Voyage de Humboldt et Bonpland" abgebildeten Fragmente. Die hier von Humboldt vorgenommene Zusammenstellung wird mit der Farbpalette der in Berlin archivierten originalen Schriftstücke verglichen. Die Interpretation der Ergebnisse gibt einen Hinweis auf die Zuordnung oder auch Zusammengehörigkeit dieser einzigartigen Dokumente amerikanischer Geschichte. Hierbei wird die Frage aufgeworfen, inwiefern davon auszugehen ist, dass diese mit weiteren Fragmenten in Verbindung gebracht werden können, was für die Beleuchtung der kulturhistorischen Zusammenhänge von großer Bedeutung ist.
Non-invasive Cereal Analysis by GC-MS detection of Trichodiene as a Volatile Mycotoxin Biomarker
(2018)
Due to the increasing consumption of cereals worldwide, the monitoring of growth, storage and processing is becoming more and more crucial. Particularly when stored, infested grains breed fungal clusters (“hot spots”) in which mycotoxins greatly exceed allowed maximum levels. Because of their unpredictable presence, current sample drawing and procedures for mycotoxin analysis represent a complex challenge for operators, involving invasive and cost intensive steps.
Therefore, new time- and labour-saving mycotoxin control methods including sampling and analysis steps are needed. A possible approach is the non-invasive analysis of the homogeneous gas phase above the crops, instead of analyzing random samples. However, this procedure requires microbial volatile organic compounds (MVOC´s) being released by the samples and representing the present mycotoxins. Previous investigations revealed trichodiene to be a precursor in trichothecenes biosynthesis – one of the largest mycotoxin groups with over 180 compounds. Due to its non-functionalized sesquiterpene structure, trichodiene has already been quantified using Headspace GC-MS methods (for instance]). Thereby, it can possibly be used as a biomarker for trichothecene contamination in foodstuff.
However, further investigations are necessary. The correlation between trichodiene concentration in the gas phase and trichothecenes mass fraction in the sample must be examined closely to draw conclusions about the exact trichothecene content within samples. Realizing this idea, would widely extend the applicability of trichodiene and enormously simplify trichothecene quantification. Hence, this first step of an ongoing study aims to develop a laboratory reference method using trichodiene as volatile biomarker to quantify trichothecenes in cereals. Static headspace and SPME-enrichment coupled to gas chromatography with mass spectrometry (GC-MS) were employed. In a second step, this reference method is intended to validate new approaches for fast on-site screening of trichodiene in cereals.
Non-invasive Cereal Analysis by GC-MS detection of Trichodiene as a Volatile Mycotoxin Biomarker
(2018)
Due to the increasing consumption of cereals worldwide, the monitoring of growth, storage and processing is becoming more and more crucial. Particularly when stored, infested grains breed fungal clusters (“hot spots”) in which mycotoxins greatly exceed allowed maximum levels. Because of their unpredictable presence, current sample drawing and procedures for mycotoxin analysis represent a complex challenge for operators, involving invasive and cost intensive steps.
Therefore, new time- and labour-saving mycotoxin control methods including sampling and analysis steps are needed. A possible approach is the non-invasive analysis of the homogeneous gas phase above the crops, instead of analyzing random samples. However, this procedure requires microbial volatile organic compounds (MVOC´s) being released by the samples and representing the present mycotoxins. Previous investigations revealed trichodiene to be a precursor in trichothecenes biosynthesis – one of the largest mycotoxin groups with over 180 compounds. Due to its non-functionalized sesquiterpene structure, trichodiene has already been quantified using Headspace GC-MS methods (for instance). Thereby, it can possibly be used as a biomarker for trichothecene contamination in foodstuff.
However, further investigations are necessary. The correlation between trichodiene concentration in the gas phase and trichothecenes mass fraction in the sample must be examined closely to draw conclusions about the exact trichothecene content within samples. Realizing this idea, would widely extend the applicability of trichodiene and enormously simplify trichothecene quantification. Hence, this first step of an ongoing study aims to develop a laboratory reference method using trichodiene as volatile biomarker to quantify trichothecenes in cereals. Static headspace and SPME-enrichment coupled to gas chromatography with mass spectrometry (GC-MS) were employed. In a second step, this reference method is intended to validate new approaches for fast on-site screening of trichodiene in cereals.
Zearalenone (ZEN) and its sulfate and glucoside conjugates have been detected in (a broad variety of) food and feed commodities1. Both conjugated derivatives are formed as part of fungal or plant secondary metabolism and thus, belong to the group of modified mycotoxins2. After consumption of contaminated foodstuff, the conjugates can be hydrolyzed by human intestinal microbiota leading to liberation of ZEN that implies an underestimation of the true ZEN exposure. In order to include ZEN conjugates in routine analysis, as well as for toxicological investigation reliable standards are needed.
The objective of the present study was to develop a simple and economic method for biosynthesis of ZEN conjugates. Preceding experiments on the biotransformation of ZEN by Rhizopus and Aspergillus species showed a mixed metabolite formation3. Therefore, these known ZEN conjugating fungal strains were screened for their potential to selectively synthesize the ZEN derivatives ZEN-14-sulfate (Z14S), ZEN-14-glucoside (Z14G) and ZEN-16-glucoside (Z16G). The screening was conducted by adding ZEN to liquid fungal cultures. Cultivation conditions and ZEN incubation time were varied. All media samples were analyzed for metabolite formation by HPLC-MS/MS. Z14S was exclusively formed by A. oryzae. Under optimized conditions a specific biosynthesis of Z14G by R. oryzae and Z16G by R. oligosporus was achieved. After liquid-liquid-extraction and preparative chromatographic cleanup 1H-NMR purities of ≥ 73% for Z14S, ≥ 82% for Z14G and ≥ 50% for Z16G were obtained. In addition, a consecutive biosynthesis was developed by first using Fusarium graminearum for ZEN biosynthesis on rice based liquid medium. After inactivation of Fusarium the subsequent conjugation reaction was conducted utilizing Aspergillus and Rhizopus species under the various optimized conditions.
In this study an easy and cost-efficient biosynthesis for Z14S, Z14G and Z16G was developed. The developed biosynthesis could be also used for other metabolites like ZEL conjugates. Our results of the in vitro screening indicate also the formation of a ZEL-glucoside and α ZEL-sulfate as major metabolites by R. oryzae. In sum, under optimized cultivation conditions fungi can be easily utilized for a targeted and stereospecific synthesis of ZEN conjugates.
Imaging of elemental distributions in single cell assays as well as tissue sections can be performed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). This powerful technique offers precise spatially resolved measurements at the trace and ultratrace level and has been established as an excellent tool to answer analytical, biological and biomedical questions. To date, imaging mass cytometry is already able to simultaneously detect up to 40 cellular targets due to conjugation of isotopically pure lanthanides to affinity binders, e.g. antibodies.
To further enhance the ability of multiparametric analysis to more than 100 analytes at once, we investigated lanthanide nanocrystals as new, highly sensitive metal tags for identification of targets in clinical cell assays and tissue samples. Multiparametric analysis will be possible by encoding the lanthanide composition of nanocrystals associated to the affinity binders. Nanocrystals showed remarkable potential for sensitive detection in MS due to high stability and signal amplification compared to e.g. polymer tags, carrying fewer metal atoms.
Synthesis of functionalized lanthanide nanocrystals for further bioconjugation was performed with high reproducibility and monodisperse size distribution. For proof of principle, the uptake and distribution of these nanocrystals within the monolayered cell line A549 were investigated by mapping the intensities at subcellular resolution using LA-ICP-MS. It could be shown, that the cells were efficiently labeled with the nanocrystals and mostly accumulate near the nucleus. Additionally, the bioconjugation of the nanocrystals to antibodies and particularly the preservation of the antibody specificity was investigated using Dot Blot experiments. All in all, the results imply high sensitivity and the possibility of multiparametric analysis by doting various lanthanides into the nanocrystals.
Due to their toxicity and widespread application for mining and industrial purposes, cyanides are ranking among the most important inorganic pollutants which should be tested and monitored not only in the aquatic environment, but also in soils and soil-like materials. Reference materials of soils with relevant contents of cyanide to ensure reliable test results of laboratories are rare today.
New certified reference material (CRM) BAM-U116/CGL306 “Cyanide in soil” was produced within a framework of cooperation between Central Geological Laboratory (CGL) of Mongolia and Federal Institute for Materials Research and Testing (BAM) of Germany in 2013-2017.
The CRM BAM-U116/CGL306 represents a mixture of a sandy soil collected from a contaminated former gasworks area in the Berlin region (Germany) and an unpolluted sandy soil from Nalaikh region (Mongolia). The bulk candidate material for this reference material was prepared at CGL CRM Laboratory exclusively destined to the preparation of reference materials and equipped with modern technical equipment. Homogeneity, stability and shelf life were studied in full compliance with ISO Guide 35. The CRM was evaluated as sufficiently homogeneous. Statistical evaluation of certification analysis was performed using software packages SoftCRM and ProLab Plus. Certified value of total cyanide of the CRM is 12.0 mg/kg and expanded uncertainty was assigned as 0.8 mg/kg.
The intended purpose of this material is the verification of analytical results obtained for the mass fraction of total cyanide in soils and soil-like materials applying the standardized procedure ISO 11262:2011. As any reference material, it can also be used for routine performance checks (quality control charts) or validation studies.
Due to the increasing consumption of cereals worldwide, monitoring of growth, storage and processing is becoming more crucial. Particularly when stored, infested grains breed fungal clusters (“hot spots”) in which mycotoxins greatly exceed allowed maximum levels. Because of their unpredictable presence, current sampling and procedures for mycotoxin analysis are complex and contain invasive and cost intensive steps.
A possible approach to avoid sampling inaccuracies is the non-invasive analysis of the homogeneous gas phase above the crops, instead of analyzing random samples. However, this procedure requires microbial volatile organic compounds (MVOC´s) being released by the samples. Previous investigations revealed trichodiene to be a precursor in trichothecenes biosynthesis – one of the largest mycotoxin groups with more than 180 compounds. Due to its non-functionalized sesquiterpene structure, quantification of trichodiene using Headspace GC-MS methods is possible (e.g. [1]). Thereby, it could be used as biomarker for trichothecene contamination in foodstuff.
However, further studies are necessary. The correlation between trichodiene concentration in the gas phase and trichothecenes mass fraction in the sample must be examined closely to draw conclusions about the trichothecene content in samples. Realizing this idea, would widely extend the applicability of trichodiene and enormously simplify trichothecene quantification. Hence, this first step of an ongoing study aims to develop a laboratory reference method using trichodiene as volatile biomarker to quantify trichothecenes in cereals. Static headspace and SPME-enrichment coupled to gas chromatography with mass spectrometry (GC-MS) were employed. In a second step, this reference method is intended to validate new approaches for fast on-site screening of trichodiene in cereals.
Statistic process control as well as process capability demand for calibrated determination of layer thicknesses in various industries, e.g. automotive, aerospace, microelectronics manufacturing. Calibration requires well know and well characterized samples. A calibration laboratory accredited according to DIN EN ISO 17025 has the objective to distribute standards traceable to SI units to industrial laboratories for quality control of manufacturing of various products. Especially, the thickness determination of thin metallic coatings e.g. from galvanic processes or layer deposition using X-Ray Fluorescence can be significantly improved by customized calibration samples. This is essential as the measurement uncertainty directly correlates to the capability performing reliable control of processes with high yield. For calibration laboratories, the validation of results using round robins and the direct comparison to national metrology institutes is a prerequisite to demonstrate the competence to perform calibration services.
In this paper a strategy to obtain traceability and validation for thin alloy layers as well as first results are presented. The combined use of the accredited method for determination of mass per area from measurement of mass and area combined with standard free X-Ray Fluorescence as well as chemical analysis of dissolved samples with thin layers is deployed for material systems as NixZn1-x as well as NixP1-x. The obtained results are compared to reference free X-Ray Fluorescence at the BESSY II laboratories of Physikalisch-Technische Bundesanstalt. An excellent agreement of the obtained measured values as mass per unit area and alloy concentrations from the different applied methods within the measurement uncertainty was observed for NixP1-x showing the successful performed traceability of the calibration samples to SI units in combination with a validation of results by national metrology institutes and the round robin approach.
Ionische Flüssigkeiten als neuartige Sensorbeschichtung für coulometrische Spurenfeuchtesensoren
(2018)
Die Arbeit präsentiert erste Messungen mit coulometrischen Sensoren, die mit einer ionischen Flüssigkeit beschichtet sind. Diese Sensoren werden in der Industrie verwendet, um die Spurenfeuchte in unterschiedlichen Gasen zu messen. Normalerweise erfolgt eine Beschichtung der Sensoren mit Phosphorpentoxid und dessen Hydrolyseprodukte. In dieser Arbeit wurde stattdessen eine hygroskopische ionische Flüssigkeit benutzt. Die generierte Gasfeuchte für die Untersuchungen betrug bezogen auf die Frostpunkttemperatur -80 °C bis -30 °C, was gleichbedeutend mit einem Wasserdampf-Stoffmengenanteil von 0,5 μmol·mol-1 bis 376 μmol·mol-1 ist. Zusätzlich zu der Messung mit coulometrischen Sensoren erfolgte eine Referenzmessung der Gasfeuchte mittels eines Taupunkthygrometers. Erste Ergebnisse haben gezeigt, dass es möglich ist mit dieser Art der Beschichtung unterschiedliche Gasfeuchten zu messen. Aber es ergaben sich trotz gleicher Feuchte unterschiedliche Signalintensitäten bei den benutzen Sensoren und es zeigte sich eine Drift des Sensorsignales.
Ionische Flüssigkeiten als neuartige Sensorbeschichtung für coulometrische Spurenfeuchtesensoren
(2018)
Die Arbeit präsentiert erste Messungen mit coulometrischen Sensoren, die mit einer ionischen Flüssigkeit beschichtet sind. Diese Sensoren werden in der Industrie verwendet, um die Spurenfeuchte in unterschiedlichen Gasen zu messen. Normalerweise erfolgt eine Beschichtung der Sensoren mit Phosphorpentoxid und dessen Hydrolyseprodukte. In dieser Arbeit wurde stattdessen eine hygroskopische ionische Flüssigkeit benutzt. Die generierte Gasfeuchte für die Untersuchungen betrug bezogen auf die Frostpunkttemperatur -80 °C bis -30 °C, was gleichbedeutend mit einem Wasserdampf-Stoffmengenanteil von 0,5 μmol·mol-1 bis 376 μmol·mol-1 ist. Zusätzlich zu der Messung mit coulometrischen Sensoren erfolgte eine Referenzmessung der Gasfeuchte mittels eines Taupunkthygrometers. Erste Ergebnisse haben gezeigt, dass es möglich ist mit dieser Art der Beschichtung unterschiedliche Gasfeuchten zu messen. Aber es ergaben sich trotz gleicher Feuchte unterschiedliche Signalintensitäten bei den benutzen Sensoren und es zeigte sich eine Drift des Sensorsignales.
Carbamazepine (CBZ) and cetirizine (CTZ) are pharmaceutical drugs detected in the aquatic environment. However, the effects to marine invertebrates derived from the combination of these drugs with decreased pH conditions due to ocean acidification are poorly explored. This study investigated the biochemical parameters related to metabolic capacity and oxidative stress response and the transcription of genes related to the mode of action (MoA) of CBZ (1.0 μg/L) and CTZ (0.6 μg/L) in the clam Ruditapes philippinarum chronically exposed (28 days) to control (7.8) and low (7.5) pH conditions. The biochemical parameters applied were: the activity of electron transport system (indicator of organisms’ metabolic capacity); lipid peroxidation content (indicator of cell damage); total glutathione peroxidase activity (indicator of antioxidant defense). The transcription of genes related with drug neurotransmission and metabolism, cell defense and immunity and biomineralization was studied. No metabolic changes and oxidative stress was induced by the exposure to CBZ or CTZ at each pH level, but the transcription of several genes related with the MoA (neurotransmission, immunity and biomineralization) was altered by low pH, drug exposure and the combination of both stressors. In conclusion, it was shown that the interaction of drug exposure and low pH conditions can change bivalves’ sensitivity to drugs or alter drugs toxicity.
Diclofenac (DCF) is a widely used drug against fever, inflammation, pain, and rheumatic diseases. An average of 70 % of the ingested diclofenac is excreted in the urine. Thus, 63 tons per year are introduced into the water cycle in Germany. Due to insufficient removal of diclofenac in wastewater treatment plants, residues of diclofenac can be found in surface water and sometimes in drinking water. In order to establish an immunoassay, an anti-DCF antibody was required. Some antibody developments have been reported, based on an immunogen resulting from direct coupling of diclofenac to proteins via the carboxylic function. Finally, we used a monoclonal antibody, clone F01G21.
Nach 1850 wurde zur weiteren Herabsetzung der Einbrenntemperatur von Glasmalfarben Borax (Na2B4O7 · 10 H2O) zugesetzt. Das Verhältnis war nun 1 Teil SiO2, 3 Teile PbO und 0,5 Teile Borax. Der analytische Nachweis von Bor in eingebrannten Malschichten war bisher jedoch nicht möglich.Daher wurden in Laborversuchen Glasmalfarben mit unterschiedlichem Gehalt an Borax auf Modellgläser aufgetragen, eingebrannt und anschließend unter simulierten Umweltbedingungen zeitraffend im Klimaschrank bewittert.
Mit Hilfe von elektronenmikroskopischen Untersuchungen können Malschichten charakterisiert werden und somit Hinweise auf mögliche Schadensursachen liefern. Erste Versuche zum Nachweis von Bor erfolgten mit Hilfe von LIBS-Messungen (Laser Induced Breakdown Spectroscopy) an im Labor hergestellten Glasmalfarben mit unterschiedlichem Boraxgehalt.
Nach 1850 wurde zur weiteren Herabsetzung der Einbrenntemperatur von Glasmalfarben Borax (Na2B4O7 · 10 H2O) zugesetzt. Das Verhältnis war nun 1 Teil SiO2, 3 Teile PbO und 0,5 Teile Borax. Der analytische Nachweis von Bor in eingebrannten Malschichten war bisher jedoch nicht möglich.
In Laborversuchen wurden Glasmalfarben mit unterschiedlichem Gehalt an Borax auf Modellgläser aufgetragen, eingebrannt und anschließend unter simulierten Umweltbedingungen zeitraffend im Klimaschrank bewittert. Mit Hilfe von elektronenmikroskopischen Untersuchungen können Malschichten charakterisiert werden und somit Hinweise auf mögliche Schadensursachen liefern. Der Nachweis von Bor erfolgte mit Hilfe von LIBS-Messungen (Laser Induced Breakdown Spectroscopy) an im Labor hergestellten Glasmalfarben mit unterschiedlichem Boraxgehalt.
The interaction of nanoparticles (NPs) with cells has become a major field of interest, ranging from medical applications to nanotoxicology. Size, shape and surface modification of the NPs determine the uptake rate and pathway into the cells, and therefore impact specific cell components and processes.
Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is an established quantitative multi-elemental analysis and mapping technique. In recent years, it was shown that LA-ICP-MS can provide quantitative as well as distribution information of NPs in cell samples.
Here LA-ICP-MS was applied for the imaging of individual cells to study the uptake and intracellular processing of metal-containing nanostructures. Additionally, the local distribution of naturally occurring elements in cells like P was measured to indicate cell morphology. The cells were incubated with different types of NPs under varying experimental conditions. For LA analysis, the cells were fixed and dried.
Our findings show, that LA-ICP-MS is suitable for the localisation of nanoparticle aggregates within cellular compartments. The studied NPs accumulate in the perinuclear region in the course of intracellular processing, but do not enter the cell nucleus. The uptake efficiency depends strongly on the physicochemical properties of the nanostructures as well as on the incubation conditions like concentration and incubation time.
The results demonstrate the potential of LA-ICP-MS providing insight into NP uptake, intracellular distribution and cell-to-cell variation dependent on experimental parameters.
Heritage Lecture
(2018)
After finishing my diploma thesis in plasma physics in 1981, I dreamt of a future in a research lab to develop novel fusion reactors for energy production or to study universal plasmas and their emission in the cosmos. This dream never became real, however I found my first job in a team to build up a new museum dedicated to “Energy”, and this first part of my career was already finished after a year, because the funding was not extended. So, I found immediately a new job as a young scientist in the institute for analytical sciences (originally ISAS: Institute for Plasmachemistry and Applied Spectroscopy) in 1982 to develop novel plasma ion sources for inorganic mass spectrometry. The first source of interest was based on a glow discharge for direct analysis of conducting solids (technically supported by Finnigan MAT, Bremen). Here I adopted the design of the Grimm type discharge for the first time, which was well known in optical emission spectroscopy, and coupled it to a quadrupole mass analyzer. The advantage of this design was that flat craters are produced by sputtering which made this source very powerful for in-depth analysis of technical layers. This then became the topic of my PhD, which was not originally planned, and I had to learn a lot about surface analysis. However, since the first project was too successful we established a small team (in cooperation with Jose Broekaert - an expert in ICP-OES) which started with the development of our own inductively coupled plasma ion source in 1986 coupled to a quadrupole and in 1989 to a sector field mass spectrometer (funded by the Minister of Science and Technology; again in cooperation with Finnigan MAT). The latter device was launched to the market in 1993 as the Element 1.
The second decade of my career was still related to instrumental development but mainly of glow discharge sources. In an EU funded project first an automated glow discharge sector field instrument was developed where the Grimm type geometry was combined with a fast flow concept (in cooperation with Volker Hoffmann at IFW in Dresden). This was done in cooperation with VG (which became later a part of Thermo Fisher Scientific together with Finnigan MAT), so that it is not surprising that this concept for the Element GD. This project was later continued in the third phase of my career, again funded by the EU and in cooperation with the group of Alfredo Sanz-Medel (Rosario Pereiro and Jorge Pisonero), to develop a fast flow, but now rf-powered GD ion source in combination with a time-of-flight mass spectrometer, which was later launched to the market commercially by Horiba Jobin Yvon (France) for in-depth profiling of thin layers even of non-conducting materials.
In the first decade of my career I started to study already “analytical chemistry” from the scratch because the instruments developed have been applied now for direct analysis of solid materials, technical layers and environmental samples. In case of environmental applications our ICP-MS (the quadrupole and the sector field instrument) was coupled with separation techniques, so that this period of instrumental development was dominated in the second decade by development of high efficiency sample introduction systems in combination with speciation studies of Pt group elements, arsenic, selenium and phosphorus (in DNA and phosphorylated proteins), Ni and Cr. Additionally, we continued with the analysis of solid ceramic materials (Al2O3, SiC, SiN) and ambient air-born particles. At the end of the second decade we complemented our instrumental pool by a collision and reaction cell instrument in cooperation with Micromass and used this instrument for speciation studies of peptides and proteins and demonstrated that by ICP-HEX-MS quantitative proteomics is feasible. Therefore, we more and more focused in the following years on metalloproteins and published a famous paper on “Metallobiomolecules: The basis of life, the challenge of atomic spectroscopy” (together with Luc Moens and Ryszard Lobinski). For detection of metalloproteins we applied typical workflows of biochemistry and proteomics, for which I had to extend my knowledge about biochemistry and proteomics. As a new analytical tool, we used a homemade laser ablation cell for sample introduction of metalloproteins after their separation by gel electrophoresis and extended this work by applying metal-tagging of antibodies for Western blot assays. For this purpose, proteins were separated in SDS-PAGE and electroblotted onto membranes. Specific detection of proteins even not containing any metal could be performed by laser ablation ICP-MS using the metal tagged antibodies for indirect detection. This research was interrupted in 2009 by a movement from ISAS (where atomic spectroscopy was declining) to BAM (the Federal Institute for Materials Research and Testing, Berlin) where this research direction was fostered. The experience we achieved at ISAS in the previously mentioned projects were now used here at BAM in the fourth decade for materials research and the development of a quantitative elemental microscope with cellular resolution. So, at the end of my career I am trying to apply all my knowledge and expertise to develop analytical methods and to apply multimodal spectroscopies to decipher the construction code of the cellular machinery, which is the most precise and complex machinery I have ever seen. If we were able to understand how this machinery works, we can better diagnose and treat a malfunction in case of the development of a disease.
Finally, I can conclude that lifelong learning starts before school but does not end at the end of this lecture. It looks like this heritage lecture will be focused on my career only, but this is not the case because some highlights of my career will be used to illustrate a few universal principles: how to have fun, how to find friends and how this all leads to an increase of joy and joy is the basis of new ideas (which must not always be related to your profession) and novel ideas are essential for a successful and satisfying career. So, this heritage lecture wants to answer the most important question of a life which was dedicated to plasma spectrochemistry:
1) Is it possible - at all - to have fun in this research direction?
2) Can we learn already today what we need tomorrow?
3) How can we still realize our scientific dreams of cutting edge research in times of cutting budgets? Which automatically leads to the next question:
4) Is necessity the mother of invention?
All questions will be answered! Controversial discussions (for angry or disappointed colleagues) will be stimulated and my visions of future research (for students and postdocs) and instrumental developments (for manufacturer) will be presented. Finally, conclusions will be drawn by the auditorium (everybody) and thanks will be given to Ramon Barnes (by me) already in advance!
Heritage Lecture
(2018)
After finishing my diploma thesis in plasma physics in 1981, I dreamt of a future in a research lab to develop novel fusion reactors for energy production or to study universal plasmas and their emission in the cosmos. This dream never became real, however I found my first job in a team to build up a new museum dedicated to “Energy”, and this first part of my career was already finished after a year, because the funding was not extended. So, I found immediately a new job as a young scientist in the institute for analytical sciences (originally ISAS: Institute for Plasmachemistry and Applied Spectroscopy) in 1982 to develop novel plasma ion sources for inorganic mass spectrometry. The first source of interest was based on a glow discharge for direct analysis of conducting solids (technically supported by Finnigan MAT, Bremen). Here I adopted the design of the Grimm type discharge for the first time, which was well known in optical emission spectroscopy, and coupled it to a quadrupole mass analyzer. The advantage of this design was that flat craters are produced by sputtering which made this source very powerful for in-depth analysis of technical layers. This then became the topic of my PhD, which was not originally planned, and I had to learn a lot about surface analysis. However, since the first project was too successful we established a small team (in cooperation with Jose Broekaert - an expert in ICP-OES) which started with the development of our own inductively coupled plasma ion source in 1986 coupled to a quadrupole and in 1989 to a sector field mass spectrometer (funded by the Minister of Science and Technology; again in cooperation with Finnigan MAT). The latter device was launched to the market in 1993 as the Element 1.
The second decade of my career was still related to instrumental development but mainly of glow discharge sources. In an EU funded project first an automated glow discharge sector field instrument was developed where the Grimm type geometry was combined with a fast flow concept (in cooperation with Volker Hoffmann at IFW in Dresden). This was done in cooperation with VG (which became later a part of Thermo Fisher Scientific together with Finnigan MAT), so that it is not surprising that this concept for the Element GD. This project was later continued in the third phase of my career, again funded by the EU and in cooperation with the group of Alfredo Sanz-Medel (Rosario Pereiro and Jorge Pisonero), to develop a fast flow, but now rf-powered GD ion source in combination with a time-of-flight mass spectrometer, which was later launched to the market commercially by Horiba Jobin Yvon (France) for in-depth profiling of thin layers even of non-conducting materials.
In the first decade of my career I started to study already “analytical chemistry” from the scratch because the instruments developed have been applied now for direct analysis of solid materials, technical layers and environmental samples. In case of environmental applications our ICP-MS (the quadrupole and the sector field instrument) was coupled with separation techniques, so that this period of instrumental development was dominated in the second decade by development of high efficiency sample introduction systems in combination with speciation studies of Pt group elements, arsenic, selenium and phosphorus (in DNA and phosphorylated proteins), Ni and Cr. Additionally, we continued with the analysis of solid ceramic materials (Al2O3, SiC, SiN) and ambient air-born particles. At the end of the second decade we complemented our instrumental pool by a collision and reaction cell instrument in cooperation with Micromass and used this instrument for speciation studies of peptides and proteins and demonstrated that by ICP-HEX-MS quantitative proteomics is feasible. Therefore, we more and more focused in the following years on metalloproteins and published a famous paper on “Metallobiomolecules: The basis of life, the challenge of atomic spectroscopy” (together with Luc Moens and Ryszard Lobinski). For detection of metalloproteins we applied typical workflows of biochemistry and proteomics, for which I had to extend my knowledge about biochemistry and proteomics. As a new analytical tool, we used a homemade laser ablation cell for sample introduction of metalloproteins after their separation by gel electrophoresis and extended this work by applying metal-tagging of antibodies for Western blot assays. For this purpose, proteins were separated in SDS-PAGE and electroblotted onto membranes. Specific detection of proteins even not containing any metal could be performed by laser ablation ICP-MS using the metal tagged antibodies for indirect detection. This research was interrupted in 2009 by a movement from ISAS (where atomic spectroscopy was declining) to BAM (the Federal Institute for Materials Research and Testing, Berlin) where this research direction was fostered. The experience we achieved at ISAS in the previously mentioned projects were now used here at BAM in the fourth decade for materials research and the development of a quantitative elemental microscope with cellular resolution. So, at the end of my career I am trying to apply all my knowledge and expertise to develop analytical methods and to apply multimodal spectroscopies to decipher the construction code of the cellular machinery, which is the most precise and complex machinery I have ever seen. If we were able to understand how this machinery works, we can better diagnose and treat a malfunction in case of the development of a disease.
Finally, I can conclude that lifelong learning starts before school but does not end at the end of this lecture. It looks like this heritage lecture will be focused on my career only, but this is not the case because some highlights of my career will be used to illustrate a few universal principles: how to have fun, how to find friends and how this all leads to an increase of joy and joy is the basis of new ideas (which must not always be related to your profession) and novel ideas are essential for a successful and satisfying career. So, this heritage lecture wants to answer the most important question of a life which was dedicated to plasma spectrochemistry:
1) Is it possible - at all - to have fun in this research direction?
2) Can we learn already today what we need tomorrow?
3) How can we still realize our scientific dreams of cutting edge research in times of cutting budgets? Which automatically leads to the next question:
4) Is necessity the mother of invention?
All questions will be answered! Controversial discussions (for angry or disappointed colleagues) will be stimulated and my visions of future research (for students and postdocs) and instrumental developments (for manufacturer) will be presented. Finally, conclusions will be drawn by the auditorium (everybody) and thanks will be given to Ramon Barnes (by me) already in advance!
Mykotoxine werden als sekundäre Metabolite von Schimmelpilzen gebildet und haben diverse schädliche Effekte auf Menschen, Tiere und Pflanzen. Laut FAO sind weltweit bis zu 25 % aller Lebens- und Futtermittel mit Mykotoxinen kontaminiert, wodurch jährlich immense ökonomische Verluste entstehen.
Neben den eigentlichen Mykotoxinen rücken zunehmend deren Transformationsprodukte (TPs) in den Fokus. Diese können als natürliche Stoffwechselprodukte toxischer sein als das eigentliche Mykotoxin und stellen eine potenzielle zusätzliche Gefahr für den Verbraucher dar. TPs werden überwiegend mit in vitro und in vivo Techniken untersucht, welche sowohl zeit- als auch kostenintensiv sind. Ziel war es nun, schnelle und zudem verlässliche Techniken zur Simulation von TPs diverser Mykotoxine zu testen. Die Kopplung von Elektrochemie und Massenspektrometrie, kurz EC/MS, als rein instrumenteller Ansatz ist seit vielen Jahren in der pharmazeutischen Forschung etabliert. Hierbei wird mithilfe einer elektrochemischen Durchflusszelle der oxidative Metabolismus einer Substanz simuliert und zugleich analysiert.
Unter Verwendung von EC/MS, EC/LC/MS und HPLC-MS Techniken (MS/MS und FT-ICR) wurden nun die Mykotoxine Zearalenon, Citrinin und Dihydroergocristin (als Modellsubstanz für die Ergotalkaloide) elektrochemisch bei Potentialen bis zu 2500 mV vs. Pd/H2 oxidiert und deren TPs mit mikrosomalen in vitro Ansätzen verglichen. Hierbei konnten mehrere Übereinstimmungen hydroxylierter Spezies, sowohl elektrochemisch als auch biochemisch generiert, festgestellt werden. Die EC/MS ist somit auch in der Lebensmittelanalytik als nützliches und vielseitiges Werkzeug verwendbar.
Hydrogen determination in weld seams is standardized in ISO 3690. In accordance to this standard, a defined time for hydrogen collection has to be anticipated for different extraction temperatures. In other words, the temperature is the most important value that has to be monitored in addition to the aimed hydrogen determination.
The specimen geometry has influence on the real sample temperature during CGHE vs. the adjusted furnace temperature. This presentation gives a short summary on possible influences on the "correct" hydrogen determination temperature during carrier gas hot extraction (CGHE) using infrared radiation driven furnace. The main findings are: (1) specimen surface is important in terms of polished or oxidized condition, (2) specimen geometry is important for fast heating, (3) PID-values of control software are a considerable influence to accelerate the heating process depite thick specimens and (4) independent sample temperature determination before CGHE is strongly recommended.
Silver nanoparticles (AgNPs), have a high scientific and commercial impact due to their important antibacterial properties. However, there are serious concerns about their toxicological adverse effects as a consequence of their broad range of applications. Particularly, the impact of AgNPs on cells is not very well understood yet and there is a current demand to develop analytical methodologies providing information about the interaction and distribution of AgNPs at a single cell level. In this research, mass cytometry was used to introduce a new quantitative approach to study the uptake of AgNPs by individual THP-1 macrophages as a cell model system. Here, we show that this methodology provides not only multi-variate phenotypic information of individual cells but enables the quantitative analysis of AgNPs associated to cells in a single measurement by performing an external calibration using AgNPs suspension. Using differentiated THP-1 cells, we monitored and quantified the uptake of 50 nm AgNPs in a time and dose-dependent manner by mass cytometry. 7 to 120 AgNPs per cell (2 to 89 fg Ag/cell) were determined after exposure of differentiated THP-1 cells to low AgNPs concentrations of 0.1 and 1.0 mg L-1, at time points of 4 and 24 h. The results were validated by mass cytometric analysis of digested cells working as a conventional inductively coupled plasma mass spectrometry, ICP-MS. This study demonstrates the power of single cell analysis by mass cytometry even for low doses experiments as a new analytical tool for hitherto unaddressed questions in nanotoxicology.
Alternariol (AOH) and Alternariol monomethylether (AME) are two secondary metabolites of Alternaria fungi which can be found in various foodstuffs like tomatoes, nuts and grains. Due to their toxicity and potential mutagenic activity the need for the development of high-throughput methods for the supervision of AOH- and AME-levels is of increasing interest. As the availability of both native and labelled AOH and AME analytical standards is very limited we herein wish to present a novel concise approach towards their synthesis employing a ruthenium-catalyzed ortho-arylation4 as the key step.
Multivariate analysis of MALDI imaging mass spectrometry data of mixtures of single pollen grains
(2018)
Here, we present an advanced approach to identify pollen grains in mixtures based on:
- a simplified sample preparation procedure
- MALDI imaging mass spectrometry
- chemometric tools
Our goals are to:
- explore the biomolecular variations in pollen
- determine species-specific peak patterns
- discriminate and identify single pollen grains in mixtures using MSI
Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is gaining importance for bioimaging cytometry to answer analytical, biological and biomedical questions. High sensitivity and spatial resolution make it an excellent tool for imaging of metal and heteroelement distribution in single cells. Comparable to CyTOF imaging mass cytometry, metal coded antibodies can be used for multiparametric analysis as well as quantification.
In this project, nanocrystals are investigated as new highly sensitive metal tags for identification and quantification of biomarkers, like Alzheimer’s or breast cancer, in clinical cell assays and tissue samples. Of high significance is the simultaneous analysis of several biomarkers at once, which is possible by special coding of lanthanide tags on the biomarker associated antibody. Nanocrystals show potential for sensitive measurement in MS due to high stability and signal amplification compared to tags with fewer metal atoms. For proof of principle, synthesis and characterization of lanthanide doped nanocrystals was performed by a nanoPET pharma GmbH with great reproducibility and homogenous size. In A549 cell cultures, the uptake and distribution of these nanocrystals within the monolayered cells was investigated by LA-ICP-MS measurements using subcellular resolution. The nanocrystals showed high sensitivity and the possibility of multiparametric analysis by doting different lanthanides. Additionally, stability of the bioconjugation of the nanocrystals and target antibodies was investigated using Dot Blot experiments and LA-ICP-MS.
The common characterization and identification of pollen is a time-consuming task that mainly relies on microscopic determination of the genus-specific pollen morphology. A variety of spectroscopic and spectrometric approaches have been proposed to develop a fast and reliable pollen identification using specific molecular information. Amongst them, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) shows a high potential for the successful investigation of such complex biological samples. Based on optimized MALDI sample preparation using conductive carbon tape, the application of multivariate statistics (e.g. principal components analysis, PCA) yields an enormous improvement concerning taxonomic classification of pollen species compared to common microscopic techniques.
Since multivariate evaluation of the recorded mass spectra is of vital importance for classification, it’s helpful to implement the applied sequence of standard Matlab functions into a graphical user interface (GUI). In this presentation, a stand-alone application (GUI) is shown, which provides multiple functions to perform fast multivariate analysis on multiple datasets. The use of a GUI enables a first overview on the measured dataset, conducts spectral pretreatment and can give classification information based on HCA and PCA evaluation. Moreover, it can be used to improve fast spectral classification and supports the development of a simple routine method to identify pollen based on mass spectrometry.
Hepcidin-25 has attracted much attention ever since its discovery in 2001. It is widely recognized that this peptide hormone plays a major role in the regulation of iron levels in mammals and can reveal important clinical information about several iron-related disorders. However, the development of a reliable assay to quantify hepcidin proved to be problematic and serum hepcidin-25 concentrations determined by various assays differ substantially. Challenges arise in the MS analysis of hepcidin due to the “sticky” character of the peptide and the lack of suitable standards.
With the aim to tackle the current difficulties in hepcidin quantification and improve the status of this promising biomarker in the clinical field, we developed a rapid and robust analytical strategy for the quantification of hepcidin-25 in human samples based on HPLC-MS/MS (QqQ) as a reference method candidate to be implemented in routine laboratories. The novelty of the method is the use of amino- and fluoro-silanized autosampler vials to reduce hepcidin interaction to laboratory glassware surfaces. Furthermore, we have investigated two sample preparation strategies and two chromatographic separation conditions where the use of acidic mobile phases was compared with a novel approach involving solvents at high pH containing 0.1% of ammonia. Both methods were carefully validated and applied to clinical samples in an intra-laboratory comparison of two LC-MS/MS methods using the same hepcidin-25 calibrators with very good correlation of the results.
Analyse des Tausalzeintrages in Fahrbahndeckenbetone im Kontext der Alkali-Kieselsäure-Reaktion
(2018)
In den letzten Jahren sind im deutschen Bundesautobahnnetz (BAB-Netz) vermehrt AKR-Schäden an Betonfahrbahndecken aufgetreten, die zum Teil zu einer Halbierung ihrer geplanten Nutzungsdauer von 30 Jahren führte. Ursächlich hierfür ist die Verwendung alkaliempfindlicher Gesteinskörnung, die bei gleichzeitiger Anwesenheit von Wasser infolge der Exposition der Fahrbahndecke und dem alkalischen Milieu durch den Einsatz alkalireicher Portlandzemente bei der Betonherstellung zu einer Alkali-Kieselsäure-Reaktion (AKR) führt. Zusätzlich wird der AKR-Schädigungsprozess in Betonfahrbahndecken durch den externen Tausalzeintrag (primär NaCl) im Winter begünstigt. Vor diesem Hintergrund kommt der Ermittlung des Tausalzeintrags in den Fahrbahndeckenbeton eine große Bedeutung zu. Die Analyse des Tausalzeintrags erfolgte bisher ausschließlich nasschemisch an gemahlenen Bohrkernsegmenten. Nachteilig ist hierbei die fehlende differenzierte Betrachtung des Natriumgehaltes im Zementstein und in der Gesteinskörnung. Der alternative Einsatz von LIBS (Laser-induced breakdown spectroscopy) eröffnet in diesem Kontext neue Möglichkeiten. So wird in diesem Beitrag an Hand von Bohrkernen aus einem AKR-geschädigten BAB-Abschnitt exemplarisch die Vorgehensweise bei der LIBS-Analyse zur Ermittlung der Na- und interagierenden Cl-Verteilung an vertikalen Schnittflächen des Bohrkerns aufgezeigt. Da der Tausalzeintrag primär über den Zementstein erfolgt, wurde der verfälschende Na-Grundgehalt der Gesteinskörnung mittels Zementsteinkriteriums (Nutzung unterschiedlichen Ca-Gehalts in Zementstein und Gesteinskörnung) eliminiert. Vergleichend durchgeführte Cl-Mappings mit Mikroröntgenfluoreszenzanalyse (MRFA) belegen die Güte der durchgeführten LIBS-Messungen.
Aber auch bei der Verifizierung der Übertragbarkeit der Ergebnisse der zum Ausschluss reaktiver Gesteinskörnung bei Neubau und Erneuerung im BAB-Netz eingesetzten Performanceprüfungen mit externem Alkalieintrag auf Praxisverhältnisse hat sich das LIBSVerfahren bewährt. So wurde festgestellt, dass die mit NaCl-Lösung beaufschlagten Laborprüfkörper aus einem repräsentativen Fahrbahndeckenbeton bei der Klimawechsellagerung (KWL) über ihre gesamte Höhe von 10 cm einen Eintrag von Na und Cl erfahren. Weiterhin konnte im Gegensatz zu bisherigen Annahmen erstmals mit LIBS und Nasschemie gezeigt werden, dass die Frost-Tauwechsel-Phase bei der KWL zu keinem erhöhten Tausalzeintrag führt.
Small organic molecule drugs are one of the key classes, taking increasingly important roles in modern drug development strategies. With the focus on small molecule drugs, difficulties originate frequently from a pronounced lipophilic character, resulting in poor water solubility, low bioavailability and unfavored pharmacokinetics. Recently, peptide-poly(ethylene glycol) conjugates (peptide-PEG conjugates) were described as precisely tunable platforms to solubilize a broad scope of fluorescent or non-fluorescent small organic molecules [1-2]. Selection of drug hosting peptides was achieved by combinatorial means, which can further be extended by implementation of a drug release screening step.
One-bead-one-compound peptide libraries are powerful tools to select high affinity binders. However, the selection of positive hits from the peptide libraries remains tedious as it occurs by handpicking, strongly limiting the pool of investigated beads. Here we report our recent results on improving the analytical platform, using automated fluorescence scanning and MALDI-ToF-ToF MS/MS imaging to screen larger sets of beads, broadening the statistical base and unraveling more precisely suitable peptides. The screening puts special emphasis on loading capacities and drug-release of transporters by performing additional washing steps in different media (cf. Fig. 1). Peptides representing strong, medium, weak releaser were chosen for further analysis and synthesized as peptide-polymer transporters. Release was analyzed by fluorescence anisotropy and fluorescence correlation spectroscopy, due to the fluorescent characteristics of the drug.
Solubilization studies confirmed sufficient loading capacities for a potential anti-Alzheimer disease drug of three transporter molecules representing strong/weak drug releaser, reaching solubilization of up to 1:3.4 (µmol drug/µmol conjugate). Fluorescence anisotropy and fluorescence correlation spectroscopy of the drug-loaded transporter showed significant differences in drug releasing properties, confirming the screening process.
An immunohistochemical method is described to visualize the distribution of metallothioneins 1/2 (MT 1/2) and metallothionein 3 (MT 3) in human ocular tissue. It is making use of (a) antibodies conjugated to gold nanoclusters (AuNCs) acting as labels, and (b) laser ablation (LA) coupled to inductively coupled plasma – mass spectrometry (ICP-MS). Water-soluble fluorescent AuNCs (with an average size of 2.7 nm) were synthesized and then conjugated to antibody by carbodiimide coupling. The surface of the modified AuNCs was then blocked with hydroxylamine to avoid nonspecific interactions with biological tissue. Immunoassays for MT 1/2 and MT 3 in ocular tissue sections (5 μm thick) from two post mortem human donors were performed. Imaging studies were then performed by fluorescence using confocal microscopy, and LA-ICP-MS was performed in the retina to measure the signal for gold. Signal amplification by the >500 gold atoms in each nanocluster allowed the antigens (MT 1/2 and MT 3) to be imaged by LA-ICP-MS using a laser spot size as small as 4 μm. The image patterns found in retina are in good agreement with those obtained by conventional fluorescence immunohistochemistry which was used as an established reference method.
In chemical elements with three or more stable isotopes, mass-dependent stable isotope fractionation is expressed by co-varying isotope ratios. In the three-isotope space ((δ’m2/δ’m1)/(( δ’m3/δ’m1)) these plot along a line with a slope (β), the so called ‘terrestrial fractionation line’. This partitioning of stable isotopes results from both kinetic and equilibrium reactions that are characterized by specific β-values.
For the natural range of isotope ratios of ‘novel’ stable isotope systems such as Si, Mg, Fe, Zn, Cu this information cannot be accessed because samples fall close to the delta-zero standard where the current measurement precision is too low to resolve small differences in β. We present a new approach to resolve deviations from a reference slope β by standard-sample bracketing against material offset from the natural range. We use this approach to explore the isotope fractionation mechanism in the mammalian food web. We have analyzed Mg stable isotope ratios in bone bioapatite of herbivore, omnivore and carnivore mammals. Positive shifts in δ26/24Mg along the trophic chain (from herbivore to carnivore) together with β= 0.513 suggest the presence of two isotope fractionation mechanisms operating during biomineralization. While positive shifts in δ26/24Mg are in favor of equilibrium isotope fractionation process, the proximity of β to the theoretically calculated β(kinetic) of typically 0.511 suggests the presence of a second component that fractionates stable isotopes kinetically. The herein presented approach is applicable to any element with 3+ stable isotopes analyzed by multi-collector inductively coupled plasma mass spectrometry.
Planar coulometric sensors were investigated in humidified synthetic air at various absolute gas pressures, i. e. 2 bar, 5, bar, 10 bar, and 15 bar. Humidified gas flow at adjusted gas pressure was split into two flows, one passed a coulometric sensor and the other one passed a reference hygrometer after decompression. Both signals were recorded and then compared after calculation of resulting frost point temperature. Calculation is based on a calibration function obtained at ambient pressure. Comparison showed that an increasing pressure resulted in a higher derivation between sensor signal (calculated frost point temperature) and reference frost point temperature. At an absolute pressure of 2 bar the differences were minor in consideration of the uncertainty, however at 15 bar the differences were 6.77 K. Nevertheless, it was possible to measure the gas humidity at higher pressure with coulometric trace humidity sensors.
Planar coulometric sensors were investigated in humidified synthetic air at various absolute gas pressures, i. e. 2 bar, 5, bar, 10 bar, and 15 bar. Humidified gas flow at adjusted gas pressure was split into two flows, one passed a coulometric sensor and the other one passed a reference hygrometer after decompression. Both signals were recorded and then compared after calculation of resulting frost point temperature. Calculation is based on a calibration function obtained at ambient pressure. Comparison showed that an increasing pressure resulted in a higher derivation between sensor signal (calculated frost point temperature) and reference frost point temperature. At an absolute pressure of 2 bar the differences were minor in consideration of the uncertainty, however at 15 bar the differences were 6.77 K. Nevertheless, it was possible to measure the gas humidity at higher pressure with coulometric trace humidity sensors.
Nanoparticles (NPs) have found a wide range of applications in research and industry. Thereby the interaction of NPs with biological systems like cells has become a major field of interest, ranging from medical applications to nanotoxicology. Size, shape and surface modification of the nanomaterials determine the uptake rate and pathway into the cells, and therefore impact specific cell components and processes.
In recent years, elemental imaging of biological samples using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is gaining more and more importance. Improvements concerning both spatial resolution (down to 1 µm) and signal-to-background ratio due to low-dispersion LA chambers make LA-ICP-MS particularly interesting for single cell analysis.
Here LA-ICP-MS was applied for the imaging of individual cells to study the uptake and intracellular processing of metal-containing nanostructures. The cells were incubated with different NPs under varying experimental conditions and afterwards fixed with para-formaldehyde and dried for LA analysis. High-spatial resolution LA-ICP-MS was achieved by careful optimisation of the laser ablation parameters.
Our findings show, that LA-ICP-MS is applicable to localize NP aggregates within cellular compartments. The uptake efficiency depends strongly on the physicochemical properties of the nanostructures as well as on the incubation conditions like concentration and incubation time.
The results demonstrate the potential of LA-ICP-MS providing insight into nanoparticle-cell interaction dependent on experimental parameters.
Ionophore antibiotics are used to cure and prevent coccidiosis by chicken especially in broiler farming. The residues are found not only in food products (chicken and eggs) but also in the environment (manure, soil or water). In this work the ionophores monensin (MON), salinomycin (SAL), maduramicin (MAD) and lasalocid (LAS) are investigated aiming to study their transformation products (TPs) through biotransformation processes. Biotransformation can be divided into two phases, phase I: oxidation, reduction or hydrolysis and Phase II: conjugation reactions. It is necessary to further examine the biotransformation pathways to determine TPs to be able to detect residues more specifically in different matrices.
The technique of electrochemistry (EC) offers the opportunity to simulate biotransformation processes and to generate TPs for further analysis. The combination of EC with liquid chromatography and mass spectrometry (EC-LC-MS) provide a fast and simple tool to separate and determine the EC-generated TPs. The electrochemical flow through cell is coupled to the (LC)-MS system, allowing the reaction mixture to be separated by a RP-18 column and then analyzed in the MS. The oxidation products are generated at different potentials between 0.0 – 2.5 V vs. Pd/H2 using glassy carbon or boron doped diamond as working electrode materials .
The results show a broad spectrum of different TPs depending on used solvents and working electrode materials. Among the generated TPs already known as well as unknown TPs of the drugs can be found. Further investigations on structure elucidation of unkown TPs are planned.
Contamination of natural bodies of water with oil and lubricants (or generally, hydrocarbon derivatives such as petrol, fuel and others) is a commonly found phenomenon around the world due to the extensive production, transfer and use of fossil fuels. The timely identification of these contaminants is of utmost importance, since they directly affect water quality and represent a risk for wildlife and human health even in trace amounts.
In this work, we develop a simple system for the on-field detection of total petroleum hydrocarbons (TPH) in water and soil, the "Spectrocube". The test is based on the measurement of the fluorescence signal emitted by the molecular rotor 4-DNS-OH dye. This dye is embedded in a hydrophobic polymeric matrix (PVDF), avoiding interactions of water with the dye and providing a robust support for use in test-strip fashion. The test-strip’s fluorescence intensity increases linearly at low concentrations of TPH, reaching a saturation value at higher concentrations.
For excitation and evaluation of the test-strip fluorescence, a simple miniature optical system was designed. The system works semi-quantitatively as solvent-free TPH detection kit, as well as quantitatively when using a simple cyclopentane extraction step. To simplify the fluorescence read-out, the device is coupled to a tablet computer via Bluetooth, running a self-programmed software ("app").
Ultrasound echo is a widely used NDT technique for determining the internal geometry of structures. Reverse-time migration (RTM) has been recently introduced to NDT applications, as an imaging method for ultrasound data, to overcome some of the limitations (e.g. imaging steeply dipping reflector) experienced by the Synthetic Aperture Focusing Technique (SAFT), the most commonly used imaging algorithm for these measurements.
The standard implementation of RTM also experiences some drawbacks caused by its imaging condition, which is based on the zero-lag of the cross-correlation between source and receiver wavefields and generates high-amplitude low-frequency artifacts. Three alternative imaging conditions, developed for seismic data applications, were tested for their ability to provide better images than the standard cross-correlation: illumination compensation, deconvolution and wavefield decomposition. A polyamide specimen was chosen for the simulation of a synthetic experiment and for real data acquisition. The migrations of both synthetic and real data were performed with the software Madagascar. The illumination imaging condition was able to reduce the low-frequency noise and had a good performance in terms of computing time. The deconvolution improved the resolution in the synthetic tests, but did not showed such benefit for the real experiments. Finally, as for the wavefield decomposition, although it presented some advantages in terms of attenuating the low-frequency noise and some unwanted reflections, it was not able to image the internal structure of the polyamide as well as the cross-correlation did. Suggestions on how to improve the cost-effectiveness of the implementation of the deconvolution and wavefield decomposition were presented, as well as possible investigations that could be carried out in the future, in order to obtain better results with those two imaging conditions.
We are using LA-ICP-MS to quantify metals in biological cells and thin cuts of tissues from varies organs. Different applications will be presented to demonstrate the state of the art of bioimaging to visualize the elemental distribution pattern in soft bio-materials (tissue, single cells) of metals, metal containing stains and metal-tagged antibodies. For this purpose, different strategies for metal tagging will be presented and will be compared in terms of analytical figures of merit. First applications for detection of biomarkers in animal and human tissue samples will be presented.
In a first example, we have applied LA-ICP-MS to visualize the local distribution of proteins, which are used as bio-markers for neurodegenerative diseases. For this purpose, brain tissues from mice experiments have been stained by metal-tagged antibodies. House-keeping proteins have been investigated as internal cellular standards. Additionally, ink-jet printing of metal doped inks onto the surface of tissue samples has been applied for drift corrections and quantification. Validation of our results are achieved in comparison to immune-histochemical staining and optical microscopy.
In a second example, we used specific metal-tagged antibodies for detection of biomarker specific for prostate cancer. For this purpose, micro tissue arrays are incubated with metal-tagged antibodies for bioimaging of samples from many patients using simultaneous detection of all relevant biomarkers and their tags.
For improvement of sensitivity in the next example application nanoparticle tagged antibodies for detection of metallothionines in eye lens tissue samples will be discussed.
Recently we have used our tagging and staining strategies to determine the cell cycle of single cells, which is of future interest for toxicological studies.
Finally, future trends in elemental microscopy and mass cytometry imaging will be discussed.
To keep up with emerging mycotoxins and their transformation products fast and reliable toxicity tests are needed. Toxicity testing of mycotoxins is carried out usually by performing in vitro assays or is evaluated by using laboratory animals like mice, rats or chicken in in vivo studies.
Settled between classical in vitro approaches and in vivo studies with higher animals are tests with the nematode Caenorhabditis elegans. Since Sydney Brenner described 1974 the cultivation and handling of C. elegans, this worm is widely used as model organism in developmental biology and neurology. Due to many benefits like easy and cheap cultivation, a completely sequenced genome and short generation time, it also plays an important role in toxicological research. Finally, the high number of conserved genes between human and C. elegans make the worm an ideal candidate for toxicological investigations.
In this study we used C. elegans to assess the toxic effects of the relevant food mycotoxin citrinin (CIT), the mycoestrogen zearalenone (ZEN) and the modified mycotoxin ZEN-14-sulfate (ZEN-14-S) on different lifetable parameters including reproduction, thermal and oxidative stress tolerance and lifespan. All tested mycotoxins significantly decreased the amount of offspring. In case of ZEN and CIT also significant negative effects on stress tolerance and lifespan were observed compared to the control group.
Moreover, metabolization of mycotoxins in the worms was investigated by using LC MS/MS. Extraction of the worms treated 5 days with mycotoxin-containing and UVC-killed bacteria showed metabolization of ZEN to α-ZEL and β-ZEL (ZEL = zearalenol, ratio about 3:2). ZEN 14-S was reduced to ZEL 14-S and CIT was metabolized to mono hydroxylated CIT.
Nanoparticles (NPs) have found a wide range of applications in research and industry. Thereby the interaction of NPs with biological systems like cells has become a major field of interest, ranging from medical applications to nanotoxicology. Size, shape and surface modification of the nanomaterials determine the uptake rate and pathway into the cells, and therefore impact specific cell components and processes.
Inductively coupled plasma mass spectrometry (ICP-MS) is a well-established analytical method offering high sensitivity and multi-element capability. By coupling a laser ablation (LA) system to an ICP-MS the analysis of different kinds of solid samples is possible. In recent years, it was shown that LA-ICP-MS can provide quantitative as well as distribution information of metal containing nanoparticles (NPs) in cell samples.
Here LA-ICP-MS was applied for the imaging of individual fibroblast cells to study the uptake and intracellular processing of NPs. Our results show that LA-ICP-MS can be used to localize nanoparticle aggregates within cellular compartments. The studied NPs accumulate in the perinuclear region in the course of intracellular processing, but do not enter the cell nucleus. The uptake efficiency depends strongly on the physico-chemical properties of the nanostructures as well as on the incubation conditions like concentration and incubation time.
ICP-MS was used to determine the composition of the nanomaterials as well as the number of NPs in cells after acid digestion of the samples.
Die Spurenfeuchte ist eine wichtige Messgröße bei der Qualitätsbeurteilung von technischen und medizinischen Gasen und muss daher zuverlässig gemessen werden. Der Spurenbereich ist definiert durch einen Wasserdampf-Stoffmengenanteil kleiner als 2600 µmol/mol bzw. einer Frostpunkttemperatur kleiner -10 °C. Eine geeignete Methode für die kontinuierliche Spurenfeuchtemessung stellt das Elektrolyseverfahren bzw. coulometrische Messprinzip dar. Bei diesem Prinzip strömt ein feuchtes Gas über eine hygroskopische Phosphorpentoxid-Schicht, welche kontinuierlich Wasserdampf absorbiert. Durch das Anlegen einer Zersetzungsspannung wird das absorbierte Wasser elektrolysiert und der resultierende Elektrolysestrom korreliert zum Feuchtegehalt im Gas. Neben dem Einfluss von unterschiedlichen Gasen auf das Messverfahren, wurde der Einfluss der Druckfeuchte im Druckbereich von 2 bis 15 bar untersucht. Des Weiteren wurde eine neuartige Sensorbeschichtung basierend auf einer ionischen Flüssigkeit getestet und es wurde ein Prototyp für die abgestufte Bestimmung der Wasseraktivität und der Materialfeuchte aufgebaut.
The antimicrobial photodynamic approach has been demonstrated as an efficient and sustainable process for the eradication of microbial pathogens. In this work, silica-coated Magnetite nanoparticles (NPs) were used as carriers of glycosylated porphyrins and phthalocyanines. Their subsequent cationization
resulted in the production of stable antimicrobial photosensitizing materials, effective against E. coli. Suspensions of the photocatalysts in water present bimodal size distributions formed by big clusters and small NPs with hydrodynamic diameters between 8 and 38 nm. The presence of small NPs in the suspensions is related to an effective photodynamic inactivation (PDI) of E. coli cells. Glycosylation of the PS showed a positive effect on the PDI performance, which could be related to a higher accumulation of the photocatalyst over the bacterial cell membrane. In addition, these biocidal agents proved to be photostable and their photoactive performance decreased only between 23% and 28% upon 5 PDI cycles, mostly because of the loss of material between cycles, which makes them promising materials for water disinfection purposes.
Gegenstand der vorzustellenden Arbeiten ist die Prüfung der Umwelt-beständigkeit und -verträglichkeit von Materialien und Produkten hinsichtlich der Emission von potenziellen Schadstoffen in die Umwelt. Hierzu werden chemisch-physikalische Einflüsse (Bewitterung) und mikrobielle Beanspruchungen an Modellmaterialien evaluiert. So werden die Freisetzungsraten von Schadstoffen in Abhängigkeit der Beanspruchung beschrieben. Als Modellmaterialien kommen die Polymere Polystyrol (PS) und Polypropylen (PP) zum Einsatz. Synergistische Effekte der Bewitterungsparameter und der mikrobiologischen Beanspruchung sollen dabei ebenso betrachtet werden, wie die gezielte Alterung. Auch findet eine Beschreibung des Verhaltens der ausgetragenen Schadstoffe in den Umweltkompartimenten Boden oder Wasser statt. Hier sind mit Hilfe der zu entwickelnden Screening- und non-Target-Analyseverfahren die Transformation und der Metabolismus durch Mikroorganismen zu beschreiben. Aus den Ergebnissen sollen Korrelationen zwischen den künstlichen Alterungsverfahren und realen Szenarien abgeleitet werden.
Molecularly Imprinted Polymers with Integrated Fluorescence as Versatile Biomimetic Sensing Matrices
(2018)
Molecularly imprinted polymers (MIPs) are an established, versatile and high-performance matrix for the selective separation or enrichment of (bio)chemical species, especially small molecules of biochemical or environmental relevance. MIPs are prepared through the polymerization of a mixture of functional monomers and cross-linkers in the presence of the template with subsequent extraction of the latter. Conceptionally, this process can be seen as mimicking in a strongly accelerated, though single-step manner a biological process such as antibody formation. Because the resulting MIPs contain cavities in their matrix that are complementary in size, shape and electronic/ electrostatic or hydrogen bonding demand to the imprinted target molecule or template, these polymers are frequently termed “artificial antibodies”. Compared to natural antibodies, they are chemically and physically much more robust. Regarding sensitivity and selectivity, however, there is still a gap to bridge before MIPs can fully compete with antibodies.
Another favorable aspect that distinguishes MIPs from antibodies is that they can be endowed with an explicit function, allowing the use of MIPs in applications that require more than only an efficient binder. For instance, if specifically designed and polymerizable fluorescent indicators are integrated as functional monomers into a MIP, direct fluorescence sensing can be accomplished. Because MIPs can be prepared in a variety of different formats, their combination with miniaturized or other specific analytical techniques or sensory devices is possible, especially when the transduction mode is light. This presentation will introduce basic design considerations, challenges, limitations and the potential that lies with such sensor materials with some recent examples of our group, targeting various organic oxoanions as analytes.
Nanoparticles (NPs) have found a wide range of applications in research and industry. Thereby the interaction of NPs with biological systems like cells has become a major field of interest, ranging from medical applications to nanotoxicology. Size, shape and surface modification of the nanomaterials determine the uptake rate and pathway into the cells, and therefore impact specific cell components and processes.
Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) is an established quantitative multi-elemental analysis and mapping technique. In recent years, it was shown that LA-ICP-MS can provide quantitative as well as distribution information of metal containing nanoparticles (NPs) in cell samples.
Here LA-ICP-MS was applied for the imaging of individual fibroblast cells to study the uptake and intracellular processing of NPs. Our results show that LA-ICP-MS can be used to localize nanoparticle aggregates within cellular compartments. The studied NPs accumulate in the perinuclear region in the course of intracellular processing, but do not enter the cell nucleus. The uptake efficiency depends strongly on the physico-chemical properties of the nanostructures as well as on the incubation conditions like concentration and incubation time.
ICP-MS was used to determine the composition of the nanomaterials as well as the number of NPs in cells after acid digestion of the samples.
Imaging of elemental distributions in single cell assays as well as tissue sections can be performed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). This powerful technique offers precise spatially resolved measurements at trace and ultratrace levels and has been established as an excellent tool to answer analytical, biological and biomedical questions. To date, mass cytometry is already able to simultaneously detect up to 40 cellular targets due to conjugation of isotopically pure lanthanides to affinity binders, e.g. antibodies.
To further enhance the ability of multiparametric analysis to more than 100 analytes at once, we investigated lanthanide nanocrystals as new, highly sensitive metal tags for identification of targets in clinical cell assays and tissue samples. Multiparametric analysis will be possible by encoding the lanthanide composition of nanocrystals associated to the affinity binders. Nanocrystals showed remarkable potential for sensitive detection in MS due to high stability and signal amplification compared to e.g. polymer tags, carrying fewer metal atoms. Furthermore, the nanocrystals allow multimodal imaging due fluorescence of Eu3+ as well as contrast enhancing properties of Gd3+ in magnetic resonance imaging.
Synthesis of functionalized lanthanide nanocrystals for further bioconjugation was performed with high reproducibility and monodisperse size distribution. For proof of principle, the uptake and distribution of these nanocrystals within the monolayered cell line A549 were investigated by mapping the intensities at subcellular resolution using LA-ICP-MS. It could be shown, that the cells were efficiently labeled with the nanocrystals. Additionally, the bioconjugation of the nanocrystals to antibodies and particularly the preservation of the antibody specificity was investigated using Dot Blot experiments. All in all, the results imply high sensitivity and the possibility of multiparametric analysis by doting various lanthanides into the nanocrystals.
In der klinischen Diagnostik werden für zytometrische Messverfahren bereits eine Reihe von Reagenzien eingesetzt zur Markierung von Antikörper eingesetzt, um die Detektion von Biomarkern mittels Fluoreszenz- oder Flugzeitmassenspektrometrie zu ermöglichen.
Seit kurzem ist auch eine Imaging Mass Cytometry Kombination direkt erhältlich, wodurch der Nachweis von Biomarkern in Gewebeschnitten erreicht werden kann. Dazu wird eine Kopplung von Laser Ablation und induktiv gekoppeltem Plasma Massenspektrometrie eingesetzt, wobei ähnlich der Massenzytometrie, zuvor Antikörper mit Metallen markiert, und im Anschluss mit dem Gewebeschnitt inkubiert werden. Durch die hohe Ortsauflösung können die Biomarker lokalisiert, und zukünftig vielleicht auch quantifiziert werden.
Insbesondere Lanthanide eignen sich als Markierungsmetalle, da sie einen niedrigen Untergrund und chemisch ähnliches Verhalten zueinander aufweisen. Allein durch diese Elemente können bereits etwa 15 Parameter unterschieden werden, was durch isotopenreine Standards weiter gesteigert werden kann.
Vom Markierungsgrad abhängig werden unterschiedlich viele Metalle am Antikörper gebunden, und beeinflussen so die Sichtbarkeit im ICP-MS. Nanopartikel könnten daher eine deutliche Steigerung der Sensitivität bewirken. GdVO4 Nanokristalle scheinen bisher sehr vielversprechend und bieten neben multiparametrischen Anwendungen auch Multimodalität.
Die Synthese der Nanokristalle zeigte hohe Homogenität und Reproduzierbarkeit in Partikelgröße in der Zusammensetzung. Ein erstes Experiment mit einer Zellkultur konnte bereits die effiziente Markierung der Zellen unter Beweis stellen, wobei durch hohe Signalstärke auch subzelluläre Auflösung in der LA-ICP-MS erreicht werden konnte.
Imaging of elemental distributions in single cell assays as well as tissue sections can be performed by laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). This powerful technique offers precise spatially resolved measurements at trace and ultratrace levels and has been established as an excellent tool to answer analytical, biological and biomedical questions. To date, mass cytometry is already able to simultaneously detect up to 40 cellular targets due to conjugation of isotopically pure lanthanides to affinity binders, e.g. antibodies.
To further enhance the ability of multiparametric analysis to more than 100 analytes at once, we investigated lanthanide nanocrystals as new, highly sensitive metal tags for identification of targets in clinical cell assays and tissue samples. Multiparametric analysis will be possible by encoding the lanthanide composition of nanocrystals associated to the affinity binders. Nanocrystals showed remarkable potential for sensitive detection in MS due to high stability and signal amplification compared to e.g. polymer tags, carrying fewer metal atoms. Furthermore, the nanocrystals allow multimodal imaging due fluorescence of Eu3+ as well as contrast enhancing properties of Gd3+ in magnetic resonance imaging.
Synthesis of functionalized lanthanide nanocrystals for further bioconjugation was performed with high reproducibility and monodisperse size distribution. For proof of principle, the uptake and distribution of these nanocrystals within the monolayered cell line A549 were investigated by mapping the intensities at subcellular resolution using LA-ICP-MS. It could be shown, that the cells were efficiently labeled with the nanocrystals. Additionally, the bioconjugation of the nanocrystals to antibodies and particularly the preservation of the antibody specificity was investigated using Dot Blot experiments. All in all, the results imply high sensitivity and the possibility of multiparametric analysis by doting various lanthanides into the nanocrystals.
For years there have been more and more reports on the presence of drugs in the aquatic environment. Due to the demographic change, the consumption of pharmaceuticals has risen sharply. After taking the drugs, they are partly metabolized in the human body. However, the metabolism is not complete so that both the metabolites and non-metabolized amounts of the parent compounds are excreted. These compounds reach the waste water and afterwards the sewage treatment plants. In sewage treatment plants transformation products can be formed by the oxidative conditions during wastewater treatment processes. The transformation products may have a higher toxicity than the actual environmental pollutants and are often only partly removed during the waste water treatment. Since a lot of these compounds are still unknown, the transformation products are not detected by target analysis used in sewage treatment plants and are often released undetected in the aquatic ecosystems. The released substances may be subject to additional transformation processes in the environment. Pharmaceuticals produced in high amounts can be already detected in the μg/L range in water bodies worldwide.
Metformin and its major transformation product guanylurea are one of the main representatives. Metformin is the drug of choice for treating type 2 diabetes. The drug therapy for diabetes mellitus has increased significantly in recent years. In the year 2015 1500 tons of metformin were prescribed in Germany (for statutory insured persons). Metformin is not metabolized in the human body and is excreted unchanged therefore concentrations between 57 μg/L and 129 μg/L are found in German waste water treatment plants influents.
In this work the transformation of the antidiabetic drug metformin is investigated. The degradation of metformin is initialize by commercial water treatment techniques like UV-radiation or noncommercial techniques like heterogenous photocatalysis based on titanium dioxide. The degradation of metformin and resulting transformation products are analyzed by LC-MS/MS and LC-HRMS.