NanoBioDetect

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NanoBioDetect – Nanoparticles in the tissue: detection, quantification and presentation of biological effect markers

 

Inhaled nanoparticles which enter the alveolar region of the lung are largely taken up and cleared from the organ by alveolar macrophages. However, a minor fraction appears to reach other cells inside the lungs or becomes distributed to remote organs where hitherto unknown effects may be induced.

To describe these processes more closely, the partners of the NanoBioDetect project aim to visualize nanoparticles with state-of-the-art imaging methods within the lungs and other target organs. To better understand effects of nanoparticles inside the body, cell types containing nanoparticles shall be identified and the mass of particles within these cells shall be quantified. Further research will focus on the detection of altered cell constituents such as protein or DNA modifications in nanoparticle-laden cells, or in regions where nanoparticles may have accumulated. Although effects of nanoparticles have been widely described for cells in vitro, most often secondary to high concentrations of nanoparticles, the meaning of these results for the complex organism still remains elusive. Knowledge of the in vivo dose of nanoparticles in experimental animals, to be collected during the project, will shed more light on these questions. Results shall furthermore be used to strengthen the predictability of in vitro assays and for setting up more appropriate in vitro assays.

The interdisciplinary work of biomedical research on cells and tissues and physico-chemical expertise shall enable the partners to solve the “dose-effect problem” for a representative selection of different nanoparticles. By means of enhanced darkfield-, Raman-, and hyperspectral microscopy particle laden sites within tissue sections will by identified and results will be controlled by electron microscopy. A special device will be developed in order to subject tissue areas pre-selected by light microscopy to further imaging tools: Ion beam microscopy (IBM) can quantitatively determine the element content via proton bombardment with high spatial resolution. Time-of-flight mass spectrometry (ToF-SIMS) is already capable to detect nanoparticles together with organic molecules but will receive further instrumental development during the project to increase efficacy and resolution. Laser ablation-inductively coupled plasma mass spectrometry (LA-ICP-MS) will also be refined and used together with further methods (µXRF) as a quantitative approach. All these techniques shall be made compatible with biological (immuno-)detection methods. A validation of results will be achieved by comparing results from different techniques.

Eventually the best suited physical and biological detection methods will be combined in such a way that the particle content in identified cells and tissues in conjunction with biological effects becomes quantitatively describable in a reliable and cost-efficient manner.

Grant Number: BMBF - FKZ 03X0146
Duration: 01.08.2014 - 31.12.2017

Project Lead

IBE R&D Institute for Lung Health gGmbH Logo
Prof. Dr. Martin Wiemann, IBE R&D Institute for Lung Health gGmbH

Project Partners

IBE R&D Institute for Lung Health gGmbH Logo
IBE R&D Institute for Lung Health gGmbH, Muenster (DE)
IONTOF Logo
ION-TOF Technologies GmbH, Muenster (DE)
TASCON GmbH Logo
Tascon GmbH, Muenster (DE)
Universität Leipzig Logo Deutsch
Institute for Medical Physics and Biophysics (IMBP), Leipzig University, Leipzig (DE
University pf Muester (WWU) Logo
Institute of Inorganic and Analytical Chemistry (IAAC), University of Muenster, Muenster (DE)
FH Dortmund Logo
Biomedical Imaging Group (BIG), University of Applied Science and Arts Dortmund, Dortmund (DE)

Subcontractor

OxProtect GmbH, Muenster (DE)
Surflay Nanotec GmbH, Berlin (DE)
Institute of Pathology, Ruhr-University Bochum (RUB), Bochum (DE)
Proteome Sciences R&D GmbH & Co. KG (ProSci), Frankfurt/Main (DE)

Publications

2018

  • Grossgarten M., Holzlechner M., Vennemann A., Balbekova A., Wieland K., Sperling M., Lendl B., Marchetti-Deschmann M., Karst U., Wiemann M. (2018). Phosphonate coating of SiO2 nanoparticles abrogates inflammatory effects and local changes of the lipid composition in the rat lung: a complementary bioimaging study. Part Fibre Toxicol, 15(1): 31.
  • Bishop D.P., Grossgarten M., Dietrich D., Vennemann A., Cole N., Sperling M., Wiemann M., Doble P.A., Karst U. (2018). Quantitative imaging of translocated silver following nanoparticle exposure by laser ablation-inductively coupled plasma-mass spectrometry. Anal. Methods 10(8): 836-840.
  • Veith L., Bottner J., Vennemann A., Breitenstein D., Engelhard C., Meijer J., Estrela-Lopis I., Wiemann M., Hagenhoff B. (2018). Detection of ZrO2 Nanoparticles in Lung Tissue Sections by Time-of-Flight Secondary Ion Mass Spectrometry and Ion Beam Microscopy. Nanomaterials, 8(1): 44.
  • Veith L., Dietrich D., Vennemann A., Breitenstein D., Engelhard C., Karst U., Sperling M., Wiemann M., Hagenhoff B. (2018). Combination of micro X-ray fluorescence spectroscopy and time-of-flight secondary ion mass spectrometry imaging for the marker-free detection of CeO2 nanoparticles in tissue sections. J. Anal. At. Spectrom., 33(3): 491-501.
  • Vennemann A., Alessandrini F., Wiemann M. (2017). Differential Effects of Surface-Functionalized Zirconium Oxide Nanoparticles on Alveolar Macrophages, Rat Lung, and a Mouse Allergy Model. Nanomaterials (Basel), 7(9): 280.

2017

  • Heller D., Ter Veen R., Hagenhoff B., Engelhard C. (2017). Hidden information in principal component analysis of ToF-SIMS data: On the use of correlation loadings for the identification of significant signals and structure elucidation. Surf Interface Anal, 49(10): 1028-1038.
  • Veith L., Vennemann A., Breitenstein D., Engelhard C., Wiemann M., Hagenhoff B. (2017). Detection of SiO2 nanoparticles in lung tissue by ToF-SIMS imaging and fluorescence microscopy. Analyst, 142(14): 2631-2639.
  • Vennemann A., Alessandrini F., Wiemann M. (2017). Differential Effects of Surface-Functionalized Zirconium Oxide Nanoparticles on Alveolar Macrophages, Rat Lung, and a Mouse Allergy Model. Nanomaterials (Basel), 7(9): 280.
  • Wiemann M., Vennemann A., Blaske F., Sperling M., Karst U. (2017). Silver Nanoparticles in the Lung: Toxic Effects and Focal Accumulation of Silver in Remote Organs. Nanomaterials (Basel), 7(12): 441.

2016

  • Erdenetsogt U., Vennemann A., Wiemann M., Lipinski H.-G. (2016). Nanopartikeldetektion in Zellpräparaten mit dem Hyperspektral-Imaging-Verfahren, in Bildverarbeitung für die Medizin 2016: Algorithmen – Systeme – Anwendungen, Tolxdorff, Deserno, Handels, and Meinzer, Eds., ed Berlin, Heidelberg: Springer Berlin Heidelberg, pp. 242-247. ISBN:978-3-662-49465-3.

All available final reports of the NanoBioDetect consortium can be found on the pages of TIB Hannover https://www.tib.eu/en/  
  • IBE R&D gGmbH
  • ION-TOF Technologies GmbH
  • Tascon GmbH
  • University Leipzig (2018). Anwendung von Ionenstrahlmikroskopie und konfokaler Raman Mikrospektroskopie zur Detektion und Quantifizierung von Nanopartikeln in Zellen und Geweben : Abschlussbericht : NanoBioDetect : Laufzeit des Vorhabens: 01.08.2014-31.12.2017 : Berichtzeitraum: 01.08.2014-31.12.2017. FKZ 03X0146D, TIB Hannover
  • University of Muenster
  • University of Applied Sciences Dortmund (2018). Forschungsvorhaben: NanoBioDetect - Nanopartikel im Gewebe: Detektion, Quantifizierung und Darstellung biologischer Effektmarker : Abschlussbericht NanoBioDetect- Teilvorhaben der FH Dortmund. FKZ 03X0146F. TIB Hannover (DOI)

2018

  • Wiemann M. (2018). Moderne Imaging-Methoden zum Nachweis von Nanomaterialien in Geweben. Fenomeno Workshop, 21.3.2018 Siegen, Germany. [oral]
 

2017

  • Breitenstein D., Veith L, Hagenhoff B., Fartmann M, Kersting R., ter Veen R. (2017). Detection of Nanoparticles in Lung Tissue by Time-of-Flight Secondary Ion Mass Spectrometry. 17th European Conference on Applications of Surface and Interface Analysis, 24.-29.09.2017, Montpellier, France. [Oral]
  • Dietrich D., Vennemann A., Wiemann M., Sperling M., Karst U. (2017). Imaging of Cerium Oxide Nanoparticles in Rat Lung Tissue by Means of LA-ICP-MS. EWCPS 19.-24.2.2017, St. Anton, Austria. [Oral]
  • Dietrich D., Vennemann A., Wiemann M., Sperling M., Karst U. (2017). Imaging of Cerium Oxide Nanoparticles and their Effects in Rat Lung Tissue. ANAKON, 3.-6.4.2017, Tuebingen, Germany. [Oral]
  • Dietrich D., Vennemann A., Wiemann M., Sperling M., Karst U. (2017). Imaging of Cerium Oxide Nanoparticles and Phospholipids in Rat Lung Tissue by Means of LA-ICP-MS and MALDI-MS. DGMS 5.-8.4.17, Kiel, Germany. [Oral]
  • Hagenhoff B., Heller D. (2017). Use of Multivariate Analytical Techniques for the Analysis of SIMS Data: Opportunities and Risks. Seminar: "Moderne Analytische Chemie", 13.01.2017, Vienna, Austria. [Oral]
  • Hagenhoff B., Veith L., Breitenstein D. (2017). Imaging of Nanoparticles in Tissue Sections: Results of the NanoBioDetect Project. 79. IUVSTA Workshop, 15.-19.05.2017, Santa Margherita di Pula, Italy. [Oral]
  • Hagenhoff B., Veith L., Breitenstein D., Tallarek E., Kersting R., Fartmann M. (2017). Detection of Nanoparticles in Lung Tissue by Time-of-Flight Secondary Ion Mass Spectrometry. 21st International Conference on Secondary Ion Mass Spectrometry, 10.-15.09.2017, Krakow, Poland. [Oral]
  • Heller D., Kersting R., Fartmann M., ter Veen R., Engelhard C., Hagenhoff B. (2017). Identifizierung charakteristischer Signale in der Fehleranalytik: Effiziente multivariate Datenanalyse von Massenspektrometriedaten. ANAKON 2017, 03.-06.04.2017, Tuebingen, Germany. [Poster]
  • Heller D., Kersting R., Fartmann M., ter Veen R., Engelhard C., Hagenhoff B. (2017). Multivariate Data Analysis to Simplify ToF-SIMS Data Analysis in an Industrial Context. 21st International Conference on Secondary Ion Mass Spectrometry, 10.-15.09.2017, Krakow, Poland. [Oral]
  • Kersting R., Lamann K., Breitenstein D., Brock W., Bock B., Fartmann M., Hagenhoff B. (2017). Comparison of Surface Analytical Techniques on Atomic Layer Deposition Samples. 21st International Conference on Secondary Ion Mass Spectrometry, 10.-15.09.2017, Krakow, Poland. [Oral]
  • ter Veen R., Lamann K., Veith L, Breitenstein D., Bock B., Fartmann M., Hagenhoff B. (2017). Comparison of Surface Analytical Techniques on Atomic Layer Deposition Samples. 17th European Conference on Applications of Surface and Interface Analysis, 24.-29.09.2017, Montpellier, France. [Oral]
  • Wiemann M., Großgarten M., Vennemann A., Holzlechner M., Balbekova A., Wieland K., Sperling M., Marchetti-Deschmann, M., Karst, U. (2017). SiO2 but not phosphonated SiO2 nanoparticles change the local lipid composition in the rat lung. Society of Toxicology, 12.-16.3 2017, Baltimore, USA. [Poster]
  • Vennemann A., Reifschneider O., Blaske F., Sperling M., Wiemann M., Karst U. (2017). Quantitative Elemental Bioimaging Reveals a Predominant Uptake of Silver Nanoparticles by Alveolar Macrophages in Lung Tissue. Society of Toxicology 12.-16.3 2017, Baltimore, USA. [Poster]
 

2016

  • Böttner J., Vennemann A., Wiemann M., Estrela-Lopis I. (2016). Dose-Response relationship of nanoparticles in alveolar cells. 11th International Particle Toxicology Conference, 26.-30. 9.2016, Singapore. [Poster]
  • Böttner J., Vennemann A., Wiemann M. Estrela-Lopis I. (2016). Ionenstrahlmikroskopie und konfokale Raman Mikrospektroskopie zur Detektion von ZrO2 und SrCO3 Nanopartikeln in biologischer Umgebung. NanoCare Cluster-Treffen, 3.-4.5.2016, Frankfurt/M., Germany. [Poster]
  • Erdenetsogt U., Vennemann A., Wiemann M., Lipinski H.-G. (2016). Nanopartikel-Detektion in Zellpräparaten mit dem Hyper-Spektral-Imaging-Verfahren. Bildverarbeitung fuer die Medizin, 13.-15.3. 2016, Berlin, Germany. [Poster]
  • Dietrich D., Vennemann A., Wiemann M., Sperling M., Karst U. (2016). LA-ICP-MS Analysis to reveal the Distribution of Cerium Oxide Nanoparticles in Rat Lung Tissue after Instillation. EWLA 12.-15.7.2016, Ljubljana, Slovenia. [Poster]
  • Dietrich D., Vennemann A., Wiemann M., Sperling M., Karst U. (2016). Determining the distribution of cerium oxide nanoparticles in rat lung tissue after instillation by means of LA-ICP-MS. ICP-Anwendertreffen 12.-15.9.16, Siegen, Germany. [Oral]
  • Dietrich D., Vennemann A., Wiemann M., Sperling M., Karst U. (2016). LA-ICP-MS-Studie zur Verteilung von Ceroxid-Nanopartikeln nach intratrachealer Instillation. NanoCare Cluster-Treffen, 3.-4.5.2016, Frankfurt/M., Germany. [Poster]
  • Dietrich D., Vennemann A., Wiemann M., Sperling M., Karst U. (2016). Determining the Distribution of Aluminum-doped Cerium Oxide Nanoparticles and their Effects in Rat Lung Tissue after Instillation. DAAS Doktorandenseminar, 6.-8.0.16, Ulm, Germany. [Oral]
  • Großgarten M., Vennemann A., Wiemann M., Deiting D., Schorn D., Ahrens H., Sperling M., Karst U. (2016). Application of µXRF in elemental bioimaging: Answering biomedical questions. 8. TXRF- und µXRF-Workshop, 28.9.2016, Muenster, Germany. [Oral]
  • Hagenhoff B. (2016). Analyse von Nanomaterialien mit ToF-SIMS und LEIS. 12. Symposion Massenspektrometrische Verfahren der Elementspurenanalyse und 25. ICPMS-Anwendertreffen, 12.-15.09.2016, Siegen, Germany. [Oral]
  • Heller D., ter Veen R., Hagenhoff B, Engelhard C. (2016). Multivariate Data Analysis to Simplify ToF-SIMS Data Analysis in an Industrial Context. European Conference and Workshop on Secondary Ion Mass Spectrometry, 18.-20.09.2016, Muenster, Germany. [Oral]
  • Heller D., Albert A., Ebert F., Leffers L., Schwerdtle T., Hagenhoff B., Engelhard C. (2016).Multivariate Datenanalyse in der Massenspektrometrie: Fallbeispiele zum Einfluss der Datenvorbehandlung. DGMS 2016 – 49. Jahrestagung der Deutschen Gesellschaft fuer Massenspektrometrie, 28.02.-02.03.2016, Hamburg, Germany. [Poster]
  • Heller D., Hagenhoff B., Engelhard C. (2016). Identifizierung unbekannter Substanzen in SIMS-Spektren - Multivariate Datenanalyse zur Beschreibung wenig charakterisierter Datensätze. DGMS 2016 – 49. Jahrestagung der Deutschen Gesellschaft fuer Massenspektrometrie, 28.02.-02.03.2016, Hamburg, Germany. [Poster]
  • Veith L., Breitenstein D., Vennemnan A., Wiemann M., Hagenhoff B., Engelhard C. (2016). Analysis of Nanoparticles in Lung Tissue Sections by Time-of-Flight Secondary Ion Mass Spectrometry. 19. Arbeitstagung Angewandte Oberflächenanalytik (AOFA), Soest, Germany. [Poster]
  • Veith L., Breitenstein D., Vennemnan A., Wiemann M., Hagenhoff B., Engelhard C. (2016). Fluorescence Microscopy/ToF-SIMS Detection of Nanoparticles in Lung Tissue Sections - A Combined Approach. 12. Symposion Massenspektrometrische Verfahren der Elementspurenanalyse und 25. ICPMS-Anwendertreffen, 2016, Siegen, Germany. [Poster]
  • Veith L., Breitenstein D., Vennemnan A., Wiemann M., Hagenhoff B., Engelhard C. (2016). Fluorescence Microscopy/ToF-SIMS Detection of Nanoparticles in Lung Tissue Sections - A Combined Aproach. European Conference and Workshop on Secondary Ion Mass Spectrometry, 2016, Muenster, Germany. [Poster]
  • Veith L., Breitenstein D., Vennemnan A., Wiemann M., Hagenhoff B., Engelhard C. (2016). Fluorescence Microscopy/ToF-SIMS Detection of Nanoparticles in Lung Tissue Sections - A Combined Approach. Cluster NanoMikro-Werkstoffe Photonik NRW, 2016, Muenster, Germany. [Poster]
  • Wagner T., Wiemann M., Kägi R., Kroll A., Lipinski H.-G. (2016). Characterization and classification of nanoparticles and their trajectories by computational methods. 7. NRW. Nano-Konferenz, 7.-8.12.2016, Muenster, Germany. [Poster]
  • Wagner T., Vennemann A., Wiemann M., Lipinski H.-G. (2016). Visualisierung multimodaler Bilddaten nach Korrektur durch Bildregistrierung. Clustertreffen NanoCare, 3.-4.5.2016, Frankfurt/M., Germany. [Poster]
  • Wiemann M. (2016). An Integrative Approach for the Quantitative Detection of Nanoparticles and Biological Markers in Tissues: The NanoBioDetect-Project. 7th NRW Nano-Conference, 7.-8.12.2016 Muenster, Germany. [Oral]
  • Zakel J., Veith L., Breitenstein D., Hagenhoff B., Niehuis E. (2016). ToF-SIMS Technik zur Analyse von Nanopartikeln: Geräte- und Methodenweiterentwicklung. Clustertreffen NanoCare, 3.-4.5.2016, Frankfurt/M., Germany. [Poster]
 

2015

  • Böttner J., Vennemann A., Wiemann M. Estrela-Lopis I. (2015). Raman-Mikrospektroskopie und Hyperspektrale Mikroskopie zur Detektion von Nanopartikeln in Zellen und Geweben. Cluster-Treffen 19.-20.05.15, Frankfurt/M., Germany. [Poster]
  • Dietrich D., Vennemann A., Wiemann M., Sperling M., Karst U. (2015). Determination of the distribution of silver nanoparticles in the gastro-intestinal tract of rats after oral application by means of LA-ICP-MS. EWCPS 2015, 22.-26.2.2015, Muenster, Germany. [Poster]
  • Dietrich D., Vennemann A., Wiemann M., Sperling M., Karst U. (2015). Untersuchung der Verteilung von Silbernanopartikeln nach oraler, Gabe im Gastrointestinaltrakt von Ratten mit LA-ICP-MS. DGMS 1.-4.03.2015, Wuppertal, Germany. [Poster]
  • Dietrich D., Vennemann A., Wiemann M., Sperling M., Karst U. (2015). Determination of the distribution of silver nanoparticles by means of LA-ICP-MS. ANAKON, 23.-26.03. 2015 Graz, Austria. [Poster]
  • Dietrich D., Vennemann A., Wiemann M., Sperling M., Karst U. (2015). Determination of the distribution of silver nanoparticles in the gastro-intestinal tract of rats after oral application by means of LA-ICP-MS. Cluster-Treffen 19.-20.05.15, Frankfurt/M., Germany. [Poster]
  • Dietrich D., Vennemann A., Wiemann M., Sperling M., Karst U. (2015). Imaging of Nanoparticles in Lung Tissue by Means of LA-ICP-MS. OURCON 27.-29.10. 2015, Pisa, Italy. [Poster]
  • Großgarten M., Mueller J.C., Holtkamp M., Sperling M., Karst U. (2015). Quantitative elemental bioimaging of titanium in rat lung tissue by means of LA-ICP-MS and µXRF. Colloquium Analytische Atomspektroskopie, 11.3.2015, Leipzig, Germany. [Oral]
  • Großgarten M., Mueller J.C., Holtkamp M., Sperling M., Karst U. (2015). Quantitative elemental bioimaging of titanium in rat lung tissue by means of LA-ICP-MS and µXRF. ANAKON 26.3.2015, Graz, Austria. [Oral]
  • Großgarten M., Vennemann A., Wiemann M., Sperling M., Karst U. (2015). Elemental bioimaging by means of LA-ICP-MS to visualize nanoparticle uptake by alveolar macrophages in vivo and in vitro. CiM International Symposium Moving Cells in Development and Disease, 14.9.2015, Muenster, Germany. [Oral]
  • Großgarten M., Mueller J.C., Holtkamp M., Sperling M., Karst U. (2015). Quantitative elemental bioimaging of titanium in rat lung tissue by means of LA-ICP-MS. European Winter Conference on Plasma Spectrochemistry, 25.2.2015, Muenster, Germany. [Poster]
  • Großgarten M., Mueller J.C., Holtkamp M., Sperling M., Karst U. (2015). Quantitative elemental bioimaging of titanium in rat lung tissue by means of LA-ICP-MS and µXRF. ANAKON, 26.3.2015, Graz, Austria. [Poster]
  • Heller D., Veith L., Fartmann M., ter Veen R., Hagenhoff B., Engelhard C. (2015). Multivariate Datenanalyse von Massenspektrometriedaten. ANAKON 2015, 23.-26.05.2015, Graz, Austria. [Poster]
  • Heller D., Veith L., Fartmann M., ter Veen R., Hagenhoff B., Engelhard C. (2015). ToF-SIMS as a Screening Technique - A Multivariate Data Analysis Approach. 20th International Conference on Secondary Ion Mass Spectrometry, 13.-18.09.2015, Seattle, USA. [Oral]
  • Wagner T., Wiemann M., Lipinski H.-G. (2015). Positionsbestimmungen in multimodalen nanotoxikologischen Bilddaten. Clustertreffen Nanocare, 3.-4.5.2015, Frankfurt/M., Germany. [Poster]
  • Veith L., Hagenhoff B., Heller D., Zakel J., Niehuis E. (2015). ToF-SIMS Analytik in der Nanotoxikologie. Clustertreffen Nanocare,03.-04.05.2015, Frankfurt/M., Germany. [Poster]
  • Veith L., Engelhard C., Hagenhoff B. (2015). Nanoparticle Analysis in biological Systems. 20th International Conference on Secondary Ion Mass Spectrometry, 13.-18-9.2015, Seattle, USA. [Oral]
 

2014

  • Blaske F., Reifschneider O., Großgarten M., Sperling M., Karst U. (2014). Quantitative LA-ICP-MS imaging of silver in different target organs of rats after intratracheal instillation of silver nanoparticles. 62th ASMS Conference on Mass Spectrometry and Allied Topics 2014, 17.6.2014, Baltimore, MD, USA. [Poster]
  • Großgarten M., Blaske F., Reifschneider O., Sperling M., Karst U. (2014). Quantitative LA-ICP-MS imaging of silver in rat target organs after intratracheal nanoparticle instillation using matrix-matched standards. Analytica, 1.-4.4.2014, Muenchen, Germany. [Poster]
  • Großgarten M., Blaske F., Reifschneider O., Sperling M., Karst U.(2014). Quantitative elemental bioimaging of silver in rat target organs by means of laser ablation-ICP-MS. Forschung der Chemischen Industrie, 22.5.2014, Muenster, Germany. [Poster]
  • Großgarten M., Reifschneider O., Blaske F., Mueller J.C., Holtkamp M., Sperling M., Karst U. (2014). Quantitative elemental bioimaging of silver and titanium in rat target organs by means of LA-ICP-MS and µXRF. 24. ICP-MS-Anwendertreffen und 11. Symposium Massenspektrometrische Verfahren Elementspurenanalyse. 16.9.2014, Geesthacht, Germany. [Oral]
   

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