TY  - THES
AB  - The increasing use of nanoparticle (NP)-containing products leads to an enhanced emis-sion of NP into the environment. The potential dangers associated with the exposition of organisms to these materials are barely investigated and the fate of the NP upon uptake into the body is not completely understood. One reason is the lack of suitable analytical techniques, which allow the sensitive detection of NP in tissue at high spatial resolution. Prerequisites for a reliable identification are high sensitivity, high mass resolution and high spatial resolution without the need for markers.
Time-of-Flight secondary ion mass spectrometry (ToF-SIMS) is promising in this regard because it allows the simultaneous detection of atomic and molecular species from sur-faces without markers. However, its potential for the detection of NP in tissue has not yet been adequately explored. In the scope of this work, a suitable ToF-SIMS method is developed and optimised for the analysis of a variety of oxidic NP in lung tissue sec-tions. The suitability of ToF-SIMS for the successful detection of nanomaterials in bio-logical tissue is demonstrated by means of correlations and cross-validations of ToF-SIMS data with the results of reference techniques. 
In this thesis, rat lung tissue sections, containing different kinds of nanoparticles are analysed by ToF-SIMS and compared with reference techniques. Paramagnetic Fe2O3/SiO2 (core/shell) NP (primary particle size 10-20 nm; aggregate size 190 ± 20 nm) are detected by microscopic techniques (dark-field and bright-field microscopy) and ToF-SIMS colocalizing in the tissue sections. The NP are mostly attached to alveolar wall and only marginally internalized by cells. The colocalization of ToF-SIMS signal distributions for 56Fe+ and 28Si+ proves that the core/shell structure of the particles re-mains intact in the tissue. The phosphocholine head group (C5H15NPO4+) is colocalized with tissue (CH4N+) but not with the NP indicating that lipids do not adsorb onto NP under these conditions.
The distribution of fluorescence-tagged SiO2 NP (25 nm) in rat lung tissue is revealed by fluorescence microscopy and ToF-SIMS. Extremely similar signal distributions for the fluorescence tag and ToF-SIMS signals (SiO3-) are obtained. Furthermore, the distribu-tions of protein (CN-) and phosphate-based signals (PO3-) can be related to the particle distribution.
Rat lung tissue sections inhomogenously laden with CeO2 NP (10-200 nm) are subjected to successive analyses by first micro X-ray fluorescence (µ-XRF) and second ToF-SIMS. This approach allows a relatively fast screening of the complete section for ele-vated Ce levels at 25 µm lateral resolution, before selecting suitable regions-of-interest for high-resolution ToF-SIMS analysis at submicrometer lateral resolution (670 nm). Ce-related signal distributions (e.g. 140Ce+, 140CeO+, 140CeO2+) are detected along tissue-related signals (K2CN+) at a mass resolution of R = 4000. Besides pre-analyses, the µ-XRF also allows a coarse cross-validation of the ToF-SIMS signal distributions.
ZrO2 NP (primary sizes of 9-10 nm) are mainly detected as agglomerates in phagocytic cells by both high-spatial resolution techniques, ToF-SIMS and ion beam microscopy (IBM). Both techniques detect ZrO2 related signals at high lateral resolutions (400-600 nm for ToF-SIMS and about 1000 nm for IBM). Only small quantities of NP are found in the lung epithelium. Besides the NP-related signals, S and P signal from IBM colocalize with PO+ and SO2+ from ToF-SIMS. The presence of S-, P- and Zr-related signals in both techniques enables a cross-validation of the results. Additionally, ToF-SIMS signals indicating the distribution of certain compounds such as phospholip-ids (C4H8N+, C6H12N+, C5H15NPO4+) and amino acids (K2CN+, C2H6N+, C3H8N+) are detected at mass resolutions of up to 9000.
In summary, different oxidic nanoparticle types with sizes from 9 nm to more than 200 nm are directly detected by ToF-SIMS (without the need for markers) in rat lung tissue sections. The results are confirmed by independent techniques such as bright- and dark-field microscopy, µ-XRF and IBM. The presented ToF-SIMS analyses reveal the distribution of nanoparticles at high confidence and provide further elemental and mo-lecular information from the particle-surrounding matrix (e.g. amino acids or lipid resi-dues). Lateral resolutions of 400 nm and mass resolutions of up to 9000 with the ability to acquire organic and inorganic signals simultaneously across the whole mass-range are unique features highlighting the great potential of ToF-SIMS for the detection of nano-particles in tissue. These results serve as a basis for the analysis of the fate of the nano-particles in mammalian bodies for future nanotoxicology studies.
AU  - Veith, Lothar
DA  - 2018
KW  - Flugzeitspektrometrie
KW  - Flugzeitsekundärionenmassenspektrometrie
KW  - Lungengewebe
KW  - Gewebeschnitte
KW  - Time-of-flight secondary ion mass spectrometry
KW  - Lung tissue
KW  - Tissue sections
KW  - Nanoparticles
LA  - eng
PY  - 2018
TI  - Optimization and application of Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) for the detection of nanomaterials in tissue thin sections
UR  - https://nbn-resolving.org/urn:nbn:de:hbz:467-14284
Y2  - 2024-11-22T17:42:01
ER  -