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M. Bonta:
"Quantification strategies for elemental imaging of biological samples using LA-ICP-MS";
Supervisor, Reviewer: A. Limbeck, C. Streli; Institut für Chemische Technologien und Analytik, 2016; oral examination: 2016-10-20.

Metals are an important part of every functioning biological system. Variations in their concentration can indicate altered physiological conditions in an organism. Besides endogenous abundance, trace elements can also be introduced into organisms from external sources such as the environment or intentionally during medical treatments. Either way, accurate assessment of metal concentrations including their spatial distribution in biological samples (e.g., tissues) is an important aspect of modern medical research.
This PhD thesis aims at the development of improved analytical procedures for elemental imaging of biological samples using Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS). Especially the extremely low limits of detection for most elements and the wide accessible range of elements make LA-ICP-MS perfectly suitable for elemental mapping analysis of biological samples. Main target of the research was the optimization of quantification strategies for multi-element imaging in biological samples. The detected signal intensity during an LA-ICP-MS measurement is usually highly influenced by the matrix of the analyzed sample. Laser-material interaction, transport of the generated aerosol towards the ICP-MS device, as well as atomization and ionization of the analytes in the ICP strongly depend on the bulk composition of the investigated sample. Thus, suitable external standards are necessary if quantification of the detected signals is desired. Methods for simple but still accurate quantification should be developed within this PhD thesis, including the evaluation of internal standards to compensate aforementioned matrix effects to a certain extent. Besides analytical method development, also method application for medical questions was an important aspect of this work. One special target of analysis was platinum which is commonly used as functional part of anti-cancer treatments. LA-ICP-MS was aspired to visualize the actual drug distribution in tumor samples, complementing histological investigations.
Within this PhD thesis, attention was also be directed towards the development of a metric for determination of the image quality of LA-ICP-MS distribution images. Additionally, it was desired to increase the number of elements detected during the analysis of one sample. Besides extending the quantification capabilities of LA-ICP-MS to a multi-elemental approach, the simultaneous use of Laser Induced Breakdown Spectroscopy (LIBS) in a Tandem LA/LIBS system allowed the detection of elements which are not accessible for LA-ICP-MS (e.g., H, O, N).

LA-ICP-MS, elemental imaging, quantitative analysis, biological samples