Doktoratskolleg MEIBio - Molecular and Elemental Imaging in Bioscience
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PhD Fellow #5

Quantification strategies for elemental imaging of biological samples using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICPMS)

Faculty: Andreas Limbeck

Bio-imaging analytical techniques are today of crucial interest in life science studies to achieve a deeper understanding of the role of trace elements in biological systems. LA-ICP-MS is an attractive option for probing metal biochemistry due to the technique's impressive detection limits (typically below parts-per-million), wide dynamic range (up to 9 orders of magnitude) and spatial resolution capacity in the micrometer range. Further advantages are high sample throughput, access to isotopic patterns and the lack of any charging-effects during analysis. However, achieving robust and reliable quantitative analysis, which is required to assess whether element variation within a sample is significant or merely a characteristic of heterogeneity, is an elusive goal of LA-ICP-MS analysis since the ablation process and the subsequent ionization in the plasma are affected by the physical and chemical properties of the sample matrix. For example varies the interaction between laser and sample surface with sample composition, changes in the surface characteristics (reflectivity, thermal conductivity, density, ...) can therefore cause differences in signal response. Furthermore the problem of elemental fractionation has to be considered, which comprises the problems associated with differences in volatilization, vaporization, ionization and transport of the analytes to the ICP-MS during sample ablation, resulting in a non-stoichiometric representation of the initial sample composition. Thus quantification of trace elements by LA-ICP-MS relies upon suitable calibration or measurement against fully characterized reference materials. Procurement of matrix-matched reference materials with a defined homogeneity at the micrometer scale for the sample in question is often not possible, thus imaging experiments using LA-ICP-MS have employed a number of diverse and novel methods for the quantification of trace elements within biological samples. Proposed procedures include the use of internal standards (IS) such as 13C+, the deposition of thin polymeric films spiked with suitable elements as IS on the sample surface, or the preparation of matrix matched standards to account for matrix effects as well as for variations in ablated mass, transported mass and instrumental drift normally present in laser-based analysis techniques.

Within this project innovative approaches for the correction of matrix effects as well as for variations in ablated mass, transported mass and instrumental drifts normally present in LA-ICPMS analysis will be developed. Furthermore the online addition of internal standards to the ablated material prior to ICP-MS measurement will be examined as a possible means for accurate quantification. For method optimization reference measurements with complementary methods are required, which will be performed in collaboration with the faculty partners offering alternative techniques for elemental imaging - in particular secondary ion mass spectrometry (SIMS) and synchrotron radiation induced micro X-ray spectrometry (SR-µ-XRS). Finally derived procedures will be applied for quantitative measurement of trace element distributions in tissue sections, where also molecular distribution will be measured to align elemental with molecular information.



  • The Lawrence Berkeley National Laboratory (LBNL), California, the Ghent University, Department of Analytical Chemistry, Belgium and the BAM Federal Institute for Materials Research and Testing, Berlin, Germany will contribute their expertise in the field of LA-ICPMS analysis of biological samples.
  • The development of methods and strategies for elemental detection will be established in close collaboration with Ch. Streli and M. Marchetti-Deschmann (both TU Vienna) benefitting from their documented experience for biological samples.
  • Additional results for element distributions will be gathered by Ch. Streli and H. Hutter (both TU Vienna) using different techniques. These results will subsequently be supplemented by molecular information from M. Marchetti-Deschmann (TU Vienna).