preparation-of-nanoparticles-for-tof-sims-and-xps-analysis

Preparation of Nanoparticles for ToF-SIMS and XPS Analysis

Nanoparticles have gained increasing attention in recent years due to their potential and application in different fields including medicine, cosmetics, ...

German Federal Institute for Risk Assessment (BfR)

Oxidative stress is more and more recognized as the underlying motif for a broad variety of diseases including cancer. Medicine faces the paramount task to develop better diagnostic tools and drug treatment prediction models in the future to significantly enhance the quality of life. Special interest will focus on earlystage disease biomarkers and biomarkers that could predict healing success at the earliest time point after the treatment started. The accelerated formation of so-called reactive oxygen species (ROS) is becoming widely regarded as the underlying process associated with many diseases like myocardial infarction, Alzheimer's, Parkinson's and kidney disease, etc. Once generated within cells and tissues, ROS can react with a variety of cellular metabolites like fatty acids, proteins or DNA. This review investigates the possibilities for various oxidized metabolites as well as proteomics, genomics and bioimaging biomarkers to serve as early-stage disease biomarkers or biomarkers for drug treatment success. We also assess the value of a step-by-step or cascade biomarker approach as a new paradigm in medical diagnostics. Examples are given for possible analytical methodology and tools as well as statistical methods that could be applied. Such an approach may straighten the road toward new medical diagnostics and treatment regimes, which ultimately could lead to a significantly enhanced medical service for patients suffering from chronic and debilitating or deadly diseases including cancer. Examples from recent research are given to show the progress and possibilities for the proposed model.

Monitoring oxidative stress biomarkers in the lipidome: is there a roadmap for "human inspection"?

Considering the holy grail of future medical treatment being personalized medicines, biomarker research will become more and more the focus for attention not only to develop new medical treatment regimes, based on changes in biomarker patterns, but also for nutritional advice to guarantee a lifelong optimized health condition. The current review gives an outline of how personalized medicine can become established for actual medical treatment using new biomarker concepts. Starting from the development of biomarker research using mainly immunological techniques, the review gives an overview about biomarkers of prediction evolved and focuses on new methodology for the identification of biomarkers using hyphenated analytical techniques like metabolomics and lipidomics. The actual use of multivariate statistical methods in combination with metabolomics and lipidomics is discussed not only for medical treatment but also for precautionary risk identification in human biomonitoring studies.

A personalized life: biomarker monitoring from cradle to grave.

Plastic particles smaller than 5mm, so called microplastics have the capability to accumulate in rivers, lakes and the marine environment and therefore have begun to be considered in eco-toxicology and human health risk assessment. Environmental microplastic contaminants may originate from consumer products like body wash, tooth pastes and cosmetic products, but also from degradation of plastic waste; they represent a potential but unpredictable threat to aquatic organisms and possibly also to humans. We investigated exemplarily for polyethylene (PE), the most abundant constituent of microplastic particles in the environment, whether such fragments could be produced from larger pellets (2mm×6mm). So far only few analytical methods exist to identify microplastic particles smaller than 10μm, especially no imaging mass spectrometry technique. We used at first time-of-flight secondary ion mass spectrometry (ToF-SIMS) for analysis and imaging of small PE-microplastic particles directly in the model system Ottawa sand during exposure to sea surf simulation. As a prerequisite, a method for identification of PE was established by identification of characteristic ions for PE out of an analysis of grinded polymer samples. The method was applied onto Ottawa sand in order to investigate the influence of simulated environmental conditions on particle transformation. A severe degradation of the primary PE pellet surface, associated with the transformation of larger particles into smaller ones already after 14days of sea surf simulation, was observed. Within the subsequent period of 14days to 1month of exposure the number of detected smallest-sized particles increased significantly (50%) while the second smallest fraction increased even further to 350%. Results were verified using artificially degraded PE pellets and Ottawa sand. 

Time-of-flight secondary ion mass spectrometry (ToF-SIMS)-based analysis and imaging of polyethylene microplastics formation during sea surf simulation.

Single cell imaging mass spectrometry opens up a complete new perspective for strategies in toxicological risk assessment and drug discovery. In particular, time-of-flight secondary ion mass spectrometry (ToF-SIMS) with its high spatial and depth resolution is becoming part of the imaging mass spectrometry toolbox used for single cell analysis. Recent instrumentation advancements in combination with newly developed cluster ion guns allow 3-dimensional reconstruction of single cells together with a spatially resolved compound location and quantification on nanoscale depth level. The exact location and quantification of a single compound or even of a set of compounds is no longer restricted to the two dimensional space within single cells, but is available for voxels, a cube-sized 3-dimensional space, rather than pixels. The information gathered from one voxel is further analysed using multivariate statistical methodology like maximum autocorrelation factors to co-locate the compounds of interest within intracellular organelles like nucleus, mitochondria or golgi apparatus. Furthermore, the cell membrane may be resolved, including adhering compounds and potential changes of the lipid patterns. The generated information can be used further for a first evaluation of intracellular target specifity of new drug candidates or for the toxicological risk assessment of environmental chemicals and their intracellular metabolites. Additionally, single cell lipidomics and metabolomics enable for the first time an in-depth understanding of the activation or inhibition of cellular biosynthesis and signalling pathways.

Article	Year
Monitoring oxidative stress biomarkers in the lipidome: is there a roadmap for "human inspection"? Current molecular medicine\| PubMed ID: 22292439	2012
A personalized life: biomarker monitoring from cradle to grave. Experientia supplementum (2012)\| PubMed ID: 22945580	2012
Time-of-flight secondary ion mass spectrometry (ToF-SIMS)-based analysis and imaging of polyethylene microplastics formation during sea surf simulation. The Science of the total environment\| PubMed ID: 27135589	2016
Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS): A New Tool for the Analysis of Toxicological Effects on Single Cell Level. Toxics\| PubMed ID: 29051411	2016

Harald Jungnickel

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