TY - JOUR A1 - Kennedy, D.C. A1 - Orts-Gil, G. A1 - Lai, C.-H. A1 - Müller, Larissa A1 - Haase, A. A1 - Luch, A. A1 - Seeberger, P. H. T1 - Carbohydrate functionalization of silver nanoparticles modulates cytotoxicity and cellular uptake N2 - Background Increasing use of silver nanoparticles (Ag-NPs) in various products is resulting in a greater likelihood of human exposure to these materials. Nevertheless, little is still known about the influence of carbohydrates on the toxicity and cellular uptake of nanoparticles. Methods Ag-NPs functionalized with three different monosaccharides and ethylene glycol were synthesized and characterised. Oxidative stress and toxicity was evaluated by protein carbonylation and MTT assay, respectively. Cellular uptake was evaluated by confocal microscopy and ICP-MS. Results Ag-NPs coated with galactose and mannose were considerably less toxic to neuronal-like cells and hepatocytes compared to particles functionalized by glucose, ethylene glycol or citrate. Toxicity correlated to oxidative stress but not to cellular uptake. Conclusions Carbohydrate coating on silver nanoparticles modulates both oxidative stress and cellular uptake, but mainly the first has an impact on toxicity. These findings provide new perspectives on modulating the bioactivity of Ag-NPs by using carbohydrates. KW - Silver KW - Nanoparticles KW - Carbohydrates KW - Nanotoxicology KW - Bio-Interfaces PY - 2014 UR - http://www.jnanobiotechnology.com/content/12/1/59 DO - https://doi.org/10.1186/s12951-014-0059-z SN - 1477-3155 VL - 12 IS - 59 SP - 1 EP - 8 PB - BioMed Central CY - London AN - OPUS4-34345 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Hoesl, Simone A1 - Neumann, B. A1 - Techritz, Sandra A1 - Sauter, G. A1 - Simon, R. A1 - Schlüter, H. A1 - Linscheid, M. W. A1 - Theruing, F. A1 - Müller, Larissa A1 - Jakubowski, Norbert T1 - Internal standardization of LA-ICP-MS immunoimaging via printing of universal metal spiked inks onto tissue sections N2 - Formalin-fixed paraffin-embedded (FFPE) specimen from biopsy materials are a widespread sample format for pathologists and medical researchers. Pathologists are archiving vast numbers of FFPE samples which can be stored for decades. Conventional immunohistochemical staining (IHC) of biomarkers on FFPE tissue sections is one of the most important analytical techniques for cancer diagnosis and pathology in general. However standardization for IHC samples and quality management is tedious and differs significantly from clinic to clinic. Combining established IHC staining strategies with modern mass spectrometry mediated methods would increase it`s potential and enable access of large FFPE archives for multiplexed quantitation purposes. In this work element mass spectrometry and a new ink-jet printed internal standardization approach was successfully combined with IHC staining to facilitate quantitative multiplex assays for archived FFPE samples. The printing strategy improves elemental image resolution and reproducibility of paraffin embedded breast cancer tissue sections in laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) using conventional IHC staining as a model system to investigate the new capabilities of this technique. For the internal standardization we applied a conventional CD-ink-jet printer to print a metal spiked ink onto the top of thin layer tissue sections with constant density. Printing was carried out in a direct comparison to an iodination of the tissue section as previously described as an alternative standardization method. The use of the printed internal standard allowed correction of the fluctuation during the laser ablation process and compensated instrumental drift effects. Mediated by the ink correction approach we achieved better signal-to-background-ratios (SBR) of 74 and better spatial resolution of 30 µm compared to iodination (SBR=23). This improved performance was demonstrated on tumorous areas in FFPE breast cancer tissue sections and allowing detection of Her-2 in tumorous areas of this tissue with significantly improved contrast. KW - Internal standardization KW - LA-ICP-MS KW - Immuno imaging PY - 2016 DO - https://doi.org/10.1039/c5ja00409h SN - 0267-9477 SN - 1364-5544 VL - 31 IS - 3 SP - 801 EP - 808 AN - OPUS4-35711 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Scharlach, C. A1 - Müller, Larissa A1 - Wagner, S. A1 - Kobayashi, Y. A1 - Kratz, H. A1 - Ebert, M. A1 - Jakubowski, Norbert A1 - Schellenberger, E. T1 - LA-ICP-MS allows quantitative microscopy of europium-doped iron oxide nanoparticles and is a possible alternative to ambiguous Prussian blue iron staining N2 - The development of iron oxide nanoparticles for biomedical applications requires accurate histological evaluation. Prussian blue iron staining is widely used but may be unspecific when tissues contain substantial endogenous iron. Here we tested whether microscopy by laser ablation coupled to inductively coupled plasma mass spectrometry (LA-ICP-MS) is sensitive enough to analyze accumulation of very small iron oxide particles (VSOP) doped with europium in tissue sections. KW - Atherosclerotic plaques KW - LA-ICP-MS microscopy KW - Quantification KW - Element microscopy KW - Histology PY - 2016 DO - https://doi.org/10.1166/jbn.2016.2230 SN - 1550-7033 SN - 1550-7041 VL - 12 IS - 5 SP - 1001 EP - 1010 AN - OPUS4-36189 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Müller, Larissa A1 - Herrmann, Antje T1 - Bilder einzelner Zellen aus dem Elementmikroskop N2 - Welche Rolle spielt eine einzelne Zelle im biologischen System? Einen neuen Ansatz, diese Frage zu beantworten, bietet ein Mikroskop auf Basis der Laserablations-ICP-MS, das Elemente in biologischen Materialien analysiert, und zwar mit einer Ortsauflösung im Submikrometerbereich. KW - Elementmikroskop KW - Bio-Imaging KW - LA-ICP-MS KW - Labelilng KW - Nanopartikel PY - 2015 SN - 1439-9598 SN - 1521-3854 VL - 12 IS - 63 SP - 1196 EP - 1199 PB - Wiley-VCH Verl. CY - Weinheim AN - OPUS4-35116 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Schwarz, G. A1 - Müller, Larissa A1 - Beck, S. A1 - Linscheid, M.W. T1 - DOTA based metal labels for protein quantification: a review N2 - Today, quantitative data play a pivotal role in the understanding of biological processes. This is particularly true for the proteome: protein quantification always follows protein identification. To obtain useful and reliable quantitative data, rather sophisticated strategies using electrospray and MALDI mass spectrometry have been developed, which allow relative and sometimes even absolute quantification. All of those strategies have merits and limitations. In order to overcome some of these limits, methods based on the reliable and sensitive detection and quantification of heavy metals present in proteins using inductively coupled plasma (ICP)-MS have been reported. With specific labels carrying heavy metals, the applicability of ICP-MS has been extended to almost every protein. One of such covalently bound metal tags, allowing the quantification of low abundant proteins, uses 1,4,7,10-tetraazacyclododecane N,N',N'',N''-tetraacetic acid (DOTA) chelate complexes carrying lanthanides as the metal core. In this review the scope and limitations of peptide and protein quantification will be addressed. The metal tags do not only provide low detection limits, but also due to the large number of different lanthanides and lanthanide isotopes, multiplexing capabilities and previously unknown accuracy based on inherently possible isotope dilution methods came into reach. The developed workflows, including electrophoretic and chromatographic separation and preconcentration techniques, will be addressed to allow a comparison with already established procedures. KW - Protein quantification KW - ICP-MS KW - DOTA KW - Labeling PY - 2014 DO - https://doi.org/10.1039/c3ja50277e SN - 0267-9477 SN - 1364-5544 VL - 29 IS - 2 SP - 221 EP - 233 PB - Royal Society of Chemistry CY - London AN - OPUS4-30730 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Müller, Larissa T1 - Development and application of new metal-based multiplexing diagnosis methods T2 - eingeladener Seminar-Vortrag an der ETH Zürich CY - Zurich, Switzerland DA - 2013-12-12 PY - 2013 AN - OPUS4-29965 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Hösl, Simone A1 - Neumann, B. A1 - Techritz, Sandra A1 - Linscheid, M. A1 - Theuring, F. A1 - Scheler, C. A1 - Jakubowski, Norbert A1 - Müller, Larissa T1 - Development of a calibration and standardization procedure for LA-ICP-MS using a conventional ink-jet printer for quantification of proteins in electro- and western-blot assays N2 - We developed new procedures for internal standardization and calibration to be used for laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS) for elemental micro mapping imaging of biological samples like Western blot membranes and tissue sections. These procedures are based on printing of metal spiked inks onto the top of thin layer samples for simultaneous internal standardization and calibration of LA-ICP-MS. In the case of internal standardization the ink is spiked with indium as an internal standard and homogenously printed over the entire membrane (size 56 cm2) prior to LA-ICP-MS detection, a standard deviation (RSD) value of 2% was achieved. In the second approach the metal content of lanthanide tagged proteins and antibodies after biological work flows was quantified by LA-ICP-MS on nitro-cellulose membranes. In this case the inks spiked with varying metals were printed with different densities on the same nitrocellulose membranes in well-defined squares to produce matrix-matched calibration standards. For validation and calibration the ink squares were excised and the specific metal content was measured by liquid ICP-MS after solubilization of the membrane slice. For the printed calibration standard limits of detection (LOD) of <4 fmol for different metals and relative process standard deviations of 1–2% only were determined via LA-ICP-MS. PY - 2014 DO - https://doi.org/10.1039/c4ja00060a SN - 0267-9477 SN - 1364-5544 VL - 29 IS - 7 SP - 1282 EP - 1291 PB - Royal Society of Chemistry CY - London AN - OPUS4-31171 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Müller, Larissa A1 - Mairinger, T. A1 - Hermann, G. A1 - Koellensperger, G. A1 - Hann, S. T1 - Characterization of metal-tagged antibodies used in ICP-MS-based immunoassays N2 - A detailed characterization of metal-tagged antibodies is the prerequisite for the implementation of quantitative concepts in inductively coupled plasma–mass spectrometry (ICP-MS)-based bioanalysis or future medical diagnosis. In this paper, the common modification with bifunctional ligands containing maleimide residues as a reactive group was investigated in detail via size exclusion chromatography (SEC)-ICP-MS and liquid chromatography–time-of-flight (LC-TOF)-MS to determine the preservation of the antibody structure after tagging. Mouse monoclonal IgG modified with metal-coded tags (MeCATs) was used as a model system. Several antibody fragments were identified carrying different numbers of metal tags. In a second step, a functionality test was performed with isolated fragments where the antigen specificity was tested in a dot blot immunoassay. KW - Bioanalytical methods KW - Mass spectrometry KW - ICP-MS KW - Antibody tagging KW - Antibodies KW - Immunoassay KW - Maleimide DOTA KW - Tags PY - 2014 DO - https://doi.org/10.1007/s00216-013-7416-x SN - 1618-2642 SN - 1618-2650 VL - 406 IS - 1 SP - 163 EP - 169 PB - Springer CY - Berlin AN - OPUS4-30037 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Müller, Larissa A1 - Jakubowski, Norbert A1 - Roos, P.H. T1 - Multi-parametric analysis of cytochrome P450 expression in rat liver microsomes by LA-ICP-MS N2 - Quantitative analysis of cytochrome P450 (CYP) patterns of cells and tissues is an important aspect in toxicological and pharmacological research as this group of enzymes is largely involved in the metabolism of toxic compounds and drugs. Here we present a method for the multi-parametric and simultaneous quantitative determination of several cytochromes P450 in liver microsomes of untreated and inducer treated rats. The method is based on the binding of specifically lanthanide labelled antibodies to electrophoretically separated and blotted CYP proteins and their subsequent identification and quantification by LA-ICP-MS. CYP1A1, CYP2B1, CYP2C11, CYP2E1 and CYP3A1 were simultaneously quantified and the patterns between microsomal samples were compared. Microsomes of rats treated with 3-methylcholanthrene, phenobarbital and dexamethasone showed increased levels of CYP1A1, CYP2B1 and CYP3A1, respectively. These results coincide with data obtained by independent methods for CYP quantification, i.e. ethoxyresorufin O-deethylase activity for CYP1A1 and pentoxyresorufin O-depentylase for CYP2B1. The presented method is useful for multi-parametric CYP profiling and has further large potential with respect to the number of analysed parameters/proteins and sensitivity. PY - 2011 DO - https://doi.org/10.1039/c0ja00077a SN - 0267-9477 SN - 1364-5544 N1 - Geburtsname von Müller, Larissa: Wäntig, L. - Birth name of Müller, Larissa: Wäntig, L. VL - 26 IS - 2 SP - 310 EP - 319 PB - Royal Society of Chemistry CY - London AN - OPUS4-23465 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Müller, Larissa T1 - Development of multiplex immunoassays for protein detection by Laser Ablation (LA-) ICP-MS T2 - Third International Symposium on Metallomics CY - Münster, Germany DA - 2011-06-15 PY - 2011 N1 - Geburtsname von Müller, Larissa: Wäntig, L. - Birth name of Müller, Larissa: Wäntig, L. N1 - Geburtsname von Hösl, Simone: Hardt, S. - Birth name of Hösl, Simone: Hardt, S. AN - OPUS4-24110 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Müller, Larissa T1 - Multiplexed probing of antibodies using laser ablation ICP-MS T2 - 9. Symposium Massenspektrometrische Verfahren der Elementspurenanalyse und 22. ICP-MS-Anwendertreffen CY - Berlin, Germany DA - 2010-09-06 PY - 2010 N1 - Geburtsname von Müller, Larissa: Wäntig, L. - Birth name of Müller, Larissa: Wäntig, L. AN - OPUS4-23819 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Müller, Larissa T1 - Method development for iodination of proteins for LA-ICP-MS based proteomics T2 - European Winter Conference on Plasma Spectrochemistry CY - Zaragoza, Spain DA - 2011-01-30 PY - 2011 N1 - Geburtsname von Müller, Larissa: Wäntig, L. - Birth name of Müller, Larissa: Wäntig, L. AN - OPUS4-23821 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Müller, Larissa A1 - Jakubowski, Norbert A1 - Hayen, H. A1 - Roos, P.H. T1 - Iodination of proteins, proteomes and antibodies with potassium triodide for LA-ICP-MS based proteomic analyses N2 - A fast and mild method for iodine labelling of proteins is presented which is specifically designed and optimized for laser ablation (LA-)ICP-MS based proteomics. Single proteins (lysozyme, bovine serum albumin, cytochrome c and β-casein), whole proteomes (microsomal proteome of rats) and antibodies (anti-bovine casein, anti-bovine serum albumin) can be efficiently iodinated by means of potassium triiodide with minimal losses of antigen properties and antibody binding to iodinated proteins. A comparison with iodination by use of IODO-Beads is presented and it is shown that triiodide labelling is a fast, cheap and less laborious alternative without compromising the analytical figures of merit. PY - 2011 DO - https://doi.org/10.1039/c1ja10090d SN - 0267-9477 SN - 1364-5544 N1 - Geburtsname von Müller, Larissa: Wäntig, L. - Birth name of Müller, Larissa: Wäntig, L. VL - 26 SP - 1610 EP - 1618 PB - Royal Society of Chemistry CY - London AN - OPUS4-24209 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Müller, Larissa T1 - Development of multiplex immunoassays for protein detection by LA-ICP-MS T2 - Winter Conference on Plasma Spectrochemistry 2012 CY - Tucson, AZ, USA DA - 2012-01-09 PY - 2012 N1 - Geburtsname von Müller, Larissa: Wäntig, L. - Birth name of Müller, Larissa: Wäntig, L. N1 - Geburtsname von Hösl, Simone: Hardt, S. - Birth name of Hösl, Simone: Hardt, S. AN - OPUS4-25983 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Müller, Larissa T1 - Development of multiplex immunoassays for protein detection by LA-ICP-MA T2 - Winter Conference on Plasma Spectrochemistry 2012 CY - Tucson, AZ, USA DA - 2012-01-09 PY - 2012 N1 - Geburtsname von Müller, Larissa: Wäntig, L. - Birth name of Müller, Larissa: Wäntig, L. N1 - Geburtsname von Hösl, Simone: Hardt, S. - Birth name of Hösl, Simone: Hardt, S. AN - OPUS4-25985 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Müller, Larissa T1 - Development and application of new metal-based diagnosis methods T2 - "Clinical Immunology & Hot Technologies" club; Deutsches Rheuma-Forschuungszentrum CY - Berlin, Germany DA - 2012-05-22 PY - 2012 N1 - Geburtsname von Müller, Larissa: Wäntig, L. - Birth name of Müller, Larissa: Wäntig, L. N1 - Geburtsname von Hösl, Simone: Hardt, S. - Birth name of Hösl, Simone: Hardt, S. AN - OPUS4-25944 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Müller, Larissa T1 - Development of multiplex immunoassays for protein detection by LA-ICP-MS T2 - Anwendertreffen Plasmaspektrometrie 2012 CY - Berlin, Germany DA - 2012-02-27 PY - 2012 N1 - Geburtsname von Müller, Larissa: Wäntig, L. - Birth name of Müller, Larissa: Wäntig, L. N1 - Geburtsname von Hösl, Simone: Hardt, S. - Birth name of Hösl, Simone: Hardt, S. AN - OPUS4-25945 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Müller, Larissa T1 - Metal coded tags for development of multiplexing diagnosis methods T2 - 4th International Symposium on Metallomics 2013 CY - Oviedo, Spain DA - 2013-07-08 PY - 2013 N1 - Geburtsname von Hösl, Simone: Hardt, S. - Birth name of Hösl, Simone: Hardt, S. AN - OPUS4-28954 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Müller, Larissa T1 - Multi-parametric microarray for protein profiling T2 - Proteomic Forum 2013 CY - Berlin, Germany DA - 2013-03-17 PY - 2013 N1 - Geburtsname von Müller, Larissa: Wäntig, L. - Birth name of Müller, Larissa: Wäntig, L. AN - OPUS4-27964 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Müller, Larissa T1 - Development and application of new metal-based multiplexing diagnosis methods T2 - Proteomic Forum 2013 CY - Berlin, Germany DA - 2013-03-17 PY - 2013 N1 - Geburtsname von Müller, Larissa: Wäntig, L. - Birth name of Müller, Larissa: Wäntig, L. N1 - Geburtsname von Hösl, Simone: Hardt, S. - Birth name of Hösl, Simone: Hardt, S. AN - OPUS4-27965 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - CONF A1 - Müller, Larissa T1 - Development and application of new metal-based diagnosis methods T2 - 23. ICPMS Anwendertreffen und 10. Symposium Massenspektrometrische Verfahren der Elementspurenanalyse CY - Tulln an der Donau, Austria DA - 2012-09-10 PY - 2012 N1 - Geburtsname von Müller, Larissa: Wäntig, L. - Birth name of Müller, Larissa: Wäntig, L. N1 - Geburtsname von Hösl, Simone: Hardt, S. - Birth name of Hösl, Simone: Hardt, S. AN - OPUS4-27479 LA - deu AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER - TY - JOUR A1 - Müller, Larissa A1 - Techritz, Sandra A1 - Jakubowski, Norbert A1 - Roos, P.H. T1 - A multi-parametric microarray for protein profiling: simultaneous analysis of 8 different cytochromes via differentially element tagged antibodies and laser ablation ICP-MS N2 - The paper presents a new multi-parametric protein microarray embracing the multi-analyte capabilities of laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The combination of high throughput reverse phase protein microarrays with element tagged antibodies and LA-ICP-MS makes it possible to detect and quantify many proteins or biomarkers in multiple samples simultaneously. A proof of concept experiment is performed for the analysis of cytochromes particularly of cytochrome P450 enzymes, which play an important role in the metabolism of xenobiotics such as toxicants and drugs. With the aid of the LA-ICP-MS based multi-parametric reverse phase protein microarray it was possible to analyse 8 cytochromes in 14 different proteomes in one run. The methodology shows excellent detection limits in the lower amol range and a very good linearity of R² ≥ 0.9996 which is a prerequisite for the development of further quantification strategies. KW - Multi-parametric KW - Multiplexing KW - Microarray KW - Immunoassay KW - LA-ICP-MS KW - Cytochrome P450 PY - 2013 DO - https://doi.org/10.1039/c3an00468f SN - 0003-2654 SN - 1364-5528 VL - 138 IS - 21 SP - 6309 EP - 6315 PB - Royal Society of Chemistry CY - Cambridge AN - OPUS4-29275 LA - eng AD - Bundesanstalt fuer Materialforschung und -pruefung (BAM), Berlin, Germany ER -