Uwe Karst

University of Münster, Muenster, North Rhine-Westphalia, Germany

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Publications (238)855.79 Total impact

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    ABSTRACT: RATIONALETwo different approaches to improve the limits of detection (LODs) in elemental bioimaging have been developed. They both consider the fact that for the widely applied quadrupole-based instruments, metals in the mass range <100 u are analyzed with the best figures of merit in the kinetic energy discrimination (KED) mode; much better LODs are achieved for some metalloids and nonmetals by the introduction of more reactive gases, e.g., oxygen, into the collision/reaction cell (CRC).METHODS While the first approach simultaneously utilizes two inductively coupled plasma mass spectrometry (ICP-MS) detectors hyphenated to one laser ablation (LA) system, the second is based on a single ICP-MS instrument with fast cell mode switching (CMS) of the CRC between individual line scans.RESULTSBoth methods were evaluated concerning their respective improvements by the analysis of rat brain samples. The utilization of two detectors showed improved LODs compared with conventional KED-only analysis in dependency on the gas flow splitting ratio, e.g., for sulfur by about 3.5 orders of magnitude. CMS provided even better results with a further improvement by a factor of 1.6.CONCLUSIONS As a CRC with a small inner volume was used, fast cell gas switches at the end of every line prevented issues related to the reproducibility of the laser ablation stage for the CMS approach. Linear interpolation was found to be a valuable tool without affecting the spatial resolution of the images. In addition, a software macro is presented, which facilitates data evaluation. Copyright © 2014 John Wiley & Sons, Ltd.
    Rapid Communications in Mass Spectrometry 12/2014; 28(23). · 2.51 Impact Factor
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    ABSTRACT: Low gas flow ICP-OES with a total argon consumption below 0.7 L/min is introduced for the analysis of trace elements in blood samples to investigate the influence of samples containing an organic solvent in a demanding matrix on the performance of this plasma for the first time. Therefore, gadolinium was determined in human plasma samples and mercury in red blood cells, human plasma and the precipitated plasma protein fraction. Limits of detection (LOD) were determined to be in the low microgram per liter range for the analytes and the accuracy of the method was assessed by comparison with a conventional Fassel type torch-based ICP-OES. It was proven that the low gas flow ICP-OES leads to comparable results with the instrument based on the Fassel type torch.
    Analytical and Bioanalytical Chemistry 08/2014; · 3.66 Impact Factor
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    ABSTRACT: An analytical method using laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was developed and applied to assess enrichment of (10)B-containing p-boronophenylalanine-fructose (BPA-f) and its pharmacokinetic distribution in human tissues after application for boron neutron capture therapy (BNCT). High spatial resolution (50 μm) and limits of detection in the low parts-per-billion range were achieved using a Nd:YAG laser of 213 nm wavelength. External calibration by means of (10)B-enriched standards based on whole blood proved to yield precise quantification results. Using this calibration method, quantification of (10)B in cancerous and healthy tissue was carried out. Additionally, the distribution of (11)B was investigated, providing (10)B enrichment in the investigated tissues. Quantitative imaging of (10)B by means of LA-ICP-MS was demonstrated as a new option to characterise the efficacy of boron compounds for BNCT.
    Analytical and Bioanalytical Chemistry 07/2014; · 3.66 Impact Factor
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    ABSTRACT: The combination of electrochemistry (EC) and mass spectrometry (MS) has become a more and more frequently used approach in metabolism studies in the last decade. This review provides insight into the importance of metabolism studies during the drug development process and gives a short overview about the conventionally used methods since electrochemistry is often intended to substitute or minimize animal-based studies. The optimization of the electrochemical conditions is of great importance for a successful comparison with in vitro approaches. The type of metabolism reactions, which can be simulated by EC, has been extended with new cell types and working electrodes. Although the mechanism differs from the enzyme-catalyzed turnover, electrochemistry can be used to simulate a significant number of the respective reactions. An expanded set-up consisting of EC, a chromatographic separation and MS allows to distinguish between an electrospray ionization (ESI) in-source and an electrochemical oxidation and provides information on the polarity of the electrogenerated compounds. A main advantage of EC for metabolite generation is the possibility to isolate reactive species because of the purely instrumental approach. Especially when a preparative electrochemical cell with a larger working electrode surface is used, metabolites can be generated in sufficient quantities for their subsequent structure elucidation. Besides, the compounds can also be used for selective trapping experiments with different cell components such as small peptides, proteins or DNA bases. Current and possible future developments and applications of EC are presented and discussed as well.
    Analytica chimica acta. 06/2014; 834C:9-21.
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    ABSTRACT: The first combination of electrochemistry (EC), non-aqueous capillary electrophoresis (NACE) and electrospray mass spectrometry (ESI-MS) to mimic the metabolic fate of drugs is described. While the combination of EC, HPLC and ESI-MS has been used for this purpose before, NACE is able to deliver valuable additional information about possible metabolites of harmane when compared to HPLC. In this paper, NACE is used as a comprehensive separation technique in metabolism studies of harmane, a naturally occurring monoaminooxidase inhibitor, since it exhibits beneficial properties for the separation of polar compounds. Harmane is known to be metabolized via the oxidative metabolism catalyzed by Cytochrome P450 enzymes (CYP450), which are the most important metabolizing superfamily of enzymes in the human liver. The application of HPLC and NACE enabled the detection of 37 products in total, with 14 different mass to charge ratios. A total of 31 products could be detected in HPLC-MS and 26 in NACE-MS analysis. The combination of both NACE and RP-HPLC allows the identification of significantly more potential metabolites than any of the separation techniques alone. This article is protected by copyright. All rights reserved.
    Electrophoresis 06/2014; · 3.26 Impact Factor
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    ABSTRACT: Purpose To explore the feasibility of tracking thulium (Tm)-1,4,7,10-tetraazacyclododecane-α,α',α'',α'''-tetramethyl-1,4,7,10-tetraacetic acid (DOTMA)-labeled cells in vivo by means of highly shifted proton magnetic resonance (MR) imaging as a potential alternative to established cell-tracking methods. Materials and Methods All animal experiments were approved by the local ethics committee for animal experiments. Highly shifted proton MR imaging is based on the principle that the shifted resonances on Tm and dysprosium (Dy)-DOTMA can be detected separately from the tissue water signal at MR imaging with very short echo time and radial center-out readout (UTE, or "ultrashort echo time"). MR imaging of aqueous solutions and in mice in vivo was performed at 9.4 T. Human fibrosarcoma cells (HT-1080) and murine macrophages were labeled with different amounts of Tm-DOTMA. Labeled fibrosarcoma cells were injected subcutaneously into three mice. For cell tracking, labeled macrophages were administered intravenously into eight mice bearing local granulomatous inflammation. Three-dimensional UTE MR imaging was performed during 1 week. Macrophage viability and activity and fibrosarcoma cell viability were statistically analyzed by performing an unpaired two-tailed t test for labeled versus unlabeled cells by using data of at least six independent experiments. Results The strongly shifted MR lines of Tm- and Dy-DOTMA can be separated from the tissue water signal and from each other. A detection limit of about 25 µmol/L of Tm-DOTMA was calculated from in vitro MR measurements. A mean ± standard error of the mean intracellular uptake of (4.19 ± 0.88) × 10(9) (HT-1080) and (10.1 ± 3.0) × 10(10) (macrophages) of Tm-DOTMA molecules per cell was achieved. In vivo, Tm-DOTMA signal was detectable for 1 week in both tumors and macrophages, with a detection limit of approximately 10(4) HT-1080 and 600 macrophages. Histologic examination results and elemental bioimaging confirmed labeled cells as source of MR signal. Conclusion Strongly shifted proton three-dimensional UTE MR imaging of Tm-DOTMA-labeled cells is a highly specific and sensitive tool for in vivo cell tracking. © RSNA, 2014 Online supplemental material is available for this article.
    Radiology 05/2014; · 6.34 Impact Factor
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    ABSTRACT: In this work, the potential of electrochemical oxidation as a tool for the rapid prediction of transformation products in water appearing after ozonation is investigated. These two approaches were compared by choosing the two environmentally relevant model compounds diclofenac and metoprolol and comparison of their transformation products after electrochemical oxidation and treatment with ozone. Within these two approaches, certain similarities were observed in the resulting chromatograms: Six transformation products of the electrochemical oxidation of metoprolol were also detected in the ozone samples. For diclofenac two transformation products matched. Additionally, five of the electrochemically generated oxidation products were reported in literature to occur after water treatment processes. The application of a boron-doped diamond working electrode for electrochemical oxidation allowed the generation of hydroxyl radicals, which was shown by spin trapping experiments with p-chlorobenzoic acid. This allowed the generation of certain transformation products previously not obtained by electrochemical oxidation. Concluding, the hyphenation of electrochemistry with liquid chromatography and mass spectrometry offers a useful tool in transformation studies.
    Journal of Chromatography A 04/2014; · 4.61 Impact Factor
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    ABSTRACT: The toxicologically most relevant mercury (Hg) species for human exposure is methylmercury (MeHg). Thiomersal is a common preservative used in some vaccine formulations. The aim of this study is to get further mechanistic insight into the yet not fully understood neurotoxic modes of action of organic Hg species. Mercury species investigated include MeHgCl and thiomersal. Additionally HgCl2 was studied, since in the brain mercuric Hg can be formed by dealkylation of the organic species. As a cellular system astrocytes were used. In vivo astrocytes provide the environment necessary for neuronal function. In the present study, cytotoxic effects of the respective mercuricals increased with rising alkylation level and correlated with their cellular bioavailability. Further experiments revealed for all species at subcytotoxic concentrations no induction of DNA strand breaks, whereas all species massively increased H2O2-induced DNA strand breaks. This co-genotoxic effect is likely due to a disturbance of the cellular DNA damage response. Thus, at nanomolar, sub-cytotoxic concentrations, all three mercury species strongly disturbed poly(ADP-ribosyl)ation, a signalling reaction induced by DNA strand breaks. Interestingly, the molecular mechanism behind this inhibition seems to be different for the species. Since chronic PARP-1 inhibition is also discussed to sacrifice neurogenesis and learning abilities, further experiments on neurons and in vivo studies could be helpful to clarify whether the inhibition of poly(ADP-ribosyl)ation contributes to organic Hg induced neurotoxicity.
    Metallomics 02/2014; · 4.10 Impact Factor
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    ABSTRACT: A new method for elemental bioimaging with laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was developed and applied to study the uptake of manganese (Mn) in Caenorhabditis elegans (C. elegans). C. elegans is a well-established model organism in neuroscience, genetics and genomics, which has been extensively studied to decipher mechanisms of heavy metal induced toxicity. Knowledge about the distribution of manganese (Mn) and other metals in this organism will be helpful in elucidating pathways and mechanisms of transport, distribution and excretion. The LA-ICP-MS method requires limited sample preparation and can be used rapidly and easily to visualize the Mn distribution in C. elegans. Due to thorough optimization of the analytical parameters, intense Mn signals in C. elegans wild-type (WT) and mutants were obtained at a spatial resolution as small as 4 μm, thus proving the suitability of LA-ICP-MS to study the uptake of metals in C. elegans.
    Metallomics 01/2014; · 4.10 Impact Factor
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    ABSTRACT: Parkinson's disease (PD) is a neurodegenerative brain disorder characterized by selective dopaminergic (DAergic) cell loss that results in overt motor and cognitive deficits. Current treatment options exist to combat PD symptomatology, but are unable to directly target its pathogenesis due to a lack of knowledge concerning its etiology. Several genes have been linked to PD, including three genes associated with an early-onset familial form: parkin, pink1 and dj1. All three genes are implicated in regulating oxidative stress pathways. Another hallmark of PD pathophysiology is Lewy body deposition, associated with the gain-of-function genetic risk factor α-synuclein. The function of α-synuclein is poorly understood, as it shows both neurotoxic and neuroprotective activities in PD. Using the genetically tractable invertebrate Caenorhabditis elegans (C. elegans) model system, the neurotoxic or neuroprotective role of α-synuclein upon acute Mn exposure in the background of mutated pdr1, pink1 or djr1.1 was examined. The pdr1 and djr1.1 mutants showed enhanced Mn accumulation and oxidative stress that was reduced by α-synuclein. Moreover, DAergic neurodegeneration, while unchanged with Mn exposure, returned to wild-type (WT) levels for pdr1, but not djr1.1 mutants expressing α-synuclein. Taken together, this study uncovers a novel, neuroprotective role for WT human α-synuclein in attenuating Mn-induced toxicity in the background of PD-associated genes, and further supports the role of extracellular dopamine in exacerbating Mn neurotoxicity.
    Metallomics 01/2014; · 4.10 Impact Factor
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    ABSTRACT: In order to reveal the time-depending mercury species uptake by human astrocytes, a novel approach for total mercury analysis is presented, which uses an accelerated sample introduction system combined on-line with an inductively coupled plasma mass spectrometer equipped with a collision/reaction cell. Human astrocyte samples were incubated with inorganic mercury (HgCl2), methylmercury chloride (MeHgCl), and thimerosal. After 1-h incubation with Hg(2+), cellular concentrations of 3 μM were obtained, whereas for organic species, concentrations of 14-18 μM could be found. After 24 h, a cellular accumulation factor of 0.3 was observed for the cells incubated with Hg(2+), whereas the organic species both showed values of about 5. Due to the obtained steady-state signals, reliable results with relative standard deviations of well below 5 % and limits of detection in the concentration range of 1 ng L(-1) were obtained using external calibration and species-unspecific isotope dilution analysis approaches. The results were further validated using atomic fluorescence spectrometry.
    Analytical and Bioanalytical Chemistry 01/2014; · 3.66 Impact Factor
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    ABSTRACT: In this work, novel methods based on gas chromatography (GC) for the investigation of common organic carbonate-based electrolyte systems are presented, which are used in lithium ion batteries. The methods were developed for flame ionization detection (FID), mass spectrometric detection (MS). Further, headspace (HS) sampling for the investigation of solid samples like electrodes is reported. Limits of detection are reported for FID. Finally, the developed methods were applied to the electrolyte system of commercially available lithium ion batteries as well as on in-house assembled cells.
    Journal of Power Sources 01/2014; 245:836-840. · 5.26 Impact Factor
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    ABSTRACT: Because of its bactericidal and fungicidal properties, thimerosal is used as a preservative in drugs and vaccines and is thus deliberately injected into the human body. In aqueous environment, it decomposes into thiosalicylic acid and the ethylmercury cation. This organomercury fragment is a potent neurotoxin and is suspected to have similar toxicity and bioavailability like the methylmercury cation. In this work, human whole blood and physiological simulation solutions were incubated with thimerosal to investigate its behaviour and binding partners in the blood stream. Inductively coupled plasma with optical emission spectrometry (ICP-OES) was used for total mercury determination in different blood fractions, while liquid chromatography (LC) coupled to electrospray ionisation time-of-flight (ESI-TOF) and inductively coupled plasma mass spectrometry (ICP-MS) provided information on the individual mercury species in plasma surrogate samples. Analogous behaviour of methylmercury and ethylmercury species in human blood was shown and an ethylmercury-glutathione adduct was identified.
    Journal of Trace Elements in Medicine and Biology 01/2014; 28(2):125-130. · 1.96 Impact Factor
  • Analytica Chimica Acta. 01/2014; 834:9–21.
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    ABSTRACT: In this work, the recently introduced low flow inductively coupled plasma optical emission spectrometry (ICP-OES) with a total argon consumption below 0.7L/min is applied for the first time to the field of food analysis. One goal is the investigation of the performance of this low flow plasma compared to a conventional ICP-OES system when non-aqueous samples with a certain matrix are introduced into the system. For this purpose, arsenic is determined in three different kinds of fish samples. In addition several nutrients (K, Na, Mg, Ca) and trace metals (Co, Cu, Mn, Cd, Pb, Zn, Fe, and Ni) are determined in honey samples (acacia) after microwave digestion. The precision of the measurements is characterized by relative standard deviations (RSD) and compared to the corresponding precision values achieved using the conventional Fassel-type torch of the ICP. To prove the accuracy of the low flow ICP-OES method, the obtained data from honey samples are validated by a conventional ICP-OES. For the measurements concerning arsenic in fish, the low flow ICP-OES values are validated by conventional Fassel-type ICP-OES. Furthermore, a certified reference material was investigated with the low gas flow setup. Limits of detection (LOD), according to the 3σ criterion, were determined to be in the low microgram per liter range for all analytes. Recovery rates in the range of 96-106% were observed for the determined trace metal elements. It was proven that the low gas flow ICP-OES leads to results that are comparable with those obtained with the Fassel-type torch for the analysis of food samples.
    Talanta 01/2014; 129:575-578. · 3.50 Impact Factor
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    ABSTRACT: Two different analytical approaches, external calibration and isotope dilution analysis both using flow-injection inductively coupled plasma mass spectrometry, have been developed and applied to determine the intracellular platinum concentration after Cisplatin incubation of two different medulloblastoma cell lines (UW228 and DAOY). As the internal or isotopically enriched standard was already used for cell lysis, maximum accuracy of the results was obtained, whereas a new home-built and inert injection system dramatically lowered carry-over effects and analyte loss. With limits of the detection well below 0.4 μg L−1 and typical relative standard deviations of 2%, a strong correlation between the cell viability in MTT assays and the incorporated amount of Pt could be shown, which was subsequently normalized to the protein content of the samples. DAOY cells did significantly ingest more Pt and showed a higher mortality, which supports the fact that transporter expression needs to be taken into account in order to obtain meaningful results.
    Journal of Trace Elements in Medicine and Biology 01/2014; · 1.96 Impact Factor
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    ABSTRACT: Biological functions of metals are not only specified by the element itself, but also by its chemical form and by its organ, cell and subcellular location. The developed laser ablation based setup enables spatially resolved analysis with simultaneous elemental and molecular mass spectrometry (MS) and promises therefore localization, identification and quantification of metal or heteroelement-containing species in biological samples such as tissue sections. A UV laser ablation (LA) system is hyphenated in parallel both with an elemental and a molecular mass spectrometer via flow splitted transfer lines to simultaneously obtain data from both of the mass spectrometers. Elemental MS was performed using inductively coupled plasma (ICP)-MS, whereas atmospheric pressure chemical ionization (APCI)-MS with an orbitrap mass analyzer was utilized for molecular MS. Simultaneous elemental and molecular MS imaging with high lateral resolution down to 25 µm was presented for the staining agents eosin Y and haematoxylin as well as for the chemotherapy drug cisplatin in thin tissue sections. For molecular MS, target compounds were identified by their exact masses and by characteristic fragment ions. The first simultaneous elemental and molecular MS imaging approach based on laser ablation sampling was introduced for spatially resolved speciation analysis. The combination of the advantages of LA-ICP-MS such as low detection limits and high spatial resolution with information on the chemical identity promises not only localization of metals, but also identification of metal species in biological samples. Therefore, this novel technique opens up new possibilities to address complex challenges in life science research. Copyright © 2013 John Wiley & Sons, Ltd.
    Rapid Communications in Mass Spectrometry 12/2013; 27(23):2588-94. · 2.51 Impact Factor
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    ABSTRACT: The functions and properties of compounds are not only specified by their chemical structures, but also by their location inside a sample. Mass spectrometry is a powerful tool for imaging, whereby the kind of sample and compound depend on the used sampling and ionization methods. The developed laser ablation mass spectrometry method delivers high resolution images of small molecules in native samples. A UV laser ablation (LA) system was combined with an atmospheric pressure chemical ionization (APCI) mass spectrometer. The spatially resolved sampling was performed by focusing the 213 nm laser beam onto a sample. The fine aerosol generated by the ns pulsed laser irradiation was then transported to the APCI mass spectrometer by a nitrogen stream. In the APCI source, post-ionization was accomplished by a corona discharge. The resulting ions were detected with an orbitrap mass spectrometer. The properties of the novel LA-APCI-MS setup are demonstrated by spatially resolved analysis of several samples including tablets, TLC plates and dried droplets. The target compounds are detected with high spatial and mass resolution. For higher molecular weight compounds like thyroxine, fragmentation was observed, whereas small molecules like caffeine stayed intact. LA-APCI-MS is introduced as an ambient molecular mass spectral imaging method for molecules with high resolution in space and mass. The combination of two independent instruments offers flexible ion source and mass analyzer exchange and therefore LA-APCI-MS opens up new possibilities for molecular imaging under ambient conditions. Copyright © 2013 John Wiley & Sons, Ltd.
    Rapid Communications in Mass Spectrometry 12/2013; 27(23):2595-600. · 2.51 Impact Factor
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    ABSTRACT: The distribution of different chemical elements from a nanosilver-coated bone implant was visualized combining the benefits of two complementary methods for elemental bioimaging, the non-destructive micro X-ray fluorescence (µ-XRF) and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). Challenges caused by the physically inhomogeneous materials including bone and soft tissues were addressed by polymer embedding. Using µ-XRF, fast sample mapping was achieved obtaining titanium and vanadium signals from the metal implant as well as phosphorous and calcium signals representing hard bone tissue and sulfur distribution representing soft tissues. Only by the use of LA-ICP-MS, the required high sensitivity and low detection limits for the determination of silver were obtained. Metal migration to soft tissue was revealed for silver as well as implant constituents titanium, vanadium and aluminum. Furthermore, the detection of coinciding high local zirconium and aluminum signals at the implant surface indicates remaining blasting abrasive from preoperative surface treatment of the nanosilver-coated device.
    Analytical Chemistry 12/2013; 86(1):615-620. · 5.82 Impact Factor
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    ABSTRACT: In this study, the cellular uptake of the second generation photosensitizer 5,10,15,20-tetrakis(3-hydroxyphenyl)porphyrin (mTHPP) was investigated using laser ablation coupled to inductively coupled plasma mass spectrometry (LA-ICP-MS) at a spatial resolution of 10 μm. To achieve high sensitivity, the photosensitizer was tagged with palladium. As a tumor model system, a 3D cell culture of the TKF-1 cell line was used. These tumor spheroids were incubated with the Pd-tagged photosensitizer embedded in poly(lactic-co-glycolic acid) (PLGA) nanoparticles to investigate the efficiency of nanoparticle based drug delivery. An accumulation of the drug in the first cell layers of the tumor spheroid was observed. In the case of nanoparticle based drug delivery, a significantly more homogeneous distribution of the photosensitizer was achieved, compared to tumor spheroids incubated with the dissolved photosensitizer without the nanoparticular drug delivery system. The infiltration depth of the Pd-tagged photosensitizer could not be increased with rising incubation time, which can be attributed to the adsorption of the photosensitizer onto cellular components.
    Metallomics 12/2013; 6(1):77-81. · 4.10 Impact Factor

Publication Stats

2k Citations
855.79 Total Impact Points

Institutions

  • 1992–2014
    • University of Münster
      • Institute of Inorganic and Analytical Chemistry
      Muenster, North Rhine-Westphalia, Germany
  • 2002–2010
    • Universiteit Twente
      • • Institute for Nanotechnology (MESA+)
      • • Group of Polymer Chemistry and Biomaterials (PBM)
      Enschede, Overijssel, Netherlands
  • 2007
    • Ludwig-Maximilians-University of Munich
      München, Bavaria, Germany
  • 2005
    • University College Dublin
      • Centre for Synthesis and Chemical Biology
      Dublin, L, Ireland
  • 1997
    • Universität des Saarlandes
      Saarbrücken, Saarland, Germany