TY - JOUR AB - Field cancerization (FC) refers to spatially distributed premalignant tissue changes that lead to the appearance of local malignancy, and its detection can improve cancer screening. In this work, we employ combined Raman and partial wave spectroscopy (RS-PWS) to detect FC in gastroesophageal (L2-IL1B) and intestinal (Villin-Cre, Apcfl/wt) tumor mouse models. Using a hybrid RS-PWS microscope, we acquire both molecular and morphological information from macroscopically normal tumor-adjacent tissue and investigate the individual and combined performance of each modality. For data analysis, we use partial least-squares discriminant analysis (PLS-DA). In the normal tissue of L2-IL1B mice, we demonstrate a statistically significant increase (p < 0.001) in Raman band intensities associated with free amino acids and a decrease in bands associated with lipids (p < 0.005) and carotenoids (p < 0.001) compared to healthy controls. Similarly, in the normal mucosa of Villin-Cre, Apcfl/wt mice, the intensities of RS bands associated with amino acids increase significantly (p < 0.05) compared to controls, while the intensities of lipid-associated bands decrease significantly (p < 0.05). Transcriptomic profiling using RNA-sequencing analysis on these samples identified a significant correlation between gene expression and optical findings. Moreover, we demonstrate that combining RS and PWS data further improves the significance of our classification results. When macroscopically normal tumor-adjacent tissue is compared with tissue from healthy controls, we observe that PWS increases the R2 of RS results by ∼9% in L2-IL1B mice and ∼5% in Villin-Cre, Apcfl/wt mice. Combining molecular RS with structural PWS information enhances the ability to detect precancerous changes and provides insights into tissue alterations during cancer development. AU - Kriukova, E. AU - Mazurenka, M. AU - Marcazzan, S. AU - Tschurtschenthaler, M.* AU - Puppels, G.J.* AU - Glasl, S. AU - Saur, D.* AU - Jesinghaus, M.* AU - Pouliou, M.* AU - Agelopoulos, M.* AU - Klinakis, A.* AU - Quante, M.* AU - Ripoll, J.* AU - Ntziachristos, V. AU - Gorpas, D. C1 - 74904 C2 - 57713 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 12642-12653 TI - Probing field cancerization in the gastrointestinal tract using a hybrid raman and partial wave spectroscopy microscope. JO - Anal. Chem. VL - 97 IS - 24 PB - Amer Chemical Soc PY - 2025 SN - 0003-2700 ER - TY - JOUR AB - Given the long hardware lifespan, fixed installation, and comparatively high investment required to procure them, Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) instruments tend to have a long operational life. The field is constantly evolving with rapidly advancing instrumental developments, and FT-ICR research groups work with a range of instrument designs from different generations. Consequently, compositional spectra comparability between instruments is a critical concern in FT-ICR-MS, particularly due to the variability introduced by commonly used direct infusion methods. This study demonstrates interlaboratory comparability of FT-ICR-MS molecular profiles using a 12 T solariX with an Infinity Cell and a 7 T scimaX with a ParaCell, with closely matched sample introduction and ion guide systems. Using analytically challenging pet food samples, we achieved similar instrument performance metrics, including resolving power, mass error, feature count, signal-to-noise ratios, and m/z distribution. The improved field homogeneity and sensitivity of the ParaCell reduced ICR cell space-charge interferences, making specialized calibration methods beyond linear calibration obsolete. We observed up to 78% overlap in annotated signals of the spectra increasing to 95%, when higher-intensity features are considered. Relative abundances showed great similarity, despite sample-dependent fluctuations (median coefficient of variation 23.4% to 49.2% and 15.5% to 29.5%, respectively). Unsupervised multivariate analysis (PCA) revealed consistent sample profiles with no systematic bias. Our study demonstrates that with careful instrument adjustment, molecular profile comparability can be achieved, ensuring the continued relevance of extensive databases and large chemical data sets acquired in long-term and collaborative projects measured on different instrumentation. AU - Pieczonka, S. AU - Thomas, M.J.* AU - Schmitt-Kopplin, P. AU - Marshall, J.W.* C1 - 74039 C2 - 57302 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 8491−8498 TI - Harmonization of FT-ICR-MS instruments for interoperable multi-laboratory comprehensive compositional profiling. JO - Anal. Chem. VL - 97 IS - 15 PB - Amer Chemical Soc PY - 2025 SN - 0003-2700 ER - TY - JOUR AB - Infrared ion spectroscopy (IRIS) is a tandem mass spectrometry (MS) technique that generates structurally diagnostic vibrational spectra for mass-selected ions trapped in a mass spectrometer. Until now, IRIS applications for biological samples have primarily focused on solution-based analyses, such as body fluids (e.g., plasma and urine) and tissue homogenates, using electrospray ionization (ESI) coupled with liquid chromatography-mass spectrometry (LC-MS). In this study, we have combined matrix-assisted laser desorption/ionization (MALDI) with IRIS for the direct analysis of small molecules from biological tissues on a Fourier-transform ion cyclotron resonance mass spectrometer. We applied this technique alongside MALDI mass spectrometry imaging to analyse brain tissue from two knockout mouse models of l-lysine catabolism disorders: pyridoxine-dependent epilepsy (ALDH7A1) and glutaric aciduria type 1 (GCDH). The MALDI-IRIS platform, now available for users at HFML-FELIX, represents a significant advance in the direct structural characterization of metabolites in complex biological tissues and opens new possibilities for structure elucidation in the field of MALDI mass spectrometry imaging. AU - Schuurman, J.L.* AU - van Tetering, L.* AU - Houthuijs, K.J.* AU - Kooijman, P.* AU - Gailus-Durner, V. AU - Leuchtenberger, S. AU - Fuchs, H. AU - Hrabě de Angelis, M. AU - Engelke, U.F.H.* AU - Lefeber, D.J.* AU - van Karnebeek, C.D.M.* AU - Wevers, R.A.* AU - Grgic, A.* AU - Balluf, B.* AU - Vandenbosch, M.* AU - Vreeken, R.* AU - Heeren, R.M.A.* AU - Berden, G.* AU - Oomens, J.* AU - Martens, J.W.M.* C1 - 74935 C2 - 57679 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa TI - Structure elucidation for MALDI mass spectrometry imaging using infrared ion spectroscopy. JO - Anal. Chem. PB - Amer Chemical Soc PY - 2025 SN - 0003-2700 ER - TY - JOUR AB - To our knowledge, this study presents the first implementation of wavelength-resolved resonance-enhanced multiphoton ionization (REMPI) spectroscopy under atmospheric pressure ionization conditions using a high-resolution mass spectrometric system. Atmospheric pressure laser ionization MS spectroscopic measurements were conducted on over 70 different polycyclic aromatic hydrocarbons (PAHs) and hetero-PAHs (N, S, and O) in standard solutions, as well as three complex PAH-containing samples. The results demonstrate the successful transfer of REMPI spectroscopy from vacuum to atmospheric pressure conditions, maintaining spectral integrity without significant band broadening. The obtained spectral data add an orthogonal dimension to mass spectrometry, providing structural insights into aromatic core motifs and enabling isomeric differentiation. This differentiation is further enhanced by linear regression algorithms, which allow for the semiquantitative analysis of isomer mixtures. Comparison between standard spectra and complex sample spectra reveals high correlation values for certain peaks, strongly indicating the presence of specific PAHs and distinguishing between phenanthrene and anthracene in fossil- and biobased samples. AU - Etscheidt, F.* AU - Rüger, C.P.* AU - Schwarz, C.* AU - Tiemann, O.* AU - Neumann, A.* AU - Hansen, H.J.* AU - Streibel, T. AU - Ehlert, S.* AU - Zimmermann, R. C1 - 72887 C2 - 56773 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa TI - Atmospheric pressure laser ionization Mass Spectrometry with tunable UV wavelength utilizing an optical parametric oscillator. JO - Anal. Chem. PB - Amer Chemical Soc PY - 2024 SN - 0003-2700 ER - TY - JOUR AB - Antibiotic resistance has become a primary concern in medicine because of the overuse and misuse of classical pharmaceuticals. Recently, nonbiological complex drugs (NBCDs) have gained interest for their complex pharmacological profiles. Bituminosulfonates, which have lately been tentatively allocated toward NBCDs, are pharmacologically well-studied and show low potential in resistance development. However, molecular composition knowledge is limited. With this work, we present a comprehensive approach to investigate the manufacturing process of complex pharmaceuticals like bituminosulfonates on a molecular level via Fourier-transform ion cyclotron resonance mass spectrometry. The application of various hyphenations and ionization techniques comprehensively covers the entire mass and polarity range of the matrix, and the high sensitivity enables the identification of significant and minor chemical alterations caused by the multistep manufacturing process. The distillation of the shale crude oil eliminates highly aromatic PAH and PASH constituents. ESI(-) revealed strong PAH- and PASH-sulfonate formation after reacting the shale oil distillate with sulfuric acid. Increasing alkylation reduced the sulfonation yield, instead causing oligomerization side reactions, as observed by APPI analysis. Furthermore, multidimensional gas chromatography coupled with high-resolution mass spectrometry verified core structural motifs. With this work, we demonstrate the high potential of FT-ICR MS in NBCD process analysis. The results also give valuable information for future pharmacological investigations focusing on specific compound classes or properties. AU - Tiemann, O.* AU - Rüger, C.P.* AU - Schwalb, L. AU - Chacón-Patiño, M.L.* AU - Gröger, T.M. AU - Zimmermann, R. C1 - 71371 C2 - 56080 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 13050-13060 TI - Rock-to-Pharma: Characterization of shale oil-based nonbiological complex drugs along the production process by high-resolution mass spectrometry. JO - Anal. Chem. VL - 96 IS - 32 PB - Amer Chemical Soc PY - 2024 SN - 0003-2700 ER - TY - JOUR AB - The nonenzymatic reaction between amino acids (AAs) and reducing sugars, also known as the Maillard reaction, is the primary source of free glycation products (GPs) in vivo and in vitro. The limited number of MS/MS records for GPs in public libraries hinders the annotation and investigation of nonenzymatic glycation. To address this issue, we present a mass spectral library containing the experimental MS/MS spectra of diverse GPs from model systems. Based on the conceptional reaction processes and structural characteristics of products, we classified GPs into common GPs (CGPs) and modified AAs (MAAs). A workflow for annotating GPs was established based on the structural and fragmentation patterns of each GP type. The final spectral library contains 157 CGPs, 499 MAAs, and 2426 GP spectra with synthetic model system information, retention time, precursor m/z, MS/MS, and annotations. As a proof-of-concept, we demonstrated the use of the library for screening GPs in unidentified spectra of human plasma and urine. The AAs with the C6H10O5 modification, fructosylation from Amadori rearrangement, were the most found GPs. With the help of the model system, we confirmed the existence of C6H10O5-modified Valine in human plasma by matching both retention time, MS1, and MS/MS without reference standards. In summary, our GP library can serve as an online resource to quickly screen possible GPs in an untargeted metabolomics workflow, furthermore with the model system as a practical synthesis method to confirm their identity. AU - Yan, Y. AU - Hemmler, D. AU - Schmitt-Kopplin, P. C1 - 69993 C2 - 55354 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 3569-3577 TI - Discovery of glycation products: Unraveling the unknown glycation space using a mass spectral library from in vitro model systems. JO - Anal. Chem. VL - 96 IS - 8 PB - Amer Chemical Soc PY - 2024 SN - 0003-2700 ER - TY - JOUR AB - Cyclodextrin polymers (CDPs) are promising next-generation adsorbents in water purification technologies. The selectivity of the polymer derivate cross-linked with tetrafluoroterephthalonitrile (TFN-CDP) for nonionic and cationic micropollutants (MPs) over dissolved organic matter (DOM) renders the adsorbent also attractive for many analytical applications. The molecular drivers of the observed selectivity are, nonetheless, not yet fully understood. To provide new insights into the sorption mechanism, we (i) synthesized TFN-CDPs with different cavity sizes (α-, β-, γ-CDP); (ii) assessed their extraction efficiencies for selected nonionic MPs in competition with different DOM size fractions (<1, 1-3, 3-10, >10 kDa) to test for size-selectivity; and (iii) performed nontargeted, ultrahigh resolution Fourier transform ion cyclotron resonance mass spectrometry analysis on CDP-extracted DOM compounds (<1 kDa) to probe for molecular sorbate properties governing their selective sorption. First, no evidence of size-selectivity was obtained through either the different CD cavity sizes (i) or the two independent approaches (ii) and (iii). Second, we found a dominant impact of sorbate oxygenation and polarity on the extraction of DOM and MPs, respectively, with relatively oxygen-poor/nonpolar molecules favorably retained on all α-, β-, and γ-CDP. Third, our data indicates exclusion of an anionic matrix, such as carboxylic acids, but preferential sorption of cationic nitrogen-bearing DOM, pointing at repulsive and attractive forces with the negatively charged cross-linker as a likely reason. Therefore, we ascribe TFN-CDP's selectivity to nonpolar and electrostatic interactions between MPs/DOM and the polymer building blocks. These molecular insights can further aid in the optimization of efficient and selective sorbent design for environmental and analytical applications. AU - Glöckler, D.* AU - Harir, M. AU - Schmitt-Kopplin, P. AU - Elsner, M.* AU - Bakkour, R.* C1 - 68621 C2 - 54790 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 14582-14591 TI - Discriminative behavior of cyclodextrin polymers against dissolved organic matter: Role of cavity size and sorbate properties. JO - Anal. Chem. VL - 95 IS - 39 PB - Amer Chemical Soc PY - 2023 SN - 0003-2700 ER - TY - JOUR AB - Selectivity in solid-phase extraction (SPE) materials has become increasingly important for analyte enrichment in sensitive analytical workflows to alleviate detrimental matrix effects. Molecular-level investigation of matrix constituents, which are preferentially extracted or excluded, can provide the analytical chemist with valuable information to learn about their control on sorbent selectivity. In this work, we employ nontargeted Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) to elucidate the molecular chemodiversity of freshwater-derived dissolved organic matter (DOM) extracted by the selective model sorbent β-cyclodextrin polymer (β-CDP) in comparison to conventional, universal SPE sorbents (i.e., Oasis HLB, Supel-Select HLB, and LiChrolut EN). Statistical analysis of MS data corroborated the highly selective nature of β-CDP by revealing the extracted DOM spectra that are most dissimilar to original compositions. We found that its selectivity was characterized by pronounced discrimination against highly oxygenated and unsaturated DOM compounds, which were associated with the classes of lignin-like, tannin-like, and carboxylic-rich alicyclic molecules. In contrast, conventional sorbents excluded less highly oxygenated compounds and showed a more universal extraction behavior for a wide range of DOM compositional space. We lay these findings in a larger context that aids the analyst in obtaining an a priori estimate of sorbent selectivity toward any target analyte of interest serving thereby an optimization of sample preparation. This study highlights the great value of nontargeted ultrahigh-resolution MS for better understanding of targeted analytics and provides new insights into the selective sorption behavior of novel sorbents. AU - Glöckler, D.* AU - Harir, M. AU - Schmitt-Kopplin, P. AU - Elsner, M.* AU - Bakkour, R.* C1 - 68657 C2 - 54862 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 15505-15513 TI - Selectivity of β-cyclodextrin polymer toward aquatic contaminants: Insights from ultrahigh-resolution mass spectrometry of dissolved organic matter. JO - Anal. Chem. VL - 95 IS - 42 PB - Amer Chemical Soc PY - 2023 SN - 0003-2700 ER - TY - JOUR AB - Spectral similarity networks, also known as molecular networks, are crucial in non-targeted metabolomics to aid identification of unknowns aiming to establish a potential structural relation between different metabolite features. However, too extensive differences in compound structures can lead to separate clusters, complicating annotation. To address this challenge, we developed an automated Annotation Propagation through multiple EXperimental Networks (APEX) workflow, which integrates spectral similarity networks with mass difference networks and homologous series. The incorporation of multiple network tools improved annotation quality, as evidenced by high matching rates of the molecular formula derived by SIRIUS. The selection of manual annotations as the Seed Nodes Set (SNS) significantly influenced APEX annotations, with a higher number of seed nodes enhancing the annotation process. We applied APEX to different Caenorhabditis elegans metabolomics data sets as a proof-of-principle for the effective and comprehensive annotation of glycerophospho N-acyl ethanolamides (GPNAEs) and their glyco-variants. Furthermore, we demonstrated the workflow's applicability to two other, well-described metabolite classes in C. elegans, specifically ascarosides and modular glycosides (MOGLs), using an additional publicly available data set. In summary, the APEX workflow presents a powerful approach for metabolite annotation and identification by leveraging multiple experimental networks. By refining the SNS selection and integrating diverse networks, APEX holds promise for comprehensive annotation in metabolomics research, enabling a deeper understanding of the metabolome. AU - Salzer, L. AU - Novoa-del-Toro, E.M.* AU - Frainay, C.* AU - Kissoyan, K.A.B.* AU - Jourdan, F.* AU - Dierking, K.* AU - Witting, M. C1 - 68917 C2 - 53769 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 17550–17558 TI - APEX: An annotation propagation workflow through multiple experimental networks to improve the annotation of new metabolite classes in Caenorhabditis elegans. JO - Anal. Chem. VL - 95 IS - 48 PB - Amer Chemical Soc PY - 2023 SN - 0003-2700 ER - TY - JOUR AB - Shortening the laser pulse length opens up new opportunities for laser desorption (LD) of molecules, with benefits for mass spectrometry (MS) sampling and ionization. The capability to ablate any material without the need for an absorbing matrix and the decrease of thermal damage and molecular fragmentation has promoted various applications with very different parameters and postionization techniques. However, the key issues of the optimum laser pulse length and intensity to achieve efficient and gentle desorption of molecules for postionization in MS are not resolved, although these parameters determine the costs and complexity of the required laser system. Here, we address this research gap with a systematic study on the effect of the pulse length on the LD of molecules. Keeping all other optical and ionization parameters constant, we directly compared the pulses in the femtosecond, picosecond, and nanosecond range with respect to LD-induced fragmentation and desorption efficiency. To represent real-world applications, we investigated the LD of over-the-counter medicaments naproxen and ibuprofen directly from tablets as well as the LD of retene and ship emission aerosols from a quartz filter. With our study design, we excluded interfering effects on fragmentation and LD efficiency from, for example, collisional cooling or postionization by performing the experiments in vacuum with resonance-enhanced multiphoton ionization as the postionization technique. Regarding LD-induced fragmentation, we already found benefits for the picosecond pulses. However, the efficiency of LD was found to continuously increase with decreasing pulse length, pointing to the application potential of ultrashort pulses in trace analytics. Because many interfering effects beyond the LD pulse length could be excluded in the experiment, our results may be directly transferable to the LD applied in other techniques. AU - Schmidt, M. AU - Irsig, R.* AU - Duca, D. AU - Peltz, C.* AU - Passig, J. AU - Zimmermann, R. C1 - 68981 C2 - 53799 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 18776-18782 TI - Laser-pulse-length effects in ultrafast laser desorption. JO - Anal. Chem. VL - 95 IS - 51 PB - Amer Chemical Soc PY - 2023 SN - 0003-2700 ER - TY - JOUR AB - Mass spectrometry is a popular and powerful analytical tool to study the effects of food processing. Industrial sampling, real-life sampling, or challenging academic research on process-related volatile and aerosol research often demand flexible, time-sensitive data acquisition by state-of-the-art mass analyzers. Here, we show a laboratory-scaled, miniaturized, and highly controllable setup for the online monitoring of aerosols and volatiles from thermal food processing based on dielectric barrier discharge ionization (DBDI) mass spectrometry (MS). We demonstrate the opportunities offered by the setup from a foodomics perspective to study emissions from the thermal processing of wheat bread rolls at 210 °C by Fourier transformation ion cyclotron resonance MS. As DBDI is an emerging technology, we compared its ionization selectivity to established atmospheric pressure ionization tools: we found DBDI preferably ionizes saturated, nitrogenous compounds. We likewise identified a sustainable overlap in the selectivity of detected analytes with APCI and electrospray ionization (ESI). Further, we dynamically recorded chemical fingerprints throughout the thermal process. Unsupervised classification of temporal response patterns was used to describe the dynamic nature of the reaction system. Compared to established tools for real-time MS, our setup permits one to monitor chemical changes during thermal food processing at ultrahigh resolution, establishing an advanced perspective for real-time mass spectrometric analysis of food processing. AU - Weidner, L. AU - Hemmler, D. AU - Rychlik, M. AU - Schmitt-Kopplin, P. C1 - 67186 C2 - 54236 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 1694-1702 TI - Real-time monitoring of miniaturized thermal food processing by advanced mass spectrometric techniques. JO - Anal. Chem. VL - 95 IS - 2 PB - Amer Chemical Soc PY - 2023 SN - 0003-2700 ER - TY - JOUR AB - Identification of chemically modified peptides in mass spectrometry (MS)-based glycation studies is a crucial yet challenging task. There is a need to establish a mode for matching tandem mass spectrometry (MS/MS) data, allowing for both known and unknown peptide glycation modifications. We present an open search approach that uses classic and modified peptide fragment ions. The latter are shifted by the mass delta of the modification. Both provide key structural information that can be used to assess the peptide core structure of the glycation product. We also leverage redundant neutral losses from the modification side chain, introducing a third ion class for matching referred to as characteristic fragment ions. We demonstrate that peptide glycation product MS/MS spectra contain multidimensional information and that most often, more than half of the spectral information is ignored if no attempt is made to use a multi-step matching algorithm. Compared to regular and/or modified peptide ion matching, our triple-ion strategy significantly increased the median interpretable fraction of the glycation product MS/MS spectra. For reference, we apply our approach for Amadori product characterization and identify all established diagnostic ions automatically. We further show how this method effectively applies the open search concept and allows for optimized elucidation of unknown structures by presenting two hitherto undescribed peptide glycation modifications with a delta mass of 102.0311 and 268.1768 Da. We characterize their fragmentation signature by integration with isotopically labeled glycation products, which provides high validity for non-targeted structure identification. AU - Berger, M. AU - Hemmler, D. AU - Diederich, P. AU - Rychlik, M.* AU - Marshall, J.W.* AU - Schmitt-Kopplin, P. C1 - 64805 C2 - 52500 SP - 5953-5961 TI - Open search of peptide glycation products from tandem mass spectra. JO - Anal. Chem. VL - 94 IS - 15 PY - 2022 SN - 0003-2700 ER - TY - JOUR AB - Lateral-flow immunoassays and laboratory diagnostic tests like enzyme-linked immunosorbent assays (ELISAs) are powerful diagnostic tools to help fight the COVID-19 pandemic using them as antigen or antibody tests. However, the need emerges for alternative bioanalytical systems that combine their favorable features─simple, rapid, and cost-efficient point-of-care (POC) analysis of lateral-flow immunoassays and higher reliability of laboratory tests─while eliminating their disadvantages (limited sensitivity and specificity of lateral-flow assays and prolonged time and work expenditure of laboratory analysis). An additional need met by only a few tests is multiplexing, allowing for the analysis of several immunorecognition patterns at the same time. We herein present a strategy to combine all desirable attributes of the different test types by means of a flow-based chemiluminescence microarray immunoassay. Laminated polycarbonate microarray chips were developed for easy production and subsequent application in the fully automated microarray analysis platform MCR-R, where a novel flow cell design minimizes the sample volume to 40 μL. This system was capable of detecting IgG antibodies to SARS-CoV-2 with 100% sensitivity and specificity using recombinant antigens for the SARS-CoV-2 spike S1 protein, nucleocapsid protein, and receptor binding domain. The analysis was accomplished within under 4 min from serum, plasma, and whole blood, making it also useful in POC settings. Additionally, we showed the possibility of serosurveillance after infection or vaccination to monitor formerly unnoticed breakthrough infections in the population as well as to detect the need for booster vaccination after the natural decline of the antibody titer below detectable levels. This will help in answering pressing questions on the importance of the antibody response to SARS-CoV-2 that so far remain open. Additionally, even the sequential detection of IgM and IgG antibodies was possible, allowing for statements on the time response of an infection. While our serodiagnostic application focuses on SARS-CoV-2, the same approach is easily adjusted to other diseases, making it a powerful tool for future serological testing. AU - Klüpfel, J.* AU - Paßreiter, S.* AU - Weidlein, N.* AU - Knopp, M.* AU - Ungerer, M.* AU - Protzer, U. AU - Knolle, P.* AU - Hayden, O.* AU - Elsner, M.* AU - Seidel, M.* C1 - 64254 C2 - 52160 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 2855-2864 TI - Fully automated chemiluminescence microarray analysis platform for rapid and multiplexed. SARS-CoV-2 serodiagnostics. JO - Anal. Chem. VL - 94 IS - 6 PB - Amer Chemical Soc PY - 2022 SN - 0003-2700 ER - TY - JOUR AB - The comprehensive chemical description of air pollution is a prerequisite for understanding atmospheric transformation processes and effects on climate and environmental health. In this study, a prototype vacuum photoionization Orbitrap mass spectrometer was evaluated for field-suitability by an online on-site investigation of emissions from a ship diesel engine. Despite remote measurements in a challenging environment, the mass spectrometric performance could fully be exploited. Due to the high resolution and mass accuracy in combination with resonance-enhanced multiphoton ionization, the aromatic hydrocarbon profile could selectively and sensitively be analyzed. Limitations from commonly deployed time-of-flight platforms could be overcome, allowing to unraveling the oxygen- and sulfur-containing compounds. Scan-by-scan evaluation of the online data revealed no shift in exact m/z, assignment statistics with root mean square error (RMSE) below 0.2 ppm, continuous high-resolution capabilities, and good isotopic profile matches. Emissions from three different feed fuels were investigated, namely, diesel, heavy fuel oil (HFO), and very low sulfur fuel oil (VLSFO). Regulations mainly concern the fuel sulfur content, and thus, exhaust gas treatment or new emerging fuels, such as the cycle-oil-based VLSFO, can legally be applied. Unfortunately, despite lower CHS-class emissions, a substantial amount of PAHs is emitted by the VLSFO with higher aromaticity compared to the HFO. Hence, legislative measures might need to take further chemical criteria into account. AU - Kösling, P.* AU - Rüger, C.P.* AU - Schade, J.* AU - Ehlert, S.* AU - Etzien, U.* AU - Kozhinov, A.N.* AU - Tsybin, Y.O.* AU - Rigler, M.* AU - Adam, T.* AU - Walte, A.* AU - Buchholz, B.* AU - Zimmermann, R. C1 - 66862 C2 - 53333 SP - 16855–16863 TI - Real-time investigation of primary ship engine emissions by vacuum resonance-enhanced multiphoton ionization high-resolution orbitrap mass spectrometry. JO - Anal. Chem. VL - 94 IS - 48 PY - 2022 SN - 0003-2700 ER - TY - JOUR AB - Non-targeted metabolomics via high-resolution mass spectrometry methods, such as direct infusion Fourier transform-ion cyclotron resonance mass spectrometry (DI-FT-ICR MS), produces data sets with thousands of features. By contrast, the number of samples is in general substantially lower. This disparity presents challenges when analyzing non-targeted metabolomics data sets and often requires custom methods to uncover information not always accessible via classical statistical techniques. In this work, we present a pipeline that combines a convolutional neural network with traditional statistical approaches and an adaptation of a genetic algorithm. The developed method was applied to a lifestyle intervention cohort data set, where subjects at risk of type 2 diabetes underwent an oral glucose tolerance test. Feature selection is the final result of the pipeline, achieved through classification of the data set via a neural network, with a precision-recall score of over 0.9 on the test set. The features most relevant for the described classification were then chosen via a genetic algorithm. The output of the developed pipeline encompasses approximately 200 features with high predictive scores, providing a fingerprint of the metabolic changes in the prediabetic class on the data set. Our framework presents a new approach which allows to apply complex modeling based on convolutional neural networks for the analysis of high-resolution mass spectrometric data. AU - Lisitsyna, A. AU - Moritz, F. AU - Liu, Y.* AU - Al Sadat, L.* AU - Hauner, H.* AU - Claussnitzer, M.* AU - Schmitt-Kopplin, P. AU - Forcisi, S. C1 - 64771 C2 - 52442 SP - 5474-5482 TI - Feature selection pipelines with classification for non-targeted metabolomics combining the neural network and genetic algorithm. JO - Anal. Chem. VL - 94 IS - 14 PY - 2022 SN - 0003-2700 ER - TY - JOUR AB - Modern biomarker and translational research as well as personalized health care studies rely heavily on powerful omics' technologies, including metabolomics and lipidomics. However, to translate metabolomics and lipidomics discoveries into a high-throughput clinical setting, standardization is of utmost importance. Here, we compared and benchmarked a quantitative lipidomics platform. The employed Lipidyzer platform is based on lipid class separation by means of differential mobility spectrometry with subsequent multiple reaction monitoring. Quantitation is achieved by the use of 54 deuterated internal standards and an automated informatics approach. We investigated the platform performance across nine laboratories using NIST SRM 1950-Metabolites in Frozen Human Plasma, and three NIST Candidate Reference Materials 8231-Frozen Human Plasma Suite for Metabolomics (high triglyceride, diabetic, and African-American plasma). In addition, we comparatively analyzed 59 plasma samples from individuals with familial hypercholesterolemia from a clinical cohort study. We provide evidence that the more practical methyl-tert-butyl ether extraction outperforms the classic Bligh and Dyer approach and compare our results with two previously published ring trials. In summary, we present standardized lipidomics protocols, allowing for the highly reproducible analysis of several hundred human plasma lipids, and present detailed molecular information for potentially disease relevant and ethnicity-related materials. AU - Ghorasaini, M.* AU - Mohammed, Y.* AU - Adamski, J. AU - Bettcher, L.* AU - Bowden, J.A.* AU - Cabruja, M.* AU - Contrepois, K.* AU - Ellenberger, M.* AU - Gajera, B.* AU - Haid, M. AU - Hornburg, D.* AU - Hunter, C.* AU - Jones, C.M.* AU - Klein, T.* AU - Mayboroda, O.* AU - Mirzaian, M.* AU - Moaddel, R.* AU - Ferrucci, L.* AU - Lovett, J.* AU - Nazir, K.* AU - Pearson, M.* AU - Ubhi, B.K.* AU - Raftery, D.* AU - Riols, F. AU - Sayers, R.* AU - Sijbrands, E.J.G.* AU - Snyder, M.P.* AU - Su, B.* AU - Velagapudi, V.* AU - Williams, K.J.* AU - de Rijke, Y.B.* AU - Giera, M.* C1 - 63724 C2 - 51463 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 16369-16378 TI - Cross-laboratory standardization of preclinical lipidomics using differential mobility spectrometry and multiple reaction monitoring. JO - Anal. Chem. VL - 93 IS - 49 PB - Amer Chemical Soc PY - 2021 SN - 0003-2700 ER - TY - JOUR AB - State-of-the-art mass spectrometry with ultraviolet (UV) photoionization is mostly limited to time-of-flight (ToF) mass spectrometers with 1000-10 000 m/Δm mass resolution. However, higher resolution and higher spectral dynamic range mass spectrometry may be indispensable in complex mixture characterization. Here, we present the concept, implementation, and initial evaluation of a compact ultrahigh-resolution mass spectrometer with gas-phase laser ionization. The concept is based on direct laser photoionization in the ion accumulation and ejection trap (C-trap) of an Orbitrap mass spectrometer. Resonance-enhanced multiphoton ionization (REMPI) using 266 nm UV pulses from a frequency-quadrupled Nd:YAG laser was applied for selective and efficient ionization of monocyclic and polycyclic aromatic hydrocarbons. The system is equipped with a gas inlet for volatile compounds and a heated gas chromatography coupling. The former can be employed for rapid system m/z-calibration and performance evaluation, whereas the latter enables analysis of semivolatile and higher-molecular-weight compounds. The capability to evaluate complex mixtures is demonstrated for selected petrochemical materials. In these experiments, several hundred to over a thousand compounds could be attributed with a root-mean-square mass error generally below 1 ppm and a mass resolution of over 140 000 at 200 m/z. Isobaric interferences could be resolved, and narrow mass splits, such as 3.4 mDa (SH4/C3), are determined. Single laser shots provided limits of detection in the 20-ppb range for p-xylene and 1,2,4-trimethylbenzene, similar to compact vacuum REMPI-ToF systems. AU - Kösling, P.* AU - Rüger, C.P.* AU - Schade, J.* AU - Fort, K.L.* AU - Ehlert, S.* AU - Irsig, R.* AU - Kozhinov, A.N.* AU - Nagornov, K.O.* AU - Makarov, A.* AU - Rigler, M.* AU - Tsybin, Y.O.* AU - Walte, A.* AU - Zimmermann, R. C1 - 62461 C2 - 50887 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 9418–9427 TI - Vacuum laser photoionization inside the C-trap of an orbitrap mass spectrometer: Resonance-enhanced multiphoton ionization high-resolution mass spectrometry. JO - Anal. Chem. VL - 93 IS - 27 PB - Amer Chemical Soc PY - 2021 SN - 0003-2700 ER - TY - JOUR AB - Atmospheric pressure single photon ionization (APSPLI) mass spectrometry utilizing a fluorine excimer laser (157 nm, 7.9 eV) is presented for the first time. For evaluation and optimization, polycyclic aromatic hydrocarbon (PAH) standard mixtures were used. The presented technique allowed for the selective ionization of semi- to nonpolar compounds in a single photon ionization process using VUV photons. Molecular radical cations were found as a base peak, whereas protonated species were almost absent. Although the ionization chamber is flushed by pure nitrogen, remaining oxygen and water traces caused unwanted oxidized ionization artifacts. Installation of water and oxygen filter cartridges significantly reduced the abundance of artifacts. For evaluating complex mixture analysis, APSPLI was applied to characterize a light crude oil. In addition to aromatic hydrocarbons, APSPLI allowed for the sensitive ionization of sulfur-containing aromatic constituents (PASH). A comparison of APSPLI to atmospheric pressure laser ionization (266 nm, 4.7 eV) revealed the additional compositional space accessible by the single photon process. APLI, conducted with UV radiation, is mainly restricted to PAH analysis. APSPLI overcomes this limitation, and PAH and PASH, which often occur simultaneously in complex mixtures, can be detected. This novel ionization concept is envisioned to have a high analytical potential further explored in the future. AU - Rüger, C.P.* AU - Neumann, A.* AU - Sklorz, M. AU - Zimmermann, R. C1 - 61500 C2 - 50319 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 3691-3697 TI - Atmospheric pressure single photon laser ionization (APSPLI) mass spectrometry using a 157 nm fluorine excimer laser for sensitive and selective detection of non- to semipolar hydrocarbons. JO - Anal. Chem. VL - 93 IS - 8 PB - Amer Chemical Soc PY - 2021 SN - 0003-2700 ER - TY - JOUR AB - Vibrational microscopy methods based on Raman scattering or infrared absorption provide a label-free approach for chemical-contrast imaging, but employ point-by-point scanning and impose a compromise between the imaging speed and field-of-view (FOV). Optothermal microscopy has been proposed as a promising imaging modality to avoid this compromise, although at restrictively small FOVs capable of imaging only few cells. Here, we present wide-field optothermal mid-infrared microscopy (WOMiM) for wide-field chemical-contrast imaging based on snapshot pump-probe detection of optothermal signal, using a custom-made condenser-free phase contrast microscopy to capture the phase change of samples after mid-infrared irradiation. We achieved chemical contrast for FOVs up to 180 μm in diameter, yielding 10-fold larger imaging areas than the state-of-the-art, at imaging speeds of 1 ms/frame. The maximum possible imaging speed of WOMiM was determined by the relaxation time of optothermal heat, measured to be 32.8 μs in water, corresponding to a frame rate of μ30 kHz. This proof-of-concept demonstrates that vibrational imaging can be achieved at an unprecedented imaging speed and large FOV with the potential to significantly facilitate label-free imaging of cellular dynamics. AU - Yuan, T. AU - Pleitez, M.A. AU - Gasparin, F. AU - Ntziachristos, V. C1 - 63569 C2 - 51592 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 15323-15330 TI - Wide-field mid-infrared hyperspectral imaging by snapshot phase contrast measurement of optothermal excitation. JO - Anal. Chem. VL - 93 IS - 46 PB - Amer Chemical Soc PY - 2021 SN - 0003-2700 ER - TY - JOUR AB - From microbes to human beings, nontargeted metabolic profiling by liquid chromatography (LC)-mass spectrometry (MS) has been commonly used to investigate metabolic alterations. Still, a major challenge is the annotation of metabolites from thousands of detected features. The aim of our research was to go beyond coverage of metabolite annotation in common nontargeted metabolomics studies by an integrated multistep strategy applying data-dependent acquisition (DDA)-based ultrahigh-performance liquid chromatography (UHPLC)-high-resolution mass spectrometry (HRMS) analysis followed by comprehensive neutral loss matches for characteristic metabolite modifications and database searches in a successive manner. Using pooled human urine as a model sample for method establishment, we found 22% of the detected compounds having modifying structures. Major types of metabolite modifications in urine were glucuronidation (33%), sulfation (20%), and acetylation (6%). Among the 383 annotated metabolites, 100 were confirmed by standard compounds and 50 modified metabolites not present in common databases such as human metabolite database (HMDB) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were structurally elucidated. Practicability was tested by the investigation of urines from pregnant women diagnosed with gestational diabetes mellitus vs healthy controls. Overall, 83 differential metabolites were annotated and 67% of them were modified metabolites including five previously unreported compounds. To conclude, the systematic modifying group-assisted strategy can be taken as a useful tool to extend the number of annotated metabolites in biological and biomedical nontargeted studies. AU - Zheng, S.* AU - Zhang, X.* AU - Li, Z.* AU - Hoene, M.* AU - Fritsche, L. AU - Zheng, F.* AU - Li, Q.* AU - Fritsche, A. AU - Peter, A. AU - Lehmann, R. AU - Zhao, X.* AU - Xu, G.* C1 - 62775 C2 - 51057 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 10916-10924 TI - Systematic, modifying group-assisted strategy expanding coverage of metabolite annotation in liquid chromatography-mass spectrometry-based nontargeted metabolomics studies. JO - Anal. Chem. VL - 93 IS - 31 PB - Amer Chemical Soc PY - 2021 SN - 0003-2700 ER - TY - JOUR AB - Optoacoustic (photoacoustic) imaging has seen marked advances in detection and data analysis, but there is less progress in understanding the photophysics of common optoacoustic contrast agents. This gap blocks the development of novel agents and the accurate analysis and interpretation of multispectral optoacoustic images. To close it, we developed a multimodal laser spectrometer (MLS) to enable the simultaneous measurement of optoacoustic, absorbance, and fluorescence spectra. Herein, we employ MLS to analyze contrast agents (methylene blue, rhodamine 800, Alexa Fluor 750, IRDye 800CW, and indocyanine green) and proteins (sfGFP, mCherry, mKate, HcRed, iRFP720, and smURFP). We found that the optical absorption spectrum does not correlate with the optoacoustic spectrum for the majority of the analytes. We determined that for dyes, the transition underlying an aggregation state has more optoacoustic signal generation efficiency than the monomer transition. For proteins we found a favored optoacoustic relaxation that stems from the neutral or zwitterionic chromophores and unreported photoswitching behavior of tdTomato and HcRed. We then crystalized HcRed in its photoswitch optoacoustic state, confirming structurally the change in isomerization with respect to HcReds' fluorescence state. Finally, on the example of the widely used label tdTomato and the dye indocyanine green, we show the importance of correct photophysical (e.g., spectral and kinetic) information as a prerequisite for spectral-unmixing for in vivo imaging. AU - Fuenzalida Werner, J.P. AU - Huang, Y. AU - Mishra, K. AU - Janowski, R. AU - Vetschera, P. AU - Heichler, C.* AU - Chmyrov, A. AU - Neufert, C.* AU - Niessing, D. AU - Ntziachristos, V. AU - Stiel, A.-C. C1 - 59711 C2 - 48935 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 10717-10724 TI - Challenging a preconception: Optoacoustic spectrum differs from the absorption spectrum of proteins and dyes for molecular imaging. JO - Anal. Chem. VL - 92 IS - 15 PB - Amer Chemical Soc PY - 2020 SN - 0003-2700 ER - TY - JOUR AB - The development of sensitive analytical techniques for the real-time detection of aromatic hydrocarbons (AHs) and polycyclic aromatic hydrocarbons (PAHs) is of high importance, because of their impact on human health and the environment. A promising approach, regarding to direct determination of (P)AHs in aqueous samples, is resonance-enhanced multiphoton ionization (REMPI) coupled to external-membrane introduction mass spectrometry (eMIMS). In eMIMS, analytes are extracted from the water phase into the gas phase, which is supplied to the MS by using an external semipermeable membrane setup. As a result, no laborious enrichment techniques are needed. With REMPI, ions are formed by the subsequent absorption of two photons via an excited molecular state. The unique ionization scheme of REMPI provides selective and sensitive detection of (P)AHs. When combining the capabilities of REMPI and MIMS, direct measurements of sub-mu g/L concentrations of small (polycyclic)aromatic compounds are feasible. In this study, we present an external sheet membrane probe (ESMP) for the determination of selected (polycyclic)aromatic species in water samples by using REMPI time-of-flight mass spectrometry (REMPI-TOFMS). This inlet design shows promising results with respect to the direct analysis of (P)AHs in aquatic environments. With this early stage system, concentrations down to tens of ng/L for selected small (polycyclic)aromatic compounds are accessible within minutes without any sample preparation. AU - Gehm, C.* AU - Streibel, T. AU - Ehlert, S.* AU - Schulz-Bull, D.* AU - Zimmermann, R. C1 - 57534 C2 - 47827 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 15547-15554 TI - Development and optimization of an external-membrane introduction photoionization mass spectrometer for the fast analysis of (polycyclic)aromatic compounds in environmental and process waters. JO - Anal. Chem. VL - 91 IS - 24 PB - Amer Chemical Soc PY - 2019 SN - 0003-2700 ER - TY - JOUR AB - In metabolomics, nuclear magnetic resonance (NMR) spectroscopy allows to identify and quantify compounds in biological samples. The sample preparation generally requires only few steps; however, an indispensable factor is the addition of a locking substance into the biofluid sample, such as deuterium oxide (D2O). While creatinine loss in pure D2O is well-described, the effects of different D2O concentrations on the signal profile of biological samples are unknown. In this work, we investigated the effect of D2O levels in the NMR buffer system in urine samples, in dependence on dwell time and temperature exposition. We reveal a decrease of the urinary creatinine peak area up to 35% after 24 h of dwell time at room temperature (RT) using 25% (v/v) D2O, but only 4% loss using 2.5% D2O. 1H, inverse-gated (IG) 13C, DEPT-HSQC NMR, and mass spectrometry (MS) experiments confirmed a proton-deuterium (H/D) exchange at the CH2. This leads to underestimation of creatinine levels and has an extensive effect when creatinine is used for normalization. This work offers a sample stability examination, depending on the D2O concentration, dwell time, and temperature and enables a method to correct for the successive loss. We propose an equation to correct the creatinine loss for samples prepared with various D2O concentrations and storage temperatures for dwell times up to 24 h. The correction function was validated against an external data set with n = 26 samples. To ensure sufficient creatinine stability in future studies, we suggest that a maximum of 10% D2O should be used at 4 °C or 2.5% D2O at RT, respectively. AU - Haslauer, K.E. AU - Hemmler, D. AU - Schmitt-Kopplin, P. AU - Heinzmann, S.S. C1 - 56782 C2 - 47394 SP - 11063-11069 TI - Guidelines for the use of deuterium oxide (D2O) in 1H NMR metabolomics. JO - Anal. Chem. VL - 91 IS - 17 PY - 2019 SN - 0003-2700 ER - TY - JOUR AB - Increasing applications of compound-specific chlorine isotope analysis (CSIA) emphasize the need for chlorine isotope standards that bracket a wider range of isotope values in order to ensure accurate results. With one exception (USGS38), however, all international chlorine isotope reference materials (chloride and perchlorate salts) fall within the narrow range of one per mille. Furthermore, compound-specific working standards are required for chlorine CSIA but are not available for most organic substances. We took advantage of isotope effects in chemical dehalogenation reactions to generate (i) silver chloride (CT16) depleted in 37Cl/35Cl and (ii) compound-specific standards of the herbicides acetochlor and S-metolachlor (Aceto2, Metola2) enriched in 37Cl/35Cl. Calibration against the international reference standards USGS38 (-87.90 ‰) and ISL-354 (+0.05 ‰) by complementary methods (gas chromatography-isotope ratio mass spectrometry, GC-IRMS, versus gas chromatography-multicollector inductively coupled plasma mass spectrometry, GC-MC-ICPMS) gave a consensus value of δ37ClCT16 = -26.82 ± 0.18 ‰. Preliminary GC-MC-ICPMS characterization of commercial Aceto1 and Metola1 versus Aceto2 and Metola2 resulted in tentative values of δ37ClAceto1 = 0.29 ± 0.29 ‰, δ37ClAceto2 = 18.54 ± 0.20 ‰, δ37ClMetola1 = -4.28 ± 0.17 ‰ and δ37ClMetola2 = 5.12 ± 0.27 ‰. The possibility to generate chlorine isotope in-house standards with pronounced shifts in isotope values offers a much-needed basis for accurate chlorine CSIA. AU - Lihl, C. AU - Renpenning, J.* AU - Kümmel, S.* AU - Gelman, F.* AU - Schürner, H.K.V. AU - Daubmeier, M. AU - Heckel, B.* AU - Melsbach, A. AU - Bernstein, A.* AU - Shouakar-Stash, O.* AU - Gehre, M.* AU - Elsner, M. C1 - 57021 C2 - 47494 SP - 12290-12297 TI - Towards improved accuracy in chlorine isotope analysis: Synthesis routes for in-house standards and characterization via complementary mass spectrometry methods. JO - Anal. Chem. VL - 91 IS - 19 PY - 2019 SN - 0003-2700 ER - TY - JOUR AB - The widespread application of herbicides impacts surface water and groundwater. Metabolites (e.g., desphenylchloridazon from chloridazon) may be persistent and even more polar than the parent herbicide, which increases the risk of groundwater contamination. When parent herbicides are still applied, metabolites are constantly formed and may also be degraded. Evaluating their degradation on the basis of concentration measurements is, therefore, difficult. This study presents compound-specific stable isotope analysis (CSIA) of nitrogen- and carbon-isotope ratios at natural abundances as an alternative analytical approach to track the origin, formation, and degradation of desphenylchloridazon (DPC), the major degradation product of the herbicide chloridazon. Methods were developed and validated for carbon- and nitrogen-isotope analysis (delta C-13 and delta N-15) of DPC by liquid chromatography-isotope-ratio mass spectrometry (LC-IRMS) and derivatization gas chromatography-IRMS (GC-IRMS), respectively. Injecting standards directly onto an Atlantis LC-column resulted in reproducible delta(13)-isotope analysis (standard deviation <0.5 parts per thousand) by LC-IRMS with a limit of precise analysis of 996 ng of DPC on-column. Accurate and reproducible delta N-15 analysis with a standard deviation of <0.4 parts per thousand was achieved by GC-IRMS after derivatization of >100 ng of DPC with 160-fold excess of (trimethylsilyl)diazomethane. Application of the method to environmental-seepage water indicated that newly formed DPC could be distinguished from "old" DPC by the different isotopic signatures of the two DPC sources. AU - Melsbach, A. AU - Ponsin, V.* AU - Torrentó, C.* AU - Lihl, C. AU - Hofstetter, T.B.* AU - Hunkeler, D.* AU - Elsner, M. C1 - 55602 C2 - 46415 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 3412-3420 TI - 13C- and 15N-isotope analysis of desphenylchloridazon by Liquid chromatography-isotope-ratio mass spectrometry and derivatization gas chromatography-isotope-ratio mass spectrometry. JO - Anal. Chem. VL - 91 IS - 5 PB - Amer Chemical Soc PY - 2019 SN - 0003-2700 ER - TY - JOUR AB - Photocontrollable proteins revolutionized life-science imaging due to their contribution to subdiffraction-resolution optical microscopy. They might have yet another lasting impact on photo- or optoacoustic imaging (OA). OA combines optical contrast with ultrasound detection enabling high-resolution real-time in vivo imaging well-beyond the typical penetration depth of optical methods. While OA already showed numerous applications relying on endogenous contrast from blood hemoglobin or lipids, its application in the life-science was limited by a lack of labels overcoming the strong signal from the aforementioned endogenous absorbers. Here, a number of recent studies showed that photocontrollable proteins provide the means to overcome this barrier eventually enabling OA to image small cell numbers in a complete organism in vivo. In this Feature article, we introduce the key photocontrollable proteins, explain the basic concepts, and highlight achievements that have been already made. AU - Mishra, K. AU - Fuenzalida Werner, J.P. AU - Ntziachristos, V. AU - Stiel, A.-C. C1 - 55920 C2 - 46661 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 5470-5477 TI - Photocontrollable proteins for optoacoustic imaging. JO - Anal. Chem. VL - 91 IS - 9 PB - Amer Chemical Soc PY - 2019 SN - 0003-2700 ER - TY - JOUR AB - A gas chromatography-single quadrupole mass spectrometry method was developed and validated for compound-specific chlorine isotope analysis (Cl-CSIA) of three chlorinated herbicides, atrazine, acetochlor, and metolachlor, which are widespread contaminants in the environment. For each compound, the two most abundant ions containing chlorine (202/200 for atrazine, 225/223 for acetochlor, and 240/238 for metolachlor) and a dwell time of 30 ms were determined as optimized MS parameters. A limit of precise isotope analysis for ethyl acetate solutions of 10 mg/L atrazine, 10 mg/L acetochlor, and 5 mg/L metolachlor could be reached with an associated uncertainty between 0.5 and 1‰. To this end, samples were measured 10-fold and bracketed with two calibration standards that covered a wide range of δ37Cl values and for which amplitudes matched those of the samples within 20% tolerance. The method was applied to investigate chlorine isotope fractionation during alkaline hydrolysis of metolachlor, which showed a shift in δ37Cl of +46‰ after 98% degradation, demonstrating that chlorine isotope fractionation could be a sensitive indicator of transformation processes even when limited degradation occurs. This method, combined with large-volume solid-phase extraction (SPE), allowed application of Cl-CSIA to environmentally relevant concentrations of widespread herbicides (i.e., 0.5-5 μg/L in water before extraction). Therefore, the combination of large-volume SPE and Cl-CSIA is a promising tool for assessing the transformation processes of these pollutants in the environment. AU - Ponsin, V.* AU - Torrentó, C.* AU - Lihl, C. AU - Elsner, M. AU - Hunkeler, D.* C1 - 57241 C2 - 47637 SP - 14290-14298 TI - Compound-specific chlorine isotope analysis of the herbicides atrazine, acetochlor, and metolachlor. JO - Anal. Chem. VL - 91 IS - 22 PY - 2019 SN - 0003-2700 ER - TY - JOUR AB - Polycyclic aromatic hydrocarbons (PAHs) are toxic organic trace components in atmospheric aerosols that have impacts on climate and human health. They are bound to airborne particles and transported over long distances. Observations of their distribution, transport pathways, and degradation are crucial for risk assessment and mitigation. Such estimates would benefit from online detection of PAHs along with analysis of the carrying particles to identify the source. Typically, laser desorption/ionization (LDI) in a bipolar mass spectrometer reveals the inorganic constituents and provides limited molecular information. In contrast, two-step ionization approaches produce detailed PAH mass spectra from individual particles but without the source-specific inorganic composition. Here we report a new technique that yields the single-particle PAH composition along with both positive and negative inorganic ions via LDI. Thus, the complete particle characterization and source apportionment from conventional bipolar LDI-analysis becomes possible, combined with a detailed PAH spectrum for the same particle. The key idea of the method is spatiotemporal matching of the ionization laser pulse to the transient component distribution in the particle plume after laser desorption. The technique is robust and field-deployable with only slightly higher costs and complexity compared to two-step approaches. We demonstrate its capability to reveal the PAH-distribution on different particle types in combustion aerosols and ambient air. AU - Schade, J.* AU - Passig, J. AU - Irsig, R.* AU - Ehlert, S.* AU - Sklorz, M. AU - Adam, T. AU - Li, C.* AU - Rudich, Y.* AU - Zimmermann, R. C1 - 56567 C2 - 47144 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 10282-10288 TI - Spatially shaped laser pulses for the simultaneous detection of polycyclic aromatic hydrocarbons as well as positive and negative inorganic ions in single particle mass spectrometry. JO - Anal. Chem. VL - 91 IS - 15 PB - Amer Chemical Soc PY - 2019 SN - 0003-2700 ER - TY - JOUR AB - Modern high-resolution mass spectrometry provides the great potential to analyze exact masses of thousands of molecules in one run. In addition, the high instrumental mass accuracy allows for high precision formula assignments narrowing down tremendously the chemical space of unknown compounds. The adequate values for a mass accuracy are normally achieved by a proper calibration procedure that usually implies using known internal or external standards. This approach might not always be sufficient in cases when systematic error is highly prevalent. Therefore, additional recalibration steps are required. In this work, the concept of mass difference maps (MDiMs) is introduced with a focus on the visualization and investigation of all the pairwise differences between considered masses. Given an adequate reference list of sufficient size, MDiMs can facilitate the detection of a systematic error component. Such a property can be potentially applied for spectral recalibration. Consequently, a novel approach to describe the process of the correction of experimentally derived masses is presented. The method is based on the estimation of the density of data points on MDiMs using Gaussian kernels followed by a curve fitting with an adapted version of the particle swarm optimization algorithm. The described recalibration procedure is examined on simulated as well as real mass spectrometric data. For the latter case, blood plasma samples were analyzed by Fourier transform ion cyclotron resonance mass spectrometry. Nevertheless, due to its inherent flexibility, the method can be easily extended to other low- and high-resolution platforms and/or sample types. AU - Smirnov, K. AU - Forcisi, S. AU - Moritz, F. AU - Lucio, M. AU - Schmitt-Kopplin, P. C1 - 55643 C2 - 46459 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 3350-3358 TI - Mass difference maps and their application for the recalibration of mass spectrometric data in non-targeted metabolomics. JO - Anal. Chem. VL - 91 IS - 5 PB - Amer Chemical Soc PY - 2019 SN - 0003-2700 ER - TY - JOUR AB - A challenge facing metabolomics in the analysis of large human cohorts is the cross-laboratory comparability of quantitative metabolomics measurements. In this study, 14 laboratories analyzed various blood specimens using a common experimental protocol provided with the Biocrates AbsoluteIDQ p400HR kit, to quantify up to 408 metabolites. The specimens included human plasma and serum from male and female donors, mouse and rat plasma, as well as NIST SRM 1950 reference plasma. The metabolite classes covered range from polar (e.g., amino acids and biogenic amines) to nonpolar (e.g., diacyl-and triacyl-glycerols), and they span 11 common metabolite classes. The manuscript describes a strict system suitability testing (SST) criteria used to evaluate each laboratory's readiness to perform the assay, and provides the SST Skyline documents for public dissemination. The study found approximately 250 metabolites were routinely quantified in the sample types tested, using Orbitrap instruments. Interlaboratory variance for the NIST SRM-1950 has a median of 10% for amino acids, 24% for biogenic amines, 38% for acylcarnitines, 25% for glycerolipids, 23% for glycerophospholipids, 16% for cholesteryl esters, 15% for sphingolipids, and 9% for hexoses. Comparing to consensus values for NIST SRM-1950, nearly 80% of comparable analytes demonstrated bias of <50% from the reference value. The findings of this study result in recommendations of best practices for system suitability, quality control, and calibration. We demonstrate that with appropriate controls, high-resolution metabolomics can provide accurate results with good precision across laboratories, and the p400HR therefore is a reliable approach for generating consistent and comparable metabolomics data. AU - Thompson, K.* AU - Adams, K.J.* AU - Adamski, J. AU - Asad, Y.* AU - Borts, D.* AU - Bowden, J.A.* AU - Byram, G.* AU - Gang, V.* AU - Dunn, W.B.* AU - Fernández, F.* AU - Fiehn, O.* AU - Gaul, D.A.* AU - Hühmer, A.F.* AU - Kalli, A.* AU - Koal, T.* AU - Koeniger, S.* AU - Mandal, R.* AU - Meier, F.* AU - Naser, F.J.* AU - O'Neil, D.* AU - Pal, A.* AU - Patti, G.J.* AU - Pham-Tuan, H.* AU - Prehn, C. AU - Raynaud, F.I.* AU - Shen, T.* AU - Southam, A.D.* AU - St John-Williams, L.* AU - Sulek, K.* AU - Vasilopoulou, C.G.* AU - Viant, M.* AU - Winder, C.L.* AU - Wishart, D.S.* AU - Zhang, L.* AU - Zheng, J.* AU - Moseley, M.A.* C1 - 57300 C2 - 47671 SP - 14407–14416 TI - International ring trial of a high Resolution targeted metabolomics and lipidomics platform for serum and plasma analysis. JO - Anal. Chem. VL - 91 IS - 22 PY - 2019 SN - 0003-2700 ER - TY - JOUR AB - Reversibly switchable fluorescent proteins (rsFPs) have had a revolutionizing effect on life science imaging due to their contribution to sub-diffraction-resolution optical microscopy (nanoscopy). Initial studies showed that their use as labels could also be highly beneficial for emerging photo- or optoacoustic imaging. It could be shown that their use in optoacoustics (i) strongly improves the imaging contrast-to-noise ratio due to modulation and locked-in detection, (ii) facilitates fluence calibration, affording precise measurements of physiological parameters, and finally (iii) could boost spatial resolution following similar concepts as used for nanoscopy. However, rsFPs show different photophysical behavior in optoacoustics than in optical microscopy because optoacoustics requires pulsed illumination and depends on signal generation via nonradiative energy decay channels. This implies that rsFPs optimized for fluorescence imaging may not be ideal for optoacoustics. Here, we analyze the photophysical behavior of a broad range of rsFPs with optoacoustics and analyze how the experimental factors central to optoacoustic imaging influence the different types of rsFPs. Finally, we discuss how knowledge of the switching behavior can be exploited for various optoacoustic imaging approaches using sophisticated temporal unmixing schemes. AU - Vetschera, P. AU - Mishra, K. AU - Fuenzalida Werner, J.P. AU - Chmyrov, A. AU - Ntziachristos, V. AU - Stiel, A.-C. C1 - 54352 C2 - 45481 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 10527-10535 TI - Characterization of reversibly switchable fluorescent proteins in optoacoustic imaging. JO - Anal. Chem. VL - 90 IS - 17 PB - Amer Chemical Soc PY - 2018 SN - 0003-2700 ER - TY - JOUR AB - Investigating the biogeochemistry of dissolved organic matter (DOM) requires the synthesis of data from several complementary analytical techniques. The traditional approach to data synthesis is to search for correlations between measurements made on the same sample using different instruments. In contrast, data fusion simultaneously decomposes data from multiple instruments into the underlying shared and unshared components. Here, Advanced Coupled Matrix and Tensor Factorization (ACMTF) was used to identify the molecular fingerprint of DOM fluorescence fractions in Arctic fjords. ACMTF explained 99.84% of the variability with six fully shared components. Individual molecular formulas were linked to multiple fluorescence components and vice versa. Molecular fingerprints differed in diversity and oceanographic patterns, suggesting a link to the biogeochemical sources and diagenetic state of DOM. The fingerprints obtained through ACMTF were more specific compared to traditional correlation analysis and yielded greater compositional insight. Multivariate data fusion aligns extremely complex, heterogeneous DOM data sets and thus facilitates a more holistic understanding of DOM biogeochemistry. AU - Wünsch, U.* AU - Acar, E.* AU - Koch, B.P.* AU - Murphy, K.* AU - Schmitt-Kopplin, P. AU - Stedmon, C.A.* C1 - 54948 C2 - 45954 CY - 1155 16th St, Nw, Washington, Dc 20036 Usa SP - 14188-14197 TI - The molecular fingerprint of fluorescent natural organic matter offers insight into biogeochemical sources and diagenetic state. JO - Anal. Chem. VL - 90 IS - 24 PB - Amer Chemical Soc PY - 2018 SN - 0003-2700 ER - TY - JOUR AB - Compound-specific chlorine isotope analysis of tetrachloromethane (CCl4) and trichloromethane (CHCl3) was explored by both, gas chromatography-isotope ratio mass spectrometry (GC-IRMS) and GC-quadrupole MS (GC-qMS), where GC-qMS was validated in an interlaboratory comparison between Munich and Neuchâtel with the same type of commercial GC-qMS instrument. GC-IRMS measurements analyzed CCl isotopologue ions, whereas GC-qMS analyzed the isotopologue ions CCl3, CCl2, CCl (of CCl4) and CHCl3, CHCl2, CHCl (of CHCl3), respectively. Lowest amount dependence (good linearity) was obtained (i) in H-containing fragment ions where interference of (35)Cl- to (37)Cl-containing ions was avoided; (ii) with tuning parameters favoring one predominant rather than multiple fragment ions in the mass spectra. Optimized GC-qMS parameters (dwell time 70 ms, 2 most abundant ions) resulted in standard deviations of 0.2‰ (CHCl3) and 0.4‰ (CCl4), which are only about twice as large as 0.1‰ and 0.2‰ for GC-IRMS. To compare also the trueness of both methods and laboratories, samples from CCl4 and CHCl3 degradation experiments were analyzed and calibrated against isotopically different reference standards for both CCl4 and CHCl3 (two of each). Excellent agreement confirms that true results can be obtained by both methods provided that a consistent set of isotopically characterized reference materials is used. AU - Heckel, B. AU - Rodríguez-Fernández, D.* AU - Torrentó, C.* AU - Meyer, A.H. AU - Palau, J.* AU - Domènech, C.* AU - Rosell, M.* AU - Soler, A.* AU - Hunkeler, D.* AU - Elsner, M. C1 - 50647 C2 - 42763 SP - 3411-3420 TI - Compound-specific chlorine isotope analysis of tetrachloromethane and trichloromethane by gas chromatography-isotope ratio mass spectrometry vs gas chromatography-quadrupole mass spectrometry: Method development and evaluation of precision and trueness. JO - Anal. Chem. VL - 89 IS - 6 PY - 2017 SN - 0003-2700 ER - TY - JOUR AB - Direct infusion resonance-enhanced multiphoton ionization (DI-REMPI) was performed on liquid samples, which were introduced to the ion source via a direct liquid interface, to enable the investigation of dissolved aromatic compounds. Desolvation and nebulization of the samples were supported by a heated repeller using flow rates in the upper nL min -1 range. The obtained mass spectra of five pure polycyclic aromatic hydrocarbons as well as complex petroleum samples revealed predominantly molecular ions without evidence of solvent or dopant effects as observed in atmospheric pressure photoionization (APPI) and laser ionization (APLI) with limits of detection in the lower pmol range. Furthermore, it is demonstrated by the analysis of different complex oil samples that DI-REMPI covers a larger m/z range than external volatilization of the sample prior to introduction to the ion source by using thermogravimetry (TG) hyphenated to REMPI time-of-flight mass spectrometry (TOFMS). Analogous to reported setups with direct liquid interface and electron ionization, direct-REMPI may be an option for soft ionization in liquid chromatography. (Figure Presented). AU - Kruth, C.* AU - Czech, H.* AU - Sklorz, M. AU - Passig, J. AU - Ehlert, S.* AU - Cappiello, A.* AU - Zimmermann, R. C1 - 52175 C2 - 43755 CY - Washington SP - 10917-10923 TI - Direct infusion resonance-enhanced multiphoton ionization mass spectrometry of liquid samples under vacuum conditions. JO - Anal. Chem. VL - 89 IS - 20 PB - Amer Chemical Soc PY - 2017 SN - 0003-2700 ER - TY - JOUR AB - Online Studies of single airborne particles represent a demanding challenge in aerosol chemistry. New technologies that help to unravel the role of ambient aerosols in earth climate and to assess local and specific health risks from air pollution are highly desired. Of particular relevance are polycyclic aromatic hydrocarbons (PAHs) from combustion processes that are associated with both acute and long-term health effects. Usually, online single particle analyses apply laser desorption/ionization (LDI) in a bipolar mass spectrometer, revealing elemental constituents and limited molecular information by detection of both positive and negative ions. Approaches for the detection of PAHs from single particles have been developed but the elemental information from LDI that allows particle classification and source apportionment is lost in that case. Here we present a novel laser desorption. and ionization method delivering both the PAH-profile and the inorganic composition from the same, individual particle. Test measurements demonstrate the technique's capability to reveal the single-particle PAIL-distribution in aerosols (mixing state) and its assignment to specific pollution sources in a new and direct way. AU - Passig, J. AU - Schade, J.* AU - Oster, M. AU - Fuchs, M. AU - Ehlert, S.* AU - Jäger, C.* AU - Sklorz, M. AU - Zimmermann, R. C1 - 51516 C2 - 43162 CY - Washington SP - 6341-6345 TI - Aerosol mass spectrometer for simultaneous detection of polyaromatic hydrocarbons and inorganic components from individual particles. JO - Anal. Chem. VL - 89 IS - 12 PB - Amer Chemical Soc PY - 2017 SN - 0003-2700 ER - TY - JOUR AB - Lipidomes undergo permanent extensive remodeling, but how the turnover rate differs between lipid classes and molecular species is poorly understood. We employed metabolic 15 N labeling and shotgun ultra-high-resolution mass spectrometry (sUHR) to quantify the absolute (molar) abundance and determine the turnover rate of glycerophospholipids and sphingolipids by direct analysis of total lipid extracts. sUHR performed on a commercial Orbitrap Elite instrument at the mass resolution of 1.35 × 10 6 (m/z 200) baseline resolved peaks of 13 C isotopes of unlabeled and monoisotopic peaks of 15 N labeled lipids (Δm = 0.0063 Da). Therefore, the rate of metabolic 15 N labeling of individual lipid species could be determined without compromising the scope, accuracy, and dynamic range of full-lipidome quantitative shotgun profiling. As a proof of concept, we employed sUHR to determine the lipidome composition and fluxes of 62 nitrogen-containing membrane lipids in human hepatoma HepG2 cells. AU - Schuhmann, K.* AU - Srzentić, K.* AU - Nagornov, K.O.* AU - Thomas, H.* AU - Gutmann, T. AU - Coskun, Ü. AU - Tsybin, Y.O.* AU - Shevchenko, A.* C1 - 52601 C2 - 44076 CY - Washington SP - 12857-12865 TI - Monitoring membrane lipidome turnover by metabolic15N labeling and shotgun ultra-high-resolution orbitrap fourier transform mass spectrometry. JO - Anal. Chem. VL - 89 IS - 23 PB - Amer Chemical Soc PY - 2017 SN - 0003-2700 ER - TY - JOUR AB - A critical question facing the field of metabolomics is whether data obtained from different centers can be effectively compared and combined. An important aspect of this is the interlaboratory precision (reproducibility) of the analytical protocols used. We analyzed human samples in six laboratories using different instrumentation but a common protocol (the AbsoluteIDQ p180 kit) for the measurement of 189 metabolites via liquid chromatography (LC) or flow injection analysis (FIA) coupled to tandem mass spectrometry (MS/MS). In spiked quality control (QC) samples 82% of metabolite measurements had an interlaboratory precision of <20%, while 83% of averaged individual laboratory measurements were accurate to within 20%. For 20 typical biological samples (serum and plasma from healthy individuals) the median interlaboratory coefficient of variation (CV) was 7.6%, with 85% of metabolites exhibiting a median interlaboratory CV of <20%. Precision was largely independent of the type of sample (serum or plasma) or the anticoagulant used but was reduced in a sample from a patient with dyslipidaemia. The median interlaboratory accuracy and precision of the assay for standard reference plasma (NIST SRM 1950) were 107% and 6.7%, respectively. Likely sources of irreproducibility were the near limit of detection (LOD) typical abundance of some metabolites and the degree of manual review and optimization of peak integration in the LC–MS/MS data after acquisition. Normalization to a reference material was crucial for the semi-quantitative FIA measurements. This is the first interlaboratory assessment of a widely used, targeted metabolomics assay illustrating the reproducibility of the protocol and how data generated on different instruments could be directly integrated in large-scale epidemiological studies. AU - Siskos, A.P.* AU - Jain, P.* AU - Römisch-Margl, W. AU - Bennett, M.J.* AU - Achaintre, D.* AU - Asad, Y.* AU - Marney, L.* AU - Richardson, L.* AU - Koulman, A.* AU - Griffin, J.L.* AU - Raynaud, F.* AU - Scalbert, A.* AU - Adamski, J. AU - Prehn, C. AU - Keun, H.C.* C1 - 50045 C2 - 42055 CY - Washington SP - 656-665 TI - Interlaboratory reproducibility of a targeted metabolomics platform for analysis of human serum and plasma. JO - Anal. Chem. VL - 89 IS - 1 PB - Amer Chemical Soc PY - 2017 SN - 0003-2700 ER - TY - JOUR AB - In research and clinical settings formalin-fixed and paraffin-embedded (FFPE) tissue specimens are collected routinely and therefore this material constitutes a highly valuable source to gather insight in metabolic changes of diseases. Among mass spectrometry techniques to examine the molecular content of FFPE tissue mass spectrometry imaging (MSI) is the most appropriate when morphological and histological features shall be related to metabolic information. Currently, high resolution mass spectrometers are widely used for metabolomics studies. However, with regards to matrix-assisted laser desorption/ionization (MALDI) MSI no study has so far addressed the necessity of instrumental mass resolving power in terms of clinical diagnosis and prognosis using archived FFPE tissue. For this matter we performed for the first time a comprehensive comparison between a high mass resolution Fourier-transform ion cyclotron resonance (FT-ICR) mass spectrometer and a time-of-flight (TOF) instrument with lower mass resolving power. Spectra analysis revealed that about one third of the detected peaks remained unresolved by MALDI-TOF which led to a three to five time lower number of m/z features compared to FT-ICR measurements. Overlaid peak information and background noise in TOF images made a precise assignment of molecular attributes to morphological features more difficult and limited classification approaches. This clearly demonstrates the need for high mass resolution capabilities for metabolite imaging. Nevertheless, MALDI-TOF allowed reproducing and verifying individual markers identified previously by MALDI-FT-ICR MSI. The systematic comparison gives rise to synergistically combine the different MSI platforms for high-throughput discovery and validation of biomarkers. AU - Buck, A. AU - Balluff, B.* AU - Voss, A. AU - Langer, R.* AU - Zitzelsberger, H. AU - Aichler, M. AU - Walch, A.K. C1 - 48442 C2 - 41097 CY - Washington SP - 5281-5289 TI - How suitable is MALDI-TOF for metabolite imaging from clinical formalin-fixed and paraffin-embedded tissue samples in comparison to MALDI-FT-ICR mass spectrometry? JO - Anal. Chem. VL - 88 IS - 10 PB - Amer Chemical Soc PY - 2016 SN - 0003-2700 ER - TY - JOUR AB - Mass spectrometry imaging (MSI) is a powerful molecular imaging technique. In microprobe MSI, images are created through a grid-wise interrogation of individual spots by mass spectrometry across a surface. Classical statistical tests for within-sample comparisons fail as close-by measurement spots violate the assumption of independence of these tests, which can lead to an increased false-discovery rate. For spatial data this effect is referred to as spatial autocorrelation. In this study we investigated spatial autocorrelation in three different matrix-assisted laser desorption/ionization MSI datasets. These datasets cover different molecular classes (metabolites/drugs, lipids, and proteins) and different spatial resolutions ranging from 20 µm to 100 µm. Significant spatial autocorrelation was detected in all three datasets and found to increase with decreasing pixel size. To enable statistical testing for differences in mass signal intensities between regions of interest within MSI datasets, we propose the use of Conditional Autoregressive (CAR) models. We show that by accounting for spatial autocorrelation, discovery rates (i.e. the ratio between the features identified and the total number of features) could be reduced between 21% and 69%. The reliability of this approach was validated by control mass signals based on prior knowledge. In light of the advent of larger MSI datasets based on either an increased spatial resolution or 3D datasets, accounting for effects due to spatial autocorrelation becomes even more indispensable. Here we propose a generic and easily applicable workflow to enable within-sample statistical comparisons. AU - Cassese, A.* AU - Ellis, S.* AU - Ogrinc Potočnik, N.* AU - Burgermeister, E.* AU - Ebert, M.* AU - Walch, A.K. AU - van den Maagdenberg, A.M.* AU - McDonnell, L.A.* AU - Heeren, R.M.* AU - Balluff, B.* C1 - 48647 C2 - 41226 CY - Washington SP - 5871-5878 TI - Spatial autocorrelation in mass spectrometry imaging. JO - Anal. Chem. VL - 88 IS - 11 PB - Amer Chemical Soc PY - 2016 SN - 0003-2700 ER - TY - JOUR AB - Fast and selective detectors are very interesting for comprehensive two-dimensional gas chromatography (GC×GC). This is particularly true if the detector system can provide additional spectroscopic information on the compound structure and/or functionality. Other than mass spectrometry (MS), only optical spectroscopic detectors are able to provide selective spectral information. However, until present the application of optical spectroscopy technologies as universal detectors for GC×GC has been restricted mainly due to physical limitations such as insufficient acquisition speed or high detection limits. A recently developed simultaneous-detection spectrometer working in the vacuum ultraviolet (VUV) region of 125 to 240 nm overcomes these limitations and meets all the criteria of a universal detector for GC×GC. Peak shape and chromatographic resolution is preserved and unique spectral information, complementary to mass spectrometry data, is gained. The power of this detector is quickly recognized as it has the ability to discriminate between isomeric compounds or difficult to separate structurally related isobaric species, thus, it provides additional selectivity. A further promising feature of this detector is the data analysis concept of spectral filtering, which is accomplished by targeting special electronic transitions that allows for a fast screening of GC×GC chromatograms for designated compound classes. AU - Gröger, T.M. AU - Gruber, B. AU - Harrison, D.* AU - Saraji-Bozorgzad, M.R.* AU - Mthembu, M.* AU - Sutherland, A.C.* AU - Zimmermann, R. C1 - 47862 C2 - 39602 CY - Washington SP - 3031-3039 TI - A fast vacuum ultraviolet absorption array spectrometer as a fast and selective detector for comprehensive two-dimensional gas chromatography: Concept and first results. JO - Anal. Chem. VL - 88 IS - 6 PB - Amer Chemical Soc PY - 2016 SN - 0003-2700 ER - TY - JOUR AB - This paper proposes improved guidelines for dissolved organic matter (DOM) isolation by solid phase extraction (SPE) with a styrene-divinylbenzene copolymer (PPL) sorbent, which has become an estab-lished method for the isolation of DOM from natural waters due to its ease of application and apprecia-ble carbon recovery. Suwannee River water was selected to systematically study the effects of critical SPE variables such as loading mass, concentration, flow rate, and up-scaling on the extraction selectivity of the PPL sorbent. High-field Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) and proton nuclear magnetic resonance (1H NMR) spectroscopy were performed to interpret the DOM chemical space of eluates as well as permeates and wash liquids with molecular resolution. Up to 89% dissolved organic carbon (DOC) recovery was obtained with a DOC/PPL mass ratio of 1:800 at a DOC concentration of 20 mg/L. With the application of larger loading volumes, low quantities of highly oxygenated compounds were retained on the PPL sorbent. The effects of the flow rate on the extraction selectivity of the sorbent were marginal. Up-scaling had a limited effect on the extraction selectivity with the exception of increased self-esterification with a methanol solvent, resulting in methyl ester groups. Furthermore, the SPE/PPL extract exhibited highly authentic characteristics in comparison with original water and reverse osmosis samples. These findings will be useful for reproducibly isolating DOM with representative molecular compositions from various sources and concentrations and mini-mizing potential inconsistencies among interlaboratory comparative studies. AU - Li, Y. AU - Harir, M. AU - Lucio, M. AU - Kanawati, B. AU - Smirnov, K. AU - Flerus, R.* AU - Koch, B.P.* AU - Schmitt-Kopplin, P. AU - Hertkorn, N. C1 - 48655 C2 - 41242 CY - Washington SP - 6680-6688 TI - Proposed guidelines for solid phase extraction of Suwannee River dissolved organic matter. JO - Anal. Chem. VL - 88 IS - 13 PB - Amer Chemical Soc PY - 2016 SN - 0003-2700 ER - TY - JOUR AB - We introduce hyperpolarizable13C-labeled probes that identify multiple biologically important divalent metals via metal-specific chemical shifts. These features enable NMR measurements of calcium concentrations in human serum in the presence of magnesium. In addition, signal enhancement through dynamic nuclear polarization (DNP) increases the sensitivity of metal detection to afford measuring micromolar concentrations of calcium as well as simultaneous multi-metal detection by chemical shift imaging. The hyperpolarizable13C-MRI sensors presented here enable sensitive NMR measurements and MR imaging of multiple divalent metals in opaque biological samples. AU - Mishra, A. AU - Pariani, G. AU - Oerther, T.* AU - Schwaiger, M.* AU - Westmeyer, G.G. C1 - 49861 C2 - 40998 CY - Washington SP - 10785-10789 TI - Hyperpolarized multi-metal13C-sensors for magnetic resonance imaging. JO - Anal. Chem. VL - 88 IS - 22 PB - Amer Chemical Soc PY - 2016 SN - 0003-2700 ER - TY - JOUR AB - Photoacoustic imaging (PAI) is an attractive imaging modality that can volumetrically map the distribution of photoabsorbing molecules with deeper tissue penetration than multiphoton microscopy. To enable dynamic sensing of divalent cations via PAI, we have engineered a new reversible near-infrared probe that is more sensitive to calcium as compared to other biologically relevant cations. The metallochromic compound showed a strong reduction of its peak absorbance at 765 nm upon addition of calcium ions that was translated into robust signal changes in photoacoustic images. Therefore, the heptamethine cyanine dye will be an attractive scaffold to create a series of metallochromic sensors for molecular PAI. AU - Mishra, A. AU - Jiang, Y. AU - Roberts, S. AU - Ntziachristos, V. AU - Westmeyer, G.G. C1 - 49934 C2 - 41905 CY - Washington SP - 10790-10794 TI - Near-infrared photoacoustic imaging probe responsive to calcium. JO - Anal. Chem. VL - 88 IS - 22 PB - Amer Chemical Soc PY - 2016 SN - 0003-2700 ER - TY - JOUR AB - An international project developed, quality-tested, and determined isotope-δ values of 19 new organic reference materials (RMs) for hydrogen, carbon, and nitrogen stable isotope-ratio measurements, in addition to analyzing pre-existing RMs NBS 22 (oil), IAEA-CH-7 (polyethylene foil), and IAEA-600 (caffeine). These new RMs enable users to normalize measurements of samples to isotope-δ scales. The RMs span a range of δ2HVSMOW-SLAP values from -210.8 to +397.0 mUr or ‰, for δ13CVPDB-LSVEC from -40.81 to +0.49 mUr, and for δ15NAir from -5.21 to +61.53 mUr. Many of the new RMs are amenable to gas and liquid chromatography. The RMs include triads of isotopically contrasting caffeines, C16 n-alkanes, n-C20-fatty acid methyl esters (FAMEs), glycines, and L-valines, together with polyethylene powder and string, one n-C17-FAME, a vacuum oil (NBS 22a) to replace NBS 22 oil, and a 2H-enriched vacuum oil. Eleven laboratories from 7 countries used multiple analytical approaches and instrumentation for 2-point isotopic normalization against international primary measurement standards. The use of reference waters in silver tubes allowed direct normalization of δ2H values of organic materials against isotopic reference waters following the principle of identical treatment. Bayesian statistical analysis yielded the mean values reported here. New RMs are numbered from USGS61 through USGS78, in addition to NBS 22a. Due to exchangeable hydrogen, amino acid RMs currently are recommended only for carbon- and nitrogen-isotope measurements. Some amino acids contain 13C and carbon-bound organic 2H-enrichments at different molecular sites to provide RMs for potential site-specific isotopic analysis in future studies. AU - Schimmelmann, A.* AU - Qi, H.* AU - Coplen, T.B.* AU - Brand, W.A.* AU - Fong, J.* AU - Meier-Augenstein, W.* AU - Kemp, H.F.* AU - Toman, B.* AU - Ackermann, A.* AU - Assonov, S.* AU - Aerts-Bijma, A.* AU - Brejcha, R. AU - Chikaraishi, Y.* AU - Darwish, T.A.* AU - Elsner, M. AU - Gehre, M.* AU - Geilmann, H.* AU - Groening, M.* AU - Hélie, J.F.* AU - Herrero-Martín, S.* AU - Meijer, H.A.* AU - Sauer, P.E.* AU - Sessions, A.L.* AU - Werner, R.A.* C1 - 48113 C2 - 39912 CY - Washington SP - 4294-4302 TI - Organic reference materials for hydrogen, carbon, and nitrogen stable isotope-ratio measurements: Caffeines, n-alkanes, fatty acid methyl esters, glycines, L-valines, polyethylenes, and oils. JO - Anal. Chem. VL - 88 IS - 8 PB - Amer Chemical Soc PY - 2016 SN - 0003-2700 ER - TY - JOUR AB - The design of the so-called "Peltier modulator" is presented. It is a new dual-stage consumable-free thermal modulator for TA-GC-MS. It requires only electrical power for operation as it facilitates thermo-electric coolers instead of cryogenics for trapping and resistive on-column heating for re-injection. Trapping and desorption temperatures, as well as modulation cycles are freely adjustable. The stationary phase for the trapping region can be selected to suit the specific application, since common fused silica capillary is used. The Peltier modulator's performance is demonstrated with a broad range of different standard substances and with heavy crude oil as a complex real life sample. Successful modulation from n-pentane to pyrene (boiling points = 36/394 °C) is presented. The produced peaks show the narrowest bandwidths ever reported for a consumable-free thermal modulator, i.e. 12.8±1.2 ms for n-pentadecane. The Peltier modulator is rugged, cost effective, requires low maintenance and decreases security issues significantly, compared to commercial available solutions using liquid N2/CO2. AU - Wohlfahrt, S. AU - Fischer, M. AU - Varga, J.* AU - Saraji-Bozorgzad, M.R.* AU - Matuschek, G. AU - Denner, T.* AU - Zimmermann, R. C1 - 47475 C2 - 39342 SP - 640-644 TI - A dual-stage consumable-free thermal modulator for the hyphenation of Thermal Analysis, Gas Chromatography and Mass Spectrometry (TA-GC-MS). JO - Anal. Chem. VL - 88 IS - 1 PY - 2016 SN - 0003-2700 ER - TY - JOUR AB - Identification of lipids in nontargeted lipidomics based on liquid-chromatography coupled to mass spectrometry (LC-MS) is still a major issue. While both accurate mass and fragment spectra contain valuable information, retention time (t(R)) information can be used to augment this data. We present a retention time model based on machine learning approaches which enables an improved assignment of lipid structures and automated annotation of lipidomics data. In contrast to common approaches we used a complex mixture of 201 lipids originating from fat tissue instead of a standard mixture to train a support vector regression (SVR) model including molecular structural features. The cross-validated model achieves a correlation coefficient between predicted and experimental test sample retention times of r = 0.989. Combining our retention time model with identification via accurate mass search (AMS) of lipids against the comprehensive LIPID MAPS database, retention time filtering can significantly reduce the rate of false positives in complex data sets like adipose tissue extracts. In our case, filtering with retention time information removed more than half of the potential identifications, while retaining 95% of the correct identifications. Combination of high-precision retention time prediction and accurate mass can thus significantly narrow down the number of hypotheses to be assessed for lipid identification in complex lipid pattern like tissue profiles. AU - Aicheler, F.* AU - Li, J.* AU - Hoene, M.* AU - Lehmann, R. AU - Xu, G.* AU - Kohlbacher, O. C1 - 46706 C2 - 37748 CY - Washington SP - 7698-7704 TI - Retention time prediction improves identification in nontargeted lipidomics approaches. JO - Anal. Chem. VL - 87 IS - 15 PB - Amer Chemical Soc PY - 2015 SN - 0003-2700 ER - TY - JOUR AB - For the first time, Excitation Emission Matrix (EEM) fluorescence spectroscopy was combined with parallel factor statistical analysis (PARAFAC) and applied to a set of 320 dry white wines of the Chardonnay grape variety. A four component PARAFAC model (C1, C2, C3 and C4) best explained the variability of fluorescence signatures of white wines. Subtle changes were observed in EEMs of white wines from two different vintages (2006 and 2007), where different concentrations of sulfur dioxide (0, 4, and 8 g·hL(-1)) were added to the grape must at pressing. PARAFAC results clearly indicated that sulfur dioxide added to the must subsequently influenced white wine chemistry into three distinct sulfur dioxide dose-dependent aging mechanisms. For both vintages, C1 and C2 were the dominant components affected by sulfur dioxide and likely reacting with phenolic compounds associated with some presumably proteinaceous material. Distinct component combinations revealed either SO2 dependent or vintage-dependent signatures, thus, showing the extent of the complex versatile significance underlying such fluorescence spectra, even after several years of bottle aging. AU - Coelho, C.* AU - Aron, A.* AU - Roullier-Gall, C. AU - Gonsior, M.* AU - Schmitt-Kopplin, P. AU - Gougeon, R.D.* C1 - 46499 C2 - 37615 CY - Washington SP - 8132-8137 TI - Fluorescence fingerprinting of bottled white wines can reveal memories related to sulfur dioxide treatments of the must. JO - Anal. Chem. VL - 87 IS - 16 PB - Amer Chemical Soc PY - 2015 SN - 0003-2700 ER - TY - JOUR AB - This work describes an ultra-fast-cycling gas chromatography module (fast-GC module) for direct-sampling gas chromatography - mass spectrometry (GC-MS). The sample can be introduced into the fast-GC module using a common GC injector or any GC×GC modulator. The new fast-GC module offers the possibility to conduct a complete temperature cycle within 30 s. Its thermal mass is minimized by using a specially developed home-built fused silica capillary column stack and a halogen lamp for heat generation, both placed inside a gold-coated quartz glass cylinder. A high airflow blower enables rapid cooling. The new device is highly flexible concerning the used separation column, the applied temperature program and the integration into existing systems. An application of the fast-GC module is shown in this work by thermal analysis coupled to gas chromatography - mass spectrometry (TA-GC-MS). The continuously evolving gases of the TA are modulated by a liquid CO2 modulator. Due to the rapid cycling of the fast-GC module, it is possible to obtain the best separation while maintaining the online character of the TA. Restrictions in separation and retention time shifting, known from isothermal and normal ramped fast-GC systems, are overcome. AU - Fischer, M. AU - Wohlfahrt, S. AU - Varga, J. AU - Matuschek, G. AU - Saraji-Bozorgzad, M.R.* AU - Denner, T.* AU - Walte, A.* AU - Zimmermann, R. C1 - 46501 C2 - 37617 SP - 8634-8639 TI - Optically heated ultra-fast-cycling gas chromatography module for rapid separation of direct sampling and online monitoring applications. JO - Anal. Chem. VL - 87 IS - 17 PY - 2015 SN - 0003-2700 ER - TY - JOUR AB - Ultra High Pressure Liquid Chromatography coupled to mass spectrometry (UHPLC-MS) has become a widespread analytical technique in metabolomics investigations, however the benefit of high performance chromatographic separation is often blunted due to insufficient mass spectrometric accuracy. A strategy that allows for the matching of UHPLC-MS data to highly accurate Direct Infusion Electrospray Ionization (DI-ESI) Fourier Transform Ion Cyclotron Resonance / Mass Spectrometry (FT-ICR/MS) data is developed in this manuscript. Mass difference network (MDiN) based annotation of FT-ICR/MS data and matching to unique UHPLC-MS peaks enables the consecutive annotation of the chromatographic dataset. A direct comparison of experimental m/z values provided no basis for the matching of both platforms. The matching of annotation-based exact neutral masses finally enabled the integration of platform specific multivariate statistical evaluations, minimizing the danger to compare artifacts generated on either platform. The approach was developed on a Non-Alcoholic Fatty Liver disease (NAFLD) dataset. AU - Forcisi, S. AU - Moritz, F. AU - Lucio, M. AU - Lehmann, R. AU - Stefan, N. AU - Schmitt-Kopplin, P. C1 - 46498 C2 - 37614 SP - 8917-8924 TI - Solutions for low and high accuracy mass spectrometric data matching. A data-driven annotation strategy in non-targeted metabolomics. JO - Anal. Chem. VL - 87 IS - 17 PY - 2015 SN - 0003-2700 ER - TY - JOUR AB - The analysis of dissolved organic matter (DOM) using high-field Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) poses challenges in molecular formula assignment. The consideration of (13)C isotopes provides new insights into the consistent elemental formula solutions. Modern software helps to overcome misinterpretation, but false assignments of molecular classes to mass peaks have rarely been elucidated until now. It will be demonstrated that this can be important with formula assignments comprising exactly five nitrogen and two sulfur atoms in DOM data sets: the molecular class CHON5S2. The existence of such components in DOM under tripeptide Met-His-Cys formed with the formula C14H23O4N5S2 cannot be excluded; however, components containing 5 N and 2 S should be suspected to not be highly abundant. The true elemental compositions of such unusual "N5S2 moieties" were calculated using Suwannee River fulvic acid (SRFA) data from the literature and one data set from acidic pit lake pore water. The replacement of a H3N5S2 moiety with a (13)C1(12)C5O4 moiety explained more than 95% of the questionable "N5S2 moieties". This finding was proved by calculation of δ(13)C‰ values from relative peak intensities. AU - Herzsprung, P.* AU - von Tümpling, W.* AU - Hertkorn, N. AU - Harir, M. AU - Friese, K.* AU - Schmitt-Kopplin, P. C1 - 46931 C2 - 39063 SP - 9563-9566 TI - High-field FTICR-MS data evaluation of natural organic matter: Are CHON5S2 molecular class formulas assigned to 13C isotopic m/z and in reality CHO components? JO - Anal. Chem. VL - 87 IS - 19 PY - 2015 SN - 0003-2700 ER - TY - JOUR AB - A fast detection method to analyze gaseous organic compounds in complex gas mixtures was developed, using a needle trap device (NTD) in conjunction with thermal-desorption photoionization time-of-flight mass spectrometry (TD-PI-TOFMS). The mass spectrometer was coupled via a deactivated fused silica capillary to an injector of a gas chromatograph. In the hot injector the analytes collected on the NTD were thermally desorbed and directly transferred to the PI-TOFMS ion source. The molecules are softly ionized either by single photon ionization (SPI, 118 nm) or by resonance enhanced multiphoton ionization (REMPI, 266 nm) and the molecular ion signals are detected in the TOF mass analyzer. Analyte desorption and subsequent PI-TOFMS detection step only lasts ten seconds. The specific selectivity of REMPI (i.e. aromatic compounds) and universal ionization characteristics render PI-MS as a promising detection system. As a first, demonstrative application alveolar-phase breath gas of healthy, non-smoking subjects was sampled on NTDs. While smaller organic compounds as acetone, acetaldehyde, isoprene or cysteamine can be detected in the breath gas with SPI, REMPI depicts the aromatic substances phenol and indole at 266 nm. In breath gas of a healthy, smoking male subject, several xenobiotic substances such as benzene, toluene, styrene and ethylbenzene can be found as well. Furthermore, the NTD-REMPI-TOFMS setup was tested for breath gas taken from a mechanically ventilated pig under continuous intravenous propofol (2,6-diisopropylphenol, narcotic drug) infusion. AU - Kleeblatt, J. AU - Schubert, J.K.* AU - Zimmermann, R. C1 - 43065 C2 - 35960 CY - Washington SP - 1773–1781 TI - Detection of gaseous compounds by needle trap sampling and direct thermal-desorption photoionization mass spectrometry: Concept and demonstrative application to breath gas analysis. JO - Anal. Chem. VL - 87 IS - 3 PB - Amer Chemical Soc PY - 2015 SN - 0003-2700 ER - TY - JOUR AB - Raman microspectroscopy is a prime tool to characterize the molecular and isotopic composition of microbial cells. However, low sensitivity and long acquisition times limit a broad applicability of the method in environmental analysis. In this study, we explore the potential, the applicability and the limitations of stable isotope Raman microspectroscopy (SIRM), resonance SIRM, and SIRM in combination with surface-enhanced Raman scattering (SERS) for the characterization of single bacterial cells. The latter two techniques have the potential to significantly increase sensitivity and decrease measurement times in SIRM, but to date there are no (SERS-SIRM) or only a limited number (resonance SIRM) of studies in environmental microbiology. The analyzed microorganisms were grown with substrates fully labeled with the stable isotopes 13C or 2H and compounds with natural abundance of atomic isotopes (12C 98.89% or 1H 99.9844%, designated as 12C- or 1H-, respectively). Raman bands of bacterial cell compounds in stable isotope-labeled microorganisms exhibited a characteristic red-shift in the spectra. In particular the sharp phenylalanine band was found to be an applicable marker band for SIRM analysis of the Deltaproteobacterium strain N47 growing anaerobically on 13C-naphthalene. The study of G. metallireducens grown with 13C- and 2H-acetate showed that the information on the chromophore cytochrome c obtained by resonance SIRM at 532 nm excitation wavelength can be successfully complemented by whole-organism fingerprints of bacteria cells achieved by regular SIRM after photobleaching. Furthermore, we present here for the first time the reproducible SERS analysis of microbial cells labeled with stable isotopes. Escherichia coli strain DSM 1116 cultivated with 12C- or 13C-glucose was used as a model organism. Silver nanoparticles synthesized in situ were applied as SERS media. We observed a reproducible red-shift of an adenine-related marker band from 733 cm 1 to 720 cm 1 in SERS spectra for 13C-labbeled cells. Additionally, Raman measurements of 12C/13C-glucose and -phenylalanine mixtures were performed to elucidate the feasibility of SIRM for nondestructive quantitative and spatially-resolved analysis. The performed analysis of isotopically labeled microbial cells with SERS- and resonance SIRM paves the way towards novel approaches to apply Raman microspectroscopy in environmental process studies. AU - Kubryk, P.* AU - Kölschbach, J.S. AU - Marozava, S. AU - Lueders, T. AU - Meckenstock, R.U. AU - Niessner, R.* AU - Ivleva, N.P.* C1 - 45077 C2 - 37198 CY - Washington SP - 6622-6630 TI - Exploring the potential of stable isotope (resonance) raman microspectroscopy and SERS for the analysis of microorganisms at single cell level. JO - Anal. Chem. VL - 87 IS - 13 PB - Amer Chemical Soc PY - 2015 SN - 0003-2700 ER - TY - JOUR AB - In this study, the hyphenation of a thermobalance to an ultra-high resolution Fourier transform ion cyclotron resonance mass spectrometer (UHR FT-ICR MS) is presented. Atmospheric pressure chemical ionization (APCI) is used for efficient ionization. The evolved gas analysis (EGA), using high resolution mass spectrometry allows the time-resolved molecular characterization of thermally induced processes in complex materials or mixtures, such as biomass or crude oil. The most crucial part of the setup is the hyphenation between the thermobalance and the APCI source. Evolved gases are forced to enter the atmospheric pressure ionization interface of the MS by applying a slightly over-pressure at the thermobalance side of the hyphenation. Using the FT-ICR exact mass data, detailed chemical information is gained by calculation of elemental compositions from the organic species, enabling a time and temperature resolved, highly selective detection of the evolved species. An additional selectivity is gained by the APCI ionization, which is particularly sensitive towards polar compounds. This selectivity on the one hand misses bulk components of petroleum samples such as alkanes and does not deliver a comprehensive view, but on the other hand focuses particularly on typical evolved components from biomass samples. As proof of principle the thermal behavior of different fossil fuels: heavy fuel oil, light fuel oil and a crude oil, and different lignocellulosic biomass, namely beech, birch, spruce, ash, oak and pine as well as commercial available softwood and birch-bark pellets were investigated. The results clearly show the capability to distinguish between certain wood types through their molecular patterns and compound classes. Additionally, typical literature known pyrolysis biomass marker were confirmed by their elemental composition, such as coniferyl aldehyde (C10H10O3), sinapyl aldehyde (C11H12O4), retene (C18H18), and abietic acid (C20H30O2). AU - Rüger, C.P.* AU - Miersch, T.* AU - Schwemer, T.* AU - Sklorz, M. AU - Zimmermann, R. C1 - 45074 C2 - 37195 CY - Washington SP - 6493–6499 TI - Hyphenation of thermal analysis to ultra-high resolution Mass Spectrometry (FT-ICR MS) using Atmospheric Pressure Chemical Ionization (APCI) for studying composition and thermal degradation of complex materials. JO - Anal. Chem. VL - 87 IS - 13 PB - Amer Chemical Soc PY - 2015 SN - 0003-2700 ER - TY - JOUR AB - Atmospheric pressure chemical ionization (APCI) offers the advantage of molecular ion information with low fragmentation. Hyphenating APCI to gas chromatography (GC) and ultrahigh resolution mass spectrometry (FT-ICR MS) enables an improved characterization of complex mixtures. Data amounts acquired by this system are very huge, and existing peak picking algorithms are usually extremely time-consuming, if both gas chromatographic and ultrahigh resolution mass spectrometric data are concerned. Therefore, automatic routines are developed that are capable of handling these data sets and further allow the identification and removal of known ionization artifacts (e.g., water- and oxygen-adducts, demethylation, dehydrogenation, and decarboxylation). Furthermore, the data quality is enhanced by the prediction of an estimated retention index, which is calculated simply from exact mass data combined with a double bond equivalent correction. This retention index is used to identify mismatched elemental compositions. The approach was successfully tested for analysis of semivolatile components in heavy fuel oil and diesel fuel as well as primary combustion particles emitted by a ship diesel research engine. As a result, 10-28% of the detected compounds, mainly low abundant species, classically assigned by using only the mass spectrometric information, were identified as not valid and removed. Although GC separation is limited by the slow acquisition rate of the FT-ICR MS (<1 Hz), a database driven retention time comparison, as commonly used for low resolution GC/MS, can be applied for revealing isomeric information. AU - Schwemer, T.* AU - Rüger, C.P. AU - Sklorz, M. AU - Zimmermann, R. C1 - 47638 C2 - 39456 SP - 11957-11961 TI - Gas chromatography coupled to atmospheric pressure chemical ionization FT-ICR mass spectrometry for improvement of data reliability. JO - Anal. Chem. VL - 87 IS - 24 PY - 2015 SN - 0003-2700 ER - TY - JOUR AB - The highly dynamic, heterogeneous combustion process within a burning cigarette was investigated by a miniaturized extractive sampling probe (microprobe) coupled to photoionization mass spectrometry using soft laser single photon ionization (SPI) for online real-time detection of molecular ions of combustion and pyrolysis products. Research cigarettes smoked by a smoking machine are used as a reproducible model system for solid-state biomass combustion, which up to now is not addressable by current combustion-diagnostic tools. By combining repetitively recorded online measurement sequences from different sampling locations in an imaging approach, highly time- and space-resolved quantitative distribution maps of, e.g.; nitrogen monoxide, benzene, and oxygen concentrations were obtained at a near microscopic level. The obtained quantitative distribution maps represent a time-resolved, movie-like imaging of the respective compounds formation and destruction zones in the various combustion and pyrolysis regions of a cigarette during puffing. Furthermore, spatially resolved kinetic data were ascertainable. The here demonstrated methodology can also be applied to various heterogenic combustion/pyrolysis or reaction model systems, such as fossil- or biomass-fuel pellet combustion or to a positional resolved analysis of heterogenic catalytic reactions. AU - Zimmermann, R. AU - Hertz-Schünemann, R.* AU - Ehlert, S.* AU - Liu, C.* AU - McAdam, K.* AU - Baker, R.* AU - Streibel, T. C1 - 43276 C2 - 36335 CY - Washington SP - 1711-1717 TI - Highly time-resolved imaging of combustion and pyrolysis product concentrations in solid fuel combustion: NO formation in a burning cigarette. JO - Anal. Chem. VL - 87 IS - 3 PB - Amer Chemical Soc PY - 2015 SN - 0003-2700 ER - TY - JOUR AB - Modifications of genes and proteins have been extensively studied in systems biology using comprehensive analytical strategies. Although metabolites are frequently modified, these modifications have not been studied using -omics approaches. Here a general strategy for the nontargeted profiling of modified metabolites, which we call nontargeted modification-specific metabolomics, is reported. A key aspect of this strategy was the combination of in-source collision-induced dissociation liquid chromatographymass spectrometry (LC-MS) and global nontargeted LC-MS-based metabolomics. Characteristic neutral loss fragments that are specific for acetylation, sulfation, glucuronidation, glucosidation, or ribose conjugation were reproducibly detected using human urine as a model specimen for method development. The practical application of this method was demonstrated by profiling urine samples from liver cirrhosis patients. Approximately 900 features were identified as modified endogenous metabolites and xenobiotics. Moreover, this strategy supports the identification of compounds not included in traditional metabolomics databases (HMDB, Metlin, and KEGG), which are currently referred to as unknowns in metabolomics projects. Nontargeted modification-specific metabolomics opens a new perspective in systems biology. AU - Dai, W.* AU - Yin, P.* AU - Zeng, Z.* AU - Kong, H.* AU - Tong, H.* AU - Xu, Z.L.* AU - Lu, X.* AU - Lehmann, R. AU - Xu, G.W.* C1 - 44179 C2 - 36889 CY - Washington SP - 9146-9153 TI - Nontargeted modification-specific metabolomics study based on liquid chromatography high-resolution mass spectrometry. JO - Anal. Chem. VL - 86 IS - 18 PB - Amer Chemical Soc PY - 2014 SN - 0003-2700 ER - TY - JOUR AB - Drug efficacy strongly depends on the presence of the drug substance at the target site. As vascularization is an important factor for the distribution of drugs in tissues, we analyzed drug distribution as a function of blood vessel localization in tumor tissue. In order to explore distribution of the anti-cancer drugs afatinib, erlotinib, and sorafenib, a combined approach of matrix-assisted laser desorption/ionization (MALDI) drug imaging and immunohistochemical vessel staining was applied and examined by digital image analysis. Two xenograft models were investigated: (1) mice carrying squamous cell carcinoma (FaDu) xenografts (ntumor=13) were treated with afatinib or erlotinib, and (2) sarcoma (A673) xenograft bearing mice (ntumor=8) received sorafenib treatment. MALDI drug imaging revealed a heterogeneous distribution of all anti-cancer drugs. The tumor regions containing high drug levels were associated with a higher degree of vascularization than the regions without drug signals (p<0.05). When correlating the impact of blood vessel size to drug abundance in the sarcoma model, a higher amount of small vessels was detected in the tumor regions with high drug levels compared to the tumor regions with low drug levels (p<0.05). With the analysis of co-registered MALDI imaging and CD31 immunohistochemical data by digital image analysis, we demonstrate for the first time the potential of correlating MALDI drug imaging and immunohistochemistry. Here we describe a specific and precise approach for correlating histological features and pharmacokinetic properties of drugs at microscopic level, that will provide information for the improvement of drug design, administration formula or treatment schemes. AU - Huber, K. AU - Feuchtinger, A. AU - Borgmann, D.M. AU - Li, Z.* AU - Aichler, M. AU - Hauck, S.M. AU - Zitzelsberger, H. AU - Schwaiger, M.* AU - Keller, U.* AU - Walch, A.K. C1 - 32545 C2 - 35117 SP - 10568-10575 TI - A novel approach of MALDI drug imaging, immunohistochemistry, and digital image analysis for drug distribution studies in tissues. JO - Anal. Chem. VL - 86 IS - 21 PY - 2014 SN - 0003-2700 ER - TY - JOUR AB - Using proton-transfer-reaction time-of-flight mass-spectrometry (PTR-ToF-MS), we investigated the extraction dynamic of 95 ion traces in real time (time resolution: 1 second) during espresso coffee preparation. Fifty-two of these ions were tentatively identified. This was achieved by on-line sampling of the volatile organic compounds (VOCs) in close vicinity to the coffee flow, at the exit of the extraction hose of the espresso machine (single serve capsules). Ten replicates of six different single serve coffee types were extracted to a final volume of between 30 - 110 mL, according to the recommended cup size of the respective coffee capsule (Ristretto, Espresso and Lungo), and analyzed. The results revealed considerable differences in the extraction kinetics between compounds, which led to a fast evolution of the volatile profiles in the extract flow and consequently to an evolution of the final aroma balance in the cup. Besides exploring the time-resolved extraction dynamics of VOCs, the dynamic data also allowed the coffees types (capsules) to be distinguished from one another. Both Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA) showed full separation between the coffees types. The methodology developed provides a fast and simple means of studying the extraction dynamics of VOCs and differentiating between different coffee types. AU - Sánchez, J.* AU - Zimmermann, R. AU - Yeretzian, C.* C1 - 42769 C2 - 35300 SP - 11696-11704 TI - Insight into the time-resolved extraction of aroma compounds during espresso coffee preparation: Online monitoring by PTR-ToF-MS. JO - Anal. Chem. VL - 86 IS - 23 PY - 2014 SN - 0003-2700 ER - TY - JOUR AB - This study aimed to examine the recently proposed idea that the ionic contribution to atomic bonds is essential in determining the charge state of sputtered atoms. Use was made of negative secondary ion yields reported by Wilson for a large number of elements implanted in silicon and then sputter profiled by Cs bombardment. The derived normalized ion yields (or fractions) P vary by 6 orders of magnitude, but the expected exponential dependence on the electron affinity EA is evident only vaguely. Remarkably, a correlation of similar quality is observed if the data are presented as a function of the ionization potential IP. With IP being the dominant (if not sole) contributor to the electronegativity π, one is led to assume that P depends on the sum π + EA. About 72% of the "nonsaturated" ion yields are in accordance with a dependence of the form P ∝ exp[(π + EA)/ε], with ε ≃ 0.2 eV, provided the appropriate value of π is selected from the electronegativity tables of Pauling (read in eV), Mulliken or Allen. However, each of the three sources contributes only about one-third to the favorable electronegativity data. This unsatisfactory situation initiated the idea to derive the "true" electronegativity πSIMS from the measured ion yields P(π + EA), verified for 48 elements. Significant negative deviations of πSIMS from a smooth increase with increasing atomic number are evident for elements with special outer-shell electron configurations such as (n-1)dg-1ns1 or (n-1)d 10ns2np1. The results strongly support the new model of secondary ion formation and provide means for refining electronegativity data. AU - Wittmaack, K. C1 - 31723 C2 - 34727 CY - Washington SP - 5962-5968 TI - Novel model of negative secondary ion formation and its use to refine the electronegativity of almost fifty elements. JO - Anal. Chem. VL - 86 IS - 12 PB - Amer Chemical Soc PY - 2014 SN - 0003-2700 ER - TY - JOUR AB - The development of fast, mobile, and sensitive detection systems for security-relevant substances is of enormous importance. Because of the low vapor pressures of explosives and improvised explosive devices, adequate sampling procedures are crucial. Ion mobility spectrometers (IMSs) are fast and sensitive instruments that are used as detection systems for explosives. Ambient pressure laser desorption (APLD) and ambient pressure laser-induced acoustic desorption (AP-LIAD) are new tools suitable to evaporate explosives in order to detect them in the vapor phase. Indeed, the most important advantage of APLD or AP-LIAD is the capability to sample directly from the surface of interest without any transfer of the analyte to other surfaces such as wipe pads. A much more gentle desorption, compared to classical thermal-based desorption, is possible with laser-based desorption using very short laser pulses. With this approach the analyte molecules are evaporated in a very fast process, comparable to a shock wave. The thermal intake is reduced considerably. The functionality of APLD and AP-LIAD techniques combined with a hand-held IMS system is shown for a wide range of common explosives such as EGDN (ethylene glycol dinitrate), urea nitrate, PETN (pentaerythritol tetranitrate), HMTD (hexamethylene triperoxide diamine), RDX (hexogen), tetryl (2,4,6-trinitrophenylmethylnitramine), and TNT (trinitrotoluene). Detection limits down to the low nanogram range are obtained. The successful combination of IMS detection and APLD/AP-LIAD sampling is shown. AU - Ehlert, S.* AU - Walte, A.* AU - Zimmermann, R. C1 - 28614 C2 - 33486 SP - 11047-11053 TI - Ambient pressure laser desorption and laser-induced acoustic desorption ion mobility spectrometry detection of explosives. JO - Anal. Chem. VL - 85 IS - 22 PB - Amer. Chemical Soc. PY - 2013 SN - 0003-2700 ER - TY - JOUR AB - Investigations of complex metabolic mechanisms and networks have become a focus of research in the postgenomic area, thereby creating an increasing demand for sophisticated analytical approaches. One such tool is lipidomics analysis that provides, a detailed picture of the lipid composition of a system at a given time Introducing stable isotopes into the studied system can additionally provide information on the synthesis, transformation and degradation of individual lipid species. However, capturing the entire dynamics of lipid networks is still a challenge. We developed and evaluated a novel strategy for the in-depth analysis of the dynamics of lipid metabolism with the capacity for high molecular specificity and network coverage. The general workflow consists of stable isotope-labeling experiments, ultrahigh-performance liquid chromatography (UHPLC)/high-resolution Orbitrap-mass spectrometry (MS) lipid profiling and data processing by a software tool for global isotopomer filtering and matching. As a proof of concept, this approach was applied to the network-wide mapping of dynamic lipid metabolism in primary human skeletal muscle cells cultured for 4, 12, and 24 h with [U-C-13]-palmitate. In the myocellular lipid extracts, 692 isotopomers were detected that could be assigned to 203 labeled lipid species spanning 12 lipid (sub)classes. Interestingly, some lipid classes showed high turnover rates but stable total amounts while the amount of others increased in the course of palmitate treatment. The novel strategy presented here has the potential to open new detailed insights into the dynamics of lipid metabolism that may lead to a better understanding of physiological mechanisms and metabolic perturbations. AU - Li, J.* AU - Hoene, M. AU - Zhao, X.J.* AU - Chen, S.L.* AU - Wei, H.* AU - Häring, H.-U. AU - Lin, X.H.* AU - Zeng, Z.D.* AU - Weigert, C. AU - Lehmann, R. AU - Xu, G.W.* C1 - 25153 C2 - 31831 SP - 4651-4657 TI - Stable isotope-assisted lipidomics combined with nontargeted isotopomer filtering, a tool to unravel the complex dynamics of lipid metabolism. JO - Anal. Chem. VL - 85 IS - 9 PB - Amer. Chemical Soc. PY - 2013 SN - 0003-2700 ER - TY - JOUR AB - Analysis of volatile organic compounds (VOCs) in breath holds great promise for noninvasive diagnostic applications. However, concentrations of VOCs in breath may change quickly, and actual and previous uptakes of exogenous substances, especially in the clinical environment, represent crucial issues. We therefore adapted proton-transfer-reaction-time-of-flight-mass spectrometry for real time breath analysis in the clinical environment. For reasons of medical safety, a 6 m long heated silcosteel transfer line connected to a sterile mouth piece was used for breath sampling from spontaneously breathing volunteers and mechanically ventilated patients. A time resolution of 200 ms was applied. Breath from mechanically ventilated patients was analyzed immediately after cardiac surgery. Breath from 32 members of staff was analyzed in the post anesthetic care unit (PACU). In parallel, room air was measured continuously over 7 days. Detection limits for breath-resolved real time measurements were in the high pptV/low ppbV range. Assignment of signals to alveolar or inspiratory phases was done automatically by a matlab-based algorithm. Quickly and abruptly occurring changes of patients' clinical status could be monitored in terms of breath-to-breath variations of VOC (e.g. isoprene) concentrations. In the PACU, room air concentrations mirrored occupancy. Exhaled concentrations of sevoflurane strongly depended on background concentrations in all participants. In combination with an optimized inlet system, the high time and mass resolution of PTR-ToF-MS provides optimal conditions to trace quick changes of breath VOC profiles and to assess effects from the clinical environment. AU - Trefz, P.* AU - Schmidt, M.* AU - Oertel, P.* AU - Obermeier, J.* AU - Brock, B.* AU - Kamysek, S.* AU - Dunkl, J.* AU - Zimmermann, R. AU - Schubert, J.K.* AU - Miekisch, W.* C1 - 28578 C2 - 33469 SP - 10321-10329 TI - Continuous real time breath gas monitoring in the clinical environment by proton-transfer-reaction-time-of-flight-mass spectrometry. JO - Anal. Chem. VL - 85 IS - 21 PB - Amer. Chemical Soc. PY - 2013 SN - 0003-2700 ER - TY - JOUR AB - Protein expression analysis is one of the most powerful tools to further the understanding of biological systems. Progress in the field of mass spectrometry has shifted focus from gel-based approaches to the upcoming LC-selected reaction monitoring (SRM) technique which combines high technical accuracy with absolute quantification of proteins and the capability for high-throughput analyses. Due to these properties, LC-SRM has the potential to become the foundation for biomarker analysis, targeted hypothesis driven proteomic studies and contribute to the field of systems biology. While the performance of LC-SRM applied to samples from various bodily fluids, particularly plasma, and microorganisms has been extensively investigated, there is only little experience with its application to animal tissue samples. Here, we show that a conventional one-dimensional LC-SRM workflow applied to mouse liver tissue suffers from a shortcoming in terms of sensitivity for lower abundance proteins. This problem could be solved through the extension of the standard workflow by an additional dimension of separation at the peptide level prior to online LC-SRM. For this purpose, we used off-gel electrophoresis (OGE) which is also shown to outperform strong cation exchange (SCX) in terms of resolution, gain of signal intensity, and predictability of separation. The extension of the SRM workflow by a high resolving peptide separation technique is an ideal combination as it allows the addition of stable isotope standards directly after trytic digestion and will increase the dynamic range of protein abundances amenable by SRM in animal tissue. AU - Schäfer, A. AU - von Toerne, C. AU - Becker, S. AU - Sarioglu, H. AU - Neschen, S. AU - Kahle-Stephan, M. AU - Hauck, S.M. AU - Ueffing, M. C1 - 10423 C2 - 30249 SP - 8853-8862 TI - Two-dimensional peptide separation improving sensitivity of selected reaction monitoring-based quantitative proteomics in mouse liver tissue: Comparing off-gel electrophoresis and strong cation exchange chromatography. JO - Anal. Chem. VL - 84 IS - 20 PB - American Chemical Society PY - 2012 SN - 0003-2700 ER - TY - JOUR AB - Plutonium (Pu) dioxide particles were produced from certified reference material (CRM) 136 solution (CRM 136-plutonium isotopic standard, New Brunswick Laboratory, Argonne, IL, U.S.A., 1987) using an atomizer system on December 3, 2009 after chemical separation of americium (Am) on October 27, 2009. The highest density of the size distribution of the particles obtained from 312 particles on a selected impactor stage was in the range of 0.7-0.8 μm. The flattening degree of 312 particles was also estimated. The isotopic composition of Pu and uranium (U) and the amount of Am were estimated by thermal ionization mass spectrometry (TIMS), inductively coupled plasma mass spectrometry (ICPMS), and α-spectrometry. Within uncertainties the isotopic composition of the produced particles is in agreement with the expected values, which were derived from the decay correction of the Pu isotopes in the CRM 136. The elemental ratio of Am to Pu in the produced particles was determined on the 317th and 674th day after Am separation, and the residual amount of Am in the solution was estimated. The analytical results of single particles by micro-Raman-scanning electron microscopy (SEM)-energy-dispersive X-ray spectrometry (EDX) indicate that the produced particles are Pu dioxide. Our initial attempts to measure the density of two single particles gave results with a spread value accompanied by a large uncertainty. AU - Shinonaga, T. AU - Donohue, D.* AU - Aigner, H.* AU - Bürger, S.* AU - Klose, D.* AU - Kärkelä, T.* AU - Zilliacus, R.* AU - Auvinen, A.* AU - Marie, O.* AU - Pointurier, F.* C1 - 7303 C2 - 29664 SP - 2638-2646 TI - Production and characterization of plutonium dioxide particles as a quality control material for safeguards purposes. JO - Anal. Chem. VL - 84 IS - 6 PB - Amer. Chemical Soc. PY - 2012 SN - 0003-2700 ER - TY - JOUR AB - Three-dimensional (3D) imaging has a significant impact on many challenges of life sciences. Three-dimensional matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) is an emerging label-free bioanalytical technique capturing the spatial distribution of hundreds of molecular compounds in 3D by providing a MALDI mass spectrum for each spatial point of a 3D sample. Currently, 3D MALDI-IMS cannot tap its full potential due to the lack efficient computational methods for constructing, processing, and visualizing large and complex 3D MALDI-IMS data. We present a new pipeline of efficient computational methods, which enables analysis and interpretation of a 3D MALDI-IMS data set. Construction of a MALDI-IMS data set was done according to the state-of-the-art protocols and involved sample preparation, spectra acquisition, spectra preprocessing, and registration of serial sections. For analysis and interpretation of 3D MALDI-IMS data, we applied the spatial segmentation approach which is well-accepted in analysis of two-dimensional (2D) MALDI-IMS data. In line with 2D data analysis, we used edge-preserving 3D image denoising prior to segmentation to reduce strong and chaotic spectrum-to-spectrum variation. For segmentation, we used an efficient clustering method, called bisecting k-means, which is optimized for hierarchical clustering of a large 3D MALDI-IMS data set. Using the proposed pipeline, we analyzed a central part of a mouse kidney using 33 serial sections of 3.5 μm thickness after the PAXgene tissue fixation and paraffin embedding. For each serial section, a 2D MALDI-IMS data set was acquired following the standard protocols with the high spatial resolution of 50 μm. Altogether, 512 495 mass spectra were acquired that corresponds to approximately 50 gigabytes of data. After registration of serial sections into a 3D data set, our computational pipeline allowed us to reveal the 3D kidney anatomical structure based on mass spectrometry data only. Finally, automated analysis discovered molecular masses colocalized with major anatomical regions. In the same way, the proposed pipeline can be used for analysis and interpretation of any 3D MALDI-IMS data set in particular of pathological cases. AU - Trede, D.* AU - Schiffler, S.* AU - Becker, M.* AU - Wirtz, S.* AU - Steinhorst, K.* AU - Strehlow, J.* AU - Aichler, M. AU - Kobarg, J.H.* AU - Oetjen, J.* AU - Dyatlov, A.* AU - Heldmann, S.* AU - Walch, A.K. AU - Thiele, H.* AU - Maass, P.* AU - Alexandrov, T.* C1 - 8203 C2 - 30081 SP - 6079-6087 TI - Exploring three-dimensional matrix-assisted laser desorption/ionization imaging mass spectrometry data: Three-dimensional spatial segmentation of mouse kidney. JO - Anal. Chem. VL - 84 IS - 14 PB - American Chemical Society PY - 2012 SN - 0003-2700 ER - TY - JOUR AB - A novel approach using a combination of capillary electrophoresis/mass spectrometry (CE/MS) and off-line Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) revealed the structural details of acidic constituents of atmospheric organic aerosol. Both techniques utilized electrospray ionization (ESI), a soft ionization method, to facilitate the analysis of complex mixtures of organic compounds. CE/ESI-MS using an UltraTrol LN-precoated capillary and acidic background electrolytes at different pH values (2.5 and 4.7) was used to differentiate between weak (carboxylic) and strong (sulfonic) organic acids. On the basis of the electrophoretic mobility, m/z constraints from CE/ESI(-)-MS, and elemental composition information retrieved from off-line FTICR-MS, a variety of aliphatic and aromatic carboxylic acids (CHO-bearing molecules), nitrogen-containing carboxylic acids (CHON-bearing molecules), organosulfates (CHOS-bearing molecules), and (nitrooxy)organosulfates (CHONS-bearing molecules) were tentatively identified in the Oasis-HLB-extracted urban PM(2.5) (particulate matter with an aerodynamic diameter of <2.5 μm). The chemical known/unknown structures of detected compounds were confirmed by the semiempirical Offord model (effective mobility linearly correlated to Z/M(2/3)). The majorities of the identified compounds are products of atmospheric reactions and are known contributors to secondary organic aerosols. AU - Yassine, M.M.* AU - Dabek-Zlotorzynska, E.* AU - Harir, M. AU - Schmitt-Kopplin, P. C1 - 8451 C2 - 30121 SP - 6586-6594 TI - Identification of weak and strong organic acids in atmospheric aerosols by capillary electrophoresis/mass spectrometry and ultra-high-resolution fourier transform ion cyclotron resonance mass spectrometry. JO - Anal. Chem. VL - 84 IS - 15 PB - American Chemical Society PY - 2012 SN - 0003-2700 ER - TY - JOUR AB - The European Commission recently established a novel test facility for heavy-duty vehicles to enhance more sustainable transport. The facility enables the study of energy efficiency of various fuels/scenarios as well as the chemical composition of evolved exhaust emissions. Sophisticated instrumentation for real-time analysis of the gas and particulate phases of exhaust has been implemented. Thereby, gas-phase characterization was carried out by a Fourier transform infrared spectrometer (FT-IR; carbonyls, nitrogen-containing species, small hydrocarbons) and a resonance-enhanced multiphoton ionization time-of-flight mass spectrometer (REMPI-TOFMS; monocyclic and polycyclic aromatic hydrocarbons). For analysis of the particulate phase, a high-resolution time-of-flight aerosol mass spectrometer (HR-TOF-AMS; organic matter, chloride, nitrate), a condensation particle counter (CPC; particle number), and a multiangle absorption photometer (MAAP; black carbon) were applied. In this paper, the first application of the new facility in combination with the described instruments is presented, whereby a medium-size truck was investigated by applying different driving cycles. The goal was simultaneous chemical characterization of a great variety of gaseous compounds and particulate matter in exhaust on a real-time basis. The time-resolved data allowed new approaches to view the results; for example, emission factors were normalized to time-resolved consumption of fuel and were related to emission factors evolved during high speeds. Compounds could be identified that followed the fuel consumption, others showed very different behavior. In particular, engine cold start, engine ignition (unburned fuel), and high-speed events resulted in unique emission patterns. AU - Adam, T.W.* AU - Chirico, R.* AU - Clairotte, M.* AU - Elsasser, M. AU - Manfredi, U.* AU - Martini, G.* AU - Sklorz, M.* AU - Streibel, T.* AU - Heringa, M.F.* AU - DeCarlo, P.F.* AU - Baltensperger, U.* AU - de Santi, G.* AU - Krasenbrink, A.* AU - Zimmermann, R. AU - Prévôt, A.S.* AU - Astorga, C.* C1 - 5259 C2 - 28731 SP - 67-76 TI - Application of modern online instrumentation for chemical analysis of gas and particulate phases of exhaust at the European Commission heavy-duty vehicle emission laboratory. JO - Anal. Chem. VL - 83 IS - 1 PB - American Chemical Soc. PY - 2011 SN - 0003-2700 ER - TY - JOUR AB - For imaging with different modalities, labels, which provide contrast for all modalities, are required. Colloidal nanoparticles composed out of an inorganic core and a polymer shell offer progress in this direction. Both, the core and the polymer shell, can be synthesized to be fluorescent, magnetic, or radioactive. When different cores are combined with different polymer shells, different types of particles for dual imaging can be obtained, as for example, fluorescent cores with radioactive polymer shells. Properties and perspectives of such nanoparticles for multimodal imaging are discussed. AU - Ali, Z.* AU - Abbasi, A.Z.* AU - Zhang, F.* AU - Arosio, P.* AU - Lascialfari, A.* AU - Casula, M.F.* AU - Wenk, A. AU - Kreyling, W.G. AU - Plapper, R.* AU - Seidel, M.* AU - Niessner, R.* AU - Knöll, J.* AU - Seubert, A.* AU - Parak, W.J. C1 - 3947 C2 - 28685 SP - 2877-2882 TI - Multifunctional nanoparticles for dual imaging. JO - Anal. Chem. VL - 83 IS - 8 PB - American Chemical Soc. PY - 2011 SN - 0003-2700 ER - TY - JOUR AB - Chlorine isotope analysis of chlorinated hydrocarbons like trichloroethylene (TCE) is of emerging demand because these species are important environmental pollutants. Continuous flow analysis of noncombusted TCE molecules, either by gas chromatography/isotope ratio mass spectrometry (GC/IRMS) or by GC/quadrupole mass spectrometry (GC/qMS), was recently brought forward as innovative analytical solution. Despite early implementations, a benchmark for routine applications has been missing. This study systematically compared the performance of GC/qMS versus GC/IRMS in six laboratories involving eight different instruments (GC/IRMS, Isoprime and Thermo MAT-253; GC/qMS, Agilent 5973N, two Agilent 5975C, two Thermo DSQII, and one Thermo DSQI). Calibrations of (37)Cl/(35)Cl instrument data against the international SMOC scale (Standard Mean Ocean Chloride) deviated between instruments and over time. Therefore, at least two calibration standards are required to obtain true differences between samples. Amount dependency of δ(37)Cl was pronounced for some instruments, but could be eliminated by corrections, or by adjusting amplitudes of standards and samples. Precision decreased in the order GC/IRMS (1σ ≈ 0.1‰), to GC/qMS (1σ ≈ 0.2-0.5‰ for Agilent GC/qMS and 1σ ≈ 0.2-0.9‰ for Thermo GC/qMS). Nonetheless, δ(37)Cl values between laboratories showed good agreement when the same external standards were used. These results lend confidence to the methods and may serve as a benchmark for future applications. AU - Bernstein, A. AU - Shouakar-Stash, O.* AU - Ebert, K.* AU - Laskov, C.* AU - Hunkeler, D.* AU - Jeannottat, S.* AU - Sakaguchi-Söder, K.* AU - Laaks, J.* AU - Jochmann, M.A.* AU - Cretnik, S. AU - Jager, J.* AU - Haderlein, S.B.* AU - Schmidt, T.C.* AU - Aravena, R.* AU - Elsner, M. C1 - 6056 C2 - 29092 SP - 7624-7634 TI - Compound-specific chlorine isotope analysis: A comparison of gas chromatography/isotope ratio mass spectrometry and gas chromatography/quadrupole mass spectrometry methods in an interlaboratory study. JO - Anal. Chem. VL - 83 IS - 20 PB - American Chemical Society PY - 2011 SN - 0003-2700 ER - TY - JOUR AB - This work describes the realization of rapid switching between hard electron ionization (EI) and soft single-photon ionization (SPI) integrated in a compact orthogonal acceleration time-of-flight mass spectrometer. Vacuum-ultraviolet (VUV) photons of 9.8 eV (126 nm) emitted from the innovative electron-beam-pumped rare-gas excimer light source (EBEL) filled with argon are focused into the ion chamber by an ellipsoidal mirror optic for accomplishing of SPI. This novel orthogonal acceleration time-of-flight mass spectrometer with switching capability was hyphenated to one-dimensional gas chromatography (GC) and comprehensive two-dimensional (2D) gas chromatography (GC × GC) for the first time. Within this demonstration study, a maximum switching frequency of 80 Hz was applied for investigation of a mineral-oil-type diesel sample. This approach allows the quasi-simultaneous acquisition of complementary information about the fragmentation pattern (EI) as well as the molecular mass (SPI) of compounds within a single analysis. Furthermore, by application of a polar GC column for separation, the SPI data can be displayed in a 2D contour plot, leading to a comprehensive 2D characterization (GC × MS), whereas the typical group-type assignment for diesel is also met. AU - Eschner, M.S.* AU - Gröger, T.M. AU - Horvath, T.* AU - Gonin, M.* AU - Zimmermann, R. C1 - 6457 C2 - 28735 SP - 3865-3872 TI - Quasi-simultaneous acquisition of hard electron ionization and soft single-photon ionization mass spectra during GC/MS analysis by rapid switching between both ionization methods: Analytical concept, setup, and application on diesel fuel. JO - Anal. Chem. VL - 83 IS - 10 PB - Amer Chemical Soc PY - 2011 SN - 0003-2700 ER - TY - JOUR AB - This work presents the direct coupling of a custom-made smoking machine (SM) to fast gas chromatography combined with single-photon ionization mass spectrometry (GC × SPI-MS) utilizing a six-port, two-position valve for online puff-resolved comprehensive two-dimensional investigation of cigarette smoke. The innovative electron-beam pumped rare gas excimer light source (EBEL) filled with argon provided vacuum ultraviolet (VUV) photons of 9.8 ± 0.4 eV (126 ± 9 nm) for SPI. Puff-by-puff quantification of 14 hazardous volatile organic smoke constituents from the 2R4F Kentucky research cigarette was enabled for two smoking regimes, i.e., ISO and Canadian Intense, after determination of photoionization cross sections. The investigated analytes comprised NO, acetaldehyde, butadiene, acrolein, propanal, acetone, isoprene, furan, crotonaldehyde, isobutanal, butanal, 2-butanone, benzene, and toluene. The determined amounts of these compounds in cigarette smoke agreed excellently with the literature values. Furthermore, the two well-known patterns of puff-by-puff behaviors for these different smoke constituents were obtained for both whole smoke and gas-phase measurements. AU - Eschner, M.S. AU - Selmani, I. AU - Gröger, T.M. AU - Zimmermann, R. C1 - 6921 C2 - 29429 SP - 6619-6627 TI - Online comprehensive two-dimensional characterization of puff-by-puff resolved cigarette smoke by hyphenation of fast gas chromatography to single-photon ionization time-of-flight mass spectrometry: Quantification of hazardous volatile organic compounds. JO - Anal. Chem. VL - 83 IS - 17 PB - Amer Chemical Soc PY - 2011 SN - 0003-2700 ER - TY - JOUR AB - This study was intended to evaluate low-volume (20 mL) multibed needle trap (NTD) sampling combined with heart-cut gas chromatography/mass spectrometry (GC/MS) and comprehensive two-dimensional gas chromatography/time-of-flight mass spectrometry (GC x GC/TOF-MS) for trace gas analysis under clinical conditions. NTDs, high-throughput automatic desorption and separation systems, were tested in vitro and within a study in 11 patients undergoing cardiac surgery with respect to reproducibility, reliability, and clinical applicability. NTD-heart-cut GC/MS analysis of standard mixtures containing different volatile organic compounds (VOCs) yielded relative standard deviations (RSDs) from 4.0% to 18.5%. Substance adsorption was stable for 1 day if NTDs were closed on both ends and was stable for approximately 7.8 h when NTD tip ends had to be left open during autosampler storage. Even in the presence of high concentrations of contaminants linearity of heart-cut GC/MS was conserved. In patients' breath potential biomarkers could be determined even in the presence of very high concentrations of sevoflurane. Profiles of blood-borne biomarkers, intravenous drugs, and clinical contaminants were characterized. Comprehensive GC x GC/TOF-MS may be used as a screening tool for new biomarkers, if patterns are generated from deconvoluted normalized areas. Needle trap sampling in combination with hyphenated chromatographic techniques can thus be used to provide well-tailored solutions for complex problems occurring in clinical breath analysis. AU - Mieth, M.* AU - Schubert, J.K.* AU - Gröger, T.M. AU - Sabel, B.* AU - Kischkel, S.* AU - Fuchs, P.* AU - Hein, D.* AU - Zimmermann, R. AU - Miekisch, W.* C1 - 5375 C2 - 27954 SP - 2541-2551 TI - Automated needle trap heart-cut GC/MS and needle trap comprehensive two-dimensional GC/TOF-MS for breath gas analysis in the clinical environment. JO - Anal. Chem. VL - 82 IS - 6 PB - American Chemical Society PY - 2010 SN - 0003-2700 ER - TY - JOUR AB - Magnetic nanoparticles (MNPs) were deposited onto multiwalled carbon nanotubes (MWCNTs) by in situ high-temperature decomposition of the magnetic precursor [iron(III)] and MWCNTs, in ethylene glycol. This one-step synthetic method was applied to commercially available carbon nanotubes (CNTs). Scanning electron micrographs of the resulting products revealed that MNPs decorated the surface of the MWCNTs. The hybrid nanoparticles thus obtained were used for sampling and cleanup in the determination of eight fluoroquinolones (FQs) and two quinolones (Qs) at trace levels by ultra performance liquid chromatography (UPLC). A systematic study of analyte adsorption and desorption was conducted with MNPs and MWCNTs separately. Although both solid phases adsorbed the analytes to some extent, the much higher recoveries were obtained by using the MNP-MWCNT composite which was thus selected to treat plasma samples containing FQs and Qs. Lower accuracies were determined at spiked plasma compared to the standard solution caused by the complexation affinity of the analytes with proteins because high recoveries were observed when deproteinization was performed before treating the sample with the magnetic MWCNTs. The performance characteristics of the optimized method were determined, and the method was applied to the analysis of plasma samples from antibiotic-treated patients. On the basis of the results, the use of an in situ synthesized MWCNT-MNP composite allows the simple, expeditious sampling and treatment of such complex biological samples for the subsequent determination of FQs and Qs present at free form. AU - Morales-Cid, G.* AU - Fekete, A. AU - Simonet, B.M.* AU - Lehmann, R.* AU - Cardenas, S.* AU - Zhang, X.M.* AU - Valcarcel, M.* AU - Schmitt-Kopplin, P. C1 - 4918 C2 - 28087 SP - 2743-2752 TI - In situ synthesis of magnetic multiwalled carbon nanotube composites for the clean-up of (fluoro)quinolones from human plasma prior to ultrahigh pressure liquid chromatography analysis. JO - Anal. Chem. VL - 82 IS - 7 PB - American Chemical Society PY - 2010 SN - 0003-2700 ER - TY - JOUR AB - Negatively charged analytes must be derivatized prior to gas chromatography-isotope ratio mass spectrometry (GC-IRMS), with stringent control of isotope fractionation. Current methods require offline sample preparation. This study tests for the first time trimethylsulfonium hydroxide (TMSH) as online methylation agent prior to isotope analysis, addressing the herbicides bentazone and MCPA. Fully automated derivatization was achieved in a temperature-programmable GC injector, where reactants were injected into a packed liner, solvents were removed by split flow, and subsequent flash heating triggered the derivatization, thereby transferring derivatives onto the chromatographic column. Stoichiometric addition of TMSH resulted in complete conversion giving accurate and reproducible nitrogen isotope values of bentazone. In contrast, reproducible carbon isotope analysis required TMSH in > or = 250-fold excess. Contrary to expectations, delta(13)C values became more negative at smaller TMSH excess. This indicates that elevated methyl group concentrations in the pore space of the injection liner facilitated close-to-equilibrium rather than kinetic isotope fractionation resulting in reproducible derivatization conditions. delta(13)C results under these conditions compared favorably with liquid chromatography-IRMS: low standard deviations (0.3 per thousand for GC-IRMS, 0.1 per thousand for LC-IRMS) and a comparable offset of 1 per thousand compared to elemental analyzer-IRMS demonstrate that both methods represent expedient ways for online isotope analysis of anionic target compounds. AU - Reinnicke, S. AU - Bernstein, A. AU - Elsner, M. C1 - 4779 C2 - 27781 SP - 2013-2019 TI - Small and reproducible isotope effects during methylation with trimethylsulfonium hydroxide (TMSH): A convenient derivatization method for isotope analysis of negatively charged molecules. JO - Anal. Chem. VL - 82 IS - 5 PB - American Chemical Society PY - 2010 SN - 0003-2700 ER - TY - JOUR AB - Multi-dimensional analysis (MDA) in analytical chemistry is often applied to improve the selectivity of an analytical device and, therefore, to achieve a better overview of a sample composition. Recently, the hyphenation of thermogravimetry with single photo ionization mass spectrometry (TG-SPIMS) using an electron beam pumped excimer lamp (EBEL) for VUV radiation was applied. The concept of MDA has been realized by upgrading the TG-SPIMS system with a quasi comprehensive chromatographic separation step before the soft ionization (TG-GCxSPIMS). The system was characterized by the thermal analysis of diesel fuel, which has often been investigated by the GCxGC-community and is therefore a well-known sample material in MDA. Data from this measurement are used to explain the three-dimensional data structure and the advantages of the online TG-GCxSPIMS as compared to TG-SPIMS. Subsequently, the thermal decomposition behavior of a polymer, acrylonitrile-butadiene-styrene (ABS), is investigated. TG-GCxSPIMS provides a two-dimensional analysis of the evolved gaseous products. TG relevant data are obtained as well as an improved resolution power to separate isobaric molecular structures without losing any fraction of the samples, as is often the case in heart cutting approaches. Additionally, this solution is not associated with any extension of the measurement time. The assignment of the substance pattern to distinct species is improved as compared to solely using mass spectrometry without a preceding separation step. Furthermore, hitherto undetected compounds have been found in the evolved gases from the thermal degradation of ABS. Finally, a first estimation of the limit of detection has been carried out. This results in a significant decrease of the LOD in case of TG-GCxSPIMS (500 ppt for toluene) as compared to 30 ppb, which could be reached with TG-SPIMS. AU - Saraji-Bozorgzad, M.R. AU - Eschner, M.* AU - Gröger, T.M. AU - Streibel, T.* AU - Geißler, R. AU - Kaisersberger, E.* AU - Denner, T.* AU - Zimmermann, R. C1 - 5132 C2 - 27836 SP - 9644-9653 TI - Highly resolved online organic-chemical speciation of evolved gases from thermal analysis devices by cryogenically modulated fast gas chromatography coupled to single photon ionization mass spectrometry. JO - Anal. Chem. VL - 82 IS - 23 PB - Amer. Chemical Soc. PY - 2010 SN - 0003-2700 ER - TY - JOUR AB - Complementary molecular and atomic signatures obtained from Fourier transform ion cyclotron resonance (FTICR) mass spectra and NMR spectra provided unequivocal attribution of CHO, CHNO, CHOS, and CHNOS molecular series in secondary organic aerosols (SOA) and high-resolution definition of carbon chemical environments. Sulfate esters were confirmed as major players in SOA formation and as major constituents of its water-soluble fraction (WSOC). Elevated concentrations of SO(2), sulfate, and photochemical activity were shown to increase the proportion of SOA sulfur-containing compounds. Sulfonation of CHO precursors by means of heterogeneous reactions between carbonyl derivatives and sulfuric acid in gas-phase photoreactions was proposed as a likely formation mechanism of CHOS molecules. In addition, photochemistry induced oligomerization processes of CHOS molecules. Methylesters found in methanolic extracts of a SOA subjected to strong photochemical exposure were considered secondary products derived from sulfate esters by methanolysis. The relative abundance of nitrogen-containing compounds (CHNO and CHNOS series) appeared rather dependent on local effects such as biomass burning. Extensive aliphatic branching and disruption of extended NMR spin-systems by carbonyl derivatives and other heteroatoms were the most significant structural motifs in SOA. The presence of heteroatoms in elevated oxidation states suggests a clearly different SOA formation trajectory in comparison with established terrestrial and aqueous natural organic matter. AU - Schmitt-Kopplin, P. AU - Gelencser, A.* AU - Dabek-Zlotorzynska, E.* AU - Kiss, G.* AU - Hertkorn, N. AU - Harir, M. AU - Hong, Y.* AU - Gebefügi, I. C1 - 5955 C2 - 27656 SP - 8017-8026 TI - Analysis of the unresolved organic fraction in atmospheric aerosols with ultrahigh-resolution mass spectrometry and nuclear magnetic resonance spectroscopy: Organosulfates as photochemical smog constituents. JO - Anal. Chem. VL - 82 IS - 19 PB - American Chemical Society PY - 2010 SN - 0003-2700 ER - TY - JOUR AB - Online single-particle (SP) laser mass spectrometry (MS) is an important tool for fundamental and applied aerosol research. Usually laser desorption/ionization (LDI) is applied for ablation and ionization of atoms and molecular fragments from the nanometer- or micrometer sized air-borne particles and time-of-flight analysers (TOFMS) are used for mass-selective detection of mainly inorganic analytes. The detection of molecular organic compounds is solely possible under very special experimental conditions and extremely dependent on the particle matrix and thus limited to special applications. Very recently it was shown that by implementation of a two-step laser desorption (LD) resonance-enhanced multiphoton ionization (REMPI) postionization approach the single-particulate molecular signature of polycyclic aromatic hydrocarbons (PAH) and their derivatives can be recorded (LD-REMPI-SP-TOFMS). By this, particles from different sources could be differentiated via the patterns of s pecific molecular source tracers such as retene for soft wood combustion or larger PAH as indicator for gasoline car emissions. One drawback of the LD-REMPI-SP-TOFMS method-in particular for field applications-is, however, the necessity of operation and adjustment of two lasers. In this paper the successful implementation of a thermal desorption step in single-particle mass spectrometry is described (TD-REMPI-SP-TOFMS). After size determination by particle velocimetry, individual particles are thermally desorbed on a heated surface in the ion source of the TOFMS. Desorbed molecules are ionized subsequently by REMPI, which addresses selectively PAH and molecular trace indicators. The TD-REMPI-SP-TOFMS concept Is tested with reference particles and applied for automotive exhaust and ambient monitoring. The comparison of the results with the ones obtained by the two-laser approach (LD-REMPI-SP-TOFMS) indicates that the patented TD-REMPI-SP-TOFMS technology presented here is nearly equally well suited for studying organic source tracers in ambient aerosols and aerosol emissions. The increased ruggedness and simplicity of the new approach, however, may favor its application for field measurements in aerosol science and technology. AU - Bente, M. AU - Sklorz, M.* AU - Streibel, T. AU - Zimmermann, R. C1 - 2053 C2 - 26274 SP - 2525-2536 TI - Thermal desorption-multiphoton ionization time-of-flight mass spectrometry of individual aerosol particles: A simplified approach for online single-particle analysis of polycyclic aromatic hydrocarbons and their derivatives. JO - Anal. Chem. VL - 81 IS - 7 PB - Amer Chemical Soc PY - 2009 SN - 0003-2700 ER - TY - JOUR AB - Coupling thermal analysis (TA) with a subsequent analytical method in order to investigate evolved gaseous products from the thermal analysis is a well established method. A popular practice to analyze the gaseous products evolving from thermal analysis is mass spectrometry using electron impact ionization (EI).(1-4) As the kinetic energy of the electrons thereby is typically far beyond the ionization energies of the assayed samples, the electron impact effects fragmentation particularly of organic compounds, hampering the correlation of the ion signals to the gaseous compounds. This applies for complex mixtures in particular. Fragmentation can be reduced using so-called soft ionization techniques. In the course of the presented setup, single photon ionization (SPI) using electron beam pumped excimer lamps (EBEL) emitting vacuum ultraviolet (VUV) light (lambda = 126 nm) is employed. For the instrumentation, a TA system has been coupled to an EBEL-SPI-oaTOFMS (oaTOFMS: orthogonal acceleration time-of-flight mass spectrometry) system using a heated transfer capillary in order to detect semivolatile organic substances from the gas flow of a thermobalance with high temporal resolution. Presented measurements focus on crude oils of different origins. In-depth analysis demonstrates that it is possible to tell apart different crude oil samples on the basis of temperature resolved mass spectra gained from the described setup. TA allows for the assay of crude oils without sample preparation via a distillation process which precedes the thermal decomposition of nonvolatile oil components, i.e., resins and asphaltenes. The gases that evolve during thermal analysis are a complex mixture of organic compounds. These can be analyzed without losing molecular information using mass spectrometry with a soft ionization technique, such as SPI. AU - Geissler, R. AU - Saraji-Bozorgzad, M.R. AU - Gröger, T.M. AU - Fendt, A.* AU - Streibel, T.* AU - Sklorz, M.* AU - Krooss, B.M.* AU - Fuhrer, K.* AU - Gonin, M.* AU - Kaisersberger, E.* AU - Denner, T.* AU - Zimmermann, R. C1 - 3115 C2 - 27957 SP - 6038-6048 TI - Single photon ionization orthogonal acceleration time-of-flight mass spectrometry and resonance enhanced multiphoton ionization time-of-flight mass spectrometry for evolved gas analysis in thermogravimetry: Comparative analysis of crude oils. JO - Anal. Chem. VL - 81 IS - 15 PB - American Chemical Society PY - 2009 SN - 0003-2700 ER - TY - JOUR AB - Thanks to recent technological advances and single-photon ionization's (SPI's) ability to detect all organics, the technique could become the long-sought universal soft ionization method. (To listen to a podcast about this feature, please go to the Analytical Chemistry Web site at pubs.acs.org/journal/ancham.). AU - Hanley, L.* AU - Zimmermann, R. C1 - 1128 C2 - 26273 SP - 4174-4182 TI - Light and molecular ions: The emergence of vacuum UV single-photon ionization in MS. JO - Anal. Chem. VL - 81 IS - 11 PB - Amer Chemical Soc PY - 2009 SN - 0003-2700 ER - TY - JOUR AB - The ultrahigh-resolution Fourier transform ion cyclotron resonance (FTICR) mass spectrum of natural organic matter (NOM) contains several thousand peaks with dozens of molecules matching the same nominal mass. Such a complexity poses a significant challenge for automatic data interpretation, in which the most difficult task is molecular formula assignment, especially in the case of heavy and/or multielement ions. In this study, a new universal algorithm for automatic treatment of FTICR mass spectra of NOM and humic substances based on total mass difference statistics (TMDS) has been developed and implemented. The algorithm enables a blind search for unknown building blocks (instead of a priori known ones) by revealing repetitive patterns present in spectra. In this respect, it differs from all previously developed approaches. This algorithm was implemented in designing FIRAN-software for fully automated analysis of mass data with high peak density. The specific feature of FIRAN is its ability to assign formulas to heavy and/or multielement molecules using "virtual elements" approach. To verify the approach, it was used for processing mass spectra of sodium polystyrene sulfonate (PSS, M(w) = 2200 Da) and polymethacrylate (PMA, M(w) = 3290 Da) which produce heavy multielement and multiply-charged ions. Application of TMDS identified unambiguously monomers present in the polymers consistent with their structure: C(8)H(7)SO(3)Na for PSS and C(4)H(6)O(2) for PMA. It also allowed unambiguous formula assignment to all multiply-charged peaks including the heaviest peak in PMA spectrum at mass 4025.6625 with charge state 6- (mass bias -0.33 ppm). Application of the TMDS-algorithm to processing data on the Suwannee River FA has proven its unique capacities in analysis of spectra with high peak density: it has not only identified the known small building blocks in the structure of FA such as CH(2), H(2), C(2)H(2)O, O but the heavier unit at 154.027 amu. The latter was identified for the first time and assigned a formula C(7)H(6)O(4) consistent with the structure of dihydroxyl-benzoic acids. The presence of these compounds in the structure of FA has so far been numerically suggested but never proven directly. It was concluded that application of the TMDS-algorithm opens new horizons in unfolding molecular complexity of NOM and other natural products. AU - Kunenkov, E.V.* AU - Kononikhin, A.S.* AU - Perminova, I.V.* AU - Hertkorn, N. AU - Gáspár, A. AU - Schmitt-Kopplin, P. AU - Popov, I.A.* AU - Garmash, A.V.* AU - Nikolaev, E.N.* C1 - 505 C2 - 26841 SP - 10106-10115 TI - Total mass difference statistics algorithm: A new approach to identification of high-mass building blocks in electrospray ionization Fourier transform ion cyclotron mass spectrometry data of natural organic matter. JO - Anal. Chem. VL - 81 IS - 24 PY - 2009 SN - 0003-2700 ER - TY - JOUR AB - An in-house-built ion trap mass spectrometer combined with a soft ionization source has been set up and tested. As ionization source, an electron beam pumped vacuum UV (VUV) excimer lamp (EBEL) was used for single-photon ionization. It was shown that soft ionization allows the reduction of fragmentation of the target analytes and the suppression of most matrix components. Therefore, the combination of photon ionization with the tandem mass spectrometry (MS/MS) capability of an ion trap yields a powerful tool for molecular ion peak detection and identification of organic trace compounds in complex matrixes. Ibis setup was successfully tested for two different applications. The first one is the detection of security-relevant substances like explosives, narcotics, and chemical warfare agents. One test substance from each of these groups was chosen and detected successfully with single photon ionization ion trap mass spectrometry (SPI-ITMS) MS/MS measurements. Additionally, first tests were performed, demonstrating that this method is not influenced by matrix compounds. The second field of application is the detection of process gases. Here, exhaust gas from coffee roasting was analyzed in real time, and some of its compounds were identified using MS/MS studies. AU - Schramm, E. AU - Kürten, A. AU - Hölzer, J. AU - Mitschke, S. AU - Mühlberger, F. AU - Sklorz, M. AU - Wieser, J.* AU - Ulrich, A.* AU - Pütz, M.* AU - Schulte-Ladbeck, R.* AU - Schultze, R.* AU - Curtius, J.* AU - Borrmann, S.* AU - Zimmermann, R. C1 - 1832 C2 - 26228 SP - 4456-4467 TI - Trace detection of organic compounds in complex sample matrixes by single photon ionization ion trap mass spectrometry: Real-time detection of security-relevant compounds and online analysis of the coffee-roasting process. JO - Anal. Chem. VL - 81 IS - 11 PB - Amer Chemical Soc PY - 2009 SN - 0003-2700 ER - TY - JOUR AB - Direct inlet aerosol mass spectrometry plays an increasingly important role in applied and fundamental aerosol and nanoparticle research. Laser desorption/ionization (LDI) based techniques for single particle time-of-flight mass spectrometry (LDI-SP-TOFMS) are a promising approach in the chemical analysis of single aerosol particles, especially for the detection of inorganic species and distinction of particle classes. However, until now the detection of molecular organic compounds on a single particle basis has been difficult due to the high laser power densities which are required for the LDI process as well as due to the inherent matrix effects associated with this ionization technique. By the application of a two-step approach, where an IR desorption laser pulse is applied to perform a gentle desorption of organic material from the single particle surface and a second UV-laser performs the soft ionization of the desorbed species, this drawback of laser based single particles mass spectrometry can be overcome. The postionization of the desorbed molecules has been accomplished in this work by resonance enhanced multiphoton ionization (REMPI) using a KrF excimer laser (248 nm). REMPI allows an almost fragmentation free trace analysis of polycyclic aromatic hydrocarbons (PAHs) and their derivatives from individual single particles (laser desorption-REMPI postionization-single particle-time-of-flight mass spectrometry or LD-REMPI-SP-TOFMS). Crucial system parameters of the home-built aerosol mass spectrometer such as the power densities and the relative timing of both lasers were optimized with respect to the detectability of particle source specific organic signatures using well characterized standard particles. In a second step, the LD-REMPI-SP-TOFMS system was applied to analyze different real world aerosols (spruce wood combustion, gasoline car exhaust, beech wood combustion, and diesel car exhaust). It was possible to distinguish the particles from different sources by their molecular signature. Finally, exemplary ambient aerosol measurements have been carried out, which demonstrate the potential of the method for investigating urban aerosol and making contributions to source attribution studies. AU - Bente, M. AU - Sklorz, M.* AU - Streibel, T. AU - Zimmermann, R. C1 - 1189 C2 - 26361 SP - 8991-9004 TI - Online laser desorption-multiphoton postionization mass spectrometry of individual aerosol particles: Molecular source indicators for particles emitted from different traffic-related and wood combustion sources. JO - Anal. Chem. VL - 80 IS - 23 PB - Amer Chemical Soc PY - 2008 SN - 0003-2700 ER - TY - JOUR AB - Sensitive and high-resolution chromatographic-driven metabonomomics studies experienced major growth with the aid of new analytical technologies and bioinformatics software packages. Hence, data collections by LC-MS and data analyses by multivariate statistical methods are by far the most straightforward steps, and the detection of biomarker candidates can easily be achieved. However, the unequivocal identification of the detected metabolite candidates, including isomer elucidation, is still a crux of current metabonomics studies. Here we present a comprehensive analytical strategy for the elucidation of the molecular structure of metabolite biomarkers detected in a metabonomics study, exemplified analyzing spot urine of a cohort of healthy, insulin sensitive subjects and clinically well characterized prediabetic, insulin resistant individuals. An integrated approach of LC-MS fingerprinting, multivariate statistic analysis, LC-MSn experiments, micro preparation, FTICR-MS, GC retention index, database search, and generation of an isotope labeled standard was applied. Overall, we could demonstrate the efficiency of our analytical approach by the unambiguous elucidation of the molecular structure of an isomeric biomarker candidate detected in a complex human biofluid. The proposed strategy is a powerful new analytical tool, which will allow the definite identification of physiologically important molecules in metabonomics studies from basic biochemistry to clinical biomarker discovery. AU - Chen, J.* AU - Zhao, X.* AU - Fritsche, J.* AU - Yin, P.* AU - Schmitt-Kopplin, P. AU - Wang, W.* AU - Lu, X.* AU - Häring, H.-U.* AU - Schleicher, E.D.* AU - Lehmann, R.* AU - Xu, G.* C1 - 3204 C2 - 25142 SP - 1280-1289 TI - Practical approach for the identification and isomer elucidation of biomarkers detected in a metabonomic study for the discovery of individuals at risk for diabetes by integrating the chromatographic and mass spectrometric information. JO - Anal. Chem. VL - 80 IS - 4 PB - American Chemical Society PY - 2008 SN - 0003-2700 ER - TY - JOUR AB - Compound-specific chlorine isotope analysis receives much interest to assess the fate of chlorinated hydrocarbons in contaminated environments. This paper provides a theoretical basis to calculate isotope ratios and quantify isotope fractionation from ion-current ratios of molecular- and fragment-ion multiplets. Because both (35)Cl and (37)Cl are of high abundance, polychlorinated hydrocarbons consist of molecules containing different numbers of (37)Cl denoted as isotopologues. We show that, during reactions, the changes in isotopologue ratios are proportional to changes in the isotope ratio assuming a nonselective isotope distribution in the initial compound. This proportionality extents even to fragments formed in the ion source of a mass spectrometer such as C 2Cl 2 (double dechlorinated fragment of perchloroethylene, PCE). Fractionation factors and kinetic isotope effects (KIE) may, therefore, be evaluated from isotope, isotopologue or even fragment ratios according to conventional simple equations. The proportionality is exact with symmetric molecules such as dichloroethylene (DCE) and PCE, whereas it is approximately true with molecules containing nonreactive positions such as trichloroethylene (TCE). If in the latter case isotope ratios are derived from dechlorinated fragments, e.g., C 2HCl 2, it is important that fragmentation in the ion source affect all molecular positions alike, as otherwise isotopic changes in reactive positions may be underrepresented. AU - Elsner, M. AU - Hunkeler, D.* C1 - 4890 C2 - 25349 SP - 4731-4740 TI - Evaluating chlorine isotope effects from isotope ratios and mass spectra of polychlorinated molecules. JO - Anal. Chem. VL - 80 IS - 12 PB - Amer. Chem. Soc. PY - 2008 SN - 0003-2700 ER - TY - JOUR AB - Soils, sediments, freshwaters, and marine waters contain natural organic matter (NOM), an exceedingly complex mixture of organic compounds that collectively exhibit a nearly continuous range of properties (size-reactivity continuum). NOM is composed mainly of carbon, hydrogen, and oxygen, with minor contributions from heteroatoms such as nitrogen, sulfur, and phosphorus. Suwannee River fulvic acid (SuwFA) is a fraction of NOM that is relatively depleted in heteroatoms. Ultrahigh resolution Fourier transform ion cyclotron (FTICR) mass spectra of SuwFA reveal several thousand molecular formulas, corresponding in turn to several hundred thousand distinct chemical environments of carbon even without accountancy of isomers. The mass difference Am among adjoining C,H,O-molecules between and within clusters of nominal mass is inversely related to molecular dissimilarity: any decrease of Am imposes an ever growing mandatory difference in molecular composition. Molecular formulas that are expected for likely biochemical precursor molecules are notably absent from these spectra, indicating that SuwFA is the product of diagenetic reactions that have altered the major components of biomass beyond the point of recognition. The degree of complexity of SuwFA can be brought into sharp focus through comparison with the theoretical limits of chemical complexity, as constrained and quantized by the fundamentals of chemical binding. The theoretical C,H,O-compositional space denotes the isomer-filtered complement of the entire, very vast space of molecular structures composed solely of carbon, hydrogen, and oxygen. The molecular formulas within SuwFA occupy a sizable proportion of the theoretical C,H,O-compositional space. A 100 percent coverage of the theoretically feasible C,H,O-compositional space by SuwFA molecules is attained throughout a sizable range of mass and H/C and O/C elemental ratios. The substantial differences between (and complementarity of) the SuwFA molecular formulas that are observed using six different modes of ionization (APCI, APPI, and ESI in positive and negative modus) imply considerable selectivity of the ionization process and suggest that the observed mass spectra represent simplified projections of still more complex mixtures. AU - Hertkorn, N. AU - Frommberger, M. AU - Witt, M.* AU - Koch, B.P.* AU - Schmitt-Kopplin, P. AU - Perdue, E. M.* C1 - 2353 C2 - 25832 SP - 8908-8919 TI - Natural Organic Matter and the Event Horizon of Mass Spectrometry. JO - Anal. Chem. VL - 80 IS - 23 PB - American Chemical Society PY - 2008 SN - 0003-2700 ER - TY - JOUR AB - Mass spectrometry (MS) is an established analytical technique to analyze evolved gas in thermogravimetry (TG). In this study, for the first time a novel SPI-MS technique using an electron beam pumped VUV excimer lamp as photon source (lambda = 126 nm) was employed in conjunction with thermogravimetry. The coupling was achieved with an improved heated interface and adjacent transfer capillary between TG and ion source of a quadrupole mass spectrometer. The feasibility of this approach was proven by investigating semivolatile substances such as long-chain alkanes (heptadecane C17H36), polymers, e.g., polystyrene, polycarbonate, and acrylonitrile-butadiene-styrene, polymer mixtures and blends. Mass spectra with almost no fragmentation were obtained, and quantification of selected substances could be achieved. Polymer mixtures could be distinguished by their SPI mass spectra, and the effect of premixing of polymers has been accessed. Its unique attributes render the TA-SPI-MS method a promising new tool for quantitative and qualitative evaluation of complex organic thermal degradation products. AU - Saraji-Bozorgzad, M.R. AU - Geißler, R. AU - Streibel, T. AU - Mühlberger, F. AU - Sklorz, M. AU - Kaisersberger, E.* AU - Denner, T.* AU - Zimmermann, R. C1 - 3545 C2 - 25631 SP - 3393-3403 TI - Thermogravimetry coupled to single photon ionization quadrupole mass spectrometry: A tool to investigate the chemical signature of thermal decomposition of polymeric materials. JO - Anal. Chem. VL - 80 IS - 9 PB - American Chemical Society PY - 2008 SN - 0003-2700 ER - TY - JOUR AB - The goal of this study was the application of a novel, fully automatic column-switching approach in a metabonomics study combining the orthogonal selectivities of hydrophilic interaction chromatography (HILIC) and reversed-phase chromatography. The temporal, pharmacodynamic effects of the ginsenoside Rg3 on the metabonome in urine of healthy and liver-tumor-bearing rats have been investigated. Within a total analysis time of 52 min we detected 5686 polar, and on the second column an additional 1808 apolar, urinary metabolite ions. The administration of a single, high dose of Rg3 in a beta-cyclodextrin-based formulation led to a considerable change of the metabolic pattern in cancer rats during 3 days studied. Seventeen biomarker candidates including three apolar metabolites, which were not retained on the HILIC column, were detected. Overall, the results suggest that the developed liquid chromatography-mass spectrometry strategy is a promising tool in metabonomics studies for global analysis of highly complex biosamples. It may not only increase the number of discovered biomarkers but consequently improve the comprehensive information on metabolic changes in a fully automatic manner. AU - Wang, Y.* AU - Wang, J.* AU - Yao, M.* AU - Zhao, X.* AU - Fritsche, J.* AU - Schmitt-Kopplin, P. AU - Cai, Z.* AU - Wan, D.* AU - Lu, X.* AU - Yang, S.* AU - Gu, J.* AU - Häring, H.-U.* AU - Schleicher, E.D.* AU - Lehmann, R.* AU - Xu, G.* C1 - 3333 C2 - 25708 SP - 4680-4688 TI - Metabonomics study on the effects of the ginsenoside Rg3 in a beta-cyclodextrin-based formulation on tumor-bearing rats by a fully automatic hydrophilic interaction/reversed-phase column-switching HPLC-ESI-MS approach. JO - Anal. Chem. VL - 80 IS - 12 PB - American Chemical Society PY - 2008 SN - 0003-2700 ER - TY - JOUR AB - A pathological increase of the permeability of the mitochondrial membranes may culminate in the irreversible rupture of the mitochondrial outer membrane. Such a permeability transition is lethal because it results in the release of death-inducing molecules from mitochondria and/or metabolic failure. Current methods to assess this outer membrane damage are mostly indirect or scarcely representative of the overall mitochondrial population. Here we present an analytical and preparative approach using free flow electrophoresis to directly distinguish rat liver mitochondria that have undergone the permeability transition from unaffected organelles or from organelles that are damaged to a minor degree. Mitochondrial populations, which considerably differ in outer membrane integrity or cytochrome c content, were separated by this means. We further show that the relative abundance of each population depends on the dose of the permeability transition inducer and the duration of the treatment time. Finally, we have employed this approach to investigate the impairment of mitochondria that were isolated from livers subjected to ischemia/reperfusion damage. AU - Zischka, H. AU - Larochette, N.* AU - Hoffmann, F.* AU - Hamöller, D. AU - Jägemann, N. AU - Lichtmannegger, J. AU - Jennen, L. AU - Müller-Höcker, J.* AU - Roggel, F.* AU - Göttlicher, M. AU - Vollmar, A.M.* AU - Kroemer, G.* C1 - 2679 C2 - 25456 SP - 5051-5058 TI - Electrophoretic analysis of the mitochondrial outer membrane rupture induced by permeability transition. JO - Anal. Chem. VL - 80 IS - 13 PB - American Chemical Society PY - 2008 SN - 0003-2700 ER - TY - JOUR AB - Orthogonal acceleration time-of-flight mass spectrometers (oaTOFMS), which are exhibiting a pulsed orthogonal extraction of ion bunches into the TOF mass analyzer from a continuous primary ion beam, are well-suited for continuous ionization methods such as electron impact ionization (EI). Recently an electron beam pumped rare gas excimer lamp (EBEL) was introduced, which emits intensive vacuum UV (VUV) radiation at, e.g., 126 nm (argon excimer) and is well suited as the light source for soft single photon ionization (SPI) of organic molecules. In this paper, a new compact oaTOFMS system which allows switching between SPI, using VUV-light from an EBEL-light source, and conventional EI is described. With the oaTOFMS system, EBEL-SPI and EI mass spectral transients can be recorded at very high repetition rates (up to 100 kHz), enabling high duty cycles and therefore good detection efficiencies. By using a transient recorder card with the capability to perform on-board accumulation of the oaTOF transients, final mass spectra with a dynamic range of 106 can be saved to the hard disk at a rate of 10 Hz. As it is possible to change the ionization modes (EI and SPI) rapidly, a comprehensive monitoring of complex gases with highly dynamic compositions, such as cigarette smoke, is possible. In this context, the EI based mass spectra address the bulk composition (compounds such as water, oxygen, carbon dioxide, etc. in the up to percentage concentration range) as well as some inorganic trace gases such as argon, sulfur dioxide, etc. down to the low ppm level. The EBEL-SPI mass spectra on the other hand are revealing the organic composition down to the lower ppb concentration range. AU - Mühlberger, F. AU - Saraji-Bozorgzad, M.R. AU - Gonin, M.* AU - Fuhrer, K.* AU - Zimmermann, R. C1 - 3742 C2 - 24845 SP - 8118-8124 TI - Compact ultrafast orthogonal acceleration time-of-flight mass spectrometer for on-line gas analysis by electron impact ionization and soft single photon ionization using an electron beam pumped rare gas excimer lamp as VUV-light source. JO - Anal. Chem. VL - 79 IS - 21 PB - American Chemical Society PY - 2007 SN - 0003-2700 ER - TY - JOUR AB - Potentially, compound-specific isotope analysis may provide unique information on source and fate of pesticides in natural systems. Yet for isotope analysis, LC-based methods that are based on the use of organic solvents often cannot be used and GC-based analysis is frequently not possible due to thermolability of the analyte. A typical example of a compound with such properties is isoproturon (3-(4-isopropylphenyl)-1,1-dimethylurea), belonging to the worldwide extensively used phenylurea herbicides. To make isoproturon accessible to carbon and nitrogen isotope analysis, we developed a GC-based method during which isoproturon was quantitatively fragmented to dimethylamine and 4-isopropylphenylisocyanate. Fragmentation occurred only partially in the injector but was mainly achieved on a heated capillary column. The fragments were then chromatographically separated and individually measured by isotope ratio mass spectrometry. The reliability of the method was tested in hydrolysis experiments with three isotopically different batches of isoproturon. For all three products, the same isotope fractionation factors were observed during conversion and the difference in isotope composition between the batches was preserved. This study demonstrates that fragmentation of phenylurea herbicides does not only make them accessible to isotope analysis but even enables determination of intramolecular isotope fractionation. AU - Penning, H. AU - Elsner, M. C1 - 3863 C2 - 24900 SP - 8399-8405 TI - Intramolecular carbon and nitrogen isotope analysis by quantitative dry fragmentation of the phenylurea herbicide isoproturon in a combined injector/capillary reactor prior to GC separation. JO - Anal. Chem. VL - 79 IS - 21 PB - American Chemical Society PY - 2007 SN - 0003-2700 ER - TY - JOUR AB - The aromatic region of two-dimensional heteronuclear 1H, 13C NMR spectra of natural organic matter and related materials (e.g., 1H and 13C chemical shifts ranging from approximately 5 to 10 and 80 to 140 ppm, respectively) is highly complex and difficult to interpret using conventional approaches. In principle, this region of the NMR spectrum should be amenable to detailed analysis, because the effects of many common substituents on the chemical shifts of aromatic carbon and hydrogen are well documented. This paper describes the development of a model for prediction of substitution patterns in aromatic rings by increment analysis (SPARIA). In the forward mode, SPARIA is used to predict the chemical shifts of 1H and 13C on aromatic moieties containing every possible combination of eight common substituents that are likely to be representative of substituents on aromatic moieties in natural organic matter. The accuracy of SPARIA in the forward mode is evaluated for 29 aromatic compounds (100 peaks) by comparison of predicted chemical shifts for 1H and 13C with experimental values and with predictions of commercially available software for prediction of NMR spectra. The most important development in this paper is the inverse mode that is built into SPARIA. Given chemical shifts for 1H and 13C (such as may be obtained from a two-dimensional, heteronuclear NMR spectrum), the inverse mode of SPARIA calculates all possible combinations of the eight selected substituents that yield chemical shifts within a specified window of chemical shift for both 1H and 13C. Both the distribution of possible substitution patterns and simple descriptive statistics of the distribution are thus obtained. The inverse mode of SPARIA has been tested on the 29 aromatic compounds (100 peaks) that were used to evaluate its forward mode, and the dependence of the inverse process on the size of the chemical shift window has been evaluated. Finally, the inverse mode of SPARIA has been applied to selected peaks from the two-dimensional heteronuclear HSQC spectrum of a sample of natural organic matter that was isolated by reverse osmosis from the Suwannee River in southeastern Georgia. AU - Perdue, E.M.* AU - Hertkorn, N. AU - Kettrup, A. C1 - 5715 C2 - 24379 SP - 1010-1021 TI - Substitution patterns in aromatic rings by increment analysis: Model development and application to natural organic matter. JO - Anal. Chem. VL - 79 IS - 3 PB - American Chem. Soc. PY - 2007 SN - 0003-2700 ER - TY - JOUR AU - Elsner, M. AU - Lacrampe Couloume, G.* AU - Sherwood Lollar, B.* C1 - 4912 C2 - 24028 SP - 7528-7534 TI - Freezing to preserve groundwater samples and improve headspace quantification limits of water-soluble organic contaminants for carbon isotope analysis. JO - Anal. Chem. VL - 78 PY - 2006 SN - 0003-2700 ER - TY - JOUR AB - The hyphenation of gas chromatography and mass spectrometry (GC/MS) revolutionized organic analysis. In GC/ MS coupling, usually electron impact ionization is applied, and molecules are identified by their fragment pattern. Although mass spectrometry in principle is a separation method, it is used predominantly as a spectrometric technique. However, if soft (i.e., fragmentation-free) ionization techniques are applied, the inherent separation character of MS is emphasized, which has similarities to a GC boiling point separation. By combining polar column GC separation and fast soft ionization time-of-flight mass spectrometry technology, a comprehensive separation of complex petrochemical samples can be obtained ( GC x MS approach). Compounds of comparable physical-chemical properties are characteristically grouped together in a two-dimensional retention time-m/z representation. This resembles the separation characteristics of comprehensive two-dimensional gas chromatography ( GC x GC) and, thus, represents a novel multidimensional separation approach. In this work, a gas chromatograph equipped with a polar separation column was coupled to a home-built laser ionization time-of-flight mass spectrometer. Laser-based, single-photon ionization was used for universal soft ionization and resonance-enhanced multiphoton ionization for selective ionization of aromatic compounds. A novel capillary-jet inlet system was used for the coupling. Multidimensional comprehensive analysis of complex petrochemical hydrocarbon samples using gas chromatography coupled to mass spectrometry with soft and selective photo ionization sources is first demonstrated. AU - Mitschke, S.* AU - Welthagen, W.* AU - Zimmermann, R. C1 - 4878 C2 - 23863 SP - 6364-6375 TI - Comprehensive gas chromatography -time-of-flight mass spectrometry using soft and selective photoionization techniques. JO - Anal. Chem. VL - 78 IS - 18 PY - 2006 SN - 0003-2700 ER - TY - JOUR AB - Atmospheric aerosols are subject to be responsible for human health effects. In this context, besides mass and number concentration of particles, their chemical composition has gained interest recently. However, knowledge about the organic content of particulate matter is still relatively scarce; i.e., only 10-40% of compounds present in the aerosol are as yet identified. By means of a newly developed measurement technique, thermal desorption/ photoionization time-of-flight mass spectrometry (TOFMS), organic species evolved from urban aerosol samples collected at Augsburg, Germany, are analyzed. Thereby, compounds desorbed according to a temperature protocol following procedures for OC/EC analysis (120, 250, and 340 degrees C as desorbing temperatures) are ionized by soft, fragmentationless resonance multiphoton ionization (REM-PI) and single photon ionization (SPI), respectively. With REMPI-TOFMS, a large variety of PAH is detectable. A comprehensive analysis is enabled by adding SPI-TOFMS, which gives access to aliphatic and carbonylic hydrocarbons as well as alkanoic acids and esters. Analysis of the data showed a high abundance of phenol and guiacol as well as retene, which are known markers for wood combustion. Similar patterns were found with ash from spruce wood combustion. An increase of volatile substances at 340 degrees C gave rise to the suggestion that these compounds are re-formed by pyrolytic decomposition reactions from oligomeric, polymeric, and polyfunctional oxygenated species. This was corroborated by the investigation of the behavior of cellulose acetate, which exhibited a similar pattern in its SPI-TOFMS spectrum at 340 degrees C as the aerosol. More thorough investigations of urban aerosol and source material with respect to problems such as the mass closure of carbonaceous material, indications for source apportionment, and allotment of organic species on a molecular level to fractions of organic and elemental carbon seem feasible with this measurement method. AU - Streibel, T. AU - Weh, J. AU - Mitschke, S.* AU - Zimmermann, R. C1 - 686 C2 - 23723 SP - 5354-5361 TI - Thermal desorption/pyrolysis coupled with photoionization time-of-flight mass spectrometry for the analysis of molecular organic compounds and oligomeric polymeric fractions in Urban particulate matter. JO - Anal. Chem. VL - 78 IS - 15 PY - 2006 SN - 0003-2700 ER - TY - JOUR AB - A new built instrument suitable for laser desorption-single photon ionization time-of-flight mass spectrometry (LD-SPI-TOFMS) with use of Vacuum-UV photons with a wavelength of 118 nm was used for the analysis of organic compounds. Fragmentation-free analysis of a variety of substances was achieved for desorption experiments with pure compounds desorbed from quartz glass filters applying low desorption energies. It was further found that the rate of fragmentation is strongly dependent on the desorption energy. Matrix effects were investigated by desorption experiments utilizing soot spiked with several organic compounds.The characteristics of the desorption process are assessed in more detail and the impact on the analysis of ambient particulate matter (PM) samples on filters are discussed. First results obtained from the application of the technique to the analysis of organic compounds from ambient PM are presented. Furthermore, possibilities of future developments of the method, in particular for analysis of ambient PM, are discussed. AU - Ferge, T. AU - Mühlberger, F. AU - Zimmermann, R. C1 - 4810 C2 - 22909 SP - 4528-4538 TI - Application of infrared laser desorption vacuum-UV single photon ionization mass spectrometry for analysis of organic compounds from particulate matter filter samplas. JO - Anal. Chem. VL - 77 IS - 14 PY - 2005 SN - 0003-2700 ER - TY - JOUR AB - Resonance-enhanced multiphoton ionization time-of-flight mass spectrometry (REMPI-TOFMS) is a powerful technique for the on-line analysis of aromatic compounds with unique features regarding selectivity and sensitivity. Aliphatic compounds, however, are difficult to address by REMPI due to their unfavorable photo ionization properties. This paper describes the proof of concept for an on-line derivatization approach for converting nonaromatic target analytes into specific, photoionizable aromatic derivatives that are readily detectable by REMPI-TOFMS. A multichannel silicone trap or poly(dimethylsiloxane) (PDMS) open tubular capillary was used as a reaction medium for the derivatization of volatile alkyl aldehydes and alkylamines with aromatic "photoionization labels"and to concentrate the resulting aromatic derivatives. The aldehydes formaldehyde, acetaldehyde, acrolein, and crotonal, which when underivatized are poorly detectable by REMPI, were converted into their easily photoionizable phenylhydrazone derivatives by the on-line reaction with phenylhydrazine as reagent. Similarly, the methyl-, ethyl-, propyl-, and butylamines were converted into their REMPI-ionizable benzaldehyde alkylimine derivatives by the on-line reaction with benzaldehyde as reagent. The derivatives were thermally desorbed from the PDMS matrix and transferred into the REMPI-TOFMS for detection. The REMPI-TOFMS detection limits obtained for acetaldehyde; acrolein; crotonal; and methyl-, ethyl-, propyl-, and butylamine using this photo ionization labeling method were in the sub-parts-per-million range and, thus, readily below the permissible exposure limits set by OSHA. AU - Fernandes-Whaley, M.* AU - Mühlberger, F. AU - Whaley, A.* AU - Adam, T. AU - Zimmermann, R. AU - Rohwer, E.* AU - Walte, A.* C1 - 968 C2 - 22489 SP - 1-10 TI - On-line derivatization for resonance-enhanced multiphoton ionization time-of-flight mass spectrometry:Detection of aliphatic aldehydes and amines via reactive coupling of aromatic photo ionization labels. JO - Anal. Chem. VL - 77 IS - 1 PY - 2005 SN - 0003-2700 ER - TY - JOUR AB - he application of soft photoionization mass spectrometry methods (PIMS) for cigarette mainstream smoke analysis is demonstrated. Resonance-enhanced multiphoton ionization (REMPI) at 260 nm and vacuum ultraviolet light single-photon ionization (SPI) at 118 nm were used in combination with time-of-flight mass spectrometry (TOFMS). An optimized smoking machine with reduced memory effects of smoke components was constructed, which in combination with the REMPI/SPI-TOFMS instrument allows PIMS smoke analysis with a time resolution of up to 10 Hz. The complementary character of both PIMS methods is demonstrated. SPI allows the detection of various aliphatic and aromatic compounds in smoke up to ∼120 m/z while REMPI is well suited for aromatic compounds. The capability of the instrument coupled to the novel sampling system for puff-by-puff resolved measurements is demonstrated. The feasibility of using the experimental system for intrapuff smoke measurements is also shown. Two main patterns of puff-by-puff behaviors are observed for different smoke constituents. The first group exhibits a constant increase in smoke constituent yield from the first to the last puff. The second group shows a high yield of the constituent in the first puff, with lower and constant or slowly increasing yields in the following puffs. A third group cannot be clearly classified and is a combination of both observed profiles. AU - Mitschke, S.* AU - Adam, T.* AU - Streibel, T.* AU - Baker, R.R.* AU - Zimmermann, R. C1 - 3357 C2 - 22638 SP - 2288-2296 TI - Application of time-of-flight mass spectrometry with laser-based photoionization methods for time-resolved on-line analysis of mainstream cigarette smoke. JO - Anal. Chem. VL - 77 IS - 8 PY - 2005 SN - 0003-2700 ER - TY - JOUR AB - The application of soft ionization methods for mass spectrometry (MS), such as single-photon ionization (SPI) using vacuum ultraviolet (VUV) light, provides powerful analytical instrumentation for real-time on-line monitoring of organic substances in gaseous matrixes. A compact and mobile quadrupole mass spectrometer (QMS) system using a novel electron beam pumped rare gas VUV lamp for SPI has been developed for on-line analysis of organic trace compounds (ppb concentrations). The VUV radiation of the light source is employed for SPI in the ion source of the QMS. The concept of the interfacing of the VUV light source with the QMS is described and the SPI-QMS is characterized. On-line detection limits down to 50 ppb for benzene, toluene, and m-xylene were achieved. The instrument is well suited for continuous measurements of aromatic and aliphatic trace compounds and can therefore be used for on-line monitoring of trace compounds in dynamically fluctuating process gases. First measurements of gas standards, petrochemical samples, and on-line monitoring of automotive exhaust are presented. AU - Mühlberger, F. AU - Wieser, J.* AU - Morozov, A.* AU - Ulrich, A.* AU - Zimmermann, R. C1 - 3112 C2 - 22665 SP - 2218-2226 TI - Single-photon ionization quadrupole mass spectrometry with an electron beam pumped excimer light source. JO - Anal. Chem. VL - 77 IS - 7 PY - 2005 SN - 0003-2700 ER - TY - JOUR AB - Single-photon ionization (SPI) using vacuum ultraviolet (VUV) light produced by an electron beam pumped rare gas excimer source has been coupled to a compact and mobile time-of-flight mass spectrometer (TOFMS). The novel device enables real-time on-line monitoring of organic trace substances in complex gaseous matrixes down to the ppb range. The pulsed VUV radiation of the light source is employed for SPI in the ion source of the TOFMS. Ion extraction is also carried out in a pulsed mode with a short time delay with respect to ionization. The experimental setup of the interface VUV light source/time-of-flight mass spectrometer is described, and the novel SPI-TOFMS system is characterized by means of standard calibration gases. Limits of detection down to 50 ppb for aliphatic and aromatic hydrocarbons were achieved. First on-line applications comprised real-time measurements of aromatic and aliphatic trace compounds in mainstream cigarette smoke, which represents a highly dynamic fluctuating gaseous matrix. Time resolution was sufficient to monitor the smoking process on a puff-by-puff resolved basis. Furthermore, human breath analysis has been carried out to detect differences in the breath of a smoker and a nonsmoker, respectively. Several well-known biomarkers for smoke could be identified in the smoker's breath. The possibility for even shorter measurement times while maintaining the achieved sensitivity makes this new device a promising tool for on-line analysis of organic trace compounds in process gases or biological systems. AU - Mühlberger, F. AU - Streibel, T. AU - Wieser, J.* AU - Ulrich, A.* AU - Zimmermann, R. C1 - 3928 C2 - 23028 SP - 7408-7414 TI - Single photon ionization time-of-flight mass spectrometry with a pulsed electron beam pumped excimer VUV lamp for on-line gas analysis: Setup and first results on cigarette smoke and human breath. JO - Anal. Chem. VL - 77 IS - 22 PY - 2005 SN - 0003-2700 ER - TY - JOUR AB - The objective of the project is to develop on-line, real-time, and noninvasive process control tools of coffee roasting that help deliver a consistent and high-quality coffee aroma. The coffee roasting process was analyzed by direct injection of the roaster gas into a time-of-flight mass spectrometer and ionized either by resonance enhanced multiphoton ionization (REMPI) at 266 and 248 nm or vacuum ultraviolet single-photon ionization (VUV-SPI) at 118 nm. The VUV ionization scheme allows detecting mainly the most volatile and abundant compounds of molecular mass below 100 m/z, while REMPI ionizes mainly aromatic compounds of molecular mass larger than 100 m/z. Combining the compounds ionized by resonant and single-photon ionization, 30 volatile organic compounds are monitored in real time. Time−intensity profiles of 10 important volatile coffee compounds were discussed in connection with their formation chemistry during roasting. Applying multivariate statistics (principle component analysis) on time−intensity traces of nine volatile coffee compounds, the roasting degree could be traced as a consistent path in the score plot of the two most significant principle components (including 68% of the total variance), for a range of roasting temperatures (200−250 °C). AU - Dorfner, R. AU - Ferge, Th. AU - Yeretzian, C.* AU - Kettrup, A. AU - Zimmermann, R. C1 - 641 C2 - 21709 SP - 1386-1402 TI - Laser Mass Spectrometry as On-line Sensor for Industrial Process Analysis: Process Control of Coffee Roasting. JO - Anal. Chem. VL - 76 IS - 5 PY - 2004 SN - 0003-2700 ER - TY - JOUR AB - The binding of cadmium to Suwannee River natural organic matter (NOM) has been investigated across a broad range of Cd/C ratios (0.00056−0.0056) and pH values (3.5−11) by 113Cd NMR spectroscopy at two magnetic field strengths (B0 = 9.4 and 11.7 T). Caused by the very peculiar and highly complex nature of the Cd−NOM exchanging system, these 113Cd NMR spectra are characterized by a pH- and concentration-dependent superposition of slow, intermediate, and fast chemical exchange. The complex interplay of solution chemistry and chemical exchange requires a thorough mapping of this Cd−NOM chemically exchanging system through NMR acquisition at two magnetic field strengths and a systematic variation of Cd/C ratios and pH values. The interpretation of 113Cd NMR spectra is greatly facilitated and constrained by simultaneous measurements of pH and pCd, which allows a model-independent calculation of organically bound Cd2+ under all experimental conditions. Within the range of chemical conditions applied in this study, 113Cd NMR spectrometric evidence is consistent with coordination of cadmium by oxygen, nitrogen, and sulfur ligands in NOM. Under all experimental conditions, cadmium is primarily coordinated to oxygen; however, several lines of evidence point to the participation of nitrogen ligands, even in acidic solutions where nitrogen ligands are primarily bound to protons. Under alkaline conditions, up to one-third of cadmium may be coordinated to nitrogen, and a small, but unquantifiable, percentage of cadmium is coordinated to sulfur ligands, as evidenced by far-low-field 113Cd NMR resonances. AU - Hertkorn, N. AU - Perdue, E.M.* AU - Kettrup, A. C1 - 3416 C2 - 22090 SP - 6327-6341 TI - A potentiometric and 113Cd NMR study of cadmium complexation by natural organic matter at two different magnetic field strengths. JO - Anal. Chem. VL - 76 IS - 21 PY - 2004 SN - 0003-2700 ER - TY - JOUR AB - This paper reports on a newly developed mobile mass spectrometer for comprehensive on-line analysis of complex gas mixtures such as ambient air or industrial process gases. Three ionization methods, namely, the resonance-enhanced multiphoton ionization (REMPI), vacuum-ultraviolet single-photon ionization (SPI), and electron impact ionization (EI) are implemented in this instrument and can be operated (quasi-) simultaneously. By means of this setup, a wide range of compounds can be analyzed due to the unique ionization selectivitiy and sensitivity profiles provided by the different ionization techniques. The mass spectrometer is designed for field application even under severe conditions. The REMPI technique is suitable for the selective and soft ionization (without fragmentation) of aromatic compounds at trace level (ppbv/pptv). The also soft but less selective SPI technique with 118-nm vacuum-ultraviolet laser pulses is used as a second laser-based ionization method. Mass spectra obtained by this technique show profiles of most organic compounds (aliphatic and aromatic species) and of some low IP inorganic substances (e.g., ammonia, nitrogen oxide) down to ppbv concentrations. In addition to the laser-based ionization techniques, EI ionization can be used for analysis of the bulk components such as water, oxygen, nitrogen, and carbon dioxide as well as for detection of inorganic minor components such as HCN or HCl from combustion flue gases at ppmv concentration levels. Each method yields specific mass spectrometric information of the sample composition. Special techniques have been developed to combine the three ionization methods in a single mass spectrometer and to allow the quasi-parallel application of all three ionization techniques. AU - Mühlberger, F. AU - Hafner, K. AU - Kaesdorf, S.* AU - Ferge, T. AU - Zimmermann, R. C1 - 4648 C2 - 22122 SP - 6753-6764 TI - Comprehensive on-line characterization of complex gas mixtures by quasi-simultaneous resonance-enhanced multiphoton ionization, vacuum-UV single-photon ionization and electron impact ionization in a time-of-flight mass spectrometer: Setup and instrument characterization. JO - Anal. Chem. VL - 76 IS - 22 PY - 2004 SN - 0003-2700 ER - TY - JOUR AB - A newly conceived compact and mobile time-of flight mass spectrometer (TOFMS) for real-time monitoring of highly complex gas mixtures is presented. The device utilizes two selective and sensitive soft ionization techniques, viz., resonance-enhanced multiphoton ionization (REMPI) and single-photon ionization (SPI) in a (quasi)-simultaneous mode. Both methods allow a fragmentationless ionization. The REMPI method selectively addresses aromatic species, while with SPI applying vacuum ultaviolet light (118 nm) in principle all compounds with an ionization potential below 10.5 eV are accessible. This provides comprehensive information of the chemical composition of complex matrixes. The combustion and pyrolysis behavior of five organic materials typically used in steel processing in China was studied. The trace amounts of organic compounds in the gas phase during combustion and pyrolysis were monitored selectively and sensitively by real-time SPI/REMPI-TOFMS. The measurements were carried out at several constant temperatures in the range from 300 to 1190 °C in both synthetic air and nitrogen. Timely resolved mass spectra reveal the formation and subsequent growth of aromatic molecules. At lower temperatures, highly alkylated PAHs predominate, while at temperatures above 800 °C, the more stable benzene and PAHs without side chains prevail. Potential hyphenation of SPI/REMPI-TOFMS to methods of thermal analysis is discussed. AU - Cao, L.* AU - Mühlberger, F. AU - Adam, T. AU - Streibel, T. AU - Wang, H.Z.* AU - Kettrup, A. AU - Zimmermann, R. C1 - 10374 C2 - 21487 SP - 5639-5645 TI - Resonance-enhanced multiphoton ionization and VUV-single photon ionization as soft and selective laser ionization methods for on-line time-of-flight mass spectrometry : Investigation of the pyrolysis of typical organic contaminants in the steel recycling process. JO - Anal. Chem. VL - 75 IS - 21 PY - 2003 SN - 0003-2700 ER - TY - JOUR AB - The described in vitro test system for allergy diagnosis is based on microscope glass slides activated with (3-glycidyloxypropyl)trimethoxysilane. Allergen solutions are immobilized as small droplets (∼10 nL) on the activated glass slides with a piezoelectric arrayer. In contrast to other tests for specific IgE, such as Pharmacia CAP FEIA, AlaSTAT, or FAST, only a 25-μL serum sample is needed for the screening of allergen-specific IgE against a multitude of allergens and the test can be performed in less than 1 h. Compared with multiallergen dipstick screening tests (e.g., IgEquick, CMG Immunodot) based on multiallergen-coated nitrocellulose strips, the measurement of the microarray-based system can be performed automatically. The chemiluminescence intensities are detected with a sensitive CCD camera. Allergen extracts and recombinant/purified allergens (24 preparations) have been used on the same modified surface for the screening of allergen-specific IgE. With these disposable microarray slides, it is possible to distinguish between patients with and without elevated levels of allergen-specific IgE. Repeated measurements of serum samples demonstrated a sufficient reproducibility. Detection limits (μg/L) of 0.35 (r Bet v1), 0.16 (PLA2), and 1.9 (Der p1) were achieved. AU - Fall, B.I.* AU - Eberlein-König, B.* AU - Behrendt, H. AU - Niessner, R.* AU - Ring, J.* AU - Weller, M.G.* C1 - 10375 C2 - 21763 SP - 556-562 TI - Microarrays for the screening of allergen-specific IgE in human serum. JO - Anal. Chem. VL - 75 IS - 3 PY - 2003 SN - 0003-2700 ER - TY - JOUR AB - Reversed-phase high-performance liquid chromatographic (RP-HPLC) retention parameters, which are determined by the intermolecular interactions in retention process, can be considered as the chemical molecular descriptors in linear free energy relationships (LFERs). On the basis of the characterization and comparison of octadecyl-bonded silica gel (ODS), cyano-bonded silica gel (CN), and phenyl-bonded silica gel (Ph) columns with linear solvation energy relationships (LSERs), a new multiple linear regression model using RP-HPLC retention parameters on ODS and CN columns as variables for estimation of soil adsorption coefficients was developed. It was tested on a set of reference substances from various chemical classes. The results showed that the multicolumn method was more promising than a single-column method was for the estimation of soil adsorption coefficients. The accuracy of the suggested model is identical with that of LSERs. AU - Guo, R.* AU - Liang, X.* AU - Chen, J.* AU - Zhang, Q.* AU - Kettrup, A. C1 - 10376 C2 - 20145 SP - 655-660 TI - Prediction of Soil Adsorption Coefficients from Retention Parameters on Three Reversed-Phase Liquid Chromatographic Colums. JO - Anal. Chem. VL - 74 IS - 3 PB - Society PY - 2002 SN - 0003-2700 ER - TY - JOUR AB - Fast on-line detection of organic compounds from complex mixtures, such as industrial process gas streams, require selective and sensitive analytical methods. One feasible approach for this purpose is the use of mass spectrometry (MS) with a selective and soft (fragment-free) ionization technique, such as chemical ionization (CI) or photo ionization (PI). Single photon ionization (SPI) with vacuum ultraviolet (VUV) light is a particularly soft ionization technique, well-suited for detection of both aromatic and aliphatic species. Problematic, however, is the generation of the VUV fight. In general, the vacuum ultraviolet (VUV) light sources for SPI-MS are based either on lasers (e.g., 118-nm radiation generated by frequency-tripling of the third harmonic of a Nd:YAG laser) or on conventional VUV lamps, such as deuterium lamps. Although the laser-based techniques are very sophisticated and expensive, the conventional lamps have serious drawbacks regarding their optical parameters, such as low-output power, low spectral power density, and broad emission bands. In this work, a novel excimer VUV light source, in which an electron beam is used to form rare gas excimer species, is used. The excimer VUV light source produces brilliant and intense VUV light. The novel VUV light source was coupled to a compact and mobile time-of-flight mass spectrometer (TOFMS). A special interface design, including optical (VUV optics) as well as electronic measures (e.g., pulsed ion extraction) was realized. The use of the excimer VUV lamp for SPI will allow the realization of very compact, rugged, and sensitive SPI-TOFMS devices, which preferably will be adapted for process analytical application or monitoring issues (e.g., chemical warfare detection). The excimer VUV-lamp technology delivers VUV light with a good beam quality and high-output power at low costs. Furthermore, it allows changing the emitted wavelength as well as the bandwidth of the excimer VUV lamp in the 100-200-nm region by changing the gas filling. Consequently, SPI-TOFMS with an excimer light source is a fast detection technique that can be used for online monitoring, for example, in environmental studies or industrial manufacturing processes. In this paper, technology and characteristics of the new excimer light source, as well as the combination with the TOFMS, are presented. Furthermore, a first characterization of the SPI-TOFMS instrument, regarding analytical parameters such as detection limits and selectivity, is given. This includes a discussion of potential improvements that probably will be achievable within a future prototype generation. Finally, first applications of the system for on-line measurement of organic trace species in a complex gas mixture (here, motorcycle exhaust gas) are presented. AU - Mühlberger, F. AU - Wieser, J.* AU - Ulrich, A.* AU - Zimmermann, R. C1 - 10377 C2 - 20372 SP - 3790-3801 TI - Single Photon Ionization (SPI) via Incoherent VUV-Excimer Light : Robust and Compact Time-of-Flight Mass Spectrometer for On-Line, Real-Time Process Gas Analysis. JO - Anal. Chem. VL - 74 IS - 15 PB - Society PY - 2002 SN - 0003-2700 ER - TY - JOUR AB - A new supersonic jet inlet system for resonance-enhanced multiphoton ionization time-of-flight mass spectrometry (REMPI-TOFMS), based on a fused-silica capillary with an integral nozzle has been developed. The new jet inlet system generates a supersonic molecular beam that originates in the center of the ion source of the time-of-flight mass spectrometer. Because of the design of the inlet system, high spatial overlap of sample and laser beam (i.e., increased detection sensitivity) and excellent let beam qualities are achieved with good adiabatic cooling properties of analyte molecules (i.e., considerably enhanced optical selectivity of the REMPI process). Furthermore, the inlet is very robust and chemically inert and contains no moving parts. As a result of these properties, the new inlet is perfectly suited for field applications of jet-REMPI. A first field application of a mobile supersonic jet-REMPI mass spectrometer equipped with the novel inlet technique is reported; namely, the concentration of monochlorobenzene, which is an indicator for the formation and emission of toxic polychlorinated dibenzo-p-dioxins/furans, PCDD/F) was measured on-line in the flue gas of a waste incineration plant. AU - Hafner, K.* AU - Zimmermann, R. AU - Rohwer, E.* AU - Dorfner, R. AU - Kettrup, A. C1 - 10372 C2 - 19853 SP - 4171-4180 TI - A capillary-based supersonic jet inlet system for resonance-enhanced laser ionization mass spectrometry : Principle and First on-line process analytical applications. JO - Anal. Chem. VL - 73 IS - 1 PB - American Chemical Society PY - 2001 SN - 0003-2700 ER - TY - JOUR AB - A newly developed compact and mobile time-of-flight mass spectrometer (TOFMS) for on-line analysis and monitoring of complex gas mixtures is presented. The instrument is designed for a (quasi-)simultaneous application of three ionization techniques that exhibit different ionization selectivities. The highly selective resonance-enhanced multiphoton ionization (REMPI) technique, using 266-nm UV laser pulses, is applied for selective and fragmentationless ionization of aromatic compounds at brace levels (parts-per-billion volume range). Mass spectra obtained using this technique show the chemical signature solely of monocyclic (benzene, phenols, etc.) and polycyclic (naphthalene, phenathrene, indol, etc.) aromatic species. Furthermore, the less selective but still fragmentationless single photon ionization (SPI) technique with 118-mn VUV laser pulses allows the ionization of compounds with an ionization potential below 10.5 eV. Mass spectra obtained using this technique show the profile of most organic compounds (aliphatic and aromatic species, like nonane, acetaldehyde, or pyrrol) and some inorganic compounds (e.g., ammonia, nitrogen monoxide). Finally, the nonselective ionization technique laser-induced electron-impact ionization (LEI) is applied. However, the sensitivity of the LEI technique is adjusted to be fairly low. Thus, the LEI signal in the mass spectra gives information on the inorganic bulk constituents of the sample (i.e., compounds such as water, oxygen, nitrogen, and carbon dioxide). Because the three ionization methods (REMPI, SPI, LEI) exhibit largely different ionization selectivities, the isolated application of each method alone solely provides specific mass spectrometric information about the sample composition. Special techniques have been developed and applied which allow the quasi-parallel use of all three ionization techniques for on-line monitoring purposes. Thus, a comprehensive characterization of complex samples is feasible jointly using the characteristic advantages of the three ionization techniques. Laboratory applications show results on rapid overview characterization of mineral oil-based fuels and coffee headspace. The first reported field applications include timely resolved on-line monitoring results on automobile exhausts and of waste incineration flue gas. AU - Mühlberger, F. AU - Zimmermann, R. AU - Kettrup, A. C1 - 10373 C2 - 19811 SP - 3590-3604 TI - A Mobile Mass Spectrometer for Comprehensive On-Line Analysis of Trace and Bulk Components of Complex Gas Mixtures : Parallel Application of the Laser-Based Ionization, Resonant Multiphoton Ionization, and Laser-Induced Electron Impact Ionization. JO - Anal. Chem. VL - 73 IS - 1 PB - American Chemical Society PY - 2001 SN - 0003-2700 ER - TY - JOUR AU - Heger, H.-J. AU - Zimmermann, R. AU - Dorfner, R. AU - Beckmann, M.* AU - Griebel, H.* AU - Kettrup, A. AU - Boesl, U.* C1 - 20835 C2 - 18891 SP - 46-57 TI - spectrometer. JO - Anal. Chem. VL - 71 PY - 1999 SN - 0003-2700 ER - TY - JOUR AB - A multicolumn method for the estimation of the octanol-air partition coefficient (K(OA)) of semivolatile compounds is described. The method is based on the retention time of a compound on gas chromatographic columns of different selectivity and polarity. Log K(OA) values of polychlorinated biphenyls (PCB) were estimated with the novel multicolumn method. The results were in excellent agreement with previously published data using a generator column method. Therefore, we used our multicolumn method to estimate K(OA) for more than 100 PCB congeners. AU - Zhang, X.* AU - Schramm, K.-W. AU - Henkelmann, B. AU - Klimm, C. AU - Kaune, A.* AU - Kettrup, A. AU - Peichang, L.* C1 - 21116 C2 - 19153 SP - 3834 TI - A method to estimate the octanol-air partition coefficient of semivolatile organic compounds. JO - Anal. Chem. VL - 71 IS - 17 PY - 1999 SN - 0003-2700 ER - TY - JOUR AB - The combination of gas chromatography (GC) and laser-based resonance-enhanced multiphoton ionization-time-of-flight mass spectrometry (REMPI-TOFMS) represents a three-dimensional analytical method, using the gas chromatographic retention time, the wavelength of the ionization laser for REMPI, and the molecular mass as analytical parameters. In this work, a novel analytical scheme for detection of chlorinated aromatic compounds, including isomeric ensembles, by GC/REMPI-TOFMS is presented. The concept uses an in-line hydrodechlorination catalyst for post- or precolumn derivatization of chlorinated aromatic compounds. The chlorinated aromatics are quantitatively reduced, forming their respective aromatic skeletons. These aromatic skeletons are detected selectively by REMPI-TOFMS. The first results for substance class selective detection of chlorinated benzene isomers are given, and potential applications in the field of the analysis of compounds such as polychlorinated dibenzo-p-dioxins and -furans are discussed. AU - Zimmermann, R. AU - Rohwer, E.R.* AU - Heger, H.J. C1 - 21045 C2 - 19085 SP - 4148-4153 TI - In-line catalytic derivatization method for selctive detection of chlorinated aromatics with a hyphenated gas chromatography/ Laser mass spectrometry technique : A concept for comprehensive detection of isomeric ensembles. JO - Anal. Chem. VL - 71 IS - 19 PY - 1999 SN - 0003-2700 ER - TY - JOUR AB - Capillary zone electrophoresis (CZE) was used to separate and determine simultaneously the pK1, pK2, and pI values of 12 environmentally relevant hydroxytriazines (hydroxymetabolites of atrazine, terbuthylazine, simazine, and propazine and four (arylamino)-s-triazines) and observe the effects of the alkylamino and arylamino substituents on the measured values. Capillary isoelectric focusing (CIEF) methods were developed to measure the pI of these compounds and compare those values with the CZE-measured pI's. CZE and CIEF can provide accurate pK and pI values reasonably fast, and pI values measured by the two techniques agree. Knowledge of the pK and pI values of hydroxytriazines is important for an understanding of the binding mechanisms of these molecules in environmental matrices. Because the hydroxytriazines may exist as a myriad of species-neutral, charged, zwitterionic, and keto-enol tautomeric-depending on structure and pH, we briefly addressed the existence of these species relative to their electrophoretic analysis. AU - Schmitt, P.* AU - Poiger, T.F.* AU - Simon, R.K. AU - Freitag, D. AU - Kettrup, A. AU - Garrison, A.W.* C1 - 33229 C2 - 35604 SP - 2559-2566 TI - Simultaneous determination of ionization constants and isoelectric points of 12 hydroxy-s-triazines by capillary zone electrophoresis and capillary isoelectric focusing. JO - Anal. Chem. VL - 69 IS - 13 PY - 1997 SN - 0003-2700 ER - TY - JOUR AU - Kettrup, A. AU - Kicinski, H.G.* AU - Masuch, G.* C1 - 34151 C2 - 40169 SP - 1047-1056 TI - Investigating the effect of hydrogen peroxide on Norway spruce trees. JO - Anal. Chem. VL - 63 IS - 21 PY - 1991 SN - 0003-2700 ER - TY - JOUR AB - We have compared the use of stable and radioactive isotopes for determining the concentration of tellurium in body fluids of animals and man, specifically in the blood plasma of rabbits. Particular effort has been devoted to developing a sample-processing technique that allows the total amount of tellurium and isotope ratios to be measured by graphite furnace atomic absorption spectrometry (GFAAS) and secondary ion mass spectrometry (SIMS), respectively. The procedure employed in the SIMS analysis is discussed in detail. Investigations on the plasma clearance and the fractional intestinal absorption were carried out on four rabbits. Tracer solutions containing stable tellurium enriched in 124Te or 126Te and radioactive tellurium (121mTe or 123mTe) were administered by gavage and/or intravenously. Blood samples were drawn during the first 2 days after application. The activity of the separated plasma was measured by standard γ ray spectrometry. After wet ashing and solvent extraction with MIBK the samples were analyzed for stable tellurium. A detection limit of 1 ng/mL of plasma could be achieved with GFAAS. For SIMS analysis the processed samples were deposited on high-purity graphite backings. Reliable isotope ratios could be determined with sample fractions containing 1 ng of tellurium or even less. The results obtained by applying stable isotopes were found to be in good agreement with the data achieved by using radioactive tracers. Studies on the intestinal absorption and the metabolic behavior of tellurium in human volunteers may thus be performed with stable isotopes. AU - Kron, T.* AU - Wittmaack, K. AU - Hansen, C.S. AU - Werner, E.E. C1 - 40794 C2 - 38043 SP - 2603-2607 TI - Stable isotopes for determining biokinetic parameters of tellurium in rabbits. JO - Anal. Chem. VL - 63 IS - 22 PY - 1991 SN - 0003-2700 ER - TY - JOUR AB - A short reactor column containing horseradish peroxidase immobilized on controlled-pore glass can replace the continuous flow of a solution of the enzyme in the detection of hydroperoxides in an HPLC system, thereby allowing the elimination of one of the three pumps previously required. The immobilized enzyme catalyzes the oxidation by hydroperoxides of (p-hydroxyphenyl)acetic acid to a fluorescent biphenyl derivative, which is the species actually detected. The simplified HPLC system is optimized for the analyste of H2O2 and a number of alkyl and 1-hydroxyalkyl hydroperoxides. The detection limit of the H2O2 analysis is 5 × 10-8 M (34 pg in a 20-μL sample), and the response is linear down to at least 10-7 M. AU - Kurth, H.H. AU - Gäb, S. AU - Turner, W.V. AU - Kettrup, A. C1 - 40780 C2 - 38874 SP - 2586-2589 TI - A high-performance liquid chromatography system with an immobilized enzyme reactor for detection of hydrophilic organic peroxides. JO - Anal. Chem. VL - 63 IS - 22 PY - 1991 SN - 0003-2700 ER - TY - JOUR AB - The kinetics of differentially small contact ion exchange processes of two adjacent resin ion exchanger beads in pure water was investigated, using radioactive tracers. Interruption tests and determination of the rates, as a function of the force with which the beads were pressed together, indicate that diffusion of the ions across the aqueous film between the beads was the rate-determining step. The experiments show that the half-times of the exchange Cs+-Na+ and Cs+-H+ decrease, if the initial Cs+ concentration in the particles is increased. With the help of the theory developed, the rate coefficients of these processes can be evaluated from the experiments. It is found that they depend strongly on the ionic composition in the case of the exchange Cs+-H+ but are almost constant when Cs+ is exchanged vs. Na+. The rate coefficients of differentially small contact ion exchange processes were closely related to those of isotopic contact exchange processes. With the help of the rate coefficients of differential exchange processes the rates observed for nondifferential exchange processes are discussed. AU - Bunzl, K.W. AU - Schultz, W.W. C1 - 33280 C2 - 38609 SP - 272-277 TI - Kinetics of differentially small conversions in contact isotopic and contact ion exchange. JO - Anal. Chem. VL - 54 IS - 2 PY - 1982 SN - 0003-2700 ER - TY - JOUR AB - This paper provides a method to directly determine beryllium in the parts-per-billion range in three standard reference materials by inductively coupled plasma (ICP) emission spectroscopy. Wavelength selection and instrument operating parameters were studied. It was found that the most sensitive wavelength, 313.04 nm, of beryllium is located between two unknown peaks, probably due to the OH molecule. Because of the spectral interference from the unknown peaks it is impossible to determine the beryllium in the sub-parts-per-billion range using the 313.04-nm analytical line. Iron, as present in biological samples, has severe spectral interferences on the Be 234.86-nm line. Due to these effects the emission line at 313.11 nm was selected as the analytical line for Be. The results obtained by the standard addition method and the calibration curve in aqueous solution were compared with the certified value of one standard reference material. The slopes of the two curves were equal. The content of Be In NBS 1571 (orchard leaves) was determined to be 0.0143 μg/g, which is different from the certified value 0.027 μg/g. AU - Schramel, P. AU - Li-Qiang, X. C1 - 42201 C2 - 38284 SP - 1333-1336 TI - Determination of beryllium in the parts-per-billion range in three standard reference materials by inductively coupled plasma atomic emission spectrometry. JO - Anal. Chem. VL - 54 IS - 8 PY - 1982 SN - 0003-2700 ER - TY - JOUR AB - The nitrogen content of 38 and 34 grain samples, in two separate experiments, was determined with the conventional micro-Kjeldahl method and with the indophenol colour reaction, manually as well as with an autoanalyzer. Values were found to be comparable. Details are presented for a simple and highly reproducible absorptiometric technique that is four times as rapid as conventional Kjeldahl. It should prove popular with plant breeders, agronomists and crop physiologists, who are interested in rapid and direct screening for nitrogen content but lack funds for automated equipment. AU - Kaul, A.K. AU - Sharma, T.R. C1 - 42445 C2 - 37907 SP - 133-138 TI - Rapid determination of nitrogen content in grain-meal samples with alkali-phenol reaction, manually and with an autoanalyzer. JO - Anal. Chem. VL - 280 IS - 2 PY - 1969 SN - 0003-2700 ER -