Characterisation and field deployment of a novel quantitative Time-of-Flight Aerosol Mass Spectrometer (ToF-AMS)

Das Time-of-Flight Aerosol Mass Spectrometer (ToF-AMS) der Firma Aerodyne ist eine Weiterentwicklung des Aerodyne Aerosolmassenspektrometers (Q-AMS). Dieses ist gut charakterisiert und kommt weltweit zum Einsatz. Beide Instrumente nutzen eine aerodynamische Linse, aerodynamische Partikelgrößenbestimmung, thermische Verdampfung und Elektronenstoß-Ionisation. Im Gegensatz zum Q-AMS, wo ein Quadrupolmassenspektrometer zur Analyse der Ionen verwendet wird, kommt beim ToF-AMS ein Flugzeit-Massenspektrometer zum Einsatz. In der vorliegenden Arbeit wird anhand von Laborexperimenten und Feldmesskampagnen gezeigt, dass das ToF-AMS zur quantitativen Messung der chemischen Zusammensetzung von Aerosolpartikeln mit hoher Zeit- und Größenauflösung geeignet ist. Zusätzlich wird ein vollständiges Schema zur ToF-AMS Datenanalyse vorgestellt, dass entwickelt wurde, um quantitative und sinnvolle Ergebnisse aus den aufgenommenen Rohdaten, sowohl von Messkampagnen als auch von Laborexperimenten, zu erhalten. Dieses Schema basiert auf den Charakterisierungsexperimenten, die im Rahmen dieser Arbeit durchgeführt wurden. Es beinhaltet Korrekturen, die angebracht werden müssen, und Kalibrationen, die durchgeführt werden müssen, um zuverlässige Ergebnisse aus den Rohdaten zu extrahieren. Beträchtliche Arbeit wurde außerdem in die Entwicklung eines zuverlässigen und benutzerfreundlichen Datenanalyseprogramms investiert. Dieses Programm kann zur automatischen und systematischen ToF-AMS Datenanalyse und –korrektur genutzt werden.

Phase contrast and time-of-flight magnetic resonance angiography of the intracerebral arteries at 1.5, 3 and 7 T

Time-of-flight (ToF) and phase contrast (PC) magnetic resonance angiographies (MRAs) are noninvasive applications to depict the cerebral arteries. Both approaches can image the cerebral vasculature without the administration of intravenous contrast. Therefore, it is used in routine clinical evaluation of cerebrovascular diseases, e.g., aneurysm and arteriovenous malformations. However, subtle microvascular disease usually cannot be resolved with standard, clinical-field-strength MRA. The purpose of this study was to compare the ability of ToF and PC MRA to visualize the cerebral arteries at increasing field strengths.

Fenofibrate metabolism in the cynomolgus monkey using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics

Fenofibrate, widely used for the treatment of dyslipidemia, activates the nuclear receptor, peroxisome proliferator-activated receptor alpha. However, liver toxicity, including liver cancer, occurs in rodents treated with fibrate drugs. Marked species differences occur in response to fibrate drugs, especially between rodents and humans, the latter of which are resistant to fibrate-induced cancer. Fenofibrate metabolism, which also shows species differences, has not been fully determined in humans and surrogate primates. In the present study, the metabolism of fenofibrate was investigated in cynomolgus monkeys by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS)-based metabolomics. Urine samples were collected before and after oral doses of fenofibrate. The samples were analyzed in both positive-ion and negative-ion modes by UPLC-QTOFMS, and after data deconvolution, the resulting data matrices were subjected to multivariate data analysis. Pattern recognition was performed on the retention time, mass/charge ratio, and other metabolite-related variables. Synthesized or purchased authentic compounds were used for metabolite identification and structure elucidation by liquid chromatographytandem mass spectrometry. Several metabolites were identified, including fenofibric acid, reduced fenofibric acid, fenofibric acid ester glucuronide, reduced fenofibric acid ester glucuronide, and compound X. Another two metabolites (compound B and compound AR), not previously reported in other species, were characterized in cynomolgus monkeys. More importantly, previously unknown metabolites, fenofibric acid taurine conjugate and reduced fenofibric acid taurine conjugate were identified, revealing a previously unrecognized conjugation pathway for fenofibrate.

Increasing Realism and Supporting Content Planning for Dynamic Scenes in a Mixed Reality System incorporating a Time-of-Flight Camera

For broadcasting purposes MIXED REALITY, the combination of real and virtual scene content, has become ubiquitous nowadays. Mixed Reality recording still requires expensive studio setups and is often limited to simple color keying. We present a system for Mixed Reality applications which uses depth keying and provides threedimensional mixing of real and artificial content. It features enhanced realism through automatic shadow computation which we consider a core issue to obtain realism and a convincing visual perception, besides the correct alignment of the two modalities and correct occlusion handling. Furthermore we present a possibility to support placement of virtual content in the scene. Core feature of our system is the incorporation of a TIME-OF-FLIGHT (TOF)-camera device. This device delivers real-time depth images of the environment at a reasonable resolution and quality. This camera is used to build a static environment model and it also allows correct handling of mutual occlusions between real and virtual content, shadow computation and enhanced content planning. The presented system is inexpensive, compact, mobile, flexible and provides convenient calibration procedures. Chroma-keying is replaced by depth-keying which is efficiently performed on the GRAPHICS PROCESSING UNIT (GPU) by the usage of an environment model and the current ToF-camera image. Automatic extraction and tracking of dynamic scene content is herewith performed and this information is used for planning and alignment of virtual content. An additional sustainable feature is that depth maps of the mixed content are available in real-time, which makes the approach suitable for future 3DTV productions. The presented paper gives an overview of the whole system approach including camera calibration, environment model generation, real-time keying and mixing of virtual and real content, shadowing for virtual content and dynamic object tracking for content planning.

Performance evaluation of a miniature laser ablation time-of-flight mass spectrometer designed for in situ investigations in planetary space research

Key performance features of a miniature laser ablation time-of-flight mass spectrometer designed for in situ investigations of the chemical composition of planetary surfaces are presented. This mass spectrometer is well suited for elemental and isotopic analysis of raw solid materials with high sensitivity and high spatial resolution. In this study, ultraviolet laser radiation with irradiances suitable for ablation (< 1 GW/cm2) is used to achieve stable ion formation and low sample consumption. In comparison to our previous laser ablation studies at infrared wavelengths, several improvements to the experimental setup have been made, which allow accurate control over the experimental conditions and good reproducibility of measurements. Current performance evaluations indicate significant improvements to several instrumental figures of merit. Calibration of the mass scale is performed within a mass accuracy (Δm/m) in the range of 100 ppm, and a typical mass resolution (m/Δm) ~600 is achieved at the lead mass peaks. At lower laser irradiances, the mass resolution is better, about (m/Δm) ~900 for lead, and limited by the laser pulse duration of 3 ns. The effective dynamic range of the instrument was enhanced from about 6 decades determined in previous study up to more than 8 decades at present. Current studies show high sensitivity in detection of both metallic and non-metallic elements. Their abundance down to tens of ppb can be measured together with their isotopic patterns. Due to strict control of the experimental parameters, e.g. laser characteristics, ion-optical parameters and sample position, by computer control, measurements can be performed with high reproducibility. Copyright © 2012 John Wiley & Sons, Ltd.

Protein quaternary structure determination using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and chemical crosslinking

A means of analyzing protein quaternary structure using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI MS) and chemical crosslinking was evaluated. Proteins of known oligomeric structure, as well as monomeric proteins, were analyzed to evaluate the method. The quaternary structure of proteins of unknown or uncertain structure was investigated using this technique. The stoichiometry of recombinant E. coli carbamoyl phosphate synthetase and recombinant human farnesyl protein transferase were determined to be heterodimers using glutaraldehyde crosslinking, agreeing with the stoichiometry found for the wild type proteins. The stoichiometry of the gamma subunit of E. coli DNA polymerase III holoenzyme was determined in solution without the presence of other subunits to be a homotetramer using glutaraldehyde crosslinking and MALDI MS analysis. Chi and psi subunits of E. coli DNA polymerase III subunits appeared to form a heterodimer when crosslinked with heterobifunctional photoreactive crosslinkers.^ Comparison of relative % peak areas obtained from MALDI MS analysis of crosslinked proteins and densitometric scanning of silver stained sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) gels showed excellent qualitative agreement for the two techniques, but the quantitative analyses differed, sometimes significantly. This difference in quantitation could be due to SDS-PAGE conditions (differential staining, loss of sample) or to MALDI MS conditions (differences in ionization and/or detection). Investigation of pre-purified crosslinked monomers and dimers recombined in a specific ratio revealed the presence of mass discrimination in the MALDI MS process. The calculation of mass discrimination for two different MALDI time-of-flight instruments showed the loss of a factor of approximately 2.6 in relative peak area as the m/z value doubles over the m/z range from 30,000 to 145,000 daltons.^ Indirect symmetry was determined for tetramers using glutaraldehyde crosslinking with MALDI MS analysis. Mathematical modelling and simple graphing allowed the determination of the symmetry for several tetramers known to possess isologous D2 symmetry. These methods also distinguished tetramers that did not fit D2 symmetry such as apo-avidin. The gamma tetramer of E. coli DNA polymerase III appears to have isologous D2 symmetry. ^

MR Angiography at 3 Tesla to Assess Proximal Internal Carotid Artery Stenoses: Contrast-Enhanced or 3D Time-of-Flight MR Angiography?

PURPOSE The aim of this study was to compare the diagnostic accuracy of 3D time-of-flight (TOF-MRA) and contrast-enhanced (CE-MRA) magnetic resonance angiography at 3 T for detection and quantification of proximal high-grade stenosis using multidetector computed tomography angiography (MDCTA) as reference standard. METHODS The institutional ethics committee approved this prospective study. A total of 41 patients suspected of having internal carotid artery (ICA) stenosis underwent both MDCTA and MRA. CE-MRA and TOF-MRA were performed using a 3.0-T imager with a dedicated eight-element cervical coil. ICA stenoses were measured according to the North American Symptomatic Carotid Endarterectomy Trial criteria and categorized as 0-25 % (minimal), 25-50 % (mild), 50-69 % (moderate), 70-99 % (high grade), and 100 % (occlusion). Sensitivity and specificity for the detection of high-grade ICA stenoses (70-99 %) and ICA occlusions were determined. In addition, intermodality agreement was assessed with κ-statistics for detection of high-grade ICA stenoses (70-99 %) and ICA occlusions. RESULTS A total of 80 carotid arteries of 41 patients were reviewed. Two previously stented ICAs were excluded from analysis. On MDCTA, 7 ICAs were occluded, 12 ICAs presented with and 63 without a high-grade ICA stenosis (70-99 %). For detecting 70-99 % stenosis, both 3D TOF-MRA and CE-MRA were 91.7 % sensitive and 98.5 % specific, respectively. Both MRA techniques were highly sensitive (100 %), and specific (CE-MRA, 100 %; TOF-MRA, 98.7 %) for the detection of ICA occlusion. However, TOF-MRA misclassified one high-grade stenosis as occlusion. Intermodality agreement for detection of 70-99 % ICA stenoses was excellent between TOF-MRA and CE-MRA [κ = 0.902, 95 % confidence interval (CI) = 0.769-1.000], TOF-MRA and MDCTA (κ = 0.902, 95 % CI = 0.769-1.000), and CE-MRA and MDCTA (κ = 0.902, 95 % CI = 0.769-1.000). CONCLUSION Both 3D TOF-MRA and CE-MRA at 3 T are reliable tools for detecting high-grade proximal ICA stenoses (70-99 %). 3D TOF-MRA might misclassify pseudo-occlusions as complete occlusions. If there are no contraindications for CE-MRA, CE-MRA is recommended as primary MR imaging modality.

A new Time-Of-Flight Mass Spectrometer (TOF-MS) for noble gas analysis

Noble gas analysis in early solar system materials, which can provide valuable information about early solar system processes and timescales, are very challenging because of extremely low noble gas concentrations (ppt). We therefore developed a new compact sized (33 cm length, 7.2cm diameter, 1.3 L internal volume) Time-of-Flight (TOF) noble gas mass spectrometer for high sensitivity. We call it as Edel Gas Time-of-flight (EGT) mass spectrometer. The instrument uses electron impact ionization coupled to an ion trap, which allows us to ionize and measure all noble gas isotopes. Using a reflectron set-up improves the mass resolution. In addition, the reflectron set-up also enables some extra focusing. The detection is via MCPs and the signals are processed either via ADC or TDC systems. The objective of this work is to understand the newly developed Time-Of-Flight (TOF) mass spectrometer for noble gas analysis in presolar grains of the meteorites. Chapter 1 briefly introduces the basic idea and importance of the instrument. The physics relevant to time-of-flight mass spectrometry technique is discussed in the Chapter 2 and Chapter 3 will present the oxidation technique of nanodiamonds of the presolar grains by using copper oxide. Chapter 4 will present the details about EGT data analysis software. Chapter 5 and Chapter 6 will explain the details about EGT design and operation. Finally, the performance results will be presented and discussed in the Chapter 7, and whole work is summarized in Chapter 8 and also outlook of the future work is given.