Spelling suggestions: "subject:"amaging mass spectrometry"" "subject:"amaging mass pectrometry""
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Molecular imaging using femtosecond laser pulsesDooley, Patrick W. Corkum, Paul B. January 2003 (has links)
Thesis (Ph.D.)--McMaster University, 2004. / Supervisor: Paul B. Corkum. Includes bibliographical references.
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The Expression Profile of Phosphatidylinositol in High Spatial Resolution Imaging Mass Spectrometry as a Potential Biomarker for Prostate Cancer / 高解像度質量顕微鏡を用いたホスファチジルイノシトールの発現プロファイルは前立腺癌のバイオマーカーとなり得るGoto, Takayuki 23 March 2016 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第19552号 / 医博第4059号 / 新制||医||1012(附属図書館) / 32588 / 京都大学大学院医学研究科医学専攻 / (主査)教授 山田 泰広, 教授 藤田 潤, 教授 松田 道行 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
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Novel methods in imaging mass spectrometry and ion time-of-flight detectionWinter, Benjamin January 2014 (has links)
Imaging mass spectrometry (IMS) in microscope mode allows the spatially resolved molecular constitution of a large sample section to be analysed in a single experiment. If performed in a linear mass spectrometer, the applicability of microscope IMS is limited by a number of factors: the low mass resolving power of the employed ion optics; the time resolution afforded by the scintillator screen based particle detector and the multi-hit capability, per pixel, of the employed imaging sensor. To overcome these limitations, this thesis concerns the construction of an advanced ion optic employing a pulsed extraction method to gain a higher ToF resolution, the development of a bright scintillator screen with short emission lifetime, and the application of the Pixel Imaging Mass Spectrometry (PImMS) sensor with multi-mass imaging and time stamping capabilities. Initial experimental results employing a three electrode ion optic to spatially map ions emitted from a sample surface are presented. By applying a static electric potential a time-of-flight resolution of t/2Δt=54 and a spatial resolution of 20 μm are determined across a field-of-view of 4 mm diameter. While the moderate time-of-flight resolution only allows particles separated by a few Dalton to be distinguished, the instrument is used to demonstrate the multi-mass imaging capabilities of the PImMS sensor when being applied to image grid structures or tissue samples. An improved time-of-flight resolution is achieved by post extraction differential acceleration of a selected range of ions (up to 100 Da) using a newly developed five electrode ion optic. This modification is shown to correct the initial velocity spread of the ions coming off the sample surface, which yields an enhanced time-of-flight resolution of t/2Δt=2000 . The spatial resolution of the instrument is found to be 20 μm across a field-of-view of 4 mm. Adjusting the extraction field strength applied to the ion optic of the constructed mass spectrometer allows the optimised mass range to be tuned to any mass of interest. Ion images are recorded for various samples with comparable spatial and ToF resolution. Hence, studies on tissue sections and multi sample arrays become accessible with the improved design and operational principle of the microscope mode IMS instrument. A fast and efficient conversion of impinging ions into detectable flashes of light, which can consequently be recorded by a fast imaging sensor, is essential to maintain the achievable time-of-flight and spatial resolution of the IMS instrument constructed. In order to find a suitable fast and bright scintillator to be applied in a microchannel based particle detector, various inorganic and organic substances are characterised in terms of their emission properties following electron excitation. Poly-para-phenylene laser dye screens are found to show an outstanding performance among all substances analysed. An emission life time of below 4 ns and a brightness exceeding that of a P47 screen (industry standard) by a factor 2× is determined. No signal degradation is observed over an extended period, and the spatial resolution is found to be comparable to commercial imaging detectors. Hence, these scintillator screens are fully compatible with any ion imaging application requiring a high time resolution. In a further series of mass spectrometric experiments, ions are accelerated onto a scintillator mounted in front of a multi pixel photon counter. The charged particle impact stimulated the emission of a few photons, which are collected by the fast photon counter. Poly-para-phenylene laser dyes again show an outstanding efficiency for the conversion of ions into photons, resulting in a signal enhancement of up to 5× in comparison to previous experiments, which employed an inorganic LYSO scintillator.
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Etude de la pénétration et du métabolisme intra-tumoral de l'oxaliplatine : proposition d'un nouveau mécanisme d'action / Study of the intra-tumoral metabolism of oxaliplatine : proposition of a new mechanism of actionBouslimani, Amina 12 September 2012 (has links)
L'oxaliplatine est un médicament anticancéreux utilisé dans la chimiohyperthermie intrapéritonéale (CHIP), pour le traitement des carcinoses péritonéales (CP). En dépit de l'efficacité de la CHIP, l'infiltration de l'oxaliplatine dans les tumeurs traitées est très peu connue. L'étude de la pénétration du médicament dans des tumeurs prélevées à partir de patients atteints de CP et traités CHIP, a fait l'objet de la première partie du projet de recherche. Par ailleurs, les mécanismes de transport du médicament jusqu'à l'ADN cellulaire n'ont pas été bien déterminés. Néanmoins, des hypothèses suggèrent que certains métabolites soufrés de l'oxaliplatine pourraient constituer des "formes réservoirs", capables de transporter le médicament jusqu'à l'ADN. La deuxième partie du projet a consisté à étudier de manière plus approfondie la réactivité d'un des métabolites soufrés de l'oxaliplatine. Nous avons développé une méthode d'imagerie par spectrométrie de masse MALDI/TOF, qui permet de déterminer la distribution de l'oxaliplatine et ses métabolites, dans les tumeurs humaines traitées CHIP. Nos résultats révèlent une pénétration du médicament limitée à quelques millimètres et une détection exclusive du métabolite oxaliplatine-méthionine (Ox-M) : un métabolite considéré « inactif », puisqu'il serait stable et incapable d'interagir avec l'ADN. Afin de démontrer la réactivité de ce métabolite, nous avons tout d'abord étudié son interaction avec les cibles de l'oxaliplatine, à savoir la guanine et l'ADN. Nos résultats démontrent la capacité de Ox-M à libérer la partie réactive de la molécule pour interagir avec la guanine, et former des adduits sur des duplexes d'oligonucléotides qui miment la structure de l'ADN. De plus, les adduits formés par Ox-M induisent un arrêt de l'élongation de l'ADN. Ces résultats démontrent la réactivité du métabolite Ox-M de l'oxaliplatine, et suggèrent son implication dans une nouvelle voie active du médicament. / Oxaliplatin is an anticancer drug used in Heated Intraoperative Chemotherapy (HIPEC) to treat peritoneal carcinomatosis. In spite of HIPEC efficiency, oxaliplatin penetration in treated tumors is not very well known. Study of oxaliplatin penetration in tumors of patients suffering from CP and treated with HIPEC, was the first part of the research project. Furthermore, transport mechanisms of the drug to cell DNA are not well established. Nevertheless, hypotheses suggest that some sulfur metabolites of oxaliplatin, could constitute "tanks" which are able to transport drug until DNA. The second part of this project aimed to study more deeply the reactivity of oxaliplatin sulfur metabolites. We have developed a MALDI imaging mass spectrometry method, which allows studying the distribution of oxaliplatin and its metabolites in human tumors. Our results reveal a drug penetration limited to few millimeters and an exclusive detection of the oxaliplatin- methionine metabolite (Ox-M): a supposed "Inactive" metabolite, because of its stability that prevents its interaction with DNA. To provide evidence of Ox-M reactivity, we studied its interaction with oxaliplatin targets: guanine and DNA. Our results showed that Ox-M is able to release the active part of the molecule to interact with guanine, and to form adducts on oligonucleotides duplexes that mimic DNA structure. Moreover, Ox-M adducts induce an arrest of DNA elongation. These results suggest the implication of Ox-M in a new active pathway of oxaliplatin cytotoxicity.
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Molecular Signatures of Neuropathic Pain : Revealing Pain-Related Signaling Processes in Spinal Cord Using Mass Spectrometric MethodologiesSui, Ping January 2015 (has links)
In this thesis, the detection of global proteomics alteration and changes in neuropeptide distribution caused by neuropathic pain in rat spinal cord tissue was the main focus. Neuropathic pain (NP) is a major clinical syndrome caused by disease or dysfunction of the nervous system and often mediated by neuronal networks in the spinal cord. The estimated prevalence of NP is 6-8% in general population. Only in the United States, the indirect cost associated with chronic pain has been estimated to 100 billion dollars each year and NP substantially contributes to this cost. So far, the underlying mechanisms of NP are not well understood. Proteomics techniques are commonly used in biology system studies, due to its high throughput, capability of unbiased analysis and sensitivity. It builds up a bridge to link genes, peptides, proteins, and the disease. Two proteomic/peptidomic approaches were developed, evaluated and discussed in this thesis. Both of them were further applied in the studies of neuropathic pain. First approach is a quantitative proteomic approach using liquid chromatography combined with Fourier transform mass spectrometry (LC-FTMS), which is developed for quantitative analysis of proteins originated from small central nervous system (CNS) samples. This approach was successfully applied in the study of the rat spinal cord tissue proteome in a neuropathic pain model. Another approach is using matrix assisted laser desorption ionization mass spectrometry (MALDI-MS) for the visualization of the distribution of neuropeptides in rat spinal cord, which in the future will be applied in investigating the ongoing signal transmission under neuropathic pain conditions. Results provided by these two methods are of high importance for the general understanding of the underlying pathophysiological mechanisms and potential identification of new targets for novel treatment of neuropathic pain.
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Extracellular N-acetylaspartylglutamate released in the nucleus accumbens modulates the pain sensation: Analysis using a microdialysis/mass spectrometry integrated systemWatanabe, Moe, Sugiura, Yuki, Sugiyama, Eiji, Narita, Michiko, Navratilova, Edita, Kondo, Takashige, Uchiyama, Naohiko, Yamanaka, Akihiro, Kuzumaki, Naoko, Porreca, Frank, Narita, Minoru 08 January 2018 (has links)
Various small molecules act as neurotransmitters and orchestrate neural communication. Growing evidence suggests that not only classical neurotransmitters but also several small molecules, including amino acid derivatives, modulate synaptic transmission. As conditions of acute and chronic pain alter neuronal excitability in the nucleus accumbens, we hypothesized that small molecules released in the nucleus accumbens might play important roles in modulating the pain sensation. However, it is not easy to identify possible pain modulators owing to the absence of a method for comprehensively measuring extracellular small molecules in the brain. In this study, through the use of an emerging metabolomics technique, namely ion chromatography coupled with high-resolution mass spectrometry, we simultaneously analyzed the dynamics of more than 60 small molecules in brain fluids collected by microdialysis, under both the application of pain stimuli and the administration of analgesics. We identified N-acetylaspartylglutamate as a potential pain modulator that is endogenously released in the nucleus accumbens. Infusion of N-acetylaspartylglutamate into the nucleus accumbens significantly attenuated the pain induced by the activation of sensory nerves through optical stimulation. These findings suggest that N-acetylaspartylglutamate released in the nucleus accumbens could modulate pain sensation.
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The feasibility of Fourier transform infrared imaging spectroscopy in discriminating benign prostatic hyperplasia from prostate cancer in blood serum samplesMonjardez, Geraldine January 2013 (has links)
The feasibility of Fourier transform infrared (FTIR)-imaging spectroscopy as a tool to discriminate samples from patients suffering from benign prostatic hyperplasia (BPH) and prostate cancer (CaP) samples in blood serum was investigated. Prostate cancer is known to be an age related disease, with the risk of developing the disease dramatically increasing in men past forty years old. Currently the PSA blood test is notoriously unreliable and is non specific for CaP thus leading to overtreatment of the disease. It is important therefore to develop diagnostic method that is non-invasive, reliable, and specific for CaP.In order to achieve the objective of establishing a robust protocol, which could be applied to a clinical study, obtaining optimal sample preparation for the FTIR analysis of serum smears, had to be achieved. A protocol was developed to prepare the serum samples prior to their FTIR analysis. First, the samples were centrifuged with ultrafiltration devices of different sizes to obtain several fractions which were then smeared to obtain thin films of serum. The spectra from the larger (>100 kDa components) and medium (containing the 10–100 kDa components) fractions were utilised for both a pilot and a clinical study, while the spectra from the smaller fractions (containing the 3–10 and <3 kDa components) were affected by fringing and could therefore not be used. A major novelty of this project involved the application of FTIR-imaging to the analysis of serum smears. The use of the Focal Plane Array detector system enabled the collection of a spectral image containing 16,384 spectra, on which a Quality Testing and pre-processing techniques were applied to select the “good spectra” and reject the spectra that failed the Quality Test. Several types of substrates were assessed to determine the most appropriate for the analysis of the smears and it was established that the spectra obtained from the serum smeared on CaF2 windows gave the most reproducible results. 5 BPH and 5 CaP samples were analysed for the pilot study following the developed protocol. While no clear separation was observed in the Principal Component Analysis (PCA) plots between the BPH and the cancerous samples, a trend emerged throughout the results, with the CaP samples clustering together and the BPH samples scattered around them. A larger clinical study was conducted with 60 BPH samples and 60 CaP samples. PCA was applied on the “good spectra” and while the over 100 kDa fraction did not show a clear separation between the two types of samples, the 10–100 kDa fraction showed a distinct classification between the BPH and CaP samples. An artificial neural network was then applied to create a model using patients from the database used for the PCA analysis to determine whether the discrimination between the two types of samples could be increased or highlight different classification trends. For the >100 kDa fraction, the sensitivity value was calculated to be 97.8% and the specificity value was calculated to be 44.3% while the sensitivity and the specificity value for the 10 to 100 kDa fraction were calculated to be 78.9% and 60% respectively. A complementary study using mass spectrometry was carried out on healthy and diseased samples to identify the components contained within the different fractions and determine whether they could be correlated with the components identified from the spectral features of the FTIR data. While no quantitative information was obtained from this study, the components found in the different fractions were identified, confirming the results of the FTIR studies.
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Zpracování a visualizace hmotnostních spekter / Processing and Visualization of Mass SpectrumsBeneš, Ondřej January 2014 (has links)
One of new techniques in the field of analytical chemistry, which has more and more practical use, is mass spectrometry imaging. With its ability to record representation of substances in samples during the tissue analyze arise problem with a lot of output data which needs to be handled programmatically. The goal of this work is to create an software for processing and visualization data of new standard imzML. As a part of the work, the field of mass spectrometry, primarily MALDI TOF mass spectrometry, is briefly introduced. There are also introduced some methods for mass spectrometry data preprocessing. The work also contains a summary of current state of available software for processing and visualization of mass spectrometry data. With requests from cooperating laboratory a novel software is designed and implemented, which besides the visualization itself, can preprocess the data for example data smoothing with Savitzky-Golay method, internal calibration or peak detection with continuous wavelet transformation. The software was successfully tested on real data sets.
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High-resolution imaging mass spectrometry reveals detailed spatial distribution of phosphatidylinositols in human breast cancer / 高解像度質量顕微鏡にて明らかになったヒト乳癌組織中のフォスファチジルイノシトールの微細な空間分布Kawashima, Masahiro 24 March 2014 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第18154号 / 医博第3874号 / 新制||医||1002(附属図書館) / 31012 / 京都大学大学院医学研究科医学専攻 / (主査)教授 武藤 学, 教授 岩田 想, 教授 松田 道行 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM
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Surface characterization of biomass by imaging mass spectrometryJung, Seokwon 13 November 2012 (has links)
Lignocellulosic biomass (e.g., non food-based agricultural resides and forestry wastes) has recently been promoted for use as a source of bioethanol instead of food-based materials (e.g., corn and sugar cane), however to fully realize these benefits an improved understanding of lignocellulosic recalcitrance must be developed. The primary goal of this thesis is to gain fundamental knowledge about the surface of the plant cell wall, which is to be integrated into understanding biomass recalcitrance. Imaging mass spectrometry by TOF-SIMS and MALDI-IMS is applied to understand detailed spatial and lateral changes of major components in the surface of biomass under submicron scale.
Using TOF-SIMS analysis, we have demonstrated a dilute acid pretreated poplar stem represented chemical differences between surface and bulk compositions. Especially, abundance of xylan was observed on the surface while sugar profile data showed most xylan (ca. 90%) removed from the bulk composition. Water only flowthrough pretreated poplar also represented difference chemistry between surface and bulk, which more cellulose revealed on the surface compared to bulk composition. In order to gain the spatial chemical distribution of biomass, 3-dimensional (3D) analysis of biomass using TOF-SIMS has been firstly introduced in the specific application of understanding recalcitrance. MALDI-IMS was also applied to visualize different molecular weight (e.g., DP) of cellulose oligomers on the surface of biomass.
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