Interaction agrégats-surface. Spectrométrie de masse par temps de vol et application analytique à des études sur des médicaments et sur la météorite Paris

Le Lebanese Atomic Energy Commission (LAEC) poursuit un programme de développement des techniques analytiques pour compléter l analyse par faisceau d ions (IBA). Il a décidé de s équiper d un spectromètre de masse couplée à l imagerie 2D puis récemment 3D avec l acquisition d un spectromètre de masse IONTOF V équipé de deux colonnes ioniques délivrant des faisceaux d agrégats de bismuth et d argon. Dans ce cadre, mon sujet de thèse a porté sur l'optimisation de l instrument nouvellement acquis pour l analyse d échantillons contenant des composés organiques. Les premiers sujets de recherche sont la mise au point du protocole d analyse quantitative de médicaments en utilisant la technique cluster-SIMS-imaging et l analyse de la météorite Paris pour localiser la matière organique et déterminer sa composition. Dans les deux cas une approche multi-technique a été utilisée: IBA au LAEC, -Raman et -IR autour des équipements de Soleil et PIXE réalisée auprès de l accélérateur AGLAE (Centre de recherche et de restauration des musées de France, C2RMF).L analyse de médicaments a été initiée au Liban en collaboration avec un fabricant local de produits pharmaceutiques (Mediphar Laboratories) dans le but d établir de nouveaux procédés de contrôle qualité de produits finis. Mon étude a montré la complexité du dosage de médicament due à la présence de plusieurs molécules actives (Principe Actif, PA) et de substances organiques et minérales inactives (excipients) mélangées dans des conditions secrètes. Les effets de matrice sont dominants et modifient l émission ionique conduisant à des erreurs systématiques importantes. Cette complexité a été analysée avec l étude du Fludinium possédant deux PAs. Les résultats de cette étude ont permis d obtenir la première courbe d étalonnage du rapport des deux PAs et de quantifier ceux-ci dans les conditions du médicament commercial. Le protocole pour effectuer cette courbe d étalonnage et les contrôles qualité ont été déterminés. Ceux-ci incorporeront une analyse en profil pour contrôler l homogénéité des échantillons et l obtention d étalons produits par le fabricant en suivant ses processus de fabrication. En effet, les expériences ont montré que la réalisation du médicament en laboratoire à partir de ses éléments (PAs et excipients) ne donnait pas la même réponse ionique que le médicament commercial. L analyse de la météorite Paris a été initiée par une collaboration avec une équipe de l Institut d Astrophysique Spatial d Orsay impliquée dans l exobiologie et la recherche des premières molécules pré-biotiques dans des échantillons extraterrestres. Le but des recherches est de caractériser la matière organique représentant quelques pourcents en poids dans une matrice minérale complexe, sans utiliser des méthodes chimiques pouvant induire une modification de ces molécules. Cette étude a démontré l intérêt de l approche multi-technique centrée autour de la spectrométrie de masse couplée à l imagerie ionique pour déterminer les éléments principaux de la matrice minérale et organique. L analyse par PIXE avec une cartographie micrométrique a permis d attribuer les distributions d ions moléculaires et agrégats des spectres de masse aux différents composés minéraux. Ces attributions se poursuivent avec la constitution d une base de données de spectres de référence. La composante organique a été extraite et les premières hypothèses de composition ont été envisagées autour des HAPs (Hydrocarbure Aromatique Polycyclique), MOI (Matière Organique Insoluble) et analogues de carbone amorphe produits par irradiation UV de glaces dont les compositions en gaz représentent différentes hypothèses pour les nuages interstellaires. Les protocoles d analyses multi-techniques établis (incorporant un suivi de l échantillon par spectrométrie de masse et imagerie ionique) permettent le démarrage d analyse d autres échantillons extra-terrestres collectés sur terre ou dans l espace.The Lebanese Atomic Energy Commission (LAEC) is incorporated in a development program of the analytical techniques in order to complete the Ion Beam Analysis (IBA). It was decided to get a mass spectrometer coupled to 2D and recently to 3D imaging, by acquiring an ION TOFVTM system equipped with two ionic columns delivering bismuth and argon cluster beams.In this context, my thesis is focused on the optimization of the instrument, recently purchased, for the analysis of samples containing organic compounds. The first subjects of research are the development of a protocol for quantitative analysis of drugs using the cluster-SIMS-imaging technique and the Paris meteorite analysis to determine its composition and to localize the organic matter. In the last case a multi-techniques approach was used : IBA in LAEC, -Raman et -IR around the Soleil synchrotron equipments and PIXE carried with the AGLAE accelerator (Centre de recherche et de restauration des musées de France, C2RMF).The drug analysis was initiated in Lebanon in collaboration with a local pharmaceutical manufacturer (Mediphar Laboratories) in order to establish new processes for quality control of the final products. My study showed the complexity of the drug quantification which is due to the presence of several active ingredients (AI) and inactive organic and minerals components (excipients) mixed in secret conditions. Matrix effects are dominant and modify the ionic emission leading to significant systematic errors. This complexity has been analyzed with the study of FludiniumTM with two active ingredients. The results of this study allowed to obtain the first calibration curves of the ratio between the two AIs and to quantify them in the commercial drug. The protocol to perform the calibration curve and the quality controls were determined. These incorporate a profile analysis to control the homogeneity of the samples and the obtaining standards produced by the pharmaceutical manufacturer following the same process used for the commercial drug. Indeed, the experiments have shown that the preparation of the drug in the laboratory from its elements (AIs and excipients) doesn t give the same ionic emission as for the commercial drug.The Paris meteorite analysis was initiated by a collaboration with the Institut d Astrophysique Spatiale d Orsay team involved in the exobiology and the research of the first prebiotic molecules in the extraterrestrial samples. The work objective is to characterize the organic matter representing few percents in mass in a complex mineral matrix, without any chemical extraction that can induce a modification of these molecules. This study has demonstrated the interest of the multi-techniques approach centered on the mass spectrometry coupled to the ionic imaging for the determination of the main mineral and organic elements of the matrix. PIXE analysis coupled to the micrometric mapping permits to attribute the distribution of molecular ions and clusters of the mass spectra with different mineral compounds. These attributions continue with the creation of the data base of standard spectra. The organic component was determined and the first hypotheses were considered concerning PAHs (Polycyclic Aromatic Hydrocarbon), IOM (Insoluble Organic Matter) and analogues of amorphous carbon produced par UV irradiation of ices with a gas composition representing different hypotheses for the interstellar clouds. The establish protocols for multi-techniques (incorporating a follow of the sample by mass spectrometry and ion imaging) permits to start the analysis of other extra terrestrial samples collected on earth or in space.PARIS11-SCD-Bib. électronique (914719901) / SudocSudocFranceF

Ion stopping in dense plasma target for high energy density physics

The basic physics of nonrelativistic and electromagnetic ion stopping in hot and ionized plasma targets is thoroughly updated. Corresponding projectile-target interactions involve enhanced projectile ionization and coupling with target free electrons leading to significantly larger energy losses in hot targets when contrasted to their cold homologues. Standard stoppping formalism is framed around the most economical extrapolation of high velocity stopping in cold matter. Further elaborations pay attention to target electron coupling and nonlinearities due to enhanced projectile charge state, as well. Scaling rules are then used to optimize the enhanced stopping of MeV/amu ions in plasmas with electron linear densities nel ~ 10 18 -10 20 cm -2 . The synchronous firing of dense and strongly ionized plasmas with the time structure of bunched and energetic multicharged ion beam then allow to probe, for the first time, the long searched enhanced plasma stopping and projectile charge at target exit. Laser ablated plasmas (SPQR1) and dense linear plasma columns (SPQR2) show up as targets of choice in providing accurate and on line measurements of plasma parameters. Corresponding stopping results are of a central significance in asserting the validity of intense ion beam scenarios for driving thermonuclear pellets. Other applications of note feature thorium induced fission, novel ion sources and specific material processing through low energy ion beams. Last but not least, the given ion beam-plasma target interaction physics is likely to pave a way to the production and diagnostics of warm dense matter (WDM)

Fusion cross section measurements of astrophysical interest for light heavy ions systems within the STELLA project

This contribution is focused on the STELLA project (STELlar LAboratory), which aims at the measurement of fusion cross sections between light heavy ions like 12C+12C, 12C+16O or 16O+16O at deep subbarrier energies. The gamma-particle coincidence technique is used in order to reduce background contributions that become dominant for measurements in the nanobarn regime. The experimental setup composed of an ultra high vacuum reaction chamber, a set of 3 silicon strip detectors, up to 36 LaBr3(Ce) scintillators from the UK FATIMA collaboration, and a fast rotating target system will be described. The 12C+12C fusion reaction has been studied from Elab = 11 to 5.6 MeV using STELLA at the Andromède facility in Orsay, France. Preliminary commissioning results are presented in this article

An integrative approach to decipher the chemical antagonism between the competing endophytes paraconiothyrium variabile and Bacillus subtilis

An integrative approach combining traditional natural products chemistry, molecular networking, and mass spectrometry imaging has been undertaken to decipher the molecular dialogue between the fungus Paraconiothyrium variabile and the bacterium Bacillus subtilis, which were isolated as endophytes from the conifer Cephalotaxus harringtonia and are characterized by a strong and mutual antibiosis. From this study, we highlight that bacterial surfactins and a fungal tetronic acid are involved in such competition and that the fungus is able to hydrolyze surfactins to fight against the bacterial partner

Energy Resolution Performance of the CMS Electromagnetic Calorimeter

The energy resolution performance of the CMS lead tungstate crystal electromagnetic calorimeter is presented. Measurements were made with an electron beam using a fully equipped supermodule of the calorimeter barrel. Results are given both for electrons incident on the centre of crystals and for electrons distributed uniformly over the calorimeter surface. The electron energy is reconstructed in matrices of 3 times 3 or 5 times 5 crystals centred on the crystal containing the maximum energy. Corrections for variations in the shower containment are applied in the case of uniform incidence. The resolution measured is consistent with the design goals

Internal Energy Distribution of Secondary Ions Under Argon and Bismuth Cluster Bombardments: “Soft” Versus “Hard” Desorption–Ionization Process

International audienceThe emission/ionization process under massive argon cluster bombardment was investigated by measuring the internal energy distributions of a series of benzylpyridinium ions. Argon clusters with kinetic energies between 10 and 20keV and cluster sizes ranging from 500 to 10,000 were used to establish the influence of their size, energy, and velocity on the internal energy distribution of the secondary ions. It is shown that the internal energy distribution of secondary ions principally depends on the energy per atom or the velocity of the cluster ion beam (E/n v(2)). Under low energy per atom (E/n?10eV), the mean internal energy and fragmentation yield increase rapidly with the incident energy of individual constituents. Beyond 10eV/atom impact (up to 40eV/atom), the internal energy reaches a plateau and remains constant. Results were compared with those generated from bismuth cluster impacts for which the mean internal energies correspond well to the plateau values for argon clusters. However, a significant difference was found between argon and bismuth clusters concerning the damage or disappearance cross section. A 20 times smaller disappearance cross section was measured under 20keV Ar-2000(+) impact compared to 25keV Bi-5(+) bombardment, thus quantitatively showing the low damage effect of large argon clusters for almost the same molecular ion yield

Preliminary Irradiation Tests Of The Apvd Circuit For The

The APVD circuit, developed in the 0.8 radiation hard SOI DMILL technology [2][3][4] from ATMEL/TEMIC-MHS Nantes, for the front end electronic of the CMS tracker, has been irradiated at CERN using a 10KeV Xray beam up to a total dose of 20Mrad. The main performances of the APVD like gain, pulse shape, noise are presented as a function of the radiation dose. In particular the cause of the DAC non linearity in the bias generator part is discussed

Role of Surface Chemistry in Conditioning of Materials in Particle Accelerators

International audienceFor the vacuum scientists and the accelerator community, finding solutions to mitigate pressure rises induced by electron, photon and ion desorption and beam instabilities induced by ion and electron clouds is a major issue. Along the time, changes in the surface chemistry of vacuum chambers are observed during beam operations in particle accelerators, leading to modifications of: outgassing rates, stimulated desorption processes and a decrease of secondary emission yields (SEY). To understand the role of the surface chemistry of air exposed materials in the electron conditioning process, typical air exposed materials used in particle accelerators : thin film coatings (NEG and TiN), copper (and its oxides Cu2O and CuO) and Niobium were conditioned by low energy electron irradiation for a better understanding of Ecloud effect. First, SEY was measured to understand the changes of surface conditioning upon particle irradiation; then, surface chemistry evolution after electron irradiation was investigated by both XPS and TOF-SIMS analyses using the ANDROMEDE facility at IJCLab. Finally, the relationship between the surface chemistry and the conditioning phenomenon will be discussed

Sputtering and secondary ion emission under gold cluster impact: Cluster size and velocity dependences of the yields

Sputtering and ion emission rates have been measured from CsI and gold targets under the impact of View the MathML source (n = 1–9) clusters at energies between 30 and 350 keV/atom. The two materials have similar behaviors in regard to the variations of the sputtering and anion emission yields with energy and cluster size. The sputtering and anion emission yields increase nonlinearly with the projectile size. The maximum anion yields are found at lower energies than the maximum sputtering yields which themselves occur substantially below the maximum energy losses. The variations with energy of the atomic ion yields differ from those of the cluster ion yields. The experimental results are in agreement with an ion emission from linear collision cascades and spike collisions, the relative contribution of these two processes depending on the size of the cluster projectile and of the emitted ion. In addition they show that the ion emission yield enhancements under cluster impact result from a more effective sputtering mechanism and not from an enhanced ionization of the ejected species