During the last decade, the CENBG (Centre d’Études Nucléaires de Bordeaux Gradignan) commissioned a new facility called AIFIRA (Applications Interdisciplinaires des Faisceaux d’ions en Région Aquitaine). It allowed the development of a multidisciplinary activity based on the “in-house” expertise of CENBG in ion beam analysis. The great flexibility offered by the five beam lines confers a lot of possibilities for chemical analysis and nuclear physics. Indeed, not only the macrobeam and the external beam lines provide the full set of IBA techniques for routine sample analysis but an additional beam line is devoted to the production of monoenergetic neutrons through the interaction of the incoming ion with selected targets. In addition, the two high-resolution microbeam lines are used for chemical analyses, 2D/3D imaging, and targeted cell irradiation. Besides, the combination of the nanobeam line flexibility, the uniqueness of the micro-irradiation design completed by the internal CENBG expertise confers a great specificity to AIFIRA in biomedical field. After a detailed technical overview of the platform, the article focuses on the two high-resolution lines as they tap most of the activity. Thus a quick overview of the most significant results concerning biomedical samples is proposed in order to highlight the analytical possibilities of AIFIRA microbeam lines. A summary of the development status of the micro-irradiation line is also done.

High resolution ion microbeams, usually used to perform elemental mapping, low dose targeted irradiation or ion beam lithography needs a very flexible beam control system. For this purpose, we have developed a dedicated system (called “CRionScan”), on the AIFIRA facility (Applications Interdisciplinaires des Faisceaux d’Ions en Région Aquitaine). It consists of a stand-alone real-time scanning and imaging instrument based on a Compact Reconfigurable Input/Output (Compact RIO) device from National Instruments™. It is based on a real-time controller, a Field Programmable Gate Array (FPGA), input/output modules and Ethernet connectivity. We have implemented a fast and deterministic beam scanning system interfaced with our commercial data acquisition system without any hardware development. CRionScan is built under LabVIEW™ and has been used on AIFIRA’s nanobeam line since 2009 (Barberet et al., 2009, 2011) [1], [2]. A Graphical User Interface (GUI) embedded in the Compact RIO as a web page is used to control the scanning parameters. In addition, a fast electrostatic beam blanking trigger has been included in the FPGA and high speed counters (15MHz) have been implemented to perform dose controlled irradiation and on-line images on the GUI. Analog to Digital converters are used for the beam current measurement and in the near future for secondary electrons imaging. Other functionalities have been integrated in this controller like LED lighting using Pulse Width Modulation and a “NIM Wilkinson ADC” data acquisition.

The energy and specific energy absorbed in the main cell compartments (nucleus and cytoplasm) in typical radiobiology experiments are usually estimated by calculations as they are not accessible for a direct measurement. In most of the work, the cell geometry is modelled using the combination of simple mathematical volumes. We propose a method based on high resolution confocal imaging and ion beam analysis (IBA) in order to import realistic cell nuclei geometries in Monte-Carlo simulations and thus take into account the variety of different geometries encountered in a typical cell population. Seventy-six cell nuclei have been imaged using confocal microscopy and their chemical composition has been measured using IBA. A cellular phantom was created from these data using the ImageJ image analysis software and imported in the Geant4 Monte-Carlo simulation toolkit. Total energy and specific energy distributions in the 76 cell nuclei have been calculated for two types of irradiation protocols: a 3 MeV alpha particle microbeam used for targeted irradiation and a 239Pu alpha source used for large angle random irradiation. Qualitative images of the energy deposited along the particle tracks have been produced and show good agreement with images of DNA double strand break signalling proteins obtained experimentally. The methodology presented in this paper provides microdosimetric quantities calculated from realistic cellular volumes. It is based on open-source oriented software that is publicly available.

A new version of the TomoRebuild data reduction software package is presented, for the reconstruction of scanning transmission ion microscopy tomography (STIMT) and particle induced X-ray emission tomography (PIXET) images. First, we present a state of the art of the reconstruction codes available for ion beam microtomography. The algorithm proposed here brings several advantages. It is a portable, multi-platform code, designed in C++ with well-separated classes for easier use and evolution. Data reduction is separated in different steps and the intermediate results may be checked if necessary. Although no additional graphic library or numerical tool is required to run the program as a command line, a user friendly interface was designed in Java, as an ImageJ plugin. All experimental and reconstruction parameters may be entered either through this plugin or directly in text format files. A simple standard format is proposed for the input of experimental data. Optional graphic applications using the ROOT interface may be used separately to display and fit energy spectra. Regarding the reconstruction process, the filtered backprojection (FBP) algorithm, already present in the previous version of the code, was optimized so that it is about 10 times as fast. In addition, Maximum Likelihood Expectation Maximization (MLEM) and its accelerated version Ordered Subsets Expectation Maximization (OSEM) algorithms were implemented. A detailed user guide in English is available. A reconstruction example of experimental data from a biological sample is given. It shows the capability of the code to reduce noise in the sinograms and to deal with incomplete data, which puts a new perspective on tomography using low number of projections or limited angle.

A high resolution focused beam line has been recently installed on the AIFIRA ("Applications Interdisciplinaires des Faisceaux d'Ions en Region Aquitaine") facility at CENBG. This nanobeam line, based on a doublet-triplet configuration of Oxford Microbeam Ltd. OM-50 (TM) quadrupoles, offers the opportunity to focus protons, deuterons and alpha particles in the MeV energy range to a sub-micrometer beam spot. The beam optics design has been studied in detail and optimized using detailed ray-tracing simulations and the full mechanical design of the beam line was reported in the Debrecen ICNMTA conference in 2008. During the last two years, the lenses have been carefully aligned and the target chamber has been fully equipped with particle and X-ray detectors, microscopes and precise positioning stages. The beam line is now operational and has been used for its first applications to ion beam analysis. Interestingly, this set-up turned out to be a very versatile tool for a wide range of applications. Indeed, even if it was not intended during the design phase, the ion optics configuration offers the opportunity to work either with a high current microbeam (using the triplet only) or with a lower current beam presenting a sub-micrometer resolution (using the doublet-triplet configuration).The performances of the CENBG nanobeam line are presented for both configurations. Quantitative data concerning the beam lateral resolutions at different beam currents are provided. Finally, the first results obtained for different types of application are shown, including nuclear reaction analysis at the micrometer scale and the first results on biological samples. (C) 2011 Elsevier B.V. All rights reserved.

The use of ion microbeams as probes for computed tomography has proven to be a powerful tool for the three-dimensional characterization of specimens a few tens of micrometers in size. Compared to other types of probes, the main advantage is that quantitative information about mass density and composition can be obtained directly, using specific reconstruction codes. At the Centre d'Etudes Nucleaires de Bordeaux Gradignan (CENBG), this technique was initially developed for applications in cellular biology. However, the observation of the cell ultrastructure requires a sub-micron resolution. The construction of the nanobeam line at the Applications Interdisciplinaires des Faisceaux d'Ions en Region Aquitaine (AIFIRA) irradiation facility has opened new perspectives for such applications.The implementation of computed tomography on the nanobeam line of CENBG has required a careful design of the analysis chamber, especially microscopes for precise sample visualization, and detectors for scanning transmission ion microscopy (STIM) and for particle induced X-ray emission (PIXE). The sample can be precisely positioned in the three directions X, Y, Z and a stepper motor coupled to a goniometer ensures the rotational motion. First images of 3D tomography were obtained on a reference sample containing microspheres of certified diameter, showing the good stability of the beam and the sample stage, and the precision of the motion. (C) 2011 Elsevier B.V. All rights reserved.

In this work, the physicochemical reactions occurring at the surface of bioactive sol-gel derived 3D glass scaffolds via a complete PIXE characterization were studied. 3D glass foams in the SiO(2)-CaO system were prepared by sol-gel route. Samples of glass scaffolds were soaked in biological fluids for periods up to 2 days. The surface changes were characterized using particle induced X-ray emission (PIXE) associated to Rutherford backscattering spectroscopy (RBS), which are efficient methods to perform quantitative chemical maps. Elemental maps of major and trace elements at the glass/biological fluids interface were obtained at the micrometer scale for every interaction time. Results revealed interconnected macropores and physicochemical reactions occurring at the surface of pores. The micro-PIXE-RBS characterization of the pores/biological fluids interface shows the glass dissolution and the rapid formation of a Ca rich layer with the presence of phosphorus that came from biological fluids. After 2 days, a calcium phosphate-rich layer containing magnesium is formed at the surface of the glass scaffolds. We demonstrate that quantities of phosphorus provided only by the biological medium have a significant impact on the development and the formation of the phosphocalcic layer.

Two years ago, the CENBG has commissioned the AIFIRA (Application Interdisciplinaire des Faisceaux Mons en Aquitaine) facility for the development of an interdisciplinary research program based on a 3.5 MV Singletron (TM) accelerator (HVEE, The Netherlands). In addition to the existing beam lines, this facility is being equipped with a high demagnification focused beam line allowing the focusing of protons, deuterons and alpha particles down to a sub-micrometer resolution. This so-called "nanobeam line", based on a long working distance doublet-triplet of Oxford Microbeams Ltd., OM-50 (TM) quadrupoles, is at its final stage of development. The chosen layout of the beam line has been computed in details using the GEANT4 simulation toolkit. In the simulations, experimental measurements of the beam emittance at the entrance slits have been used to obtain more realistic beam distributions and intensities along the full beam line. According to these simulations, a beam resolution of about 300 nm in high current mode and below 100 nm in STIM mode is expected. The components of the beam line have been mounted at the 0 degrees output of the Singletron (TM) switching magnet and the fine alignment will be performed using the ion beam in the coming weeks. In the present paper, all the major components of the CENBG nanobeam line are described in details. (C) 2009 Elsevier B.V. All rights reserved.

Microbeam facilities provide a unique opportunity to investigate the effects of ionising radiation on living biological cells with a precise control of the delivered dose. This paper describes dosimetry calculations performed at the single-cell level in the microbeam irradiation facility available at the Centre d'Etudes Nucléaires de Bordeaux-Gradignan in France, using the object-oriented Geant4 Monte Carlo simulation toolkit. The cell geometry model is based on high-resolution three-dimensional voxelised phantoms of a human keratinocyte (HaCaT) cell line. Such phantoms are built from confocal microscopy imaging and from ion beam chemical elemental analysis. Results are presented for single-cell irradiation with 3 MeV incident alpha particles.

The DISRA (Discrete Image Space Reconstruction Algorithm) reconstruction code, created by A. Sakellariou, was conceived for the ideal case of complete three-dimensional (3D) PIXET (Particle Induced X-ray Emission Tomography) data. This implies two major difficulties for biological samples: first, the long duration of such experiments and second, the subsequent damage that occurs on such fragile specimens. For this reason, the DISRA code was extended at CENBG in order to probe isolated PIXET slices, taking into account the sample structure and mass density provided by 3D STIMT (Scanning Transmission Ion Microscopy Tomography) in the volume of interest. This modified version was tested on a phantom sample and first results on human cancer cells are also presented.

In this study, we benefited from the sensitivity of ion beam analysis methods to characterise in vitro the bioactiveglass/biological fluids interface and to perform local measurements of elemental concentrations at the 10(-6) g/g level. A glass in the SiO2 -CaO composition was elaborated by sol-gel processing. Samples of glass powders were soaked in biological fluids for periods up to 4 days. The surface changes were characterised using particle-induced X-ray emission (PIXE) associated to Rutherford backscattering spectroscopy (RBS), which are efficient methods for multi-elemental analysis. In addition, these ion beam methods permit accurate trace elements quantification. Elemental maps of major and trace elements were obtained at a micrometer scale and revealed the bone-bonding ability of the material. The formation of a calcium phosphate-rich layer occurs after a few minutes of interaction and the glass particles are progressively coated with this thin film. Traces of magnesium are proved to be blended into the Ca-P layer. Kinetics of formation of the Ca-P layer shows the high reactivity of this material in contact with a biological medium. However the Ca-P-Mg layer is finally dissolved after a few days of interaction. The absence of P in the initial glass matrix may explain that SiO2 - CaO g lass particles encounter great difficulties to achieve the transformation of their peripheral amorphous Ca-P layer into a more stable bone-like apatite phase. Copyright (c) 2008 John Wiley & Sons, Ltd.

Ion beam analysis methods were used to characterize the interface of bioactive glasses with surrounding biological fluids. Glass particles in the SiO2–CaO and SiO2–CaO–P2O5 compositions were made by sol–gel processing and soaked in biological fluids for periods up to 4 days. The surface changes were characterized using PIXE–RBS, which are efficient methods for multielemental analysis and accurate trace elements quantification. Elemental maps of major and trace elements were obtained at a micrometer scale and revealed the bone bonding ability of the materials. Glass particles are quickly coated with a thin calcium phosphate-rich layer containing traces of magnesium. After a few days, SiO2–CaO–P2O5 glass particles are entirely changed into calcium phosphates, whereas SiO2–CaO particles exhibit a different behavior: the previously Ca–P enriched periphery has been dissolved and glass particles consist of a silicate network. Calculation of the Ca–P atomic ratios at the glass/biological fluids interface provides us with an explanation for this: an enduring apatitic phase seems to be formed at the periphery of SiO2–CaO–P2O5 glass particles. Presence of phosphorus in the glass matrix thus has an influence on the amplitude and the kinetics of reaction of the bioactivity process. It might result in an improved chemical bond with living tissues.

This paper demonstrates the feasibility of creating specific defects in double-heterostructure AlGaAsGaAs commercial light emitting diode by neutron irradiation. Using controlled neutron energy, only one failure mechanism can be activated. Defects are located in the side of the chip and increase the leakage current driven by the well-known Pool–Frenkel effect with Ec − ET = 130 meV electron trap energy level. The maximal amplitude of optical spectrum also reveals a drop about 20% associated to the rise of leakage current.

It is proposed in this study to observe the influence Of P2O5 on the formation of the apatite-like layer in a bioactive glass via a complete PIXE characterization. A glass in the SiO2-CaO-P2O5 ternary system was elaborated by sol-gel processing. Glass samples were soaked in biological fluids for periods up to 10 days. The surface changes were characterized by a micro-analytical technique of particle induced X-ray emission (PIXE) associated to Rutherford backscattering spectroscopy (RBS), in which multi-elemental distributions are efficiently analyzed. Elemental maps of major and trace elements were obtained at a micrometer scale and revealed the bone bonding ability of the material. A calcium phosphate-rich layer containing magnesium appears a few days after the interaction. We demonstrate that the presence of phosphorus in the material has an impact on the development and the formation rate of the bone-like apatite layer. Indeed, the Ca/P atomic ratio at the glass/biological fluids interface is closer to the nominal value of pure apatite compared to P2O5-free glasses. It would permit, in vivo, an improved chemical bond between the biomaterials and bone. (c) 2007 Elsevier B.V. All rights reserved.

A single-ended HVEE® 3.5 MV Singletron electrostatic accelerator has been installed since October 2005 at the Centre d’Etudes Nucléaires de Bordeaux-Gradignan (CENBG) in France. This facility is equipped with a microbeam line dedicated to ion beam analysis (scanning transmission ion microscopy – STIM, particle induced X-ray emission – PIXE, Rutherford back scattering) and cellular irradiation in single event mode. A high demagnification nanobeam line will be installed on the same facility in the near future. This paper focuses on the simulation of the microbeam and nanobeam lines performances using the Geant4 Monte Carlo simulation toolkit. Comparisons with experimental data collected on the microbeam line are presented.

The AIFIRA (Applications Interdisciplinaires des Faisceaux d'Ions en Region Aquitaine) ion beam facility at the CENBG (Centre d'Etudes Nucleaires de Bordeaux-Gradignan) is being equipped with a high demagnification focused microbeam line. This beam line, which is under its final stage of development, should allow focusing of protons and alpha particles down to a sub-micrometer resolution, and is therefore referred to as a "nanobeam line" in the following paper.We present the complete beam transport simulation along the chosen configuration for the nanobeam line, which consists of a long working distance doublet-triplet of Oxford Microbeam Ltd. OM-50 (R) quadrupoles. These simulations have been performed using the Geant4 Monte Carlo simulation toolkit, which has been previously validated for ray-tracing studies in the design of quadrupole microbeam systems. They include a fine modelling of the quadupole magnetic field, based on the analytical Enge's model, which is compared to a classical square field model and to a high granularity tri-dimensional field map computed with the OPERA3D (R) software. The beam emittance model is parameterized from experimental measurements performed directly on the HVEE Singletron (R) at the AIFIRA facility, allowing the computation of the beam transmitted current along the nanobeam line. Grid shadow images, acquired from simulations, for system alignment purposes and beam deflection studies on target are presented as well. (C) 2007 Elsevier B.V. All rights reserved.