Microbeam Setup Research Articles

In Vivo Microbeam Radiation Therapy at a Conventional Small Animal Irradiator

Microbeam radiation therapy (MRT) is a still pre-clinical form of spatially fractionated radiotherapy, which uses an array of micrometer-wide, planar beams of X-ray radiation. The dose modulation in MRT has proven effective in the treatment of tumors while being well tolerated by normal tissue. Research on understanding the underlying biological mechanisms mostly requires large third-generation synchrotrons. In this study, we aimed to develop a preclinical treatment environment that would allow MRT independent of synchrotrons. We built a compact microbeam setup for pre-clinical experiments within a small animal irradiator and present in vivo MRT application, including treatment planning, dosimetry, and animal positioning. The brain of an immobilized mouse was treated with MRT, excised, and immunohistochemically stained against γH2AX for DNA double-strand breaks. We developed a comprehensive treatment planning system by adjusting an existing dose calculation algorithm to our setup and attaching it to the open-source software 3D-Slicer. Predicted doses in treatment planning agreed within 10% with film dosimetry readings. We demonstrated the feasibility of MRT exposures in vivo at a compact source and showed that the microbeam pattern is observable in histological sections of a mouse brain. The platform developed in this study will be used for pre-clinical research of MRT.

Matrix Modeling of the Artificial Cell / Protocell Division with "ARTCELL DIVISION SIMULATOR-2009/2010": from Computer Simulation to Experimental Multispectral Investigations Based on Multi-Channel DPSSL Microbeam Setup

A model of the artificial cell / protocell division is proposed, which al-lows achieving similarity to different forms of cell division and emer-gence of the cell colonies by rearrangement of the parameters. The most characteristic features of cell division reproduced in this model are: cytotomy with a constriction (separatrix); cytokinetic processes after cytotomy; asynchronous nature of cell division; surface dispro-portionation during the cell division (as a consequence, the presence of both symmetrical cytotomy and budding); formation of the topological distortions; the possibility of colonial cell association; the presence of fixed cells and groups of cells (reproductive generators) like CFU and their coordinated operation. Cytokinetic processes are recorded in the systems of undifferentiated artificial cells. Such variability in the artificial cell "cultures" is observed in the form of reversible processes depending on the environmental conditions. Such instability of the regimes, probably, could have taken place in the course of evolution at the first stages of development of reproductive systems in protobionts, when mechanisms of genetic or other structural biochemical stabilization did not yet exist, but was developed during the division of the score for the future selection of these pathways

MeV-proton capillary microbeam PIXE mapping study of solution diffusion in paper

A tapered glass capillary MeV-ion microbeam setup, previously home-developed, was recently upgraded. To check the upgraded microbeam system quality and accuracy, microbeam particle induced X-ray emission (PIXE) mapping of potassium permanganate (KMnO4) solution diffusion in filter paper was carried out to study how the measured solvent diffusion followed the diffusion laws. Two initial boundary conditions and diffusion situations were applied: (1) the paper vertically placed in air with one end soaked in the solution for ten minutes, and (2) the paper horizontally placed on water with the solution dropped at a side of the paper for three minutes. 2-MeV-proton microbeam PIXE analyzed the paper pixel by pixel and the GUPIXWIN software was used to calculate the elemental concentrations in the pixels to map the concentration changes in the pixels as a function of the distance between the pixel position and the origin of the solution. The resulting maps demonstrated the solution diffusions in two cases indeed well following the diffusion laws, a steady-state diffusion dominated process where the elemental concentration was a linear function with the distance but joined by other non-diffusion factors for case 1, and a pure diffusion process where the elemental concentration was an error function with the distance for case 2.

Trans-National Access in the field of heritage science at the Laboratory of Ion Beam Applications, MTA Atomki

The Laboratory of Ion Beam Applications at MTA Atomki served as a Trans-National Access (TNA) host within the CHARISMA EU FP7 project. Although cultural heritage research is only one of the several applications in the laboratory, its importance is growing thanks to the success of CHARISMA. The variety of samples and analytical questions in this field provides constant motivation for development of the instrumentation and adaptation of new techniques. We have special expertise in investigations with high lateral resolution and the PIXE analysis of lighter elements but we can also host projects when the in-vacuum measurements are not feasible, at our external micro-beam set-up. We continue the TNA activity within the IPERION CH project.

Investigating the Distribution of Chemical Forms of Sulfur in Prostate Cancer Tissue Using X-ray Absorption Spectroscopy.

The use of synchrotron radiation may shed more light on the study of prostate cancer, one of the leading diseases among men. In the presented study the microbeam setup at the PSI Swiss Light Source combined with fluorescence detected X-ray absorption spectroscopy (XAS) was applied to determine two-dimensional (2D) imaging of distributions of various chemical sulfur forms in prostate cancer tissue sections, since sulfur is considered important and essential in cancer progression. The research focused on prostate tissues obtained during routine prostatectomies on patients suffering from prostate cancer.Our previous studies using μ-XAS point measurements on prostate cancer cell lines showed the differences in fractions of various forms of sulfur between cancerous and non-cancerous cells. Therefore, in this experiment the chosen areas of prostate cancer tissues were scanned to get the full picture of the chemical composition of tissue, which is highly heterogeneous. The incident X-ray beams of energies tuned to spectroscopic features of the near-edge region of sulfur K-edge absorption spectra were used to provide contrast between chemical species presented in the tissue. Next, the relative content of the three main sulfur forms, found in biological systems, was calculated and the results are presented in a form of 2D color maps. These maps are correlated with the microscopic histological image of the scanned area.The main findings show that sulfur occurs in prostate tissue mainly in reduced form. The oxidized form of sulfur is present mostly in prostatic stroma, while sulfur in intermediate oxidation state is present in trace amount.

Development of a new in-air micro-PIXE set-up with in-vacuum charge measurements in Atomki

A new external microbeam set-up has recently been installed as the extension of the existing microprobe system at the Laboratory of Ion Beam Applications of Atomki, Debrecen, Hungary. The external beam set-up, based on the system of Oxford Microbeams (OM), is equipped with two X-ray detectors for PIXE analysis, a digital microscope, two alignment lasers and a precision XYZ stage for easy and reproducible positioning of the sample. Exit windows with different thicknesses and of different materials can be used according to the actual demands, currently silicon-nitride (Si3N4) film with 200nm thickness is employed in our laboratory. The first application was demonstrated in the field of archaeometry, on Bronze Age hoards from Hungary.

Paintings on copper by the Flemish artist Frans Francken II: PIXE characterization by external microbeam

Resorting to an external proton microbeam, PIXE analyses of three oil paintings on copper support dated from the XVII century and attributed to the Flemish artist Frans Francken II, were undertaken. The present work aims to contribute to the compositional study of the painting materials employed by XVII century artists that exploited copper as a support for oil painting, and specifically the materials used by Francken’s workshop, particularly copper plates. Because of the low thickness of the pictorial layers of this type of paintings and its non-destructive character, PIXE is the ideal technique to study the elemental composition of the paintings. Several spots in each painting were chosen for analysis in order to cover almost all the pigments used in the colour palette. Lead and calcium were detected in practically every analysed regions, probably related to the presence of lead white and chalk, usually used as ground layer on copper paintings. Small quantities of gold were also detected, which is present in many of this artist’s works to embellish some details of the representations. Also this work reports the first application of the external proton microbeam set-up available at CTN/IST in Portugal for the characterization of oil paintings.

Highly-focused boron implantation in diamond and imaging using the nuclear reaction 11B(p, α)8Be

Diamond is an especially attractive material because of its gemological value as well as its unique mechanical, chemical and physical properties. One of these properties is that boron-doped diamond is an electrically p-type semiconducting material at practically any boron concentration. This property makes it possible to use diamonds for multiple industrial and technological applications. Boron can be incorporated into pure diamond by different techniques including ion implantation. Although typical energies used to dope diamond by ion implantation are about 100keV, implantations have also been performed with energies above MeV. In this work CMAM microbeam setup has been used to demonstrate capability to implant boron with high energies. An 8MeV boron beam with a size of about 5×3μm2 and a beam current higher than 500pA has been employed while controlling the beam position and fluence at all irradiated areas. The subsequent mapping of the implanted boron in diamond has been obtained using the strong and broad nuclear reaction 11B(p, α)8Be at Ep=660keV. This reaction has a high Q-value (8.59MeV for α0 and 5.68MeV for α1) and thus is almost interference-free. The sensitivity of the technique is studied in this work.

Ion beam induced luminescence (IBIL) system for imaging of radiation induced changes in materials

The progress of construction on the new IBIL (ion beam induced luminescence) spectrometer installed at the ion microprobe facility of the Ruđer Bošković Institute (RBI) is reported. The IBIL system can be used with beams from either 6.0MV Tandem Van de Graaff or 1.0MV Tandetron accelerators. Components of the new apparatus and current experimental set-up are described in detail. Measurements with the new IBIL system were performed using a 2MeV proton microbeam on three sets of samples. This paper gives a summary of the IBIL arrangement capabilities for various problems, emphasising the potential of this technique for radiation damage studies. Due to the relatively good sensitivity of the IBIL spectrometer, integration into the conventional ion beam analysis (IBA) microbeam setup is shown to be possible.

Focusing giga-electronvolt heavy ions to micrometers at the Institute of Modern Physics

To study the radiation effect of cosmic heavy ions of low fluxes in electronics and living samples, a focusing heavy ion microbeam facility, for ions with energies of several MeV/u up to 100 MeV/u, was constructed in the Institute of Modern Physics of the Chinese Academy of Sciences. This facility has a vertical design and an experiment platform for both in-vacuum analysis and in-air irradiation. Recently, microbeam of (12)C(6+) with energy of 80.55 MeV/u was successfully achieved at this interdisciplinary microbeam facility with a full beam spot size of 3 μm × 5 μm on target in air. Different from ions with energy of several MeV/u, the very high ion energy of hundred MeV/u level induces problems in beam micro-collimation, online beam spot diagnosis, radiation protection, etc. This paper presents the microbeam setup, difficulties in microbeam formation, and the preliminary experiments performed with the facility.

Atmospheric Pressure Free Liquid Infrared MALDI Mass Spectrometry: Toward a combined ESI/MALDI-Liquid Chromatography Interface

A new atmospheric pressure (AP)-MALDI-type interface has been developed based on a free liquid (FL) microbeam/microdroplets and a mid-infrared optical parametric oscillator (mid-IR OPO). The device is integrated into a standard on-line nanoESI interface. The generation of molecular ions in the gas phase is believed to be the result of a fast (explosive) laser-induced evaporative dispersion(not desorption) of the microbeam into statistically charged nanodroplets. Only the lowest charge states appear insignificant abundance in this type of experiment. Mass spectra of some common peptides have been acquired in positive ion mode, and the limit-of-detection of this first prototype (liquid microbeam setup) was evaluated to be 17 fmol per second. To improve the duty cycle and to reduce the sample consumption, a droplet-on-demand system was implemented (generating 100 pL droplets).With this setup, about 20 attomole of bradykinin were sufficient to achieve a signal-to-noise ratio better than five.This setup can be operated at flow rates down to 100 nL/min and represents a liquid MALDI alternative to the nanoESI. Our particular interest was the application of the developed ion source for on-line coupling of liquid chromatography with mass spectrometry. The flow rates(>100 microL/min), required for stable operation of the ion source in continuous liquid microbeam mode, matches perfectly the flow rate range of micro HPLC. Therefore, online LC/MS experiments have been realized, employing a microbore C18 reversed-phase column to separate an artificial peptide mixture and tryptic peptides of bovine serum albumin (performing a peptide mass fingerprint). In the latter case, sequence coverage of more than 90%has been achieved.

Polychromatic X-ray micro- and nanodiffraction for spatially-resolved structural studies

The availability of intense, focused synchrotron X-ray microbeams has enabled new techniques for materials investigations with sub-micron spatial resolution. The scanning microbeam setup we have developed at the XOR-UNI beamline at the Advanced Photon Source (APS) is versatile in that it provides 1D, 2D or 3D scans (including depth resolution), and can alternate between polychromatic- and monochromatic-beam modes. Focusing in both modes uses elliptical Kirkpatrick–Baez (K–B) reflecting mirrors. Beam diameters of ~ 500 nm FWHM are now routine, and 90 nm focus has been demonstrated. In white-beam mode, a CCD detector records a complete Laue diffraction pattern, which is analyzed with an automated indexing program. These X-ray diffraction patterns provide real-space maps of the local lattice structure, crystal orientation, grain morphology, and strain tensor. Spatially-resolved X-ray microdiffraction studies are now providing previously unavailable measurements of local microstructures. These measurements, in turn, yield new insights in several classic fields of materials science. This paper will illustrate the application of polychromatic scanning X-ray microscopy with examples from 1D, 2D and 3D materials systems. In 1D systems, we have mapped the structure and orientation of an individual ZnO nanorod along with the associated Ge catalyst particle used to control the nanocrystal growth. In 2D systems, X-ray microdiffraction studies have revealed the mechanisms for local crystallographic tilting in epitaxial oxide films grown on textured Ni substrates for superconducting applications. In 3D systems, X-ray microscopy investigations have included in-situ studies of microstructural evolution during thermal grain growth in polycrystalline aluminum. In general, these spatially-resolved measurements provide important new insights and are valuable as input for theoretical and computer modeling studies of a wide range of material processes.

The external scanning proton microprobe of Firenze: A comprehensive description

An external proton scanning microbeam setup is installed on the −30° line of the new 3 MV tandem accelerator in Firenze; the most relevant features of the line, such as detection setup for IBA measurements, target viewing system, beam diagnostic and transport are described here. With our facility we can work with a beam spot on sample better than 10 μm full-width half-maximum (FWHM) and an intensity of some nanoamperes. Standard beam exit windows are silicon nitride (Si 3N 4) TEM membranes, 100 nm thick and 0.5×0.5 mm 2 wide; we also successfully performed measurements using membranes 1×1 mm 2 wide, 100 nm thick, and 2×2 mm 2 wide, 200 and 500 nm thick. Exploiting the yield of Si X-rays produced by the beam in the exit window as an indirect measurement of the charge, a beam charge monitor system was implemented. The analytical capabilities of the microbeam have been extended by integrating a two-detector PIXE setup with BS and PIGE detectors; the external scanning proton microprobe in Firenze is thus a powerful instrument to fully characterize samples by ion beam analysis, through the simultaneous collection of PIXE, PIGE and BS elemental maps. Its characteristics can make it often competitive with traditional in vacuum microbeam for measurements of thick targets.

PIXE characterization of Western Mediterranean and Anatolian obsidians and Neolithic provenance studies

The possibility of non-destructive elemental analysis makes PIXE a very attractive technique in archaeological provenance studies. This technique has been fruitfully implemented on two different facilities to address the issue of obsidian provenance in the Mediterranean and in surrounding regions. At C2RMF, we took advantage of the possibility to analyze large archaeological pieces with the external micro-beam set-up. At CENBG, we used the nuclear microprobe providing a 5μm beam diameter in large scans (700×700μm2) to control the homogeneity of elemental distribution. In both cases we dosed the same set of 13 elements: Na, Al, Si, K, Ca, Ti, Mn, Fe, Zn, Ga, Rb, Sr and Zr. While at C2RMF, two Si(Li) detectors were used simultaneously to measure all elements at once with 3MeV protons, at CENBG where only one detector was available, the light elements Na to Fe were determined with a 1.5MeV beam, and the heavy ones, including Fe, with a beam energy of 2.7MeV.In Western Mediterranean, it is possible with PIXE to differentiate all obsidian sources of archaeological significance. Examples are given of obsidian provenances from Neolithic sites of France and from the islands of Corsica and Sardinia. In the Near East, we can differentiate the Cappadocian and Eastern Anatolian obsidian sources used during the early Neolithic. This is illustrated by examples taken from Neolithic sites of the Middle Euphrates Valley (Syria).

PIXE microbeam analysis of the metallic debris release around endosseous implants

The mechanical friction that occurs during the surgical insertion of endosseous implants, both in dentistry and orthopaedics, may cause the detachment of metal debris which are dislodged into the peri-implant tissues and can lead to adverse clinical effects. This phenomenon more likely happens with coated or roughened implants that are the most widely employed. In the present study were studied dental implants screws made of commercially pure titanium and coated using titanium plasma-spray (TPS) technique. The implants were inserted in the tibia of rabbits, and removed “en bloc” with the surrounding bone after one month. After proper processing and mounting on plastic holders, samples from bones were analysed by EDXRF setup at of National Laboratories of Legnaro, INFN, Italy, and consequently at 3MeV proton microbeam setup at Sandia National Laboratories. Elemental maps were drawn, showing some occasional presence of metal particles in the peri-implant bone.

Elemental mapping in slices of human brain by SR-μXRF

Cognitive deficits are repeatedly described with Pb exposure, but little is known about the distribution of lead in brain. To determine the local distribution of lead (Pb) and other trace elements, X-ray fluorescence spectroscopy measurements have been performed, using a microbeam setup and highest flux synchrotron radiation. Experiments have been carried out at ID-22, ESRF, Grenoble, France. The installed microprobe setup provides a monochromatic beam (16 keV) from an undulator station focused by Kirkpatrick-Baez X-ray optics to a spot size of 5 μm×3 μm. Brain slices from frontal cortex, thalamus, and hippocampus have been investigated (20 μm thickness, imbedded in paraffin and mounted on kapton foils). In general no significant increase in fluorescence intensities could be detected in one of the investigated brain compartments. Pb and other (trace) elements such as S, Ca, Fe, Cu, Zn, and Br could be detected in all samples and showed strong inhomogeneities within the analysed areas. While S, Ca, Fe, Cu, Zn, and Br could be clearly assigned to brain vessel structures (blood vessels, plexus choroidei), Pb was very inhomogeneously distributed. The local distribution of the detected elements in various brain structures will be discussed.

PIXE MICROBEAM IN LOCALIZING METALS RELEASED FROM DENTAL AND ORTHOPEDIC IMPLANTS

The release of metals and other elements from dental and orthopedic implants into the tissues has been a matter of numerous studies. However, the conditions that favor such a phenomenon have not been completely understood so far. PIXE microbeam technique has been applied to study the spatial distribution of the elements released from the implants. Subjects of interest have been implants made from commercially pure titanium, Ti -6 Al -4 V alloy and 316 LWM surgical steel. Block sections of five dental implants, as well as tissues surrounding one metal spine plate and two hip prostheses, have been examined. Rabbit bones containing copper inclusions have been taken for microbeam analysis to complete the study about the metal release processes. Samples from the tissues and bone slices have been analyzed using PIXE microbeam setup at National Laboratories of Legnaro, Italy. Traces of the implant metals, including titanium but with the exception of vanadium, were found in the surrounding tissues and maps of their elemental distribution at different distances from the contact surface with implants have been obtained. The origin and the differences of the release rate of the observed metals have been discussed.

Slit scattering in a microbeam set-up

Slit scattering of beam particles in a microbeam set-up becomes significant for low current applications and thus limits its lateral resolution and application potential. In this work, the angular and energy distributions of beam particles interacting with cylindrically shaped slit-jaws of different radii, surface roughnesses, and materials are calculated numerically, employing the computer code SRIM. To quantitatively investigate their effect on the beam spot quality of a microbeam set-up, a quality factor is proposed as an index to evaluate the effect of slit-scattered particles on the beam spot. The results of the investigation reveal a high sensitivity of slit scattering in relation to the slit-jaw surface roughness.

The heavy ion micro-projection setup at Bochum

A new type of microbeam setup is presented allowing MeV ion projection imaging of large area structures using the final lens of a high energy microprobe. Key issue of the new technology is the use of high aspect ratio high resolution stencil masks capable of withstanding high beam power which are now available. While the theoretical lateral resolution limit for this setup should allow the production of features well below 40 nm in size, the practical imaging resolution demonstrated so far is at 300 nm with heavy ions and typical implantation fluence. Microstructure formation is possible on substrates which do not allow the application of surface contact masks or in situations where such masks would result in sample contamination due to sputtering. A compact sample heater provides high substrate temperatures up to 1300°C during implantation for minimum damage implantation of crystalline samples. This setup opens a fascinating new field of applications in materials science since many structures can be exposed simultaneously. Fast structured implantation of stoichiometric doses of e.g. rare earth element ions gives access to the production of new materials of high purity at different substrate temperatures within reasonable time.

External microbeam set-up at the CNA (Sevilla) and its application to the study of Tartesic jewellery

A new external microbeam system has been installed recently at the +45° beam line of the 3 MV Pelletron accelerator at the Centro Nacional de Aceleradores (Sevilla, Spain). The facility, based on the system from Oxford Microbeams (OM), includes two sets of slits, a doublet of magnetic quadrupole focusing lenses, a Faraday cup and an accurate positioning device. In addition, a beam profile monitor (BPM) and a quartz viewer have been installed in the line to facilitate the microbeam production. The first PIXE application of the new facility was made in the field of Archaeometry, on the study of Tartesic gold artefacts (700–500 BC, SW of Spain) from Ébora and other archaeological sites. The aim of the analysis was to perform an exhaustive and systematic study about the soldering procedures that were employed by the goldsmiths along the Valley of Guadalquivir River after the Phoenician colonisation.