Dr Geoffrey Grime

The software package TRAX was a simulation tool for modelling the path of charged particles through linear cylindrical multipole fields described by analytical expressions and was a development of the earlier OXRAY program (Grime and Watt, 1983; Grime et al., 1982) [1,2]. In a 2005 comparison of raytracing software packages (Incerti et al., 2005) [3], TRAX/OXRAY was compared with Geant4 and Zgoubi and was found to give close agreement with the more modern codes. TRAX was a text-based program which was only available for operation in a now rare VMS workstation environment, so a new program, WinTRAX, has been developed for the Windows operating system. This implements the same basic computing strategy as TRAX, and key sections of the code are direct translations from FORTRAN to C++, but the Windows environment is exploited to make an intuitive graphical user interface which simplifies and enhances many operations including system definition and storage, optimisation, beam simulation (including with misaligned elements) and aberration coefficient determination. This paper describes the program and presents comparisons with other software and real installations. © 2013 Elsevier B.V. All rights reserved.

The nuclear microprobe was used to study elemental distributions in cultured insulin-producing cells and in pancreatic tissue. To see whether insulin producing cells are polarized, the cells were stimulated in the presence of Sr as a Ca analogue. The cells were stimulated to secrete insulin and Sr was detected in cells after momentary stimulation. We did not detect a polarized distribution of Sr in the RINm5F-cells. The distributions of Ca and Zn were affected when beta-cells (ob/ob) from a primary culture flattened out onto a substrate. In uprounded beta-cells (ob/ob) the distribution of Ca and Zn was polarized. Pancreatic tissue (ob/ob) was prepared for elemental analysis using freeze-substitution in tetrahydrofurane (THF) followed by embedding in Araldite. The resulting samples can be sectioned at room temperature, easing physiological studies.

Beam steering elements for accelerator beam transport are conventionally and conveniently incorporated into beamlines by fitting magnetic dipole elements around the vacuum tube of the line. Two steerers in each plane (X and Y) together with a quadrupole doublet constitute a module providing full control of the direction, position and focus of the beam. In some installations however, there may be insufficient space on the beamline to mount separate steerer elements. To provide steering capabilities in such a situation we have used a magnetic quadrupole doublet with the coils of each pole independently excited to synthesise the desired combination of quadrupole, horizontal dipole and vertical dipole fields. This paper describes the quadrupole steerer and its multichannel power supply and presents calculated magnetic field distributions together with raytracing simulation of its performance. © 2012 Elsevier B.V. All rights reserved.

Many disparate methods of compositional analysis of materials are underpinned by the same fundamental atomic processes: the excitation of the electronic system of the atoms followed by its subsequent relaxation. These methods include the electron spectroscopies (XPS, AES) used for surface studies, the electron microscopies used for elemental and structural characterisation (SEM using EDS and WDX; TEM using EELS), the X-ray methods (XRF, XAS) and ion beam analysis (PIXE) used for elemental and chemical characterisation. All rely on measuring the characteristic energy absorbed or emitted by the unknown target atom when its electronic system is excited by ionisation due to charged particles or electromagnetic radiation. This excitation is defined by the energy levels of the atomic electrons, determined primarily by the atomic number of the atom. (Atoms can also be excited without ionisation, as in optical and infra-red spectroscopy: this is outside the scope of this article.)
The theoretical description of the electronic structure of atoms is a major intellectual triumph of the twentieth century and this body of knowledge is exploited in the theoretical description of each of these methods, but the treatment of any particular method is usually presented by specialists in that method in isolation from all others. In this chapter we present a brief synthetic overview of materials analysis using atomic excitation, highlighting those features and physical concepts which underpin all these apparently disparate analysis methods. We hope to encourage modern analysts to appreciate the truly complementary nature of the powerful methods at their disposal.

In humans and other mammals it is known that calcium and phosphate ions are secreted from the distal small intestine into the lumen. However, why this secretion occurs is unclear. Here, we show that the process leads to the formation of amorphous magnesium-substituted calcium phosphate nanoparticles that trap soluble macromolecules, such as bacterial peptidoglycan and orally fed protein antigens, in the lumen and transport them to immune cells of the intestinal tissue. The macromolecule-containing nanoparticles utilize epithelial M cells to enter Peyer's patches, small areas of the intestine concentrated with particle-scavenging immune cells. In wild-type mice, intestinal immune cells containing these naturally formed nanoparticles expressed the immune tolerance-associated molecule 'programmed death-ligand 1', whereas in NOD1/2 double knockout mice, which cannot recognize peptidoglycan, programmed death-ligand 1 was undetected. Our results explain a role for constitutively formed calcium phosphate nanoparticles in the gut lumen and show how this helps to shape intestinal immune homeostasis.

The Oxford University Scanning Proton Microprobe Unit has been responsible for many advances in the field of focused proton beams for analytical microscopy, including being the first to develop the optimized electro-magnetic lenses used to focus high-energy protons to the micron and sub-micron level. This has led to a revolution in using the proton microprobe as an analytical tool for the study of materials. Continuing the tradition of innovation at the Oxford SPM unit, the use of laser ablation to reduce the need for sampling or cleaning of art and archaeological objects, before analysis, is being investigated. Further, information on the makeup of corrosion layers and past conservation treatments is becoming available via this technique. © 2000 Éditions scientifiques et médicales Elsevier SAS.

This paper discusses the results of a pilot study using Proton Induced X-ray Emission (PIXE) analysis of gold granulated objects from the Bronze Age site of Tell el-Ajjul in Southern Palestine obtained with the Oxford University proton microprobe. Using modern granulated samples with known smithing processes as points of comparison, it is demonstrated how information on ancient joining practices may be accurately gauged. The importance of characterizing objects of known provenance is emphasized in a discussion of archaeological context. It is argued that the building of a large Mediterranean-wide database of granulation analyses can add new depths to our understanding of temporal, social, cultural and technological relationships in the past.

The software package TRAX was a simulation tool for modelling the path of charged particles through linear cylindrical multipole fields described by analytical expressions and was a development of the earlier OXRAY program (Grime and Watt, 1983; Grime et al., 1982) [1,2]. In a 2005 comparison of raytracing software packages (Incerti et al., 2005) [3], TRAX/OXRAY was compared with Geant4 and Zgoubi and was found to give close agreement with the more modern codes. TRAX was a text-based program which was only available for operation in a now rare VMS workstation environment, so a new program, WinTRAX, has been developed for the Windows operating system. This implements the same basic computing strategy as TRAX, and key sections of the code are direct translations from FORTRAN to C++, but the Windows environment is exploited to make an intuitive graphical user interface which simplifies and enhances many operations including system definition and storage, optimisation, beam simulation (including with misaligned elements) and aberration coefficient determination. This paper describes the program and presents comparisons with other software and real installations. © 2013 Elsevier B.V. All rights reserved.

© 2014 John Wiley & Sons, Ltd.Sample elemental concentrations can be determined using the microbeam proton-induced X-ray emission (PIXE) technique, providing non-destructive simultaneous low-background multi-element analysis. Present interest concerns analysis of Ge-doped SiO2 fibres intended as high spatial-resolution thermoluminescence (TL) dosimeters for radiation measurements in place of their more typical applications in telecommunications. During fibres fabrication, defined amounts of the Ge dopant are added, the dopant more usually having a determining role in the transmission properties of the fibre. Characteristic X-rays produced in PIXE analysis provide information on the relative distribution of elements within a sample, as in for instance Ge and Si concentrations, the Ge acting as point defect centres that promote TL. With the dopant tending to diffuse in and away from the fibre core, it is essential to define the sample matrix composition in order to accurately evaluate the X-ray yield. This is determined in part using simultaneous Rutherford Back Scattering analysis. In present work, PIXE/Rutherford Back Scattering measurements have been employed to ascertain dopant concentrations of fibres that have been fabricated at the University of Malaya with a view to improving TL yield. Present results concern cylindrical fibres, nominally with 4%, 6% and 8% weight peak Ge concentrations and flat fibres of nominal 6% weight Ge concentration. For the cylindrical fibres, Ge dopant concentration has been found to be in the range of 2.41-4.56%, 6.44-8.29% and 10.27-12.25% weight, respectively, while for the flat fibres, the Ge concentration range is broader, at 0.07-6.55% weight.

Inductively coupled plasma mass spectrometry (ICP-MS) was used to quantify the total amount of trace elements in retina from adult male Sprague-Dawley rats (n = 6). Concentration of trace elements within individual retinal areas in frozen sections of the fellow eye was established with the use of two methodologies: (1) particle-induced X-ray emission (PIXE) in combination with 3D depth profiling with Rutherford backscattering spectrometry (RBS) and (2) synchrotron X-ray fluorescence (SXRF) microscopy. The most abundant metal in the retina was zinc, followed by iron and copper. Nickel, manganese, chromium, cobalt, selenium and cadmium were present in very small amounts. The PIXE and SXRF analysis yielded a non-homogenous pattern distribution of metals in the retina. Relatively high levels of zinc were found in the inner part of the photoreceptor inner segments (RIS)/outer limiting membrane (OLM), inner nuclear layer and plexiform layers. Iron was found to accumulate in the retinal pigment epithelium/choroid layer and RIS/OLM. Copper in turn, was localised primarily in the RIS/OLM and plexiform layers. The trace elements iron, copper, and zinc exist in different amounts and locations in the rat retina.

The principles of proton microprobe analysis are outlined and compared to electron beam analysis. Sample preparation methods are summarized, and the types of suitable sample are enumerated. The information that can be achieved from the analysis in terms of elemental composition and images is also described. © 1999 Elsevier Ltd All rights reserved.

Proton-induced X-ray emission (PIXE) in combination with 3D depth profiling with Rutherford backscattering spectrometry (RBS) was used to establish the distribution and concentration of trace elements within individual corneal and retinal areas in frozen sections from adult male Wistar rats (n = 6). The distribution of endogenous trace elements in the cornea and retina is non-homogenous. The most abundant metal in the cornea is calcium followed by zinc. Iron and copper are present in small amounts localised particularly to the epithelium. Iron is also identified in keratocytes. Relatively high levels of calcium occur in the corneal epithelial cell bodies. Zinc has a wide intense distribution across the corneal epithelium (with greater levels in the basal part) and posterior stroma. In the retina, zinc is the most common metal followed by iron and copper. Relatively high levels of zinc exist in the retinal pigment epithelium (RPE), photoreceptor inner segments (RIS) and inner nuclear layer (INL). Chelatable zinc was localised with fluorescent TSQ in the RPE, RIS and plexiform layers. It is interesting to note that the highest levels of total zinc and the greatest intensity of chelatable zinc staining do not coincide. In the RPE and corneal epithelium, zinc co-localised with the zinc-containing metallothioneins (MT). However, there was a clear mismatch between the localisation of the most intense levels of zinc in the neuroretina (i.e. INL) and corneal posterior stroma with that reported for MT. For example, the presence of zinc is not particularly associated with the retinal ganglion cells, retinal area that contains MTs in significant amounts. While high amounts of zinc are present in the INL and corneal posterior stroma, which are largely devoid of MTs. This probably represents pools of static, catalytic and structural zinc associated with substances other than the MTs. © 2014 The Royal Society of Chemistry.

Beam steering elements for accelerator beam transport are conventionally and conveniently incorporated into beamlines by fitting magnetic dipole elements around the vacuum tube of the line. Two steerers in each plane (X and Y) together with a quadrupole doublet constitute a module providing full control of the direction, position and focus of the beam. In some installations however, there may be insufficient space on the beamline to mount separate steerer elements. To provide steering capabilities in such a situation we have used a magnetic quadrupole doublet with the coils of each pole independently excited to synthesise the desired combination of quadrupole, horizontal dipole and vertical dipole fields. This paper describes the quadrupole steerer and its multichannel power supply and presents calculated magnetic field distributions together with raytracing simulation of its performance. © 2012 Elsevier B.V. All rights reserved.

The suite of techniques which are available with the small accelerators used for MeV ion beam analysis (IBA) range from broad beams, microbeams or external beams using the various particle and photon spectrometries (including RBS, EBS, ERD, STIM, PIXE, PIGE, NRA and their variants), to tomography and secondary particle spectrometries like MeV-SIMS. These can potentially yield almost everything there is to know about the 3-D elemental composition of types of samples that have always been hard to analyse, given the sensitivity and the spacial resolution of the techniques used. Molecular and chemical information is available in principle with, respectively, MeV-SIMS and high resolution PIXE. However, these techniques separately give only partial information - the secret of "Total IBA" is to find synergies between techniques used simultaneously which efficiently give extra information. We here review how far "Total IBA" can be considered already a reality, and what further needs to be done to realise its full potential. © 2011 Elsevier B.V. All rights reserved.

This paper describes a model for interpreting experimental transmission ion channeling results for dechanneling by 60°misfit dislocations in epitaxial Si1-xGex/Si material in terms of rotated lattice planes of the Si1-xGex epilayer with respect to the silicon substrate. A Monte Carlo channeling simulation program is used to model the trajectories of the incident MeV protons through the epilayer and the thinned Si substrate in order to calculate the average transmitted proton energy as a function of the sample-tilt angle about the beam axis and the effective rotation angle of the epilayer. The conditions under which the 60°dislocations can be resolved from the surrounding perfect crystal and also resolved from adjacent 60°dislocations causing a slightly different amount of lattice plane rotation are discussed using this model. Good agreement is demonstrated with experimental results showing the variation in transmitted proton energy across a group of five 60°dislocations for different sample-tilt angles. © 1995 The American Physical Society.

The Surrey vertical beam is a new facility for targeted irradiation of cells
in medium with singly counted ions. A duo-plasmatron ion source and a 2
MV Tandem accelerator supply a range of ions from protons to calcium for
this beamline, with energy ranges from 0.5 to 12 MeV. A magnetic quadrupole
triplet lens is used to focus the beam of ions. We present the design of this
beamline, and early results showing the capability to count single ions with
98% certainty on CR-39 track etch. We also show that the beam targeting
accuracy is within 5 microns and selectively target human broblasts with a
H2AX immuno
uorescence to demonstrate which
cell nuclei were irradiated. We discuss future commissioning steps necessary to
achieve sub-micron targeting accuracy with this beamline.

A "broadbeam" facility is demonstrated for the vertical microbeam at Surrey's Ion Beam Centre, validating the new technique used by Barazzuol et al. (Radiat Res 177:651-662, 2012). Here, droplets with a diameter of about 4 mm of 15,000 mammalian cells in suspension were pipetted onto defined locations on a 42-mm-diameter cell dish with each droplet individually irradiated in "broadbeam" mode with 2 MeV protons and 4 MeV alpha particles and assayed for clonogenicity. This method enables multiple experimental data points to be rapidly collected from the same cell dish. Initially, the Surrey vertical beamline was designed for the targeted irradiation of single cells with single counted ions. Here, the benefits of both targeted single-cell and broadbeam irradiations being available at the same facility are discussed: in particular, high-throughput cell irradiation experiments can be conducted on the same system as time-intensive focused-beam experiments with the added benefits of fluorescent microscopy, cell recognition and time-lapse capabilities. The limitations of the system based on a 2 MV tandem accelerator are also discussed, including the uncertainties associated with particle Poisson counting statistics, spread of linear energy transfer in the nucleus and a timed dose delivery. These uncertainties are calculated with Monte Carlo methods. An analysis of how this uncertainty affects relative biological effect measurements is made and discussed. © 2013 Springer-Verlag Berlin Heidelberg.

Silver-staining "senile" plaques occurring in the brain are a major part of the pathology of Alzheimer's disease. The elemental composition of these structures, and the possible presence of aluminum and silicon in these structures, has been the subject of an increasing research effort over the last decade. However, the results have often been contradictory. Using a scanning proton microprobe, the elemental composition of senile plaques has been determined. This instrument, similar to an electron probe, uses a focused beam of protons scanned across a sample to map the elements. The technique is absolutely quantitative and is sensitive down to the parts per million level. Tissue from six cases of clinically and pathologically characterized cases of Alzheimer's disease and two aged neurologically normal controls was scanned. It was found that aluminum and silicon occur at a level of 50 ppm or greater in the cores of 20% of senile plaques and that the total occurrence of aluminum or silicon in scans containing plaques was not above background. The major uncertainties affecting interpretation of results of this kind are discussed, and it is suggested that the least controllable factor is contamination in the reagents used to prepare and stain the tissue. This indicates that until plaques can be unambiguously identified and analyzed in untreated tissue, no conclusion can be reached on whether senile plaques contain aluminum and silicon.

The 12th International Conference on Proton Induced X-ray
Emission (PIXE) and its Analytical Applications was held on the
campus of the University of Surrey in Guildford, U.K. between 29
th
June and 2nd July 2010. The PIXE conferences have been held
at approximately three year intervals since the mid 1970s and
have re?ected the development of the PIXE technique and its
expanding range of applications.
This special issue of X-Ray Spectrometry contains papers
based on conference contributions which have been selected
to represent the latest developments in PIXE and its applications.

Return of materials from the Hubble Space Telescope (HST) during shuttle orbiter service missions has allowed inspection of large numbers of hypervelocity impact features from long exposure at about 615 km altitude in low Earth orbit (LEO) [1,2]. Here we describe the application of advanced X-ray microanalysis techniques on scanning electron microscopes (SEM), microprobes and a 2 MV Tandetron, to nearly 400 impacts on the painted metal surface of the Wide Field and Planetary Camera 2 (WFPC2) radiator shield [3,4]. We identified artificial Orbital Debris (OD) and natural Micrometeoroid (MM) origins for small [5] and even for larger particles [6], which usually may leave little or no detectable trace on HST solar arrays, as they penetrate through the full cell thickness [2,7].

We demonstrate that the simultaneous combination of ion beam analysis (IBA) and ion beam induced luminescence (IL) can reveal valuable information concerning the performance of strained doped silica fibre thermoluminescence microdosimeters. The micron scale spatial resolution and low detection limits of IBA allow the lateral distribution of dopant elements to be mapped and then correlated with the distribution of prompt radioluminescence. Measurement of the decay of the IL signal with dose provide information concerning the saturation of the subsequent TL signal at high doses. MeV ion beams can deposit relatively high energy in localized, well-quantified small volumes and so this method is valuable for studying high dose effects in TL dosimeters. We describe a simple modification of the target chamber microscope which enables sensitive low background light detection in two wavelength bands and present preliminary results from three types of germanium doped silica fibre dosimeter.

Ion Beam Analysis (IBA) consists of a set of analytical techniques addressing elemental composition of inorganic material normally conducted using ion beams in the MeV kinetic energy range. Secondary Ion Mass Spectrometry using MeV ions (MeV SIMS) is the only IBA technique which can provide extensive molecular information about organic materials. MeV ions can be extracted into air hence offering the potential to apply MeV SIMS under atmospheric pressure. At the University of Surrey Ion Beam Centre, a fully ambient MeV SIMS setup has been developed and termed ?Ambient Pressure MeV SIMS?. This AP MeV SIMS can be optimized for analysis and imaging of organic molecules. MeV SIMS relies upon electronic sputtering of the target material and this is much more efficient in insulating or organic targets, and less efficient in conducting metallic materials. PIXE, on the other hand, is efficient at providing good signals from elemental metallic systems, but does not readily provide molecular information from organics. The combination of the two techniques ? preferably simultaneously with the same beam ? provides useful complementary information which can readily be combined. Here we present pioneering preliminary work in simultaneous molecular and elemental imaging of a complex sample comprising of two organic species and two metallic species by combining AP MeV SIMS with Heavy Ion Particle Induced X-ray emission (HIPIXE).

The quality of the structures fabricated using proton beam writing (PBW) and other direct-write microfabrication methods is strongly influenced by the path followed by the writing beam during the exposure. In particular, it is necessary to avoid paths in which the beam makes large jumps or changes in direction close to the edges of the structure, and ideally the scan path should follow the outline of the pattern to be exposed (sometimes referred to as turtle scanning). While this is relatively easy to implement when the patterns to be created can be built up from simple geometric shapes (circles, rectangles, etc), it has not been possible to do this in the case of arbitrarily complex images, at least using software available to the PBW community.

This paper describes a simple edge-following algorithm (EFA) which uses a method of spiral searching around each pixel to determine a scan path which not only optimizes the conformity of the scan path to the edges of the required pattern, but also minimizes jumps (and hence blanking time) and scan reversals which can cause artefacts due to scanning system transients. The EFA operates on a 1-bit BMP format input image file and has been implemented in the OMDAQ-3 software package (Oxford Microbeams Ltd).

The paper is illustrated with examples of complex structures written using the EFA at the University of Surrey Ion Beam Centre which demonstrate enhanced edge smoothness compared with simple blanked raster scanning.

?Total-IBA? implies the synergistic use of multiple IBA techniques. It has been claimed that Total?IBA inherits the accuracy of the most accurate IBA technique used. A specific example is now given of this where (in vacuo) EBS/PIXE of a glass sample uniform in depth is validated against absolutely calibrated EPMA of the same sample. The EPMA results had a mass closure gap of 2.0 ± 0.6 wt%; the full PIXE analysis determined the composition of this missing 2 wt%. The PIXE calibration was against a single certified glass sample, with uncertainties per line ~10%. Benchmarking also demonstrates ~10% underestimation of the Si scattering cross-section at proton energies ~3 MeV. But the Total-IBA determination of the silica content had a low standard uncertainty of about 2%. This is due to the strong constraints of both the chemical prior and also the mass closure properties of the EBS. Irradiation-induced sodium migration in this soda-lime glass is explored.

This thesis describes the use of proton beam writing (PBW) for the fabrica- tion for microfluidic and microelectromechanical system (MEMS) devices. In particular, the fabrication of three-dimensional (3D) micro or nanostruc- tures with high aspect ratios is of growing interest in these fields. PBW is the only technique that has the capability to satisfy these requirements while providing full control of the geometrical parameters, such as the sur- face roughness and side wall angle. This technique is a direct microfabri- cation method that employs a focused, energetic (MeV) proton beam to structure the input pattern in resist materials.
In the present work, a network of buried channels is fabricated as part of a project to develop a functional microfluidic device for neuronal studies and self-powered microfluidics (capillary micropump). Proton beam with energies of 0.75 to 2.5 MeV is used to fabricate the channels in 3D with a minimum feature size of approximately 1 ¼m and depths of 40 to 60 ¼m. The roughness of the sidewalls of the written channels is approximately 3 nm root mean square roughness (Rrms).
Radio frequency (RF) MEMS switches, which consist of an overhanging structure, are also written using PBW, and new MEMS switch designs are proposed. These designs are constructed so as to provide full control of the main cantilever beam parameters, such as the thickness, spring constant, and actuation.
The three main stages of the lithography process, i.e., pre-exposure, expo- sure, and post-exposure, are investigated and optimised for application to poly(methyl methacrylate)(PMMA), pure SU-8 polymer, and SU-8/silver- nanoparticle nanocomposites (SU-8/AgNp). During the exposure process, the proton beam energies, doses, and scanning method are also optimised, in order to attain a good-quality structure (i.e., a robust structure with smooth and straight walls). The mechanical and electrical properties of the nanocomposites, which are irradiated with a range of proton beam doses, are measured.
Note that the structures written in this work are numerically validated prior to the writing process using COMSOL Multiphysics ýR software. The fluid flow in the written buried channels is investigated using numerical methods.