A Study of the Radiation Tolerance and Timing Properties of 3D Diamond Detectors.

We present a study on the radiation tolerance and timing properties of 3D diamond detectors fabricated by laser engineering on synthetic Chemical Vapor Deposited (CVD) plates. We evaluated the radiation hardness of the sensors using Charge Collection Efficiency (CCE) measurements after neutron fluences up to 1016 n/cm2 (1 MeV equivalent.) The radiation tolerance is significantly higher when moving from standard planar architecture to 3D architecture and increases with the increasing density of the columnar electrodes. Also, the maximum applicable bias voltage before electric breakdown increases significantly after high fluence irradiation, possibly due to the passivation of defects. The experimental analysis allowed us to predict the performance of the devices at higher fluence levels, well in the range of 1016 n/cm2. We summarize the recent results on the time resolution measurements of our test sensors after optimization of the laser fabrication process and outline future activity in developing pixel tracking systems for high luminosity particle physics experiments.

Single cell versus large population analysis: cell variability in elemental intracellular concentration and distribution.

The quantification of elemental concentration in cells is usually performed by analytical assays on large populations missing peculiar but important rare cells. The present article aims at comparing the elemental quantification in single cells and cell population in three different cell types using a new approach for single cells elemental analysis performed at sub-micrometer scale combining X-ray fluorescence microscopy and atomic force microscopy. The attention is focused on the light element Mg, exploiting the opportunity to compare the single cell quantification to the cell population analysis carried out by a highly Mg-selective fluorescent chemosensor. The results show that the single cell analysis reveals the same Mg differences found in large population of the different cell strains studied. However, in one of the cell strains, single cell analysis reveals two cells with an exceptionally high intracellular Mg content compared with the other cells of the same strain. The single cell analysis allows mapping Mg and other light elements in whole cells at sub-micrometer scale. A detailed intensity correlation analysis on the two cells with the highest Mg content reveals that Mg subcellular localization correlates with oxygen in a different fashion with respect the other sister cells of the same strain. Graphical abstract Single cells or large population analysis this is the question!

Where is it and how much? Mapping and quantifying elements in single cells.

The biological function of a chemical element in cells not only requires the determination of its intracellular quantity, but also the spatial distribution of its concentration. Different strategies can be employed to quantify and map the intracellular concentration of elements in single cells. The assessment of the intracellular elemental concentration, which is the relevant information, requires the measurement of cell volume. This challenging and demanding task requires combining different techniques allowing gathering of both morphological and compositional information on the same cell. Moreover, the need to analyse samples more similar to their natural state requires complex hardware equipment, and supplementary efforts in preparation protocols. Nevertheless, the response to the question: "where is it and how much?" is worth all these efforts. This review aims at providing an insight into the recent and most advanced techniques and strategies for quantifying and mapping chemical elements in single cells. We describe and discuss indirect detection techniques (label based) which make use of fluorescent dyes, and direct ones (label free), such as particle induced X-ray emission, proton backscattering spectrometry, scanning transmission ion spectrometry, nano-secondary ion mass spectrometry, X-ray fluorescence microscopy, complemented by X-ray imaging.

Quantitative chemical imaging of the intracellular spatial distribution of fundamental elements and light metals in single cells.

We report a method that allows a complete quantitative characterization of whole single cells, assessing the total amount of carbon, nitrogen, oxygen, sodium, and magnesium and providing submicrometer maps of element molar concentration, cell density, mass, and volume. This approach allows quantifying elements down to 10(6) atoms/µm(3). This result was obtained by applying a multimodal fusion approach that combines synchrotron radiation microscopy techniques with off-line atomic force microscopy. The method proposed permits us to find the element concentration in addition to the mass fraction and provides a deeper and more complete knowledge of cell composition. We performed measurements on LoVo human colon cancer cells sensitive (LoVo-S) and resistant (LoVo-R) to doxorubicin. The comparison of LoVo-S and LoVo-R revealed different patterns in the maps of Mg concentration with higher values within the nucleus in LoVo-R and in the perinuclear region in LoVo-S cells. This feature was not so evident for the other elements, suggesting that Mg compartmentalization could be a significant trait of the drug-resistant cells.

Periodically structured X-ray waveguides.

The properties of X-ray vacuum-gap waveguides (WGs) with additional periodic structure on one of the reflecting walls are studied. Theoretical considerations, numerical simulations and experimental results confirm that the periodic structure imposes additional conditions on efficient propagation of the electromagnetic field along the WGs. The transmission is maximum for guided modes that possess sufficient phase synchronism with the periodic structure (here called `super-resonances'). The field inside the WGs is essentially given at low incidence angle by the fundamental mode strongly coupled with the corresponding phased-matched mode. Both the simulated and the experimental diffraction patterns show in the far field that propagation takes place essentially only for low incidence angles, confirming the mode filtering properties of the structured X-ray waveguides.

Performance of 3D diamond detectors in small field dosimetry: The impact of pixel size.

PURPOSE: Small photon beams used in radiotherapy techniques have inherent characteristics of charge particle disequilibrium and high-dose gradient making accurate dosimetry for such fields very challenging. By means of a 3D manufacturing technique, it is possible to create arrays of pixels with a very small sensitive volume for radiotherapy dosimetry. We investigate the impact of 3D pixels size on absorbed dose sensitivity, linearity of response with dose rate, reproducibility and beam profile measurements. METHODS: Diamond detectors with different pixel sizes have been produced in the 3DOSE experiment framework. To investigate the pixels size impact, they were tested using an Elekta Synergy LINAC. Dose rate dependence, absorbed dose sensitivity, reproducibility and beam profile measurement accuracy have been investigated and compared with PTW 60019 and IBA SFD reference dosimeters. RESULTS: All of the 3D pixels had a linear and reproducible response to the dose rate. The sensitivity of a pixel decreases with its size, although even the smallest pixel has a high absorbed dose sensitivity (15 nC/Gy). The penumbra width measured with the smallest pixel size was consistent with the PTW microDiamond and differed by 0.2 mm from the IBA SFD diode. CONCLUSIONS: The study demonstrates that variation in pixel size do not affect the linearity of response with dose rate and the reproducibility of response. Due to the 3D geometry, the absorbed dose sensitivity of the detector remains high even for the smallest pixel, furthermore the pixel size was demonstrated to be of fundamental importance in the measurement of beam profiles.

Resonance modes filtering in structured x-ray waveguides.

We discuss the self-imaging effect that occurs in a multimode planar x-ray waveguide (WG) with a nanometer vacuum gap, where an additional longitudinal periodicity has been imposed by a periodical structure (a micron scale step-like grating) on the reflecting sidewalls. Taking into account the general Montgomery conditions and the particular case of Talbot effect, we show that this additional longitudinal periodicity, if suitably designed, can filter out the asymmetric and the high order resonance modes, providing a coherent beam at the exit, even if the WG is illuminated by an incoherent source.

Analysis of tapered front-coupling X-ray waveguides.

The coupling and propagation of electromagnetic waves through planar X-ray waveguides (WG) with vacuum gap and Si claddings are analyzed in detail, starting from the source and ending at the detector. The general case of linearly tapered WGs (i.e. with the entrance aperture different from the exit one) is considered. Different kinds of sources, i.e. synchrotron radiation and laboratory desk-top sources, have been considered, with the former providing a fully coherent incoming beam and the latter partially coherent beams. It is demonstrated that useful information about the parameters of the WG can be derived, comparing experimental results with computer simulation based on analytical solutions of the Helmholtz equation which take into account the amplitude and phase matching between the standing waves created in front of the WG, and the resonance modes propagating into the WG.

X-ray phase contrast microscopy at 300 nm resolution with laboratory sources.

We report the performance of an X-ray phase contrast microscope for laboratory sources with 300 nm spatial resolution. The microscope is based on a commercial X-ray microfocus source equipped with a planar X-ray waveguide able to produce a sub-micrometer x-ray beam in one dimension. Phase contrast images of representative samples are reported. The achieved contrast and resolution is discussed for different configurations. The proposed approach could represent a simple, inexpensive, solution for sub-micrometer resolution imaging with small laboratory setups.

In-line phase-contrast imaging for strong absorbing objects.

Phase-contrast imaging is one of the most important emerging x-ray imaging techniques. In this work we analyse, from a theoretical point of view, the in-line phase-contrast image formation under general assumptions. The approach is based on wave-optical theory (Fresnel/Kirchoff diffraction integrals) and on the formalism of the mutual coherence function for the evolution of the coherence wavefield properties. Our theoretical model can be applied to phase-contrast imaging realized both by using highly coherent synchrotron radiation and micro-focus x-ray laboratory sources. Thus, the model is suitable for widespread applications, ranging from material science to medical imaging of human body parts. However, it cannot be applied to polychromatic sources, although the validity of the model does not require particularly demanding characteristics of monochromaticity. In addition, for moderate phase gradients, a useful analytical formula of the phase-contrast visibility is derived, based on the a priori knowledge of source size and distance, pixel detector size, defocus distance, material/tissue dielectric susceptibility and characteristic scales of transversal and longitudinal non-uniformities of the material/tissue dielectric susceptibility. Comparisons both with experimental results published by other authors and with simulations based on a Fourier optics approach have been reported, to confirm the validity of the proposed analytical formula

Debye function analysis and 2D imaging of nanoscaled engineered bone.

The Debye Function Analysis of diffraction patterns from nanosized mineral crystals showing different average degrees of maturity was carried out on engineered bone samples. The analysis relied on a bivariate family of atomistic hydroxyapatite nanocrystal models and provided information about crystal structure, size and shape distributions of the mineral component of the newly formed bone. An average rod-like shape of nanocrystals was found in all samples, with average sizes well matching the collagen I gap region. The diffraction patterns investigated through the Debye Function Analysis were used as signal models to perform the Canonical Correlation Analysis of high resolution X-ray micro-diffraction patterns collected on porous and resorbable hydroxyapatite/silicon-stabilized tricalcium phosphate (Si-TCP) implants. The nosologic maps clearly showed a size gradient in the new formed bone that validates the mechanism (mimicking the bone remodelling in orthotopic bones) of a continuous deposition of bone by osteoblasts, an increasing mineralization of the newly deposited bone, a growth of the new crystals, at the same time that osteoclasts adhere to the scaffold surface and resorb the bioceramic. The comparison of samples at different implantation times proved that the selective resorption of Si-TCP component from the scaffold was already evident after two and almost complete after six months.

Efficiency of an elliptically shaped x-ray mirror.

Curved reflecting mirrors are widely used as x-ray optical elements for both laboratory and synchrotron radiation sources. In general, the mirror parameters are optimized by numerical simulation. We discuss an analytical approach that is useful for deriving the mirror parameters, including eccentricity, length, angular acceptance, and magnification. We have examined in particular an elliptical surface from which we learned that, given the distance between the foci of the ellipse, the magnification, and the critical angle of total external reflection, it is possible to find analytically the optimal eccentricity that maximizes the angular acceptance and the optimal mirror length. We found that the last-named parameter, in a first approximation, depends only on the distance between the foci of the ellipse and on the magnification factor. We present as well a comparison of optimal parameters obtained with analytical calculation and with ray-tracing simulation that yielded good agreement.