Laboratory Sources Research Articles

Current High-Throughput Approaches of Screening Modulatory Effects of Xenobiotics on Cytochrome P450 (CYP) Enzymes.

Cytochrome P450 (CYP) is a critical drug-metabolizing enzyme superfamily. Modulation of CYP enzyme activities has the potential to cause drug–drug/herb interactions. Drug–drug/herb interactions can lead to serious adverse drug reactions (ADRs) or drug failures. Therefore, there is a need to examine the modulatory effects of new drug entities or herbal preparations on a wide range of CYP isoforms. The classic method of quantifying CYP enzyme activities is based on high-performance liquid chromatography (HPLC), which is time- and reagent-consuming. In the past two decades, high-throughput screening methods including fluorescence-based, luminescence-based, and mass-spectrometry-based assays have been developed and widely applied to estimate CYP enzyme activities. In general, these methods are faster and use lower volume of reagents than HPLC. However, each high-throughput method has its own limitations. Investigators may make a selection of these methods based on the available equipment in the laboratory, budget, and enzyme sources supplied. Furthermore, the current high-throughput systems should look into developing a reliable automation mechanism to accomplish ultra-high-throughput screening in the near future.

X‐Ray Topography Characterization of the Bridgman‐Grown Crystals of Zinc Germanium Phosphide

AbstractSamples of the Bridgman‐grown nonlinear optic crystal of ZnGeP2 are studied using the methods of topography on a laboratory source and on a synchrotron radiation source. Methods of quasi‐plane‐wave topography, white beam topography, and rocking curve topography are used. Dislocation bundles, growth striations, small‐angle boundaries, and other defects are observed. The macroscopic distribution of defects in crystals and disorientations present in the crystal are studied. The mechanism of formation of images of growth striations is discussed. Digital analysis of the growth striations is carried out to characterize the growth process.

Characterization and performance of the DTAS detector

DTAS is a segmented total absorption γ-ray spectrometer developed for the DESPEC experiment at FAIR. It is composed of up to eighteen NaI(Tl) crystals. In this work we study the performance of this detector with laboratory sources and also under real experimental conditions. We present a procedure to reconstruct offline the sum of the energy deposited in all the crystals of the spectrometer, which is complicated by the effect of NaI(Tl) light-yield non-proportionality. The use of a system to correct for time variations of the gain in individual detector modules, based on a light pulse generator, is demonstrated. We describe also an event-based method to evaluate the summing-pileup electronic distortion in segmented spectrometers. All of this allows a careful characterization of the detector with Monte Carlo simulations that is needed to calculate the response function for the analysis of total absorption γ-ray spectroscopy data. Special attention was paid to the interaction of neutrons with the spectrometer, since they are a source of contamination in studies of β-delayed neutron emitting nuclei.

Analysis and Simulation of the Illumination Optics of Rigid Medical Endoscopes

Abstract Our work focuses on enhancing the illumination optics of a rigid medical endoscope using optomechanical simulation. We aim on improving the efficiency of the illumination optics to provide more light in the surgeon’s field of view (FOV) and therefore better image quality. We conducted an extensive market analysis and measured several rigid endoscopes and their external light sources in the lighting technology laboratory. Surprisingly, all endoscopes showed a degree of efficiency below 20 %. Our optimization approach is based first on a photometric and colorimetric analysis carried out with an integrating sphere and a goniophotometer. Secondly, the results obtained are implemented in a 3Doptomechanical simulation model developed with the raytracing software LightTools (Synopsis©). In the simulation model both the geometrical components as well as the critical interfaces are examined considering light coupling at boundary surfaces and light transfer within the illumination optics. Moreover, the optimization takes into account spectral power distribution (SPD) and angular light distribution (ALD) of the light provided from the fiberoptic cable connected to an external light source as well as additional interfering factors like gluing, dispersive absorption and total reflection at critical angles.

Beamforming shallow water propagation of mid-frequency acoustics on the Chukchi Shelf

The shallow water Canadian Basin Acoustic Propagation Experiment (CANAPE 2016–2017) was designed to study the effect of oceanographic variability on the acoustic field in the Arctic. The physics of the acoustic waveguide on the Northeastern edge of the Chukchi Shelf are influenced by dynamic boundary conditions and spatio-temporal fluctuations in temperature/salinity profiles, including the upwelling of Atlantic bottom water, sinking Bering Sea surface water and sub-mesoscale eddy formation. These fluctuations influence the acoustic waveguide characteristics of a persistent sound speed channel centered at 150 m depth. The University of Delaware (UDel) deployed seven oceanographic moorings (OM) perpendicular to the isobaths on the Chukchi Shelf (145–700 m depth). A Naval Research Lab source (S1) was deployed in-line with the OMs, generating Linear Frequency Modulated (LFM) signals in alternating 700–1100 Hz and 1400–4000 Hz bands. A Vertical Line Array (VLA) was deployed in-line and within the span of the OMs. The array aperture spanned the depth of the sound speed channel. Beamforming measurements from the VLA in combination with environmental measurements and 2D PE model output will determine the degree of influence of individual physical oceanography processes on the spatio-temporal structure of the sound channel and internal acoustic wave propagation.

Single-shot X-ray dark-field imaging with omnidirectional sensitivity using random-pattern wavefront modulator

With the development of multi-modal x-ray imaging techniques, dark-field signals have drawn increasing interest due to the complementary information to the conventional attenuation-contrast signal. The directional sensitivity of the dark-field signal can reveal the orientation of the microstructure of the imaged object. We propose to use single-shot dark-field imaging with a random-pattern wavefront modulator to achieve omni-directional sensitivity, which will be valuable for the study of strongly ordered systems. Compared to previous studies, the proposed method shows significant advance by requiring neither dedicated fabrication of x-ray optics nor prolonged scanning. The treatment has been demonstrated on images acquired both at synchrotron facilities and with a laboratory source. The flexibility and the accessibility ensure the potential for easy implementation of the method to benefit a wide range of fields.

An examination of beta dose attenuation effects in coarse grains located in sliced samples

Previous work has demonstrated the feasibility of performing spatially resolved luminescence measurements with sliced solid materials (e.g., rock and ceramic) to determine the cumulative absorbed dose to individual luminescent grains in situ. In the present study, aspects of the dosimetry of individual grains that are truncated during slicing were examined using radiation transport simulations employing simplified geometries. The results of the simulations were applied to model the effect of grain truncation on the dosimetry of grains, in particular the beta attenuation factor and the laboratory beta source dose rate for whole and partial volumes of individual spherical grains. Where a material contains a wide range of coarse grain sizes there is the potential for misinterpreting the size of the parent grain on the basis of an examination of the shape and size of the truncated grain section exposed in the slice surface. If the original grain size is underestimated, which is likely, the simulations predict an overestimation of both the beta attenuation factor and the laboratory source beta dose rate, the maximum extent of which depends on the range of grain sizes present in the material. The simulations also indicate that by limiting the depth from the surface within which the average absorbed dose is determined, approximating the effects of opacity of the mineral, the magnitude of these deviations is reduced. However, a consequence of particular interest deriving from these results is that, when evaluating the age equation, the changes in the two quantities compensate, acting to moderate the overall effect on the calculated age for an individual grain, depending on the geometry of the grain and the composition of the sample material.

CALSPEC: HST Spectrophotometric Standards at 0.115 to 32 μm with a 1% Accuracy Goal

AbstractThe flux distributions of spectrophotometric standard stars were initially derived from the comparison of stars to laboratory sources of known flux but are now based on calculated model atmospheres. For example, pure hydrogen white dwarf (WD) models provide the basis for the HST CALSPEC archive of flux standards. There is good evidence that relative fluxes from the visible to the near-IR wavelength of ∼2.5 μm are currently accurate to ∼1% for the primary reference standards.

3D Nanoprinted Plastic Kinoform X-Ray Optics.

High-performance focusing of X-rays requires the realization of very challenging 3D geometries with nanoscale features, sub-millimeter-scale apertures, and high aspect ratios. A particularly difficult structure is the profile of an ideal zone plate called a kinoform, which is manufactured in nonideal approximated patterns, nonetheless requires complicated multistep fabrication processes. Here, 3D fabrication of high-performance kinoforms with unprecedented aspect ratios out of low-loss plastics using femtosecond two-photon 3D nanoprinting is presented. A thorough characterization of the 3D-printed kinoforms using direct soft X-ray imaging and ptychography demonstrates superior performance with an efficiency reaching up to 20%. An extended concept is proposed for on-chip integration of various X-ray optics toward high-fidelity control of X-ray wavefronts and ultimate efficiencies even for harder X-rays. Initial results establish new, advanced focusing optics for both synchrotron and laboratory sources for a large variety of X-ray techniques and applications ranging from materials science to medicine.

Improved phase-attenuation duality method with space-frequency joint domain iterative regularization.

A common problem of in-line phase contrast imaging systems based on laboratory source and detector is the negative effects of finite source size, limited spatial resolution, and system noise. These negative effects swamp the fine phase contrast fringes and impede the precise retrieval of phase maps. This study aims to develop a novel phase retrieval method to restore phase information that is lost due to an imperfect system. An improved phase-attenuation duality (PAD) method based on space-frequency joint domain iterative regularization (JDIR) is proposed to overcome the problems of the analytical PAD method and the spatial-domain iterative regularization (SDIR) based PAD method. These problems include noise robustness and optical transfer function compensation. The proposed method was compared with the two former PAD methods through computer simulations and experiments for validation. Results reveal that JDIR method outperforms the other two methods in terms of improving the visibility of structures in the retrieved phase maps. Among all the phase retrieval algorithms, the TV-norm-based JDIR method performed the best in considering the contrast and noise performance. This paper provides a new method to investigate quantitative phase-contrast imaging when considering the negative effects of an imperfect system.

Three-dimensional virtual histology of human cerebellum by X-ray phase-contrast tomography

To quantitatively evaluate brain tissue and its corresponding function, knowledge of the 3D cellular distribution is essential. The gold standard to obtain this information is histology, a destructive and labor-intensive technique where the specimen is sliced and examined under a light microscope, providing 3D information at nonisotropic resolution. To overcome the limitations of conventional histology, we use phase-contrast X-ray tomography with optimized optics, reconstruction, and image analysis, both at a dedicated synchrotron radiation endstation, which we have equipped with X-ray waveguide optics for coherence and wavefront filtering, and at a compact laboratory source. As a proof-of-concept demonstration we probe the 3D cytoarchitecture in millimeter-sized punches of unstained human cerebellum embedded in paraffin and show that isotropic subcellular resolution can be reached at both setups throughout the specimen. To enable a quantitative analysis of the reconstructed data, we demonstrate automatic cell segmentation and localization of over 1 million neurons within the cerebellar cortex. This allows for the analysis of the spatial organization and correlation of cells in all dimensions by borrowing concepts from condensed-matter physics, indicating a strong short-range order and local clustering of the cells in the granular layer. By quantification of 3D neuronal "packing," we can hence shed light on how the human cerebellum accommodates 80% of the total neurons in the brain in only 10% of its volume. In addition, we show that the distribution of neighboring neurons in the granular layer is anisotropic with respect to the Purkinje cell dendrites.

Neutron spectra from Neutron Standards Laboratory (LPN/CIEMAT) sources with two Bonner sphere spectrometers

The Neutron Standards Laboratory (LPN: Laboratorio de Patrones Neutrónicos) of the Ionizing Radiation Metrology Laboratory (LMRI) of the CIEMAT (Centro de Investigaciones Energéticas Medioambientales y Tecnológicas) has two calibration neutron sources, 241Am-Be and 252Cf. Studies to verify the shielding of the facility and to characterize the neutron field in the irradiation room have been carried out using Monte Carlo methods. However, spectral measurements were not performed yet. In this study, we measured the total and direct neutron spectra of both calibration neutron sources. Two different Bonner Sphere Spectrometers (BSS) systems were allocated to 115 cm from the sources, on the calibration bench, with and without the shadow cones (SC). From the count rates obtained with both BSS systems (BSS-6LiI and BSS-3He), the total neutron spectrum and direct neutron spectrum were unfolded. Total and direct spectra obtained for the 241Am-Be and 252Cf sources with the MCNPX and different BSS systems, unfold codes and response matrices presented similar shape and are consistent with each other.

Spectral correction algorithm for multispectral CdTe x-ray detectors

Compared to the dual-energy scintillator detectors widely used today, energy-resolved photon-counting x-ray detectors show the potential to improve material identification in various radiography and tomography applications used for industrial and security purposes. However, detector effects, such as charge sharing and photon pileup, distort the measured spectra in pixelated, photon-counting detectors operating under high flux. These effects result in a significant performance degradation of the detectors when used for material identification where accurate spectral measurements are required. We have developed a semianalytical, postdata acquisition, computational algorithm that corrects the measured attenuation curve for severe spectral distortions caused by the detector. The calibration of the algorithm is based on simple attenuation measurements of commercially available materials using standard laboratory sources, enabling the algorithm to be used in any x-ray setup. The algorithm is developed for correcting spectral data acquired with the MultiX ME100 CdTe x-ray detector but could be adapted with small adjustments to other photon-counting, energy-resolved detectors with CdTe sensors. The validation of the algorithm has been done using experimental data acquired with both a standard laboratory source and synchrotron radiation. The experiments show that the algorithm is fast, reliable at x-ray flux up to 5 Mph / s / mm2 and greatly improves the accuracy of the measured spectrally resolved linear attenuation, making the algorithm useful for both security and industrial applications where photon-counting detectors are used.

In-situ X-ray diffraction on functional thin films using a laboratory source during electrical biasing

A methodology that allows the quantification of structural changes in functional thin films during the application of external electrical field is reported. The originality of this method is the development of a set-up using a laboratory X-ray source since most of previous Operando studies have used synchrotron radiations. Several technical challenges have been addressed: the (i) optimization of the electrical contact and the sample geometry within the lab-source goniometers, (ii) evaluation of any X-ray dose effect on the Metal/Insulator/Metal structure to prevent eventual charge accumulation at the electrode interfaces and (iii) the quantification of the effect of the time-delay, needed for X-ray measurement, on domain switching. The validity of our method has been demonstrated on a prototypic sol-gel lead zirconate titanate (PZT) thin film where the polarization and structural changes have been simultaneously measured. The evolution of ferroelastic domains as a function of external electric field has been quantified and two different effects have been successfully separated: (a) the cell extension and (b) domain wall motion described as the switching between a and c tetragonal domains.

X-ray fluorescence microtomography based on polycapillary-focused X-rays from laboratory source

X-ray fluorescence microtomography (mu XFCT) is a nondestructive analytical technique and has been widely used to nondestructively detect and quantify the elemental composition and distributions in samples. Usually, synchrotron radiation X-rays are used for mu XFCT, due to its high flux density. In this paper, a laboratory-sourcebased mu XFCT system was developed, in which a polycapillary lens is employed to focus the X-ray beam and improve the flux density. The maximum likelihood expectation maximization algorithm was used to reconstruct the computed tomography slices at a limited number of projections. The experimental results demonstrated that the developed system could reveal the elemental distribution inside the test sample, with an elemental sensitivity of 1000 ppm.

State of the Art of X-ray Speckle-Based Phase-Contrast and Dark-Field Imaging

In the past few years, X-ray phase-contrast and dark-field imaging have evolved to be invaluable tools for non-destructive sample visualisation, delivering information inaccessible by conventional absorption imaging. X-ray phase-sensing techniques are furthermore increasingly used for at-wavelength metrology and optics characterisation. One of the latest additions to the group of differential phase-contrast methods is the X-ray speckle-based technique. It has drawn significant attention due to its simple and flexible experimental arrangement, cost-effectiveness and multimodal character, amongst others. Since its first demonstration at highly brilliant synchrotron sources, the method has seen rapid development, including the translation to polychromatic laboratory sources and extension to higher-energy X-rays. Recently, different advanced acquisition schemes have been proposed to tackle some of the main limitations of previous implementations. Current applications of the speckle-based method range from optics characterisation and wavefront measurement to biomedical imaging and materials science. This review provides an overview of the state of the art of the X-ray speckle-based technique. Its basic principles and different experimental implementations as well as the the latest advances and applications are illustrated. In the end, an outlook for anticipated future developments of this promising technique is given.

Macroscopic X-ray Powder Diffraction Scanning, a New Method for Highly Selective Chemical Imaging of Works of Art: Instrument Optimization.

In the past decade macroscopic X-ray fluorescence imaging (MA-XRF) has become established as a method for the noninvasive investigation of flat painted surfaces, yielding large scale elemental maps. MA-XRF is limited by a lack of specificity, only allowing for indirect pigment identification based on the simultaneous presence of chemical elements. The high specificity of X-ray powder diffraction (XRPD) mapping is already being exploited at synchrotron facilities for investigations at the (sub)microscopic scale, but the technique has not yet been employed using lab sources. In this paper we present the development of a novel MA-XRPD/XRF instrument based on a laboratory X-ray source. Several combinations of X-ray sources and area detectors are evaluated in terms of their spatial and angular resolution and their sensitivity. The highly specific imaging capability of the combined MA-XRPD/XRF instrument is demonstrated on a 15th/16th century illuminated manuscript directly revealing the distribution of a large number of inorganic pigments, including the uncommon yellow pigment massicot ( o-PbO). The case study illustrates the wealth of new mapping information that can be obtained in a noninvasive manner using the laboratory MA-XRPD/XRF instrument.

Beam tracking phase tomography with laboratory sources

An X-ray phase-contrast laboratory system is presented, based on the beam-tracking method. Beam-tracking relies on creating micro-beamlets of radiation by placing a structured mask before the sample, and analysing them by using a detector with sufficient resolution. The system is used in tomographic configuration to measure the three dimensional distribution of the linear attenuation coefficient, difference from unity of the real part of the refractive index, and of the local scattering power of specimens. The complementarity of the three signals is investigated, together with their potential use for material discrimination.

Oil, bitumen, and other confusing concepts: What do lab experiments really tell us?

Using the terms bitumen and oil carelessly and failing to properly separate chemical reactions from mass transport processes can lead to models that fail when applied to natural processes. Data from both laboratory experiments and source rock measurements are used to develop a self-consistent picture of generation of C15+ extractable organic matter (EOM), lighter hydrocarbons (HC), and the fractionation that occurs during expulsion from the rock in either laboratory experiments or nature. Despite statements in the literature, hydrocarbons are generated immediately from kerogen in parallel with heavy compounds containing nitrogen, sulfur, and oxygen (NSOs) and probably with similar rate constants from kerogen and NSOs under all conditions because the same bonds are being broken to form them. Peak concentrations of C15+ EOM in the rock occur prior to peak generation of unexpelled HC because of weaker bonds being broken, not because of a sequential chemical reaction mechanism. This earlier generation of C15+ EOM relative to HC is similar for semiopen experiments, hydrous pyrolysis, and in nature, as is the fractionation of chemical types during expulsion. Properly derived activation energies for expelled oil formation from open, semiopen, and hydrous pyrolysis are similar once transport contributions are considered.

Development of high intensity X-ray sources at the National Ignition Facility

Laser heated plasmas have provided recently some of the most powerful and energetic nanosecond length laboratory sources of x-ray photons (Ephoton = 1–30 keV). The highest x-ray to laser conversion is currently accessible by using underdense (ne ∼ 0.25 nc) plasmas since optimal laser coupling is obtained in millimeter scale targets. The targets can have conversion efficiencies of up to 10%. Several types of targets can be used to produce underdense plasmas: metal lined cylindrical cavities, gas pipes, and most recently nano-wire foams. Both the experimental and simulation details of these high intensity x-ray sources are discussed.