Electron Dose Research Articles

Parameter measurement and optimization for a 3/6 dual-energy electron linear accelerator with industrial and inspection applications

Electron linear accelerator (LINAC) is a high-energy X-ray generator with extensive industrial, inspection, and medical applications. The studied LINAC uses a 2.6 MW magnetron as its RF generator derived with a Marx modulator. An electron gun of filament voltage 6 V and current 2.2 A connected to the accelerator tube is applied to establish electron current inside the drift tube. For this purpose, 9 kV and 25 kV voltages are applied to the cathode and anode of the electron gun pulse by pulse, generating dual-energy x-ray beams as outputs. An Automatic Frequency Control (AFC) system is designed for studied LINAC so that variation of output dose rate is lower than 2% and the required time to achieve the maximum output dose rate is lower than 1 s. Optimizing the Marx modulator's switching algorithm, the ripple in the output beam has been lower than 5%. The half-value layer (HVL) of steel has been measured for high and low energies equal to 6 MeV and 3 MeV, respectively. The output pulse of the electron beam and dose rate have been measured using a linear detector array (LDA) and dosimeter, respectively, with a pulse frequency of 35–400 Hz and pulse width of 2–4 μs.

Study of the backscattering of electron beams with energies typical of radiotherapy

During radiotherapy, the dose of electrons backscattered into the tissue should be taken into account. According to the available data on the electron backscattering phenomenon, the backscatter rate varies depending on the specific radiotherapy delivery configuration. Using the Monte Carlo code MCNPX, the backscattering distribution and their saturation values for electron beams with energies between 4 MeV and 25 MeV (the energies used in electron therapy) of various materials such as polystyrene, aluminum, copper and lead were obtained. Data obtained with MCNPX show that the probability of electron backscattering is strongly dependent on the effective atomic number and the energy of the electron. For low energy electrons, the backscattering probability depends less on the energy and is mainly a function of the effective atomic number of the backscatter material. The saturation values of the backscattering are distributed as a linear function of the effective atomic number of the scattering material for all investigated energies. Therefore, it is recommended that equipment and accessories used with patients in electron radiotherapy LINAC be materials with low atomic numbers (Z), and that a layer of low Z material be used over a higher Z material for protection.

Complementary ADF-STEM: a Flexible Approach to Quantitative 4D-STEM

Scanning transmission electron microscopy (STEM) has a broad range of applications in materials characterization, including real-space imaging, spectroscopy, and diffraction, at length scales from the micron to sub-Ångström. The recent development and adoption of high-speed, direct electron STEM detectors has enabled diffraction patterns to be collected at each probe position, generating four-dimensional STEM (4D-STEM) datasets and opening new imaging modalities. However, the limited pixel numbers in these detectors enforce a tradeoff between angular resolution and maximum collection angle. In this paper, we describe a straightforward method for quantifying 4D-STEM data by utilizing the full flux of the electron beam, including electrons scattered beyond the limits of the detector. This enables significantly increased experimental flexibility, including the synthesis of quantitative, high-contrast complementary annular dark field (cADF) STEM images from low-angle diffraction patterns whilst maintaining high angular resolution; as well as the optimization of electron dose and the more effective use of low dynamic range detectors.

Electronic cigarettes (vapes) are an old threat to health in a new guise

Electronic nicotine dosing systems, commonly known as electronic cigarettes or vapes, have quickly become the most common tobacco products used by teenagers and young people, largely due to the marketing and advertising of the companies that produce them. The appearance of nicotine-free vapes is a new round in the production of electronic cigarettes. Due to the widespread opinion about the harmlessness of such vapes, they are increasingly being used by children and adolescents. The review describes the composition of vaping aerosols, provides data from scientific research on their impact on human health. The danger of smoking both nicotine and nicotine-free vapes is shown. However, given the relative short duration of the use of electronic cigarettes, there are many both purely medical and legal questions. All these issues require further research, which continues all over the world. The authors recommend being wary of this habit and the newfangled hobby of teenagers and young people, applying knowledge about the dangers of vaping in everyday practice, which will indirectly help children and adolescents avoid the path of nicotine addiction, protecting the health of the younger generation.

Rapid pattern formation in model cell membranes when using an electron beam

Patterning of supported lipid bilayers (SLBs) is a fundamental tool for mimicking and modeling of biological membranes, but it still remains a challenge to achieve resetting and retriggering for the membrane-mediated processes of the patterned SLBs. This paper reports that indirect scanning of an electron beam (EB) enables repeatable patterning and remodeling of SLBs. By indirect scanning of the EB onto SLBs through a 100-nm-thick silicon nitride membrane, chemical and electrical effects of scattered electrons can be applied to lipid molecules in SLBs; application of these effects enables formation and annihilation of diffusion barriers in SLBs. Two-dimensional patterning of SLBs was demonstrated to be controllable by changing the electron dose of the EB and two phenomena were applied to realize repeatable wiping off and wetting of SLB patterns. Moreover, respreading of SLBs was determined as able to induce remodeling of a raft domain in phase-separated SLBs. The proposed method will lead to a prototyping tool for mimicking cell membranes to design interactions of cells and membrane proteins as well as SLB-based microchips.

Experimental Guidelines to Image Transient Single-Molecule Events Using Graphene Liquid Cell Electron Microscopy.

In quest of the holy grail to "see" how individual molecules interact in liquid environments, single-molecule imaging methods now include liquid-phase electron microscopy, whose resolution can be nanometers in space and several frames per second in time using an ordinary electron microscope that is routinely available to many researchers. However, with the current state of the art, protocols that sound similar to those described in the literature lead to outcomes that can differ. The key challenge is to achieve sample contrast under a safe electron dose within a frame rate adequate to capture the molecular process. Here, we present such examples from different systems─synthetic polymer, lipid assembly, DNA-enzyme─in which we have done this using graphene liquid cells. We describe detailed experimental procedures and share empirical experience for conducting successful experiments, starting from fabrication of a graphene liquid cell, to identification of high-quality liquid pockets from desirable shapes and sizes, to effective searching for target sample pockets under electron microscopy, and to discrimination of sample molecules and molecular processes of interest. These experimental tips can assist others who wish to make use of this method.

Experimental reconstructions of 3D atomic structures from electron microscopy images using a Bayesian genetic algorithm

We introduce a Bayesian genetic algorithm for reconstructing atomic models of monotype crystalline nanoparticles from a single projection using Z-contrast imaging. The number of atoms in a projected atomic column obtained from annular dark field scanning transmission electron microscopy images serves as an input for the initial three-dimensional model. The algorithm minimizes the energy of the structure while utilizing a priori information about the finite precision of the atom-counting results and neighbor-mass relations. The results show promising prospects for obtaining reliable reconstructions of beam-sensitive nanoparticles during dynamical processes from images acquired with sufficiently low incident electron doses.

Analysis and comparison of electron radiation damage assessments in Cryo-EM by single particle analysis and micro-crystal electron diffraction.

Electron radiation damage to macromolecules is an inevitable resolution limit factor in all major structural determination applications using cryo-electron microscopy (cryo-EM). Single particle analysis (SPA) and micro-crystal electron diffraction (MicroED) have been employed to assess radiation damage with a variety of protein complexes. Although radiation induced sidechain density loss and resolution decay were observed by both methods, the minimum dose of electron irradiation reducing high-resolution limit reported by SPA is more than ten folds higher than measured by MicroED using the conventional dose concept, and there is a gap between the attained resolutions assessed by these two methods. We compared and analyzed these two approaches side-by-side in detail from several aspects to identify some crucial determinants and to explain this discrepancy. Probability of a high energy electron being inelastically scattered by a macromolecule is proportional to number of layers of the molecules in its transmission path. As a result, the same electron dose could induce much more site-specific damage to macromolecules in 3D protein crystal than single particle samples. Major differences in data collection and processing scheme are the key factors to different levels of sensitivity to radiation damage at high resolution between the two methods. High resolution electron diffraction in MicroED dataset is very sensitive to global damage to 3D protein crystals with low dose accumulation, and its intensity attenuation rates at atomic resolution shell could be applied for estimating ratio of damaged and total selected single particles for SPA. More in-depth systematically radiation damage assessments using SPA and MicroED will benefit all applications of cryo-EM, especially cellular structure analysis by tomography.

Development and Evaluation of a Thimble-Like Head Bolus Shield for Hemi-Body Electron Beam Irradiation Technique

Background: The hemi-body electron beam irradiation (HBIe<sup>–</sup>) technique has been proposed for the treatment of mycosis fungoides. It spares healthy skin using an electron shield. However, shielding electrons is complicated owing to electron scattering effects. In this study, we developed a thimble-like head bolus shield that surrounds the patient’s entire head to prevent irradiation of the head during HBIe<sup>–</sup>.Materials and Methods: The feasibility of a thimble-like head bolus shield was evaluated using a simplified Geant4 Monte Carlo (MC) simulation. Subsequently, the head bolus was manufactured using a three-dimensional (3D) printed mold and Ecoflex 00-30 silicone. The fabricated head bolus was experimentally validated by measuring the dose to the Rando phantom using a metal-oxide-semiconductor field-effect transistor (MOSFET) detector with clinical configuration of HBIe<sup>–</sup>.Results and Discussion: The thimble-like head bolus reduced the electron fluence by 2% compared with that without a shield in the MC simulations. In addition, an improvement in fluence degradation outside the head shield was observed. In the experimental validation using the inhouse- developed bolus shield, this head bolus reduced the electron dose to approximately 2.5% of the prescribed dose.Conclusion: A thimble-like head bolus shield for the HBIe<sup>–</sup> technique was developed and validated in this study. This bolus effectively spares healthy skin without underdosage in the region of the target skin in HBIe<sup>–</sup>.

Optimal experiment design for element specific atom counting using multiple annular dark field scanning transmission electron microscopy detectors

This paper investigates the possible benefits for counting atoms of different chemical nature when analysing multiple 2D scanning transmission electron microscopy (STEM) images resulting from independent annular dark field (ADF) detector regimes. To reach this goal, the principles of statistical detection theory are used to quantify the probability of error when determining the number of atoms in atomic columns consisting of multiple types of elements. In order to apply this theory, atom-counting is formulated as a statistical hypothesis test, where each hypothesis corresponds to a specific number of atoms of each atom type in an atomic column. The probability of error, which is limited by the unavoidable presence of electron counting noise, can then be computed from scattering-cross sections extracted from multiple ADF STEM images. Minimisation of the probability of error as a function of the inner and outer angles of a specified number of independent ADF collection regimes results in optimal experimental designs. Based on simulations of spherical Au@Ag and Au@Pt core–shell nanoparticles, we investigate how the combination of two non-overlapping detector regimes helps to improve the probability of error when unscrambling two types of atoms. In particular, the combination of a narrow low angle ADF detector with a detector formed by the remaining annular collection regime is found to be optimal. The benefit is more significant if the atomic number Z difference becomes larger. In addition, we show the benefit of subdividing the detector regime into three collection areas for heterogeneous nanostructures based on a structure consisting of three types of elements, e.g., a mixture of Au, Ag and Al atoms. Finally, these results are compared with the probability of error resulting when one would ultimately use a pixelated 4D STEM detector and how this could help to further reduce the incident electron dose.

The influence of illumination conditions in the measurement of built-in electric field at p–n junctions by 4D-STEM

Momentum resolved 4D-STEM, also called center of mass (CoM) analysis, has been used to measure the long range built-in electric field of a silicon p–n junction. The effect of different STEM modes and the trade-off between spatial resolution and electric field sensitivity are studied. Two acquisition modes are compared: nanobeam and low magnification (LM) modes. A thermal noise free Medipix3 direct electron detector with high speed acquisition has been used to study the influence of low electron beam current and millisecond dwell times on the measured electric field and standard deviation. It is shown that LM conditions can underestimate the electric field values due to a bigger probe size used but provide an improvement of almost one order of magnitude on the signal-to-noise ratio, leading to a detection limit of 0.011 MV cm−1. It is observed that the CoM results do not vary with acquisition time or electron dose as low as 24 e−/A2, showing that the electron beam does not influence the built-in electric field and that this method can be robust for studying beam sensitive materials, where a low dose is needed.

Automated calculations for computing the sample-limited spatial resolution in (scanning) transmission electron microscopy

MATLAB scripts were designed to compute the sample-limited spatial resolution in transmission electron microscopy (TEM) and scanning TEM (STEM) as a function of different microscopy parameters including the electron dose eD, sample geometry, and materials parameters. The scripts can be used to select the optimum microscopy modality and optimize the experimental conditions to achieve the best possible resolution considering the limitations set by both the electron optics and the examined sample. The resolution can be computed as function of the objective opening semi-angle α for TEM and detector opening semi-angle β for STEM. Optional code for computing a range over the sample thickness t or eD are provided as well, whereby the opening angle is optimized for each data point. The spatial resolution depends on the type of material of the nanoscale object (for example, gold or carbon nanoparticles), the type of matrix holding the objects (for example, water or ice), the depth of the nanoscale object inside the matrix, and eD. The optimization is consistent with the typical situation that carbon nanoparticles are best examined with TEM embedded in a thin matrix (t = 0.1 µm), while STEM is better suited for high atomic number objects such as gold nanoparticles in water, irrespective of t. The script also calculates the reduction of beam broadening in thick samples (t > 1 µm) using bright field STEM.

Cryo-electron tomography related radiation-damage parameters for individual-molecule 3D structure determination.

To understand the dynamic structure–function relationship of soft- and biomolecules, the determination of the three-dimensional (3D) structure of each individual molecule (nonaveraged structure) in its native state is sought-after. Cryo-electron tomography (cryo-ET) is a unique tool for imaging an individual object from a series of tilted views. However, due to radiation damage from the incident electron beam, the tolerable electron dose limits image contrast and the signal-to-noise ratio (SNR) of the data, preventing the 3D structure determination of individual molecules, especially at high-resolution. Although recently developed technologies and techniques, such as the direct electron detector, phase plate, and computational algorithms, can partially improve image contrast/SNR at the same electron dose, the high-resolution structure, such as tertiary structure of individual molecules, has not yet been resolved. Here, we review the cryo-electron microscopy (cryo-EM) and cryo-ET experimental parameters to discuss how these parameters affect the extent of radiation damage. This discussion can guide us in optimizing the experimental strategy to increase the imaging dose or improve image SNR without increasing the radiation damage. With a higher dose, a higher image contrast/SNR can be achieved, which is crucial for individual-molecule 3D structure. With 3D structures determined from an ensemble of individual molecules in different conformations, the molecular mechanism through their biochemical reactions, such as self-folding or synthesis, can be elucidated in a straightforward manner.

Virtual particle Monte Carlo: A new concept to avoid simulating secondary particles in proton therapy dose calculation.

In proton therapy dose calculation, Monte Carlo (MC) simulations are superior in accuracy but more time consuming, compared to analytical calculations. Graphic processing units (GPUs) are effective in accelerating MC simulations but may suffer thread divergence and racing condition in GPU threads that degrades the computing performance due to the generation of secondary particles during nuclear reactions. A novel concept of virtual particle (VP) MC (VPMC) is proposed to avoid simulating secondary particles in GPU-accelerated proton MC dose calculation and take full advantage of the computing power of GPU. Neutrons and gamma rays were ignored as escaping from the human body; doses of electrons, heavy ions, and nuclear fragments were locally deposited; the tracks of deuterons were converted into tracks of protons. These particles, together with primary and secondary protons, are considered to be the realistic particles. Histories of primary and secondary protons were replaced by histories of multiple VPs. Each VP corresponded to one proton (either primary or secondary). A continuous-slowing-down-approximation model, an ionization model, and a large angle scattering event model corresponding to nuclear interactions were developed for VPs by generating probability distribution functions (PDFs) based on simulation results of realistic particles using MCsquare. For efficient calculations, these PDFs were stored in the Compute Unified Device Architecture textures. VPMC was benchmarked with TOPAS and MCsquare in phantoms and with MCsquare in 13 representative patient geometries. Comparisons between the VPMC calculated dose and dose measured in water during patient-specific quality assurance (PSQA) of the selected 13 patients were also carried out. Gamma analysis was used to compare the doses derived from different methods and calculation efficiencies were also compared. Integrated depth dose and lateral dose profiles in both homogeneous and inhomogeneous phantoms all matched well among VPMC, TOPAS, and MCsquare calculations. The 3D-3D gamma passing rates with a criterion of 2%/2mm and a threshold of 10% was 98.49% between MCsquare and TOPAS and 98.31% between VPMC and TOPAS in homogeneous phantoms, and 99.18% between MCsquare and TOPAS and 98.49% between VPMC and TOPAS in inhomogeneous phantoms, respectively. In patient geometries, the 3D-3D gamma passing rates with 2%/2mm/10% between dose distributions from VPMC and MCsquare were 98.56±1.09% in patient geometries. The 2D-3D gamma analysis with 3%/2mm/10% between the VPMC calculated dose distributions and the 2D measured planar dose distributions during PSQA was 98.91±0.88%. VPMC calculation was highly efficient and took 2.84±2.44s to finish for the selected 13 patients running on four NVIDIA Ampere GPUs in patient geometries. VPMC was found to achieve high accuracy and efficiency in proton therapy dose calculation.

Three-dimensional electron ptychography of organic–inorganic hybrid nanostructures

Three dimensional scaffolded DNA origami with inorganic nanoparticles has been used to create tailored multidimensional nanostructures. However, the image contrast of DNA is poorer than those of the heavy nanoparticles in conventional transmission electron microscopy at high defocus so that the biological and non-biological components in 3D scaffolds cannot be simultaneously resolved using tomography of samples in a native state. We demonstrate the use of electron ptychography to recover high contrast phase information from all components in a DNA origami scaffold without staining. We further quantitatively evaluate the enhancement of contrast in comparison with conventional transmission electron microscopy. In addition, We show that for ptychography post-reconstruction focusing simplifies the workflow and reduces electron dose and beam damage.

Direct Location of Organic Molecules in Framework Materials by Three-Dimensional Electron Diffraction.

In the study of framework materials, probing interactions between frameworks and organic molecules is one of the most important tasks, which offers us a fundamental understanding of host-guest interactions in gas sorption, separation, catalysis, and framework structure formation. Single-crystal X-ray diffraction (SCXRD) is a conventional method to locate organic species and study such interactions. However, SCXRD demands large crystals whose quality is often vulnerable to, e.g., cracking on the crystals by introducing organic molecules, and this is a major challenge to use SCXRD for structural analysis. With the development of three-dimensional electron diffraction (3D ED), single-crystal structural analysis can be performed on very tiny crystals with sizes on the nanometer scale. Here, we analyze two framework materials, SU-8 and SU-68, with organic molecules inside their inorganic crystal structures. By applying 3D ED, with fast data collection and an ultralow electron dose (0.8-2.6 e- Å-2), we demonstrate for the first time that each nonhydrogen atom from the organic molecules can be ab initio located from structure solution, and they are shown as distinct and well-separated peaks in the difference electrostatic potential maps showing high accuracy and reliability. As a result, two different spatial configurations are identified for the same guest molecule in SU-8. We find that the organic molecules interact with the framework through strong hydrogen bonding, which is the key to immobilizing them at well-defined positions. In addition, we demonstrate that host-guest systems can be studied at room temperature. Providing high accuracy and reliability, we believe that 3D ED can be used as a powerful tool to study host-guest interactions, especially for nanocrystals.

Use of a PLA sleeve to remove electron enhancement in superficial X-ray therapy.

A newly installed superficial X-ray unit was found to produce enhanced electron dose at the skin surface. The ACPSEM kilovoltage dosimetry recommendations suggest using nail varnish within the treatment cones as a method to reduce this dose. In this study, a 3D PLA sleeve was produced and used as an alternative to the nail varnish for energies between 55 and 100kV. Further, plastic wrap was also investigated as an alternative method to reduce dose. It was found that a 1mm printed sleeve, inserted into the treatment cone sufficiently reduced the enhanced dose as measured with a thin-window Exradin chamber to within 3.3% of the dose measured with a Farmer-type ionisation chamber. The use of plastic wrap also reduced the enhanced dose, but impracticalities in its use make it non-viable for routine clinical use.

Spatial Distribution of the Electron Dose and the Effects on Beam Damage in STEM

Spatial Distribution of the Electron Dose and the Effects on Beam Damage in STEM

Using Your Beam Efficiently: Reducing Electron Dose in the STEM via Flyback Compensation

Abstract In the scanning transmission electron microscope, fast-scanning and frame-averaging are two widely used approaches for reducing electron-beam damage and increasing image signal noise ratio which require no additional specialized hardware. Unfortunately, for scans with short pixel dwell-times (less than 5 μs), line flyback time represents an increasingly wasteful overhead. Although beam exposure during flyback causes damage while yielding no useful information, scan coil hysteresis means that eliminating it entirely leads to unacceptably distorted images. In this work, we reduce this flyback to an absolute minimum by calibrating and correcting for this hysteresis in postprocessing. Substantial improvements in dose efficiency can be realized (up to 20%), while crystallographic and spatial fidelity is maintained for displacement/strain measurement.

Electron-beam-induced charging of an Al[formula omitted]O3 nanotip studied using off-axis electron holography

Electrostatic charging of specimens during electron, photon or ion irradiation is a complicated and poorly understood phenomenon, which can affect the acquisition and interpretation of experimental data and alter the functional properties of the constituent materials. It is usually linked to secondary electron emission, but also depends on the geometry and electrical properties of the specimen. Here, we use off-axis electron holography in the transmission electron microscope to study electron-beam-induced charging of an insulating Al2O3 nanotip on a conducting support. The measurements are performed under parallel electron illumination conditions as a function of specimen temperature, electron dose, primary electron energy and surface cleanliness. We observe a lack of reproducibility of charge density measurements after cycling the specimen temperature. Surprisingly, we find both positively and negatively charged regions in closely adjacent parts of the specimen.