Primary Ion Beam Research Articles

Mass Spectrometry Imaging for the Characterization of C═C Localization in Unsaturated Lipid Isomers at the Single-Cell Level.

Unsaturated lipids with carbon-carbon double bonds (C═C) have been implicated in the pathogenesis of various diseases. While mass spectrometry imaging (MSI) has been employed to map the distribution of lipid isomers in tissue sections, the identification of lipid C═C positional isomers at the single-cell level using MSI poses a significant challenge. In this study, we developed a novel approach utilizing ToF-SIMS in conjunction with the Paternò-Büchi (P-B) photochemical reaction to characterize the C═C localization in unsaturated lipid isomers at the single-cell level. The P-B reaction was employed to produce adduct products, which were subsequently subjected to collision-induced dissociation by the primary ion beam of ToF-SIMS to generate characteristic ion pairs indicative of the presence of C═C bonds. Utilizing this approach, lipid isomers in brain and skeletal tissues from mice, as well as different cell lines, were visualized at single-cell resolution. Furthermore, distinct variations in the composition of FA 18:1 isomers across different microregions and cell types were revealed. Our P-B ToF-SIMS approach enables the accurate identification and characterization of complex lipid structures with remarkable spatial resolution and can be helpful in understanding the physiological role of these C═C positional isomers.

Signal oscillations in helium scattering by bismuth atoms in the low energy range

Low Energy Ion Scattering (LEIS) analysis of bismuth selenide (Bi2Se3), a strong 3D topological insulator, revealed oscillations of the detected signal in dependence on primary ion beam energy. Bismuth is a part of the group of elements where oscillatory behaviour was already noticed, such as gallium, indium, or lead. Generally, it is ascribed to quasi-resonant charge exchange processes between primary ion and target atom. Moreover, clear differences exist between data for target atoms in elemental form and for atoms in compound form. A study of Bi signal yields in different material forms was performed for primary He+ projectiles within the energy range from 0.50 to 6.00 keV. A foil of pure Bi, Bi2Se3, Bi2O3 and thin Bi films deposited on several substrates (SiO2, CuOx) by Molecular Beam Epitaxy were analysed. The energy shift in the position of oscillations was observed when the oxygen atoms were present at the surface and bonded to Bi atoms. A description of the Bi ion yield variation is provided to facilitate the quantification process in LEIS.

Measurement of secondary neutron spectra induced by 480 MeV proton and 430 MeV/u 4He beams with a thick aluminum target

Knowledge of the characteristics of secondary neutrons produced by the interaction of Galactic Cosmic Radiation with spacecraft shielding materials is becoming increasingly important for predicting and mitigating biological risks of space explorers during deep-space travel. Hadron accelerators for medical applications are well suited to reproduce part of the conditions found in deep-space in terms of ion species and energies. The objectives of this work are to measure the secondary neutron spectra produced by proton and helium ion beams hitting an aluminum target with energies that correspond to the Galactic Cosmic Radiation peak during solar minimal activity and to validate and compare physical models of Monte Carlo simulations. Neutron spectra were measured with the extended-range Bonner sphere system NEMUS at two positions, 0° and 90° relative to the direction of the primary ion beam. The experimental setup consisted of 480 MeV proton and 430 MeV/u 4He beams colliding with a 30×30×63.5 cm3 aluminum target. The experimental neutron spectra were analyzed using the MAXED unfolding code and compared to several Monte Carlo simulation codes. The results show deviations in terms of the shape of the neutron energy distributions ranging between 1% and 14% and of the integral quantities of fluence and ambient dose equivalent ranging between 1% and 5.2%.

Comparison of Tiling Artifact Removal Methods in Secondary Ion Mass Spectrometry Images.

Time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging is used across many fields for the atomic and molecular characterization of surfaces, with both high sensitivity and high spatial resolution. When large analysis areas are required, standard ToF-SIMS instruments allow for the acquisition of adjoining tiles, which are acquired by rastering the primary ion beam. For such large area scans, tiling artifacts are a ubiquitous challenge, manifesting as intensity gradients across each tile and/or sudden changes in intensity between tiles. Such artifacts are thought to be related to a combination of sample charging, local detector sensitivity issues, and misalignment of the primary ion gun, among other instrumental factors. In this work, we investigated six different computational tiling artifact removal methods: tensor decomposition, multiplicative linear correction, linear discriminant analysis, seamless stitching, simple averaging, and simple interpolating. To ensure robustness in the study, we applied these methods to three hyperspectral ToF-SIMS data sets and one OrbiTrapSIMS data set. Our study includes a carefully designed statistical analysis and a quantitative survey that subjectively assessed the quality of the various methods employed. Our results demonstrate that while certain methods are useful and preferred more often, no one particular approach can be considered universally acceptable and that the effectiveness of the artifact removal method is strongly dependent on the particulars of the data set analyzed. As examples, the multiplicative linear correction and seamless stitching methods tended to score more highly on the subjective survey; however, for some data sets, this led to the introduction of new artifacts. In contrast, simple averaging and interpolation methods scored subjectively poorly on the biological data set, but more highly on the microarray data sets. We discuss and explore these findings in depth and present general recommendations given our findings to conclude the work.

Quantitative and Qualitative Analyses of Mass Spectra of OEL Materials by Artificial Neural Network and Interface Evaluation: Results from a VAMAS Interlaboratory Study.

Quantitative analysis of binary mixtures of tris(2-phenylpyridinato)iridium(III) (Ir(ppy)3) and tris(8-hydroxyquinolinato)aluminum (Alq3) by using an artificial neural network (ANN) system to mass spectra was attempted based on the results of a VAMAS (Versailles Project on Advanced Materials and Standards) interlaboratory study (TW2 A31) to evaluate matrix-effect correction and to investigate interface determination. Monolayers of binary mixtures having different Ir(ppy)3 ratios (0, 0.25, 0.50, 0.75, and 1.00), and the multilayers containing these mixtures and pure samples were measured using time-of-flight secondary ion mass spectrometry (ToF-SIMS) with different primary ion beams, OrbiSIMS (SIMS with both Orbitrap and ToF mass spectrometers), laser desorption ionization (LDI), desorption/ionization induced by neutral clusters (DINeC), and X-ray photoelectron spectroscopy (XPS). The mass spectra were analyzed using a simple ANN with one hidden layer. The Ir(ppy)3 ratios of the unknown samples and the interfaces of the multilayers were predicted using the simple ANN system, even though the mass spectra of binary mixtures exhibited matrix effects. The Ir(ppy)3 ratios at the interfaces indicated by the simple ANN were consistent with the XPS results and the ToF-SIMS depth profiles. The simple ANN system not only provided quantitative information on unknown samples, but also indicated important mass peaks related to each molecule in the samples without a priori information. The important mass peaks indicated by the simple ANN depended on the ionization process. The simple ANN results of the spectra sets obtained by a softer ionization method, such as LDI and DINeC, suggested large ions such as trimers. From the first step of the investigation to build an ANN model for evaluating mixture samples influenced by matrix effects, it was indicated that the simple ANN method is useful for obtaining candidate mass peaks for identification and for assuming mixture conditions that are helpful for further analysis.

A compact radio-frequency ion source for high brightness and low energy spread negative oxygen ion beam production.

A high brightness and low energy spread (∆E) ion source is essential to the production of a high-quality primary ion beam applied in secondary ion mass spectrometry (SIMS). A compact 13.56MHz radio-frequency (RF) ion source with an external planar spiral antenna has been developed as a candidate ion source for the production of negative oxygen ion beams for SIMS application. This ion source is designed with a three-and-a-half-turn water-cooled planar antenna for RF power coupling, a multi-cusp magnetic field for effective plasma confinement, and a three-electrode extraction system. The experimental results show that more than 50 µA negative oxygen ion beams have been extracted, which consist of 56% O-, 25% O2-, and 19% O3-. The ion energy distribution of the negative oxygen ion beam exhibits a Gaussian distribution with a minimum ∆E of 6.3eV. The brightness of the O- beam is estimated to be 82.4Am-2 Sr-1V-1. The simulation, design, and experimental study results of this RF ion source will be presented in this paper.

Bismuth, by high-sensitivity low energy ion scattering

Low energy ion scattering is an analytical technique with extreme surface sensitivity. It enables qualitative and quantitative elemental analysis of the outermost atomic layer. Straightforward quantification is possible by using well-defined reference samples, as the measured signal is related to known surface atomic concentration. Bi, like Pb, exhibits strong oscillatory behavior of backscattered ion yield when primary ion beam energy is varied. Here, we present the spectra of bismuth obtained by scattering of 4He+ ions in a wide range of energies (0.5–6.0 keV). These should cover a regularly used range of energies for He analysis and serve as standards or reference spectra for analysis of bismuth if the scattering angle is 145° or similar. For this purpose, high-purity foil cleaned by ion sputtering was used. The sensitivity of the instrument in use (high-sensitivity low energy ion scattering spectrometer) is defined by the 3 keV 4He+ spectrum of copper. The related atomic sensitivity and relative sensitivity factors are determined.

Determining the oxygen detection limit with magnetic sector dynamic secondary ion mass spectrometry (SIMS)

Dynamic SIMS is often used in evaluating the concentration of impurities in solids because of its high sensitivity and depth profiling capabilities with good depth resolution and high throughput. Continuous ion beam sputtering with a high-density primary beam provides high sensitivity and reduced background contribution from residual gases within the analytical chamber. Numerical simulations along with the data acquired in the real depth profiling experiment show a good agreement of the simple model, assuming that the surface uptake of the oxygen under Cs bombardment depends on the Cs surface retention concentration. In cases where high depth resolution is desired, requiring a low primary ion beam energy, a background subtraction option will help provide better detection limits. It is proposed to perform the background subtraction based on the difference between the continuous and interleaving sputtering modes of dynamic SIMS. The experiments performed on different instruments using different sputtering rate conditions (and different impact energies) show the power function dependence of oxygen detection limit on the reversed sputter rate variation or sputtering beam density. The proposed detection limit dependence curve can be used for analytical specifications benchmarking in most magnetic sector SIMS instruments.

Development of High Throughput Microscope Mode Secondary Ion Mass Spectrometry Imaging

This paper describes the development and initial results from a secondary ion mass spectrometer coupled with microscope mode detection. Stigmatic ion microscope imaging enables us to decouple the primary ion (PI) beam focus from spatial resolution and is a promising route to attaining higher throughput for mass spectrometry imaging (MSI). Using a commercial C60+ PI beam source, we can defocus the PI beam to give uniform intensity across a 2.5 mm2 area. By coupling the beam with a position-sensitive spatial detector, we can achieve mass spectral imaging of positive and negative secondary ions (SIs), which we demonstrate using samples comprising metals and dyes. Our approach involves simultaneous desorption of ions across a large field of view, enabling mass spectral images to be recorded over an area of 2.5 mm2 in a matter of seconds. Our instrument can distinguish spatial features with a resolution of better than 20 μm, and has a mass resolution of >500 at 500 u. There is considerable scope to improve this, and through simulations we estimate the future performance of the instrument.

Detection limit for secondary ions of organic molecules under MeV ion bombardment

In the present work we have investigated the chemical sensitivity of a mass spectrometry imaging method MeV – SIMS. Primary ion beam within the MeV energy range domain was employed to bombard samples of two organic compounds; amino acid arginine, and peptide hormone angiotensin II (human), with average molecular weights of 174.2 u and 1046.2 u respectively. Secondary ion yield was measured as a function of number of molecules per area unit, and the detection limit was determined. For both molecular compounds and two different energies of primary 35Cl ion beam, the secondary ion yield exhibited a significant decrease below the area density of 1015 molecules/cm2, while the density of 1013 molecules/cm2 resulted in molecular peak / background ratio being lesser than 3, which is below the commonly used sensitivity threshold in other techniques. Other experiment related drawbacks to sensitivity were also discussed.

Development of an energy spread analyzer for secondary ion mass spectrometry ion source

The energy spread (ΔE) of an ion source is an important parameter in the production of a finely focused primary ion beam applied in secondary ion mass spectrometry (SIMS). A variable-focusing retarding field energy analyzer (RFEA) has been developed and tested with an Ar+ beam and an oxygen ion beam extracted from a 2.45 GHz microwave ion source, which is developed as a candidate ion source for SIMS applications. The simulation results show that the relative resolution ΔE/E of the designed RFEA reaches 7 × 10−5. The experimental results indicate that a focusing electrode can improve the ΔE measurement results, which is consistent with the simulation results. The ion energy distributions of the Ar+ beam and oxygen ion beam are of Gaussian distribution with the value of ΔE of 3.3 and 2.9 eV, respectively. These results indicate that the designed RFEA is reliable for measuring the ion beam energy spread. The developed RFEA is also used to study the plasma behavior in different settings, which reveals that plasma stability is critical to making a low energy spread ion beam. This paper will present the simulation, design, and test of the variable-focusing RFEA. Preliminary ion beam quality studies with this instrument will also be discussed.

NanoSIMS sulfur isotopic analysis at 100nm scale by imaging technique.

NanoSIMS has been widely used for in-situ sulfur isotopic analysis (32S and 34S) of micron-sized grains or complex zoning in sulfide in terrestrial and extraterrestrial samples. However, the conventional spot mode analysis is restricted by depth effects at the spatial resolution < 0.5-1μm. Thus sufficient signal amount cannot be achieved due to limited analytical depths, resulting in low analytical precision (1.5‰). Here we report a new method that simultaneously improves spatial resolution and precision of sulfur isotopic analysis based on the NanoSIMS imaging mode. This method uses a long acquisition time (e.g., 3h) for each analytical area to obtain sufficient signal amount, rastered with the Cs+ primary beam of ∼100nm in diameter. Due to the high acquisition time, primary ion beam (FCP) intensity drifting and quasi-simultaneous arrival (QSA) significantly affects the sulfur isotopic measurement of secondary ion images. Therefore, the interpolation correction was used to eliminate the effect of FCP intensity variation, and the coefficients for the QSA correction were determined with sulfide isotopic standards. Then, the sulfur isotopic composition was acquired by the segmentation and calculation of the calibrated isotopic images. The optimal spatial resolution of ∼ 100nm (Sampling volume of 5nm × 1.5μm2) for sulfur isotopic analysis can be implemented with an analytical precision of ∼1‰ (1SD). Our study demonstrates that imaging analysis is superior to spot-mode analysis in irregular analytical areas where relatively high spatial resolution and precision are required and may be widely applied to other isotopic analyses.

Review of Recent Advances in Gas-Assisted Focused Ion Beam Time-of-Flight Secondary Ion Mass Spectrometry (FIB-TOF-SIMS).

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) is a powerful chemical characterization technique allowing for the distribution of all material components (including light and heavy elements and molecules) to be analyzed in 3D with nanoscale resolution. Furthermore, the sample's surface can be probed over a wide analytical area range (usually between 1 µm2 and 104 µm2) providing insights into local variations in sample composition, as well as giving a general overview of the sample's structure. Finally, as long as the sample's surface is flat and conductive, no additional sample preparation is needed prior to TOF-SIMS measurements. Despite many advantages, TOF-SIMS analysis can be challenging, especially in the case of weakly ionizing elements. Furthermore, mass interference, different component polarity of complex samples, and matrix effect are the main drawbacks of this technique. This implies a strong need for developing new methods, which could help improve TOF-SIMS signal quality and facilitate data interpretation. In this review, we primarily focus on gas-assisted TOF-SIMS, which has proven to have potential for overcoming most of the aforementioned difficulties. In particular, the recently proposed use of XeF2 during sample bombardment with a Ga+ primary ion beam exhibits outstanding properties, which can lead to significant positive secondary ion yield enhancement, separation of mass interference, and inversion of secondary ion charge polarity from negative to positive. The implementation of the presented experimental protocols can be easily achieved by upgrading commonly used focused ion beam/scanning electron microscopes (FIB/SEM) with a high vacuum (HV)-compatible TOF-SIMS detector and a commercial gas injection system (GIS), making it an attractive solution for both academic centers and the industrial sectors.

Stability of MeV primary ion induced secondary ions

We report on the analysis of the onset and the intensity of metastable secondary ions, which are desorbed from the target material as a result of bombarding organic samples with MeV primary ions. The bimodal time-of-flight mass spectrometer, which can analyze secondary ion in linear and reflectron modes, was used for detection and characterization of such ions. The use of the bimodal mass spectrometer for this specific purpose is demonstrated on amino acid arginine, where three main fragments were detected. We have also analyzed the influence of the primary ion beam on the intensity of metastable ion signal. Results from chlorine ion beams with energies between 3 and 10 MeV have exhibited the importance of electronic sputtering on the product/precursor ion peak intensity ratio, which is significantly decreased when using primary ions with higher energy.

Chemical Imaging of Organic Materials by MeV SIMS Using a Continuous Collimated Ion Beam

MeV SIMS is a type of secondary ion mass spectrometry (SIMS) technique where molecules are desorbed from the sample surface with ions of MeV energies. In this work, we present a novel system for molecular imaging of organic materials using a continuous analytical beam and a start trigger for timing based on the detection of secondary electrons. The sample is imaged by a collimated primary ion beam and scanning of the target with a lateral resolution of ∼20 μm. The mass of the analyzed molecules is determined with a reflectron-type time-of-flight (TOF) analyzer, where the START signal for the TOF measurement is generated by the secondary electrons emitted from a thin carbon foil (∼5 nm) placed over the beam collimator. With this new configuration of the MeV SIMS setup, a primary ion beam with the highest possible electronic stopping can be used (i.e., highest secondary molecular yield), and samples of any thickness can be analyzed. Since the electrons are collected from the thin foil rather than from the sample surface, the detection efficiency of secondary electrons is always the same for any type of analyzed material. Due to the ability to scan the samples by a piezo stage, samples of a few cm in surface size can be imaged. The imaging capabilities of MeV SIMS are demonstrated on crossing ink lines deposited on paper, a thin section of a mouse brain, and a fingerprint deposited on a thick Si wafer to show the potential application of the presented technique for analytical purposes in biology and forensic science.

Atomistic simulations for investigation of substrate effects on lipid in-source fragmentation in secondary ion mass spectrometry.

In beam-based ionization methods, the substrate plays an important role on the desorption mechanism of molecules from surfaces. Both the specific orientation that a molecule adopts at a surface and the strength of the molecule-surface interaction can greatly influence desorption processes, which in turn will affect the ion yield and the degree of in-source fragmentation of a molecule. In the beam-based method of secondary ion mass spectrometry (SIMS), in-source fragmentation can be significant and molecule specific due to the hard ionization method of using a primary ion beam for molecule desorption. To investigate the role of the substrate on orientation and in-source fragmentation, we have used atomistic simulations-molecular dynamics in combination with density functional theory calculations-to explore the desorption of a sphingolipid (palmitoylsphingomyelin) from a model surface (gold). We then compare SIMS data from this model system to our modeling findings. Using this approach, we found that the combined adsorption and binding energy of certain bonds associated with the headgroup fragments (C3H8N+, C5H12N+, C5H14NO+, and C5H15PNO4 +) was a good predictor for fragment intensities (as indicated by relative ion yields). This is the first example where atomistic simulations have been applied in beam-based ionization of lipids, and it presents a new approach to study biointerfacial lipid ordering effects on SIMS imaging.

The Generations of Primary Ion Beam using Two Rotating Electric-field Mass (REF-MS) Separation Technique

The Generations of Primary Ion Beam using Two Rotating Electric-field Mass (REF-MS) Separation Technique

Recent Advances in Single-Cell Metabolomics Based on Mass Spectrometry

Recent Advances in Single-Cell Metabolomics Based on Mass Spectrometry

Correlative High-Resolution Imaging of Iron Uptake in Lung Macrophages.

Detection of iron at the subcellular level in order to gain insights into its transport, storage, and therapeutic prospects to prevent cytotoxic effects of excessive iron accumulation is still a challenge. Nanoscale magnetic sector secondary ion mass spectrometry (SIMS) is an excellent candidate for subcellular mapping of elements in cells since it provides high secondary ion collection efficiency and transmission, coupled with high-lateral-resolution capabilities enabled by nanoscale primary ion beams. In this study, we developed correlative methodologies that implement SIMS high-resolution imaging technologies to study accumulation and determine subcellular localization of iron in alveolar macrophages. We employed transmission electron microscopy (TEM) and backscattered electron (BSE) microscopy to obtain structural information and high-resolution analytical tools, NanoSIMS and helium ion microscopy-SIMS (HIM-SIMS) to trace the chemical signature of iron. Chemical information from NanoSIMS was correlated with TEM data, while high-spatial-resolution ion maps from HIM-SIMS analysis were correlated with BSE structural information of the cell. NanoSIMS revealed that iron is accumulating within mitochondria, and both NanoSIMS and HIM-SIMS showed accumulation of iron in electrolucent compartments such as vacuoles, lysosomes, and lipid droplets. This study provides insights into iron metabolism at the subcellular level and has future potential in finding therapeutics to reduce the cytotoxic effects of excessive iron loading.

Determination of relative sensitivity factor, sputtering rate, and detection limits of deuterium in deuterium ion‐implanted Zircaloy‐4 using secondary ion mass spectrometer

Zirconium‐based alloys are extensively used in the nuclear industry as materials for reactor core components. These alloys are used in fuel cladding and pressure tubes with 1H2O or 2H2O as the primary heat exchange fluid. Continuous usage of pressure tubes and fuel cladding inside the reactor results in heavy ingress of hydrogen (1H) or deuterium (2H), which gives rise to the formation of hydrogen (or deuterium) precipitates in the host of zirconium matrix. This is called hydrogen (or deuterium) embrittlement phenomenon. Therefore, determination of hydrogen or deuterium concentration periodically in zirconium alloy pressure tubes and cladding are crucial for safe operation of nuclear reactors. Hence, in this work, secondary ion mass spectrometry (SIMS) has been utilized to determine the relative sensitive factor (RSF), sputtering rate, and detection limits of 2H in 2H+ ion‐implanted Zircaloy‐4 sample. SIMS analysis has been carried out using O2+ and Cs+ primary ion beams. Depth profiles of various elemental and molecular secondary ions have been monitored to determine the RSF values and detection limits of 2H in the sample under different primary ion beam analysis conditions. Sputtering rate under different analysis conditions has also been determined from the correlation between the projected range of 2H+ ions in Zircaloy‐4 sample determined from Stopping and Range of Ions in Matter (SRIM) software and the depth of the crater formed by primary ion beam bombardment process. The projected range of 2H+ ions in Zircaloy‐4 was estimated to be ~524.2 nm using the simulation carried out by SRIM software. The projected range, evaluated by SRIM software, was utilized for depth scale calibration of SIMS sputtered time profiles. The SIMS depth profiles were also calibrated by determining the depth of the SIMS crater by using optical depth profilometer. The values of range estimated by SRIM as well as optical profilometer were found to be in good agreement, within instrument uncertainty.