Conventional SIMS Research Articles

Quality control in structured illumination-based super-resolution FRET imaging via machine learning.

Structured illumination-based super-resolution Förster resonance energy transfer microscopy (SISR-FRETM) has facilitated better observation of molecular behavior in living cells. However, SIM tends to produce artifacts in reconstruction, especially when the raw SIM inputs are of low signal-to-noise ratio (SNR) or out-of-focus, leading to erroneous signals in subsequent FRET. Current SIM quality evaluation metrics fail to utilize both SNR and out-of-focus features, making it challenging to classify unqualified raw data for FRET. Here, we propose an ensemble machine learning based SISR-FRETM quality control algorithm (SFQC) to evaluate the quality of SISR-FRETM raw data from the perspective of both SNR and focus quality. Specifically, SFQC extracts features with both SNR and focus quality metrics and combines them as feature vectors for machine learning models to train. To ensure high robustness of quality control, four different classifiers are trained and ensembled. In our experiment, SFQC is demonstrated to surpass all conventional SIM quality metrics on the F1-score up to 0.93 for the focus detection task and 0.95 for the SNR detection task, while also achieving the fastest processing time compared to other metrics. SFQC also provides options for researchers to generate focus error maps for error localization and masking for FRET results. Overall, by combining different quality metrics, we propose SFQC as an accurate, fast solution for selecting trust-worthy images of SR quantitative FRET imaging microscopy, which saves scientists from tedious human efforts on large scale microscopy image quality control works.

A Pilot Study of Simulation-Free Hippocampal-Avoidance Whole Brain Radiotherapy Using Diagnostic MR-Based and Online Adaptive Planning

We aimed to demonstrate the clinical feasibility and safety of a simulation-free hippocampal avoidance whole brain radiotherapy (HA-WBRT) workflow in a Phase I clinical trial (NCT05096286). Feasibility was defined as successful completion of the simulation-free HA-WBRT workflow through treatment delivery in at last 70% of treated patients. Ten candidates for HA-WBRT were enrolled for treatment on a ring gantry CT-guided Linac with online adaptive capabilities. Structures were contoured on the diagnostic brain MRI, which was then registered to a separate head computed tomography (CT) of similar head shape, obtained from an atlas-based database. A HA-WBRT "pre-plan" was generated using the atlas-based CT (AB-CT) and the NRG-CC001 constraints. At first fraction, the AB-CT was used as the primary dataset and deformed to the patient's cone-beam CT (CBCT) for dose calculation. The brain, ventricles, and brainstem contours were matched through rigid translation and rotation to the corresponding anatomy on the CBCT to aid in alignment, given the differences in rotational head positioning from diagnostic MRI to CBCT setup. Lastly, the lens, optic nerves, and brain contours were manually edited based on CBCT visualization. Plans were then optimized, and the adaptive plan was chosen for treatment if the plan met all objectives. Workflow tasks were timed. In addition, conventional plans using patients' sim CTs were created for each patient for the purpose of prospective dosimetric comparison. The dosimetric parameters were compared for each patient between the delivered sim-free plan and the conventional sim CT plan using the sign test via statistical software, with p<.05 indicating significance. Median time from approved sim order to first fraction was 4 days (range: 2-7); median time in room (door-to-door) was 49 minutes (range: 35-70). All patients successfully completed all ten fractions and 90% of the simulation-free radiation plans met all NRG-CC001 constraints. For one patient, the sim-free plan at fraction one failed the planning target volume (PTV) coverage objective (coverage of 89%); this was deemed acceptable for delivery by the treating radiation oncologist. An offline replan was then performed to meet NRG-CC001 constraints and used for the subsequent nine fractions. There was no clinically meaningful difference in dosimetric constraints between the sim-free plan (calculated on AB-CT) and conventional CT sim plan. Statistically, the sim-free plans provided improved PTV coverage to higher doses compared to the conventional plans (Table). At a median follow-up of 43 days (range: 9 -280), the intracranial progression-free survival rate was 90%. Simulation-free HA-WBRT is feasible, results in plans that are dosimetrically comparable to conventional CT sim workflows and succeeds in decreasing time to initiation of HA-WBRT by at least 50%. Further studies with a larger cohort are warranted to optimize the workflow.

Pricing eSIM Services: Ecosystem, Challenges, and Opportunities

The adoption of embedded subscriber identity module (eSIM) is accelerating rapidly and is anticipated to prevail over conventional physical SIM cards in the next few years. With several phone vendors switching to eSIMs and eSIM-only devices being launched in the market, a new ecosystem for offering and pricing cellular services will be created. The rise of the Internet of Things (IoT), expanding 5G roll-out, and upcoming enhancements available with beyond 5G (B5G) networks will further add to the complexity of this ecosystem. In this paper, we outline the disruptive effects of eSIM on pricing and business models and discuss several challenges and opportunities that will arise with its adoption. In particular, the possibility of seamless switching between providers will result in higher competition and increased churn, giving rise to interesting pricing strategies. We describe one such strategy, personalized pricing, and illustrate its advantages over traditional approaches.

A Novel Double-Sided Pulse Interval Modulation (DS-PIM) Aided SIM-OFDM for 6G Light Fidelity (LiFi) Networks

Subcarrier Index Modulation is an OFDM variant that provides superior power and bandwidth efficiency. In this paper, we present a novel, double-sided pulse interval modulation (DS-PIM)-based SIM OFDM technique. The proposed technique exploits the variable symbol size of DPIM to provide a variable sub-block size and enable dynamic assignment of subcarriers rather than the fixed size of conventional SIM OFDM. In comparison with conventional Subcarrier Index-Modulated OFDM (SIM-OFDM), the proposed approach shows a 12.5% reduction in bandwidth usage for a 2-bit index word. On average, 3.5 subcarriers are employed by the proposed technique per sub-block, in comparison with 4 subcarriers for the conventional technique. The proposed technique provides a superior spectral efficiency compared with conventional SIM-OFDM, even for higher-order modulation.

Sim–Real Mapping of an Image-Based Robot Arm Controller Using Deep Reinforcement Learning

Models trained with Deep Reinforcement learning (DRL) have been deployed in various areas of robotics with varying degree of success. To overcome the limitations of data gathering in the real world, DRL training utilizes simulated environments and transfers the learned policy to real-world scenarios, i.e., sim–real transfer. Simulators fail to accurately capture the entire dynamics of the real world, so simulation-trained policies often fail when applied to reality, termed a reality gap (RG). In this paper, we propose a search (mapping) algorithm that takes in real-world observation (images) and maps them to the policy-equivalent images in the simulated environment using a convolution neural network (CNN) model. The two-step training process, DRL policy and a mapping model, overcomes the RG problem with simulated data only. We evaluated the proposed system with a gripping task of a custom-made robot arm in the real world and compared the performance against a conventional DRL sim–real transfer system. The conventional system achieved a 15–57% success rate in gripping operation depending on the position of the target object while the mapping-based sim–real system achieved 100%. The experimental results demonstrated that the proposed DRL with mapping method appropriately corresponded the real world to the simulated environment, confirming that the scheme can achieve high sim–real generalization at significantly low training costs.

MeV TOF SIMS Analysis of Hybrid Organic/Inorganic Compounds in the Low Energy Region.

The low energy range (a few 100 keV to a few megaelectronvolts) primary ion mode in MeV secondary ion mass spectrometry (MeV SIMS) and its potential in exploiting the capabilities of conventional (keV) SIMS and MeV SIMS simultaneously were investigated. The aim is to see if in this energy range of both types of materials, inorganic and organic, can be simultaneously analyzed. A feasibility study was conducted, first by analyzing the dependence of secondary ion yields in indium tin oxide (ITO, In2O5Sn) and leucine (C6H13NO2) on various primary ion energies and charge states of a Cu beam, within the scope of equal influence of electronic and nuclear stopping. Expected behavior was observed for both targets (mainly nuclear sputtering for ITO and electronic sputtering for leucine). MeV SIMS images of samples containing separate regions of Cr and leucine were obtained using both keV and MeV primary ions. On the basis of the image contrast and measured data, the benefit of a low energy beam is demonstrated by Cr+ intensity leveling with leucine [M + H]+ intensity, as opposed to a significant contrast at a higher energy. It is estimated that, by lowering the energy, the leucine [M + H]+ yield efficiency lowers roughly 20 times as a price for gaining about 10 times larger efficiency of Cr+ yield, while the leucine [M + H]+ yield still remains sufficiently pronounced.

Efficient Simulation of Cuboid Object in Multiplanar Layered Medium by Improved Spectrum Integral Method

An efficient improved spectrum integral method (ISIM) is proposed to accelerate the scattering simulation of cuboid object by method of moment (MoM) in multiplanar layered medium (LM). The layered medium Green’s functions (LMGFs) are studied and decomposed into transmission and reflection terms, which hold the translational invariance and reverse translational invariance, respectively. By virtue of the (reverse) translational invariance of LMGF from the uniform square grids on the surface of the cuboid object, most of the coupling between the expanding basis functions and the testing basis functions can be represented by two kinds of submatrices, i.e., the Toeplitz matrix when transmission term is involved, and the conjugate Toeplitz matrix when reflection term is involved. Moreover, the submatrix coupling the expanding/testing basis functions defined on the edges with those defined on the parallel surfaces/edges is also extended to the (conjugate) Toeplitz matrixes. This will significantly alleviate the heavy computation and memory burden from the conventional SIM. With the improved operations on the basis functions associated with the edges of the cuboid object, the proposed ISIM in LM can reach the computational complexity as low as <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${O}$ </tex-math></inline-formula> ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${N} ^{1.5}$ </tex-math></inline-formula> log( <italic xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">N)) in the matrix vector production, while the computational complexity of matrix filling and the memory requirement are both <inline-formula> <tex-math notation="LaTeX">${O}$ </tex-math></inline-formula>(</i> <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${N}^{1.5}$ </tex-math></inline-formula> ). Moreover, compared with conventional SIM, both theoretical analysis and numerical results demonstrate that the memory requirement and matrix filling time are dramatically decreased.

Plasma profiling time-of-flight mass spectrometry for fast elemental analysis of semiconductor structures with depth resolution in the nanometer range

Plasma profiling time of flight mass spectrometry (PP-TOFMS) has recently gained interest as it enables the elemental profiling of semiconductor structures with high depth resolution in short acquisition times. As recently shown by Tempez et al PP-TOFMS can be used to obtain the composition within structures of modern field effect transistors []. There, the results were compared to conventional SIMS measurements. In the present study, we compare PP-TOFMS measurements of an Al-/In-/GaN quantum well multi stack to established micro- and nanoanalysis techniques like cathodoluminescence (CL), scanning transmission electron microscopy (STEM), energy dispersive x-ray spectroscopy (EDX) and x-ray diffraction (XRD). We show that PP-TOFMS is able to resolve the layer structure of the sample even more than 500 nm deep into the sample and allows the determination of a relative elemental composition with an accuracy of about 10 rel%. Therefore, it is an extremely rapid alternative method to obtain semiconductor elemental depth profiles without the expensive and time consuming sample preparation required for TEM. Besides, PP-TOFMS offers better depth resolution and more elemental information than, for example, electrochemical capacitance–voltage (ECV) evaluations, since all elements are detected in parallel and not only electrically (ECV) or optically (CL) active elements are observed.

Pb nanospheres in ancient zircon yield model ages for zircon formation and Pb mobilization

Nanospheres of lead (Pb) have recently been identified in zircon (ZrSiO4) with the potential to compromise the veracity of U-Pb age determinations. The key assumption that the determined age is robust against the effects of Pb mobility, as long as Pb is not lost from the zircon during subsequent geological events, is now in question. To determine the effect of nanosphere formation on age determination, and whether analysis of nanospheres can yield additional information about the timing of both zircon growth and nanosphere formation, zircons from the Napier Complex in Enderby Land, East Antarctica, were investigated by high-spatial resolution NanoSIMS (Secondary Ion Mass Spectrometry) mapping. Conventional SIMS analyses with >µm resolution potentially mixes Pb from multiple nanospheres with the zircon host, yielding variable average values and therefore unreliable ages. NanoSIMS analyses were obtained of 207Pb/206Pb in nanospheres a few nanometres in diameter that were resolved from 207Pb/206Pb measurements in the zircon host. We demonstrate that analysis for 207Pb/206Pb in multiple individual Pb nanospheres, along with separate analysis of 207Pb/206Pb in the zircon host, can not only accurately yield the age of zircon crystallization, but also the time of nanosphere formation resulting from Pb mobilization during metamorphism. Model ages for both events can be derived that are correlated due to the limited range of possible solutions that can be satisfied by the measured 207Pb/206Pb ratios of nanospheres and zircon host. For the Napier Complex zircons, this yields a model age of ca 3110 Ma for zircon formation and a late Archean model age of 2610 Ma for the metamorphism that produced the nanospheres. The Nanosphere Model Age (NMA) method constrains both the crystallization age and age of the metamorphism to ~±135 Ma, a significant improvement on errors derived from counting statistics.

Fast, long-term, super-resolution imaging with Hessian structured illumination microscopy.

To increase the temporal resolution and maximal imaging time of super-resolution (SR) microscopy, we have developed a deconvolution algorithm for structured illumination microscopy based on Hessian matrixes (Hessian-SIM). It uses the continuity of biological structures in multiple dimensions as a priori knowledge to guide image reconstruction and attains artifact-minimized SR images with less than 10% of the photon dose used by conventional SIM while substantially outperforming current algorithms at low signal intensities. Hessian-SIM enables rapid imaging of moving vesicles or loops in the endoplasmic reticulum without motion artifacts and with a spatiotemporal resolution of 88 nm and 188 Hz. Its high sensitivity allows the use of sub-millisecond excitation pulses followed by dark recovery times to reduce photobleaching of fluorescent proteins, enabling hour-long time-lapse SR imaging of actin filaments in live cells. Finally, we observed the structural dynamics of mitochondrial cristae and structures that, to our knowledge, have not been observed previously, such as enlarged fusion pores during vesicle exocytosis.

High-Temperature Oxidation of Zircaloy-4 in Air Studied with Labeled Oxygen and Raman Imaging

High-temperature oxidation of zirconium-based cladding materials is expected to be the primary cause of the fuel assemblies’ degradation in spent fuel storage pool loss-of-cooling accidents. Here, high-temperature Zircaloy-4 oxidation has been studied through two-stage oxidation experiments using 18O isotope. Particular attention is paid to the effect of a low-temperature pre-oxidation scale which aims to simulate the corrosion scale existing on spent fuel cladding. Raman imaging was used to investigate the 18O distribution in the scales exposed either to 18O2 or to 18O2 + N2 atmosphere at high temperature. Results were assessed against more conventional SIMS mapping. The use of the 18O isotope tracer technique associated with micro-Raman mapping of the scales is demonstrated to be a powerful method to investigate the transport properties in the scales and will help to gain understanding of the kinetic differences between different pre-oxides.

Intact lipid imaging of mouse brain samples: MALDI, nanoparticle-laser desorption ionization, and 40keV argon cluster secondary ion mass spectrometry.

We have investigated the capability of nanoparticle-assisted laser desorption ionization mass spectrometry (NP-LDI MS), matrix-assisted laser desorption ionization (MALDI) MS, and gas cluster ion beam secondary ion mass spectrometry (GCIB SIMS) to provide maximum information available in lipid analysis and imaging of mouse brain tissue. The use of Au nanoparticles deposited as a matrix for NP-LDI MS is compared to MALDI and SIMS analysis of mouse brain tissue and allows selective detection and imaging of groups of lipid molecular ion species localizing in the white matter differently from those observed using conventional MALDI with improved imaging potential. We demonstrate that high-energy (40 keV) GCIB SIMS can act as a semi-soft ionization method to extend the useful mass range of SIMS imaging to analyze and image intact lipids in biological samples, closing the gap between conventional SIMS and MALDI techniques. The GCIB SIMS allowed the detection of more intact lipid compounds in the mouse brain compared to MALDI with regular organic matrices. The 40 keV GCIB SIMS also produced peaks observed in the NP-LDI analysis, and these peaks were strongly enhanced in intensity by exposure of the sample to trifluororacetic acid (TFA) vapor prior to analysis. These MS techniques for imaging of different types of lipids create a potential overlap and cross point that can enhance the information for imaging lipids in biological tissue sections.Graphical abstractSchematic of mass spectral imaging of a mouse brain tissue using GCIB-SIMS and MALDI techniquesElectronic supplementary materialThe online version of this article (doi:10.1007/s00216-016-9812-5) contains supplementary material, which is available to authorized users.

Towards Quantification of Contaminants in Electrodeposited Cu Films

By means of linear sweep voltammetry (LSV) we studied the tendency of various suppressor additives towards the formation of stable adducts with Cu(I)-MPS intermediates which form as by-products of the SPS reaction cycle during an additive-assisted Cu electrodeposition. These LSVs demonstrate a gradual transition from a pure antagonistic SPS/suppressor interplay (superfill capabilities) to a pure synergistic SPS/suppressor interplay (leveling capabilities). SIMS depth profiling experiments on electroplated Cu films indicate that the MCs+ detection mode is superior to the conventional negative SIMS detection mode for the analysis of the N content in those Cu films.

Nanodomain analysis with cluster‐SIMS: application to the characterization of macromolecular brush architecture

We present the application of cluster‐SIMS for the analysis of the nanoscopic surface of diblock brush terpolymers (DBTs). This novel SIMS technique differs from conventional SIMS. It uses Au4004+ projectiles at 520 keV and an event‐by‐event bombardment/detection regime for the analysis of co‐localized molecular species. The performance of this SIMS method was tested on ‘bottle brush’ block molecules featuring a vertical aligned backbone structure. We were able to assess the extent of secondary ion emissions from the surface and analyze the degree of ordered alignment for DBTs by the fluorocarbon surface coverage. We demonstrate the feasibility of characterizing the homogeneity of macromolecular films at the nanoscale. Copyright © 2015 John Wiley &amp; Sons, Ltd.

Submicron mass spectrometry imaging of single cells by combined use of mega electron volt time-of-flight secondary ion mass spectrometry and scanning transmission ion microscopy

In order to better understand biochemical processes inside an individual cell, it is important to measure the molecular composition at the submicron level. One of the promising mass spectrometry imaging techniques that may be used to accomplish this is Time-of-Flight Secondary Ion Mass Spectrometry (TOF-SIMS), using MeV energy heavy ions for excitation. MeV ions have the ability to desorb large intact molecules with a yield that is several orders of magnitude higher than conventional SIMS using keV ions. In order to increase the spatial resolution of the MeV TOF-SIMS system, we propose an independent TOF trigger using a STIM (scanning transmission ion microscopy) detector that is placed just behind the thin transmission target. This arrangement is suitable for biological samples in which the STIM detector simultaneously measures the mass distribution in scanned samples. The capability of the MeV TOF-SIMS setup was demonstrated by imaging the chemical composition of CaCo-2 cells.

NanoSIMS analytical technique and its applications in earth sciences

Despite the significant improvement on spatial resolution, NanoSIMS still preserves relatively high mass resolution, sensitivity, and analytical precision. It has become an important analytical platform to determine chemical compositions of solid materials, and has been widely used in space, earth, life, and materials sciences, etc. By using a Cs+ ion beam with a size as small as 50 nm scanning over sample surfaces, we are able to obtain high spatial resolution images of up to 7 species simultaneously. When utilizing Faraday cup, high analytical precision of 0.3‰–0.5‰ (1SD) for C, O and S isotopic analysis can be achieved. Although this precision level is still lower than that of conventional SIMS, it already meets the major requirements of Earth Sciences. In 2011, the first NanoSIMS of China (Cameca NanoSIMS 50L) was installed at Institute of Geology and Geophysics, Chinese Academy of Sciences. Based on the working mechanism and analytical modes of the instrument, this paper will systematically introduce the analytical methods established with the NanoSIMS and their potential applications in earth sciences. These methods include trace element distribution images in mineral zoning, high spatial resolution (2–5 μm) Pb-Pb and U-Pb dating, water content and H isotopic analysis for silicate glass and apatite, C isotopic analysis for diamond and graphite, O isotopic analysis for carbonate, S isotopic analysis for sulfides. In addition, the specific requirements for sample preparation will also be introduced in order to facilitate domestic earth scientists’ use.

Sub-micron-scale trace-element distributions in natural zircons of known provenance: implications for Ti-in-zircon thermometry

NanoSIMS measurements of Ti, P, Y, Ce, and Hf in zircon separates from the Youngest Toba Tuff, the Bishop Tuff, the Quottoon Igneous Complex, the Sierra Nevada batholith, and an Adirondack migmatite show that micron-scale oscillatory zoning of Ti is common. The zircons we have studied typically display banded concentration gradients, having between 1 and 7 peaks in Ti abundance over length scales of 10–20 μm—the beam diameter commonly used for SIMS trace-element zircon analyses—with amplitudes of up to 4.5 ppm Ti (baseline values are ~1–4 ppm) and widths (measured at half-height) of between ~0.2 and 4 μm. Spatial correlations between concentrations of Ti and other trace elements (P, Y, and Ce) are also common, but variable in character, ranging from oscillatory co-variation of Ti, P, Y, and Ce to cases where only a subset of peaks for a given element is spatially correlated with peaks in Ti. There are also longer length-scale, generally positive correlations among concentrations of Ti, P, Y, and Ce (i.e., gradients on which narrower peaks are superimposed). In contrast, Hf concentrations are either uncorrelated or inversely correlated with these longer length-scale variations in Ti concentrations. The wide range in Ti concentrations over distances of less than 1 μm and the various correlations between Ti concentrations and those of the other analyzed elements suggest that on the micron scale and at temperatures between ~700 and 800 °C, zircon-liquid Ti partitioning is not controlled by bulk or lattice equilibrium. Treating our NanoSIMS Ti ion maps as though they were conventional SIMS analyses (i.e., generating an average Ti concentration for each map), we evaluate the hypothesis that while micron-scale variations in Ti concentrations might be kinetically controlled, when averaged over 100–400 μm2, such variations capture the thermal state of the growing zircon. Using these average Ti concentrations, independent petrologic pressure and temperature constraints, estimates of silica and titania activities based on phase assemblages as well as calculations using rhyolite-MELTS, we show that crystallization temperatures predicted by Ti-in-zircon geothermometry generally do not agree with the independently constrained temperatures for the samples.

Si− useful yields measured in Si, SiC, Si3N4 and SiO2: comparison between the Storing Matter technique and SIMS

The storing matter technique was developed to tackle quantification issues encountered in SIMS due to matrix effects. Here, we demonstrate the quantitative capabilities of the technique by comparing the useful yield for Si− in different matrices exhibiting matrix effects in conventional SIMS analysis. Additionally, the effect of the collector material (Ag, Au, Cu and Ta) on the storing matter useful yield is investigated. Copyright © 2014 John Wiley &amp; Sons, Ltd.

Analysis of liquid materials in low vacuum with Wet‐SIMS

In conventional SIMS with keV‐energy ion beams, elastic collisions occur between projectiles and atoms in the constituent molecules. The collisions produce fragments, making the acquisition of molecular information difficult. Volatile liquid samples (wet samples) are also difficult to measure using conventional SIMS because samples must be dried first and then introduced into the high‐vacuum chamber. In contrast, ion beams with MeV‐energy excite electrons near the surface and enhance the ionization of high‐mass molecules; hence, a fragment‐suppressed SIMS spectrum of ionized molecules can be obtained. We developed a SIMS analysis system for wet samples (Wet‐SIMS) that works under low‐vacuum pressures up to 1000 Pa using heavy MeV‐energy ion beams. The evaporation of heptanoic acid was suppressed under the low‐vacuum pressure of 1000 Pa, and the wet samples, which included volatile materials with different vapor pressures, could be measured using heavy MeV‐energy ions. Copyright © 2014 John Wiley &amp; Sons, Ltd.

Study on the detection limits of a new argon gas cluster ion beam secondary ion mass spectrometry apparatus using lipid compound samples

Ar gas cluster ion beam secondary ion mass spectrometry (Ar-GCIB SIMS) has been developed as one of the most powerful tools used for analyzing complex biological materials because of its distinctively high secondary ion yield of large organic molecules. However, for the practical analysis of minor components in complex biological materials, the sensitivity of the technique is still insufficient. The detection limits of our original Ar-GCIB SIMS apparatus were investigated by measuring lipid compound samples in positive ion mode. The samples were mixtures of 1,2-distearoyl-sn-glycero-3-phosphocholine (C44 H88 NO8 P, DSPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (C40 H80 NO8 P, DPPC). The primary ions were accelerated with 10 keV and the mean cluster size was 1500. The secondary [M+H](+) ions emitted from the sample were analyzed using an orthogonal acceleration time-of-flight mass spectrometer (oa-TOF-MS). In addition, the isotope abundance ratio and the ratio of the [M+H](+) ion signal to the fragment ion signal acquired with Ar-GCIB SIMS were compared with those obtained with conventional Bi cluster SIMS. Secondary [M+H](+) ions and some characteristic fragment ions were clearly observed with high quantitative accuracy in the mass spectra acquired with Ar-GCIB SIMS. The results were clearly better than those obtained with conventional Bi cluster SIMS. The detection limit of Ar-GCIB SIMS was found to be below 0.1% and was much lower than that of conventional Bi cluster SIMS because of the high [M+H](+) ion yield and the low background. The results suggested that the new Ar-GCIB SIMS apparatus has the capability to acquire valuable information on complex biological materials.