Co-Registered In Situ Secondary Electron and Mass Spectral Imaging on the Helium Ion Microscope Demonstrated Using Lithium Titanate and Magnesium Oxide Nanoparticles.

The development of a high resolution elemental imaging platform combining coregistered secondary ion mass spectrometry and high resolution secondary electron imaging is reported. The basic instrument setup and operation are discussed and in situ image correlation is demonstrated on a lithium titanate and magnesium oxide nanoparticle mixture. The instrument uses both helium and neon ion beams generated by a gas field ion source to irradiate the sample. Both secondary electrons and secondary ions may be detected. Secondary ion mass spectrometry (SIMS) is performed using an in-house developed double focusing magnetic sector spectrometer with parallel detection. Spatial resolutions of 10 nm have been obtained in SIMS mode. Both the secondary electron and SIMS image data are very surface sensitive and have approximately the same information depth. While the spatial resolutions are approximately a factor of 10 different, switching between the different images modes may be done in situ and extremely rapidly, allowing for simple imaging of the same region of interest and excellent coregistration of data sets. The ability to correlate mass spectral images on the 10 nm scale with secondary electron images on the nanometer scale in situ has the potential to provide a step change in our understanding of nanoscale phenomena in fields from materials science to life science.

An in situ correlative STEM-EDS and HRTEM based nanoscale chemical characterization of solid-liquid interfaces in an aluminium alloy.

The chemistry and the structure of solid-liquid interface in an Al-Si based alloy during high temperature phase transformation were characterized at nanoscale using scanning Transmission Electron Microscopy-EDS and HRTEM. Such studies were until recently limited by large sample drift associated with conventional heating holders. This study was made possible thanks to the modern low-drift MEMS-chip based localized heating technology. The results reveal that (i) the structural interface between solid (111) oriented Si phase and the liquid phase (i.e. decay of crystalline order) coexisting at 600°C is 3.2 nm wide (ii) the STEM-EDS chemical maps show inhomogeneous distribution of the elements with the solid phase being rich in Si and the liquid phase rich in Al (iii) the HRTEM and the HAADF images display respectively dark and bright intensity bands along the interface which could be due to apparent enrichment of Cu at the interface region resulting in enhanced amplitude-contrast (darker band in HRTEM) and Z-contrast (bright band in HAADF) and (iv) intriguingly, the concentration profiles within (i.e. compositional width) and across the solid-liquid interface display element-specific complex and asymmetric variation in the chemical widths.

High-resolution high-sensitivity elemental imaging by secondary ion mass spectrometry: from traditional 2D and 3D imaging to correlative microscopy.

Secondary ion mass spectrometry (SIMS) constitutes an extremely sensitive technique for imaging surfaces in 2D and 3D. Apart from its excellent sensitivity and high lateral resolution (50 nm on state-of-the-art SIMS instruments), advantages of SIMS include high dynamic range and the ability to differentiate between isotopes. This paper first reviews the underlying principles of SIMS as well as the performance and applications of 2D and 3D SIMS elemental imaging. The prospects for further improving the capabilities of SIMS imaging are discussed. The lateral resolution in SIMS imaging when using the microprobe mode is limited by (i) the ion probe size, which is dependent on the brightness of the primary ion source, the quality of the optics of the primary ion column and the electric fields in the near sample region used to extract secondary ions; (ii) the sensitivity of the analysis as a reasonable secondary ion signal, which must be detected from very tiny voxel sizes and thus from a very limited number of sputtered atoms; and (iii) the physical dimensions of the collision cascade determining the origin of the sputtered ions with respect to the impact site of the incident primary ion probe. One interesting prospect is the use of SIMS-based correlative microscopy. In this approach SIMS is combined with various high-resolution microscopy techniques, so that elemental/chemical information at the highest sensitivity can be obtained with SIMS, while excellent spatial resolution is provided by overlaying the SIMS images with high-resolution images obtained by these microscopy techniques. Examples of this approach are given by presenting in situ combinations of SIMS with transmission electron microscopy (TEM), helium ion microscopy (HIM) and scanning probe microscopy (SPM).

Reduction of the SIMS matrix effect using the storing matter technique: a case study on Ti in different matrices.

Matrix effects in secondary ion mass spectrometry render quantitative analysis difficult. In this paper, we report on the quantitative potential of the so-called storing matter technique. On the basis of a case study focusing on Ti sputtered from five different chemical environments (Ti, TiB2,TiC, TiN and TiO2), we demonstrate for the first time that the SIMS matrix effect can be avoided in a multitude of matrices by this novel approach. The effect of the collector material (Au, Ag, Cu, and Ta) on the overall efficiency of the storing matter process is investigated. In addition, the influence of oxygen on the obtained useful yields is exposed. Finally, the performance of the storing matter technique is compared to standard SIMS analysis.

Completing the picture for the smallest eigenvalue of real Wishart matrices.

Rectangular real N×(N+ν) matrices W with a Gaussian distribution appear very frequently in data analysis, condensed matter physics, and quantum field theory. A central question concerns the correlations encoded in the spectral statistics of WW^{T}. The extreme eigenvalues of WW^{T} are of particular interest. We explicitly compute the distribution and the gap probability of the smallest nonzero eigenvalue in this ensemble, both for arbitrary fixed N and ν, and in the universal large N limit with ν fixed. We uncover an integrable Pfaffian structure valid for all even values of ν≥0. This extends previous results for odd ν at infinite N and recursive results for finite N and for all ν. Our mathematical results include the computation of expectation values of half-integer powers of characteristic polynomials.

Structural and chemical evolution of Au-silica core-shell nanoparticles during 20 keV helium ion irradiation: a comparison between experiment and simulation.

Au-silica core-shell nanoparticles have been irradiated with 20 keV He+ ions up to a maximum fluence of 4.7 × 1017 ions/cm2. The nanoscale structural and crystallographic evolution induced by He+ ion irradiation was followed at various stages using Transmission Electron Microscopy (TEM). During irradiation satellite Au clusters are formed around the main Au core, which remained crystalline even after the maximum He+ ion fluence. The spherical silica shell deformed into a hemisphere due to He+ ion irradiation. Three dimensional Monte-Carlo simulations, based on the binary collision approximation, have been performed on stacked infinite layers and an individual particle. The stacked layers results show that the He+ beam interacts with most of the nanoparticle and Au migrates in the direction of beam incidence agreeing with experimental findings. The individual particle results match the experiment in terms of the volume which is sputtered away however additional mechanisms, not included in the simulations, are present in the experiment during the satellite formation and silica shell deformation. These results show the ability for 20 keV He+ ions to be used for the modification of nanostructures. Furthermore, these results contribute to a quantitative understanding of the dynamic evolution of materials observed using microscopy techniques based on He+ ions.

Investigation of the depth-profiling capabilities of the Storing Matter technique.

The so-called Storing Matter technique allows the matrix effect observed in secondary ion mass spectrometry to be successfully circumvented. We therefore investigate in this work the depth-profiling capabilities of the Storing Matter technique with a goal of developing protocols for quantitative depth profiles. The effect of the steps involved in the Storing Matter process on the main parameters such as the depth resolution and the dynamic range is studied experimentally and by simulations. A semi-automated process consisting of the sputter-deposition process on a rotating collector in the Storing Matter instrument followed by a complete analysis of the collector by secondary ion mass spectrometry is defined. This protocol is applied to depth profile a B implant in Si and a Sn/Zn multilayered sample, and the results are compared with those obtained with conventional secondary ion mass spectrometry.

Platelets are a previously unrecognised source of MIF.

Macrophage migration inhibitory factor (MIF) is an inflammatory cytokine with chemokine-like functions and a role in atherogenesis. MIF is secreted by various cells including endothelial cells and macrophages. Platelets are another prominent cell type with a role in atherogenesis and are a rich source of atherogenic chemokines. We asked whether platelets express and secrete MIF. In comparison, CXCL12 release was determined. We examined the subcellular localisation of MIF in platelets/megakaryocytes, studied its co-localisation with other platelet-derived mediators and asked whether platelets contain MIF mRNA. Moreover, we probed the functional role of platelet-derived MIF in inflammatory cell recruitment. Using Western blot and ELISA, we demonstrated and quantitated MIF protein in human and mouse platelets. Applying confocal-microscopy, MIF was found to localise in granular-like structures, but did not co-localise with known platelet cytokines. qPCR indicated that platelets contain low levels of MIF mRNA. ELISA measurements from human platelet supernatants showed that, whereas thrombin and collagen triggered the release of MIF and CXCL12, ADP and oxidised LDL promoted CXCL12 but not MIF secretion. Using Transwell assays, we demonstrated that platelet supernatants promoted monocyte chemotaxis and that this was blocked by neutralising MIF antibodies.This is the first report demonstrating MIF secretion from activated platelets, suggesting that platelets are a previously unrecognised source of MIF in inflammatory processes. There are distinct activating stimuli for MIF and CXCL12 secretion. A substantial portion of the chemotactic capacity of stimulated platelet supernatants is contributed by MIF, suggesting a role for platelet-derived MIF in atherogenic cell recruitment.

Engineering craniofacial scaffolds.

OBJECTIVE: To develop an integrated approach for engineering craniofacial scaffolds and to demonstrate that these engineered scaffolds would have mechanical properties in the range of craniofacial tissue and support bone regeneration for craniofacial reconstruction. EXPERIMENTAL VARIABLE: Scaffold architecture designed to achieve desired elasticity and permeability. Scaffold external shape designed to match craniofacial anatomy. OUTCOME MEASURE: Final fabricated biomaterial scaffolds. Compressive mechanical modulus and strength. Bone regeneration as measured by micro-CT scanning, mechanical testing and histology. SETTING: Departments of Biomedical Engineering, Oral/Maxillofacial Surgery, and Oral Medicine, Pathology and Oncology at the University of Michigan. RESULTS: Results showed that the design/fabrication approach could create scaffolds with designed porous architecture to match craniofacial anatomy. These scaffolds could be fabricated from a wide range of biomaterials, including titanium, degradable polymers, and degradable calcium phosphate ceramics. Mechanical tests showed that fabricated scaffolds had compressive modulus ranging 50 to 2900 MPa and compressive strength ranging from 2 to over 56 MPa, within the range of human craniofacial trabecular bone. In vivo testing of designed scaffolds showed that they could support bone regeneration via delivery of BMP-7 transduced human gingival fibroblasts in a mouse model. Designed hydroxyapatite scaffolds with pore diameters ranging from 400 to 1200 microns were implanted in minipig mandibular defects for 6 and 18 weeks. Results showed substantial bone ingrowth (between 40 and 50% at 6 weeks, between 70 and 80% at 18 weeks) for all scaffolds, with no significant difference based on pore diameter. CONCLUSION: Integrated image-based design and solid free-form fabrication can create scaffolds that attain desired elasticity and permeability while fitting any 3D craniofacial defect. The scaffolds could be manufactured from degradable polymers, calcium phosphate ceramics and titanium. The designed scaffolds supported significant bone regeneration for all pore sizes ranging from 300 to 1200 microns. These results suggest that designed scaffolds are clinically applicable for complex craniofacial reconstruction.

Ecology of adolescents' marijuana abuse.

Sixteen adolescent marijuana abusers reported data on the ecology of their use over a 3-month period. Abusers recorded data on the day, date, time, place, frequency, and amount of use. They also included information on their mood and functioning, and with whom they used marijuana. Peak use occurred just prior to school, at lunch, and in the early evening. Adolescents' homes, friends' houses, school, and cars represented 67% of locations in which marijuana was used. Happy, relaxed, and tired comprised 81% of moods experienced during time of use. Average core network was 5.8 individuals while casual networks averaged 15.5 adolescents. Presence of others during use was associated with abusers' increased use and decreased functioning.