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Functionalization and precise modulation of the electronic properties of graphene are key processes in the development of new applications of this promising material. This study examines the potential of using organic polycations as p-dopants and/or anchoring motifs for non-covalent functionalization. A library of hybrid materials was prepared through wet-chemical non-covalent functionalization. Both chemical vapor deposition graphene and reduced graphene oxide were functionalized with a series of neutral and polycationic benzimidazole-based systems. We report on how both the number of anions and the size, shape, and magnitude of the positive charge of the benzimidazole-based systems cooperatively affect the redox properties as well as the affinity for and the nature of bonding to graphene. The redox properties of the benzimidazole-based systems were studied by cyclic voltammetry. The functionalized graphene materials were characterized by Raman spectroscopy, X-ray photoelectron spectroscopy, and time-of-flight secondary ion mass spectrometry. Density functional theory calculations were performed to make contact between the experimental results obtained for molecular samples and hybrid materials. No universal dependence of the binding affinity on a single parameter, such as the amount of positive charge or the size of the system, was found. Instead, the cooperative effect of the three-dimensional structure of the benzimidazole-based systems and the number of anions was found to play a pivotal role. Together, these parameters determine the degree of partial electron sharing and magnitude of dispersion forces involved in the binding of members of this family of benzimidazole-based systems to graphene.

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.

Lead has traditionally been added to brass alloys to achieve high machinability, but the exact mechanisms at work are still debated. Lead-free brass alternatives could be developed if these mechanisms were better understood. Accordingly, machinability characteristics were investigated for two brass alloys with similar mechanical properties and phase composition, but with very different machining characteristics because one has 3 wt.% lead (CuZn38Pb3) while the other has only 0.1 wt.% (CuZn42). The effect of the lead was investigated using infrared temperature measurement, electron microscopy, secondary ion mass spectroscopy, quick-stop methods, and high-speed filming. Neither melting of lead nor its deposition on the tool rake surface takes place during machining, thus confirming its limited lubrication and tribological effects. Instead, the main role of lead is to promote discontinuous chip formation. Lead deforms to flake-like shapes that act as crack initiation points when the workpiece material passes through the primary deformation zone. This effect prevents the development of stable tool–chip contact, thus lowering cutting forces, friction, and process temperature.

ToF-SIMS analysis of copper samples after exposures to simulated groundwater with and without sulfide addition was performed to investigate the penetration of corrosive species containing H, S, O, and Cl, into copper. Depth profiles show extent of penetration and 2D/3D images reveal local elemental distribution of the corrosive species at different depths inside copper. Pre-oxidation did not reduce the penetration while sulfide additional in groundwater and exposure at 60 °C significantly promoted the penetration. The extent of penetration of the corrosive species into copper demonstrates the need for risk assessment of complex corrosion forms such as sulfide-induced embrittlement and cracking.

The preservation of biosignatures on Mars is largely associated with extensive deposits of clays formed under mild early Noachian conditions (> 3.9 Ga). They were followed by widespread precipitation of acidic sulfates considered adverse for biomolecule preservation. In this paper, an exhaustive mass spectrometry investigation of ferric subsurface materials in the Rio Tinto gossan deposit (~ 25 Ma) provides evidence of well-preserved molecular biosignatures under oxidative and acidic conditions. Time of flight secondary ion mass spectrometry (ToF-SIMS) analysis shows a direct association between physical-templating biological structures and molecular biosignatures. This relation implies that the quality of molecular preservation is exceptional and provides information on microbial life formerly operating in the shallow regions of the Rio Tinto subsurface. Consequently, low-pH oxidative environments on Mars could also record molecular information about ancient life in the same way as the Noachian clay-rich deposits, (Grant No. ANR-15-IDEX-02), European Regional Development Fund (Grant No. RYC2018-023943-I), Horizon 2020 Framework Programme (Grant No. RYC-2014-19446)

The distribution of terpinen-4-ol (TP4ol) and DMPBD inclusion complexes with 2-hydroxypropyl-β-cyclodextrin (HPbCD) in human skin has been investigated using the TOF-SIMS technique. TP4ol and DMPBD have been found to be major components of Zingiber cassumunar Roxb. (Plai) oil extracted by steam distillation. The results mainly show accumulation of TP4ol and DMPBD inclusion complexes with HPbCD in the epidermis and dermis whereas these two compounds without cyclodextrin cannot penetrate into the epidermis. This approach can be expanded for investigation of anti-inflammatory action and relief of muscle pain.

Quartz, feldspar, and olivine are minerals commonly used as bed materials for dual fluidized bed gasification of biomass. During their interaction with biomass ash, the materials develop surface layers rich in ash-derived elements. These layers decrease the concentration of tar which is an unwanted side product of gasification. The interactions of quartz, feldspar, and olivine with woody biomass ash leading to the formation of active layers were studied with X-ray diffraction, scanning electron microscopy- energy dispersive X-ray spectroscopy, and iime-of-flight secondary ion mass spectrometry, and the results were compared to calculations done with FactSage. It was found that the interaction causes the formation of three-layered structures for all materials: a Mg-rich surface layer, a Ca-rich intermediate layer, and an inner layer which varies among the three materials. For quartz and feldspar, the integration of Ca and Mg into the structure causes a transition by depolymerizing the tectosilicate structure via an inosilicate intermediate to finally a nesosilicate. As the olivine structure is a nesosilicate from the beginning, no further depolymerization of the silicate structure can occur and a substitution of Mg by Ca occurs, leading to an accumulation of expelled MgO on the surface. The interaction of the materials with K was found to differ, causing melt formation for quartz, a substitution of Na-rich feldspar by K-rich feldspar, and the formation of feldspathoids for alkali feldspar, or retention as a separate phase for olivine.

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Background: Psoriasis is a systemic inflammatory disease characterized by epidermal proliferation in the skin. Altered lipid metabolism is considered to be a central factor in the psoriatic etiopathogenesis. Thus, it is necessary to visualize chemical specificity of the samples for better medical diagnosis and treatment. Here, we investigate its role in the development of psoriatic lesions, before and after ultraviolet phototherapy, in a case study. Methods: The distribution and morphology of different lipids and fibrous proteins in psoriatic (lesional) tissues were visualized by two complementary label-free imaging techniques: 1) non-linear microscopy (NLM), providing images of lipids/proteins throughout the skin layers at submicrometer resolution; and 2) mass spectrometry imaging (MSI), offering high chemical specificity and hence the detection of different lipid species in the epidermal and dermal regions. A conventional method of histological evaluation was performed on the tissues, with no direct comparison with NLM and MSI. Results: Psoriatic tissues had a higher lipid content, mainly in cholesterol, in both the epidermal and dermal regions, compared to healthy tissues. Moreover, the collagen and elastin fibers in the psoriatic tissues had a tendency to assemble as larger bundles, while healthy tissues showed smaller fibers more homogeneously spread. Although phototherapy significantly reduced the cholesterol content, it also increased the amounts of collagen in both lesional and non-lesional tissues. Conclusion: This study introduces NLM and MSI as two complementary techniques which are chemical specific and can be used to assess and visualize the distribution of lipids, collagen, and elastin in a non-invasive and label-free manner.

Hypomineralized enamel may be found in connection with the condition molar incisor hypomineralization (MIH), which has a prevalence of around 15% in most parts of the world. Molar incisor hypomineralization is associated with extensive objective and subjective problems, such as hypersensitivity of the affected teeth, enamel breakdown, and problems with retention of restorations. The etiology behind MIH has not yet been elucidated, but a number of possible factors, which affect the same or different functions of ameloblasts during their different stages of maturation, have been suggested. The aim of this study was to utilize multi-nuclear, solid-state nuclear magnetic resonance (ss-NMR) and time-of-flight secondary ion mass spectroscopy (ToF-SIMS) to elucidate any differences, at a molecular level, between enamel powder prepared from normal, healthy teeth and enamel powder prepared from teeth diagnosed with MIH. 31P and 23Na ss-NMR confirmed the presence of HPO2-4 and two different Na+ sites in hypomineralized enamel, suggesting a heterogeneous chemical composition. The content of organic components was higher in hypomineralized enamel, as shown by both 13C ss-NMR and ToF-SIMS, indicating the presence of higher numbers of proteins and phospholipids. The interplay between both is necessary for the formation and mineralization of enamel, which might be disturbed or halted in hypomineralized enamel.

A micromolar concentration of zinc has been shown to significantly change the dynamics of exocytosis as well as the vesicle contents in a model cell line, providing direct evidence that zinc regulates neurotransmitter release. To provide insight into how zinc modulates these exocytotic processes, neurotransmitter release and vesicle content were compared with single cell amperometry and intracellular impact vesicle cytometry with a range of zinc concentrations. Additionally, time-of-flight secondary ion mass spectrometry (ToF-SIMS) images of lipid distributions in the cell membrane after zinc treatment correlate to changes in exocytosis. By combining electrochemical techniques and mass spectrometry imaging, we proposed a mechanism by which zinc changes the fusion pore and the rate of neurotransmitter release by changing lipid distributions and results in the modulation of synaptic strength and plasticity.

The drilling of the Rio Tinto basement has provided evidence of an underground microbial community primarily sustained by the Fe and S metabolism through the biooxidation of pyrite orebodies. Although the gossan is the microbial activity product, which dates back to the Oligocene (25 Ma), no molecular evidence of such activity in the past has been reported yet. A Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS) molecular analysis of a subsurface sample in the Peña de Hierro basement has provided novel data of the ancient underground microbial community. It shows that the microbial remains are preserved in a mineral matrix composed of laminated Fe-oxysulfates and K-and Na-bearing sulfates alternating with secondary silica. In such a mineral substrate, the biomolecule traces are found in five different microstructure associations, (1) 200-micron thick layer with N-bearing adducts, and sphingolipid and/or peptide traces. It suggests the mineralization of at least five microbial preserved entities with different metabolic ca-pabilities, including: (1) Acidiphilium/Tessaracoccus-like phosphate mineralizers, (2) microbial patches preserving phosphate-free acylglycerides bacteria, (3) nitrogen oxidizing bacteria (e.g., Acidovorax sp.), (4) traces of heterotrophic ammonifying bacteria, and (5) sphingolipid bearing bacteria (e.g., Sphin-gomonadales, and δ-Proteobacteria) and/or mineralized biofilms. The primary biooxidation process acted as a preservation mechanism to release the inorganic ions that ultimately mineralized the microbial structures., Science and Technology Development Fund (FDCT) of Macao (Nos. 0005/2020/A1 and 0005/2019/A1), and the project on Civil Aerospace Technologies No. D020303 funded by China National Space Administration

Cluster ion beam ToF-SIMS and/or MALDI-ToF mass spectrometry imaging (using 1,5-DAN matrix via sublimation) of a single coronal rat brain tissue section followed by classical- or immuno- histochemical staining faclilated a new multimodal chemical imaging workflow allowing complementary correlation of the lipid molecular ion images with the immuno/histological features within cerebellum region of the same brain tisue section.

Macrophages play a key role in determining the fate of implanted biomaterials, especially for biomaterials such as calcium phosphates (CaPs) where these cells play a vital role in material resorption and osteogenesis, as shown in different models, including clinical samples. Although substantial consideration is given to the design and validation of different CaPs, relatively little is known about their material-cell interaction. Specifically, the intracellular content of different CaP phases remains to be assessed, even though CaP-filled macrophages have been observed in several studies. In this study, 2D/3D ToF-SIMS imaging and multivariate analysis were directly applied on the histology samples of an explant to reveal the content of macrophages. The cellular content of the macrophages was analyzed to distinguish three CaP phases, monetite, beta-tricalcium phosphate, and pyrophosphate, which are all part of the monetite-based CaP implant composition under study. ToF-SIMS combined with histology revealed that the content of the identified macrophages was most similar to that of the pyrophosphate phase. This study is the first to uncover distinct CaP phases in macrophages from a human multiphasic CaP explant by targeted direct cell content analysis. The uncovering of pyrophosphate as the main phase found inside the macrophages is of great importance to understand the impact of the selected material in the process of biomaterial-instructed osteogenesis.

Here we demonstrate an animal-free skin permeation analytical approach suitable for testing pharmaceuticals, cosmetics, occupational skin hazards and skin allergens. The method aims to replace or significantly reduce existing in-vivo models and improve on already established in-vitro models. This by offering a more sensitive and flexible analytical approach that can replace and/or complement existing methods in the OECD guidelines for skin adsorption (no 427 and no 428) and measure multiple compounds simultaneously in the skin while being able to also trace endogenous effects in cells. We demonstrate this here by studying how active ingredients in sunscreen permeate through left-over human skin, from routine surgery, in a in a Franz-cell permeation model. Two common sunscreens were therefore applied to the human skin and Time of flight secondary ion mass spectrometry (ToF-SIMS) was used to trace the molecules through the skin. We show that that ToF-SIMS imaging can be applied in visualizing the distribution of Avobenzone, Bemotrizinol, Biscotrizole and Ethyl hexyl triazine at subcellular resolution in the skin. The UV-blockers could be visualized at the same time in one single experiment without any probes or antibodies used. The UV-blockers mostly remained in the stratum corneum. However, in certain features of the skin, such as sebaceous glands, the penetration of the UV-blockers was more prominent, and the compounds reached deeper into the epidermis.

In the microelectronic component industry, because of the miniaturization of functional units, the interaction of materials and interfaces play a much more significant role in their performance. The result of this is that ultrafine crystalline and trace impurity behavior impact a device's operation to a much greater extent. This is the case with micro-connects for 3D integration, such as micro-bumps. Any unwanted crystalline behavior or interfacial segregated impurities can drastically alter a micro-connect's performance, with a particular issue being intermetallic void formation, often known as Kirkendall voiding. Currently, it is unclear under what conditions voids form and how to prevent them. This work studies the microstructural and compositional differences between samples with different voiding densities. Results show that samples that exhibit an ultrafine crystalline have a higher propensity to exhibit voiding. Also, there is a high concentration of trace impurities located in the electrochemically deposited Cu layer. After isothermal annealing, high concentrations of impurities are located at the interface between Cu and the Cu-Sn intermetallic compound of Cu3Sn. An alternative explanation to the traditional Kirkendall void formation theory is presented. The explanation is based on the interaction of trace impurities from the electroplating process and the microstructural evolution.

Understanding FA metabolism and lipid synthesis requires a lot of information about which FAs and lipids are formed within the cells. We focused on the use of deuterated substrates of 100 μM α-linolenic acid and linoleic acid to determine the relative amounts of their converted PUFAs and specific phospholipids that are incorporated into cell plasma membranes. Time-of-flight secondary ion mass spectrometry (TOF-SIMS) was used to image and analyze lipids in model cell membranes with and without FA treatment. Because of its high spatial resolution, TOF-SIMS can be used to simultaneously provide both chemical information and distribution of various molecules in the sample surface down to the subcellular scale. Data obtained from this analysis of isotopes in the cell samples were used to calculate the relative amounts of long-chain PUFAs and phospholipids from their precursors, α-linolenic acid and linoleic acid. Our results show that the FA treatments induced an increase in the amounts of α-linolenic acid and linoleic acid and their long-chain conversion products. Moreover, an enhanced level of phospholipid turnover of these FAs in lipids such as phosphatidylcholines, phosphatidylethanolamines, and phosphatidylinositols was also observed in the cell plasma membrane.

High-temperature alloys are crucial to many important technologies that underpin our civilization. All these materials rely on forming an external oxide layer (scale) for corrosion protection. Despite decades of research on oxide scale growth, many open questions remain, including the crucial role of the so-called reactive elements and water. Here, we reveal the hitherto unknown interplay between reactive elements and water during alumina scale growth, causing a metastable ‘messy’ nano-structured alumina layer to form. We propose that reactive-element-decorated, hydroxylated interfaces between alumina nanograins enable water to access an inner cathode in the bottom of the scale, at odds with the established scale growth scenario. As evidence, hydride-nanodomains and reactive element/hydrogen (deuterium) co-variation are observed in the alumina scale. The defect-rich alumina subsequently recrystallizes to form a protective scale. First-principles modelling is also performed to validate the RE effect. Our findings open up promising avenues in oxidation research and suggest ways to improve alloy properties. The crucial interaction between reactive elements and water vapour during the oxide scale growth of alumina-forming alloys is revealed, providing insights to improve corrosion resistance of high-temperature alloys.

Two-stage 18 O 2 / 16 O 2 exposures can be used to investigate the effect that alloying elements, secondary phases, or surface treatments have on the high temperature oxidation behaviour of certain materials. During subsequent exposures to 16 O 2 - and 18 O 2 -rich atmospheres, 16 O- and 18 O-rich layers are formed. Analysis of the layers using Secondary Ion Mass Spectrometry (SIMS) depth profiling allows for conclusions to be drawn about the oxide scale growth mechanism. The conclusions are, however, not entirely unambiguous due to the limited lateral resolution of the technology. Rough surface topography and the thickness variation of the oxide scale over the analysed volume add to the ambiguity of the findings. In this study, an Fe-20%Cr alloy was exposed to both 18 O- and 16 O-rich environments at 850 °C. Two methods were used to analyse the thermally grown Cr 2 O 3 scale: (1) traditional SIMS depth profiling and (2) preparation of a cross-sectional lamellae for Transmission Electron Microscopy (TEM), which, subsequently, was analysed in a NanoSIMS. The NanoSIMS 16 O and 18 O elemental maps were then superimposed on the TEM image. In comparison with traditional SIMS depth profiling, the nanoSIMS elemental maps reveal detailed information about local oxide growth in different parts of an oxide scale. Moreover, a clear 16 O/ 18 O interface can be seen in the nanoSIMS maps, which is not the case in the sputter depth profiles. The findings of this study show that the aforementioned issues associated with sputter depth profiling can be eliminated by mapping a cross-section of an oxide scale using high resolution nanoSIMS.

Background. In spite of extensive regulation to limit exposure, nickel remains the main cause of contact allergy in the general population. More detailed knowledge on the skin uptake of haptens is required. So far, no method exists for the visualization of this clinically relevant hapten and its distribution in the skin. Objectives. To show, in terms of a proof of concept, that imaging mass spectrometry [time of flight secondary ion mass spectrometry (ToF-SIMS)] can be applied for investigation of the penetration and distribution of nickel in human skin. Method. Full-thickness human skin obtained from breast reduction surgery was exposed to nickel sulfate (5% in deionized water) for 24 h in Franz-type diffusion cells. Biopsies were obtained from nickel-treated samples and control (deionized water). The tissue was sliced, and analysed with ToF-SIMS, generating high-resolution images of ion distribution in the epidermis and upper dermis. Results. The skin layers could be discerned from the ToF-SIMS data, particularly on the basis of the collagen signal. Nickel ions were localized to the stratum corneum and upper epidermis. Conclusions. This is the first time that ToF-SIMS has been applied to trace the distribution of a hapten in human skin. Proof of principle was shown for nickel, and the technique can, in the future, be expanded for investigation of the skin distribution of clinically relevant sensitizers in general.

We applied electrochemical techniques with nano-tip electrodes to show that micromolar concentrations of zinc not only trigger changes in the dynamics of exocytosis, but also vesicle content in a model cell line. The vesicle catecholamine content in PC12 cells is significantly decreased after 100 μM zinc treatment, but, catecholamine release during exocytosis remains nearly the same. This contrasts the number of molecules stored in the exocytosis vesicles, which decreases, and we find that the amount of catecholamine released from zinc-treated cells reaches nearly 100 percent content being expelled. Further investigation shows that zinc slows down exocytotic release allowing time for this to occur. Our results provide the missing link between zinc and the regulation of neurotransmitter release processes, which might be important in memory formation and storage.

[Image: see text] Mass spectrometry imaging is a field that promises to become a mainstream bioanalysis technology by allowing the combination of single-cell imaging and subcellular quantitative analysis. The frontier of single-cell imaging has advanced to the point where it is now possible to compare the chemical contents of individual organelles in terms of raw or normalized ion signal. However, to realize the full potential of this technology, it is necessary to move beyond this concept of relative quantification. Here we present a nanoSIMS imaging method that directly measures the absolute concentration of an organelle-associated, isotopically labeled, pro-drug directly from a mass spectrometry image. This is validated with a recently developed nanoelectrochemistry method for single organelles. We establish a limit of detection based on the number of isotopic labels used and the volume of the organelle of interest, also offering this calculation as a web application. This approach allows subcellular quantification of drugs and metabolites, an overarching and previously unmet goal in cell science and pharmaceutical development.

Nine metal-organic frameworks have been prepared with the hexagon-shaped linker 1,2,3,4,5,6-hexakis(4-carboxyphenyl)-benzene (H(6)cpb) by solvothermal reactions in dimethylformamide (dmf) or dimethylacetamide (dmac) with acetic acid or formic acid as modulators: [Bi-2(cpb)(acetato)(2)(dmf)(2)]center dot 2dmf CTH-6 forms a rtl-net; 2(H2NMe2)[Cu-2(cpb)] CTH-7 forms a kgd-net; [Fe-4(cpb)-(acetato)(2)(dmf)(4)] CTH-8 and [Co-4(cpb)(acetato)(2)(dmf)(4)] CTH-9 are isostructural and form yav-nets; 2(HNEt3)[Fe-2(cpb)] CTH-10 and the two polymorphs of 2(H2NMe2)[Zn-2(cpb)]center dot 1.5dmac, Zn-MOF-888 and CTH-11, show kgd-nets; [Cu-2(cpb)-(acetato)(2)(dmf)(2)]center dot 2dmf, CTH-12, forms a mixed coordination and hydrogen-bonded sql-net; and 2(H2NMe2)[Zn-2(cpb)] CTH-13, a similarly mixed yav-net. Surface area values (Brunauer-Emmett-Teller, BET) range from 34 m(2) g(-1) for CTH-12 to 303 m(2) g(-1) for CTH-9 for samples activated at 120 degrees C in dynamic vacuum. All compounds show normal (10-fold higher) molar CO2 versus N-2 uptake at 298 K, except the 19-fold CO2 uptake for CTH-12 containing Cu(II) dinuclear paddle-wheels. We also show how perfect hexagons and triangles can combine to a new 3D topology laf, a model of which gave us the idea of foldable network topologies, as the laf-net can fold into a 2D form while retaining the local geometry around each vertex. Other foldable nets identified are cds, cds-a, ths, sqc163, clh, jem, and tfc covering the basic polygons and their combinations. The impact of this concept on "breathing" MOFs is discussed. I-2 sorption, both from gas phase and from MeOH solution, into CTH-7 were studied by time of flight secondary ion mass spectrometry (ToF-SIMS) on dried crystals. I-2 was shown to have penetrated the crystals, as layers were consecutively peeled off by the ion beam. We suggest ToF-SIMS to be a method for studying sorption depth profiles of MOFs.

Introduction Soluble copper that can be acquired by bacteria is toxic and therefore antimicrobial. Whether nanostructured copper materials, in either disperse or agglomerated form, have antimicrobial impact, aside from that of their dissolution products, is not clear and was herein addressed. Methods We took five nanostructured copper materials, two metallic, and three oxo-hydroxides with one of these being silicate-substituted. Four agglomerated in the bacterial growth media whilst the silicate-substituted material remained disperse and small (6.5 nm diameter). Antibacterial activity against E. coli was assessed with copper phase distribution measured over time. Using the dose of soluble copper, and benchmark dose non-linear regression modelling, we determined how well this phase predicted antimicrobial activity. Finally, we used Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) analysis to investigate whether membrane adhesion effects by copper were plausible or if intracellular uptake most likely explained the bacterial impact of copper. Results Comparison over time of antimicrobial activity against particulate or soluble phases of the aquated materials clearly demonstrated that soluble copper but not particulate forms were associated with inhibition of bacterial growth. Indeed, the benchmark dose modelling showed the soluble dose required to cause a 50% reduction in E. coli growth was strongly clustered – for all particle formulations – at 14.5 mg/L (10–19 mg/L 90% confidence interval). By comparison, total copper levels associated with the same reduction in viability varied widely (45–549 mg/L). Finally, in favour of this soluble product dominance in terms of antimicrobial activity, copper had low association with bacterial membrane (something both soluble and particulate materials could do) but showed high intra-bacterial levels (something only soluble copper could do). Conclusion Taken together our data show that it is the uptake of soluble but not particulate copper, and the intracellular loading not just contact and membrane association, that drives copper toxicity to bacteria. Therapeutic strategies for novel antimicrobial copper compounds should consider these findings.

Hybridizing graphene and molecules possess a high potential for developing materials for new applications. However, new methods to characterize such hybrids must be developed. Herein, the wet‐chemical non‐covalent functionalization of graphene with cationic π‐systems is presented and the interaction between graphene and the molecules is characterized in detail. A series of tricationic benzimidazolium salts with various steric demand and counterions was synthesized, characterized and used for the fabrication of graphene hybrids. Subsequently, the doping effects were studied. The molecules are adsorbed onto graphene and studied by Raman spectroscopy, XPS as well as ToF‐SIMS. The charged π‐systems show a p‐doping effect on the underlying graphene. Consequently, the tricationic molecules are reduced through a partial electron transfer process from graphene, a process which is accompanied by the loss of counterions. DFT calculations support this hypothesis and the strong p‐doping could be confirmed in fabricated monolayer graphene/hybrid FET devices. The results are the basis to develop sensor applications, which are based on analyte/molecule interactions and effects on doping., Organic star‐shaped tricationic molecules interact with graphene and a one‐electron transfer from graphene to the molecules leads to strong p‐doping.

There is emerging evidence that amyloid beta (Aβ) aggregates forming neuritic plaques lead to impairment of the lipid-rich myelin sheath and glia. In this study, we examined focal myelin lipid alterations and the disruption of the myelin sheath associated with amyloid plaques in a widely used familial Alzheimer's disease (AD) mouse model; 5xFAD. This AD mouse model has Aβ42 peptide-rich plaque deposition in the brain parenchyma. Matrix-assisted laser desorption/ionization imaging mass spectrometry of coronal brain tissue sections revealed focal Aβ plaque-associated depletion of multiple myelin-associated lipid species including sulfatides, galactosylceramides, and specific plasmalogen phopshatidylethanolamines in the hippocampus, cortex, and on the edges of corpus callosum. Certain phosphatidylcholines abundant in myelin were also depleted in amyloid plaques on the edges of corpus callosum. Further, lysophosphatidylethanolamines and lysophosphatidylcholines, implicated in neuroinflammation, were found to accumulate in amyloid plaques. Double staining of the consecutive sections with fluoromyelin and amyloid-specific antibody revealed amyloid plaque-associated myelin sheath disruption on the edges of the corpus callosum which is specifically correlated with plaque-associated myelin lipid loss only in this region. Further, apolipoprotein E, which is implicated in depletion of sulfatides in AD brain, is deposited in all the Aβ plaques which suggest apolipoprotein E might mediate sulfatide depletion as a consequence of an immune response to Aβ deposition. This high-spatial resolution matrix-assisted laser desorption/ionization imaging mass spectrometry study in combination with (immuno) fluorescence staining of 5xFAD mouse brain provides new understanding of morphological, molecular and immune signatures of Aβ plaque pathology-associated myelin lipid loss and myelin degeneration in a brain region-specific manner. Read the Editorial Highlight for this article on page 7.

Ganglioside metabolism is significantly altered in Alzheimer's disease (AD), which is a progressive neuro-degenerative disease prominently characterized by one of its pathological hallmarks, amyloid deposits or "senile plaques". While the plaques mainly consist of aggregated variants of amyloid-beta protein (A beta), recent studies have revealed a number of lipid species including gangliosides in amyloid plaques along with A beta peptides. It has been widely suggested that long chain (sphingosine) base (LCBs), C18:1-LCB and C20:1-LCB, containing gangliosides might play different roles in neuronal function in vivo. In order to elucidate region-specific aspects of amyloid-plaque associated C18:1-LCB and C20:1-LCB ganglioside accumulations, high spatial resolution (10 mu m per pixel) matrix assisted laser desorption ionization imaging mass spectrometry (MALDI-IMS) of gangliosides in amyloid plaques was performed in hippocampal and adjacent cortical regions of 12 month old 5xFAD mouse coronal brain sections from two different stereotaxic coordinates (bregma points, -2.2 and -2.7 mm). MALDI-IMS uncovered brain-region (2 and 3D) and/or LCB specific accumulations of monosialogangliosides (GMs): GM1, GM2, and GM3 in the hippocampal and cortical amyloid plaques. The results reveal monosialogangliosides to be an important component of amyloid plaques and the accumulation of different gangliosides is region and LCB specific in 12 month old 5xFAD mouse brain. This is discussed in relation to amyloid-associated AD pathogenesis such as lipid related immune changes in amyloid plaques, AD specific ganglioside metabolism, and, notably, AD-associated impaired neurogenesis in the subgranular zone.

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease that is currently the third leading cause of death worldwide. Recent reports have indicated that dysfunctional iron handling in the lungs of COPD patients may be one contributing factor. However, a number of these studies have been limited to the qualitative assessment of iron levels through histochemical staining or to the expression levels of iron-carrier proteins in cells or bronchoalveolar lavage fluid. In this study, we have used time of flight secondary ion mass spectrometry (ToF-SIMS) to visualize and relatively quantify iron accumulation in lung tissue sections of healthy donors versus severe COPD patients. An IONTOF 5 instrument was used to perform the analysis, and further multivariate analysis was used to analyze the data. An orthogonal partial least squares discriminant analysis (OPLS-DA) score plot revealed good separation between the two groups. This separation was primarily attributed to differences in iron content, as well as differences in other chemical signals possibly associated with lipid species. Further, relative quantitative analysis revealed twelve times higher iron levels in lung tissue sections of COPD patients when compared to healthy donors. In addition, iron accumulation observed within the cells was heterogeneously distributed, indicating cellular compartmentalization.

In this work, we have employed time-of-flight secondary ion mass spectrometry (ToF-SIMS) to image chemically fixed adrenal cells prepared for transmission electron microscopy (TEM) and subsequent high-spatial-resolution NanoSIMS imaging. The sample fixation methodology preserves cell morphology, allows analysis in the ultrahigh vacuum environment, and reduces topographic artifacts, thus making these samples particularly favorable for ToF-SIMS analysis. ToF-SIMS imaging enables us to determine the chemistry and preservation capabilities of the chemical fixation as well as to locate specific ion species from OsO4. The OsO4 species have been localized in lysosomes of cortical cells, a type of adrenal cell present in the culture. NanoSIMS imaging of the (190)Os(16)O(-) ion species in cortical cells reveals the same localization as a wide range of OsO4 ions shown with ToF-SIMS. Even though we did not use during NanoSIMS imaging the exact OsxOy(-) ion species discovered with ToF-SIMS, ToF-SIMS allowed us to define the specific subcellular features in a high spatial resolution imaging mode. This study demonstrates the possibility for application of ToF-SIMS as a screening tool to optimize high-resolution imaging with NanoSIMS, which could replace TEM for localization in ultrahigh resolution imaging analyses.

Alloys forming external alumina scales can be used at very high temperature because of the excellent ability of alumina to protect against further reaction with the environment. Traces, ~0.1 at. %, of the so-called reactive elements (REs) are added into alumina- (and chromia-) forming alloys in order to enhance their oxidation performance. In this talk, the formation mechanism of protective alumina scales on several FeCrAl and FeNiCrAl alloys for high temperature application will be first discussed. As demostrated in our paper [1], the interaction between water and REs faciliates the formation of the ”protective” alumina scales via the formation of a nanocrystalline alumina layer with yttrium-decorated grain boundaries at the early stages of oxidation. Using state-of-the-art analytical tools such as STEM-EDXS-EELS and NanoSIMS, it has also been revealed that the water/REs interplay leads to the formation of hydride- and hydroxide-nanodomains in the alumina scale. In this context, findings of our latest research on the failure modes of alumina scales will be also presented with the emphasis on the key role of RE particle size distribution and the alloy grain orientation in the protective charactrestics of the oxide scales. Controlled high-temperature oxidation exposures in conjunction with quasi-in-situ experiments revealed that failure of the protective oxide scale occurs at specific, predictable (deterministic) sites on the alloy surface. The new undrestaning that will be discussed in this talk are expected to open up new avenues of research on the development of the next generation of high temperature alloys with superiour properties.

Precise characterization of a monolayer of two different biomolecules in a gradient pattern on a glass surface puts high demand on the method used. Some techniques can detect protein monolayers but not on a glass surface. Others can distinguish between different proteins but not identify a gradient pattern. Here, we used ToF-SIMS to validate the complete surface composition, checking all the necessary boxes. As these types of surfaces can dictate sensitive cell behaviors, the precision on a nanolevel is crucial, and to visualize and determine the molecular distribution become essential. The dual monolayer consisted of laminin 521 and one of three other biomolecules of different sizes, epidermal growth factor, growth differentiation factor 5, or bovine serum albumin, creating opposing gradient patterns. The resulting ToF-SIMS imaging and line scan data provided detailed information on the distribution of the adsorbed proteins.