The potential of mass spectrometry imaging (MSI) has been demonstrated in cell and tissue research since 1970. MSI can reveal the spatial distribution of a wide range of atomic and molecular ions detected from biological sample surfaces, it is a powerful and valuable technique used to monitor and detect diverse chemical and biological compounds, such as drugs, lipids, proteins, and DNA. MSI techniques, notably matrix-assisted laser desorption/ionization time of flight (MALDI-TOF) and time of flight secondary ion mass spectrometry (TOF-SIMS), witnessed a dramatic upsurge in studying and investigating biological samples especially, cells and tissue sections. This advancement is attributed to the submicron lateral resolution, the high sensitivity, the good precision, and the accurate chemical specificity, which make these techniques suitable for decoding and understanding complex mechanisms of certain diseases, as well as monitoring the spatial distribution of specific elements, and compounds. While the application of both techniques for the analysis of cells and tissues is thoroughly discussed, a briefing of MALDI-TOF and TOF-SIMS basis and the adequate sampling before analysis are briefly covered. The importance of MALDI-TOF and TOF-SIMS as diagnostic tools and robust analytical techniques in the medicinal, pharmaceutical, and toxicology fields is highlighted through representative published studies.

Surfaces of polycrystalline ferritic Fe–Cr steel with grain sizes of about 13 µm in diameter were investigated with surface sensitive techniques. Thin oxide layers, with a maximum thickness of about 100 nm, were grown by oxidation in air at temperatures up to 450°C and were subsequently characterized using time-of-flight secondary ion mass spectrometry (TOF-SIMS) and atomic force microscopy. Correlative microscopy was applied, which allows for element-specific depth profiles on selected grains with a particular crystal orientation. A strong correlation between the grain orientation and the thickness of the oxide layer was found. The sequence in the oxidation growth rate of ferritic Fe–Cr steel crystal planes is found to be {011} > {111} > {001}, which is unexpectedly opposed to known Fe-based systems. Moreover, for the first time, the Cr/Fe ratio throughout the oxide layer has been determined per grain orientation. A clear order from high to low of {001} > {111} > {011} was detected.

We present the first demonstration of a general method for the chemical characterization of small surface features at high magnification via simultaneous collection of mass spectrometry (MS) imaging and tandem MS imaging data. High lateral resolution tandem secondary ion MS imaging is employed to determine the composition of surface features on poly(ethylene terephthalate) (PET) that precipitate during heat treatment. The surface features, probed at a lateral resolving power of<200 nm using a surface-sensitive ion beam, are found to be comprised of ethylene terephthalate trimer at a greater abundance than is observed in the surrounding polymer matrix. This is the first chemical identification of PET surface precipitates made without either an extraction step or the use of a reference material. The new capability employed for this study achieves the highest practical lateral resolution ever reported for tandem MS imaging.

In this paper the potential of time-of-flight secondary ion mass spectroscopy combined with focused ion beam technology to characterize the composition of a solid oxide fuel cell (SOFC) in three-dimension is demonstrated. The very high sensitivity of this method allows even very small amounts of elements/compounds to be detected and localized. Therefore, interlayer diffusion of elements between porous electrodes and presence of pollutants can be analyzed with a spatial resolution of the order of 100 nm. However, proper element recognition and mass interference still remain important issues. Here, we present a complete elemental analysis of the SOFC as well as techniques that help to validate the reliability of obtained results. A discussion on origins of probable artifacts is provided.

Molar incisor hypomineralization (MIH) is a developmental disturbance of the enamel. This study presents analyses of hypomineralized and normal enamel in first molar teeth diagnosed with MIH, utilizing time-of-flight secondary ion mass spectrometry area analyses and X-ray microanalysis of area and spot profiles in uncoated samples between gold lines which provide electrical conductivity. Statistical analysis of mean values allows discrimination of normal from MIH enamel, which has higher Mg and lower Na and P. Inductive analysis using complete data sets for profiles from the enamel surface to the enamel–dentin junction found that Mg, Cl and position in the profile provide useful discrimination criteria. Element profiles provide a visual complement to the inductive analysis and several elements also provide insight into the development of both normal and MIH enamel. The higher Mg content and different Cl profiles of hypomineralized enamel compared with normal enamel are probably related to a relatively short period during the development of ameloblasts between birth and the 1st year of life.

Sleep deprivation causes cognitive dysfunction in which impaired neuronal plasticity in hippocampus may underlie the molecular mechanisms of this deficiency. Considering calcium-mediated NMDA receptor subunit 1 (NMDAR1) and neuronal nitric oxide synthase (nNOS) activation plays an important role in the regulation of neuronal plasticity, the present study is aimed to determine whether total sleep deprivation (TSD) would impair calcium expression, together with injury of the neuronal plasticity in hippocampus. Adult rats subjected to TSD were processed for time-of-flight secondary ion mass spectrometry, NMDAR1 immunohistochemistry, nNOS biochemical assay, cytochrome oxidase histochemistry, and the Morris water maze learning test to detect ionic, neurochemical, bioenergetic as well as behavioral changes of neuronal plasticity, respectively. Results indicated that in normal rats, strong calcium signaling along with intense NMDAR1/nNOS expression were observed in hippocampal regions. Enhanced calcium imaging and neurochemical expressions corresponded well with strong bioenergetic activity and good performance of behavioral testing. However, following TSD, both calcium intensity and NMDAR1/nNOS expressions were significantly decreased. Behavioral testing also showed poor responses after TSD. As proper calcium expression is essential for maintaining hippocampal neuronal plasticity, impaired calcium expression would depress downstream NMDAR1-mediated nNOS activation, which might contribute to the initiation or development of TSD-related cognitive deficiency.

The organic interprismatic layers of the mollusc Pinctada margaritifera are studied using a variety of highly spatially-resolved techniques to establish their composition and structure. Our results show that both the interlamellar sheets of the nacre and interprismatic envelopes form layered structures. Additionally, these organic layers are neither homogeneous in composition, nor continuous in their structure. Both structures play a major role in the biomineralization process and act as a boundary between mineral units.

The technique of imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS) and dual beam depth profiling has been used to study the composition of the surface of tabular silver halide microcrystals. Analysis of individual microcrystals with a size well below 1 μm from a given emulsion is possible. The method is successfully applied for the characterization of silver halide microcrystals with subpercent global iodide concentrations confined in surface layers with a thickness below 5 nm. The developed TOF-SIMS analytical procedure is explicitly demonstrated for the molecular imaging of adsorbed thiocyanate layers (SCN) at crystal surfaces of individual crystals and for the differentiation of iodide conversion layers synthesized with KI and with AgI micrates (nanocrystals with a size between 10 and 50 nm). It can be concluded that TOF-SIMS as a microanalytical, surface-sensitive technique has some unique properties over other analytical techniques for the study of complex structured surface layers of silver halide microcrystals. This offers valuable information to support the synthesis of future photographic emulsions.