Elemental imaging gives insight into the fundamental chemical makeup of living organisms. Every cell on Earth is comprised of a complex and dynamic mixture of the chemical elements that define structure and function. Many disease states feature a disturbance in elemental homeostasis, and understanding how, and most importantly where, has driven the development of laser ablation−inductively coupled plasma−mass spectrometry (LA-ICP-MS) as the principal elemental imaging technique for biologists. This review provides an outline of ICP-MS technology, laser ablation cell designs, imaging workflows, and methods of quantification. Detailed examples of imaging applications including analyses of cancers, elemental uptake and accumulation, plant bioimaging, nanomaterials in the environment, and exposure science and neuroscience are presented and discussed. Recent incorporation of immunohistochemical workflows for imaging biomolecules, complementary and multimodal imaging techniques, and image processing methods is also reviewed.CONTENTS

Human zinc deficiency increases susceptibility to bacterial infection. Although zinc supplementation therapies can reduce the impact of disease, the molecular basis for protection remains unclear. Streptococcus pneumoniae is a major cause of bacterial pneumonia, which is prevalent in regions of zinc deficiency. We report that dietary zinc levels dictate the outcome of S . pneumoniae infection in a murine model. Dietary zinc restriction impacts murine tissue zinc levels with distribution post-infection altered, and S . pneumoniae virulence and infection enhanced. Although the activation and infiltration of murine phagocytic cells was not affected by zinc restriction, their efficacy of bacterial control was compromised. S . pneumoniae was shown to be highly sensitive to zinc intoxication, with this process impaired in zinc restricted mice and isolated phagocytic cells. Collectively, these data show how dietary zinc deficiency increases sensitivity to S . pneumoniae infection while revealing a role for zinc as a component of host antimicrobial defences.

Elemental bio-imaging using the technological advances of ICP-QQQ-MS.

Diagnosis and localization of bacterial infections remains a significant clinical challenge. Harnessing bacteria-specific metabolic pathways, such as the maltodextrin transport mechanism, may allow specific localization and imaging of small or hidden colonies. This requires that the intrabacterial tracer accumulation provided by the transporter is matched by high serum stability of the tracer molecule. Herein, radiolabeled maltodextrins of varying chain lengths and with free nonreducing/reducing ends are reported and their behavior against starch-degrading enzymes in the blood, which compromise their serum stability, is evaluated. Successful single-photon emission computed tomography (SPECT) imaging is shown in a footpad infection model in vivo by using the newly developed model tracer, [ Tc]MB1143, and the signal is compared with that of F-fluorodeoxyglucose positron emission tomography ([ F]FDG-PET) as a nonbacterial specific marker for inflammation. Although the [ Tc]MB1143 imaging signal is highly specific, it is low, most probably due to insufficient serum stability of the tracer. A series of stability tests with different F-labeled maltodextrins finally yielded clear structural guidelines regarding substitution patterns and chain lengths of maltodextrin-based tracers for nuclear imaging of bacterial infections.

This work introduces new methods to characterize dispersions of small-diameter or low-mass-fraction nanoparticles (NPs) by single-particle inductively coupled plasma-mass spectrometry (SP ICP-MS). The optimization of ion extraction, ion transport, and the operation of the quadrupole with increased mass bandwidth improved the signal-to-noise ratios significantly and decreased the size detection limits for all NP dispersions investigated. As a model system, 10.9 ± 1.0 nm Au NPs were analyzed to demonstrate the effects of increasing ion transmission. Specifically, increasing the mass bandwidth of the quadrupole improved the size detection limit to 4.2 nm and enabled the resolution of NP signals from ionic background and noise. Subsequently, the methods were applied to the characterization of lanthanide-doped upconversion nanoparticles (UCNPs) by SP ICP-MS. Three different types of UCNPs (90 nm NaYF4: 20% Yb, 2% Er; 20 nm NaGdF4: 20% Yb, 1% Er; 15 nm NaYF4: 20% Yb, 2% Er) were investigated. Y showed the best signal-to-noise ratios with optimized ion extraction and transport parameters only, whereas the signal-to-noise ratios of Gd, Er, and Yb were further improved by increasing the mass bandwidth of a quadrupole mass filter. The novel methods were suitable for detailed characterization of diluted UCNP dispersions including particle stoichiometries and size distributions. A Poisson model was further applied to assess particle–particle interactions in the aqueous dispersions. The methods have considerable potential for the characterization of small-diameter and/or low-mass-fraction nanoparticles.