Spatially Resolved Molecular Analysis of Host Response to Medical Device Implantation Using the 3D OrbiSIMS Highlights a Critical Role for Lipids.

A key goal for implanted medical devices is that they do not elicit a detrimental immune response. Macrophages play critical roles in the modulation of the host immune response and are the cells responsible for persistent inflammatory reactions to implanted biomaterials. Two novel immune-instructive polymers that stimulate pro- or anti-inflammatory responses from macrophages in vitro are investigated.

Label-free Chemical Characterization of Polarized Immune Cells in vitro and Host Response to Implanted Bio-instructive Polymers in vivo Using 3D OrbiSIMS.

The Three-dimensional OrbiTrap Secondary Ion Mass Spectrometry (3D OrbiSIMS) is a secondary ion mass spectrometry instrument, a combination of a Time of Flight (ToF) instrument with an Orbitrap analyzer. The 3D OrbiSIMS technique is a powerful tool for metabolic profiling in biological samples. This can be achieved at subcellular spatial resolution, high sensitivity, and high mass-resolving power coupled with MS/MS analysis.

Untargeted Metabolomic Characterization of Glioblastoma Intra-Tumor Heterogeneity Using OrbiSIMS.

Glioblastoma (GBM) is an incurable brain cancer with a median survival of less than two years from diagnosis. The standard treatment of GBM is multimodality therapy comprising surgical resection, radiation, and chemotherapy. However, prognosis remains poor, and there is an urgent need for effective anticancer drugs.

Time resolved growth of (N)-polycyclic aromatic hydrocarbons in engine deposits uncovered with OrbiSIMS depth profiling.

Carbonaceous deposits are ubiquitous, being formed on surfaces in engines, fuel systems and on catalysts operating at high temperatures for hydrocarbon transformations. In internal combustion engines, their formation negatively affects worldwide vehicle emissions and fuel economy, leading to premature deaths and environmental damage. Deposit composition and formation pathways are poorly understood due to their insolubility and the intrinsic complexity of their layered carbonaceous matrix.

Single-Cell Metabolic Profiling of Macrophages Using 3D OrbiSIMS: Correlations with Phenotype.

Macrophages are important immune cells that respond to environmental cues acquiring a range of activation statuses represented by pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes at each end of their spectrum. Characterizing the metabolic signature (metabolic profiling) of different macrophage subsets is a powerful tool to understand the response of the human immune system to different stimuli. Here, the recently developed 3D OrbiSIMS instrument is applied to yield useful insight into the metabolome from individual cells after in vitro differentiation of macrophages into naïve, M1, and M2 phenotypes using different cytokines.

Elucidating the molecular landscape of the stratum corneum.

SignificanceSkin is recognized as an intricate assembly of molecular components, which facilitate cell signaling, metabolism, and protein synthesis mechanisms in order to offer protection, regulation, and sensation to the body. Our study takes significant steps to characterize in more detail the complex chemistry of the skin, in particular by generating a better understanding of the uppermost layer, the stratum corneum. Using a state-of-the-art 3D OrbiSIMS technique, we were able to observe the depth distribution, in situ, for a wide range of molecular species.

Molecular Formula Prediction for Chemical Filtering of 3D OrbiSIMS Datasets.

Modern mass spectrometry techniques produce a wealth of spectral data, and although this is an advantage in terms of the richness of the information available, the volume and complexity of data can prevent a thorough interpretation to reach useful conclusions. Application of molecular formula prediction (MFP) to produce annotated lists of ions that have been filtered by their elemental composition and considering structural double bond equivalence are widely used on high resolving power mass spectrometry datasets. However, this has not been applied to secondary ion mass spectrometry data.

Spatially Resolved Molecular Compositions of Insoluble Multilayer Deposits Responsible for Increased Pollution from Internal Combustion Engines.

Internal combustion engines are used heavily in diverse applications worldwide. Achieving the most efficient operation is key to improving air quality as society moves to a decarbonized energy system. Insoluble deposits that form within internal combustion engine components including fuel injectors and filters negatively impact CO and pollutant emissions.