Mass Spectrometry Imaging in Nanomedicine: Unraveling the Potential of MSI for the Detection of Nanoparticles in Neuroscience

Mass spectrometry imaging (MSI) can uniquely detect thousands of compounds allowing both their identification and localization within biological tissue samples. MSI is an interdisciplinary science that crosses the borders of physics, chemistry and biology, and enables local molecular analysis at a broad range of length scales: From the subcellular level to whole body tissue sections. The spatial resolution of some mass spectrometers now allows nano-scale research, crucial for studies in nanomedicine. Recent developments in MSI have enabled the optimization and localization of drug delivery with nanoparticles within the body and in specific organs such as kidney, liver and brain. Combining MSI with nanomedicine has vast potential, specifically in the treatment of neurological disorders, where effective drug delivery has been hampered by the blood-brain barrier. This review provides an introduction to MSI and its different technologies, with the application of MSI to nanomedicine and the different possibilities that MSI offers to study molecular signals in the brain. Finally, we provide an outlook for the future and exciting potential of MSI in nanoparticle-related research.</p

Sequencing and Identification of Endogenous Neuropeptides with Matrix-Enhanced Secondary Ion Mass Spectrometry Tandem Mass Spectrometry

Matrix-enhanced secondary ion mass spectrometry (ME-SIMS) has overcome one of the biggest disadvantages of SIMS analysis by providing the ability to detect intact biomolecules at high spatial resolution. By increasing ionization efficiency and minimizing primary ion beam induced fragmentation of analytes, ME-SIMS has proven useful for detection of numerous biorelevant species, now including peptides. We report here the first demonstration of tandem ME-SIMS for de novo sequencing of endogenous neuropeptides from tissue in situ (i.e., rat pituitary gland). The peptide ions were isolated for tandem MS analysis using a 1 Da mass isolation window, followed by collision-induced dissociation (CM) at 1.5 keV in a collision cell filled with argon gas, for confident identification of the detected peptide. Using this method, neuropeptides up to m/z 2000 were detected and sequenced from the posterior lobe of the rat pituitary gland. These results demonstrate the potential for ME-SIMS tandem MS development in bottom-up proteomics imaging at high-spatial resolution.</p

Stigmatic imaging of secondary ions in MeV-SIMS spectrometry by linear Time-of-Flight mass spectrometer and the TimePix detector

International audienceSecondary ion mass spectrometry (SIMS), based on primary ions within the MeV energy domain, also known as MeV-SIMS, is a subject of increasing scientific interest. The main drive for the interest in the development of MeV-SIMS is the ability to desorb high yields of large non-fragmented organic molecular ions from the sample surface. This makes MeV-SIMS particulary useful in imaging of biological tissues.Imaging methods based on scanning a focused primary ion beam are associated with demanding focusing of the heavy energetic ions. As an alternative, stigmatic imaging mode has been studied here, applying point-to-point imaging characteristics of secondary ions in the linear Time-Of-Flight mass spectrometer. In stigmatic imaging approaches, spatial resolution is independent of the focussed spot size of the ionising primary ion beam, but instead dependant on the ability of the ion optics to project an image of the ion distributions removed from the surface onto a position sensitive ion detector

Distinguishing core from penumbra by lipid profiles using Mass Spectrometry Imaging in a transgenic mouse model of ischemic stroke

Abstract Detecting different lipid profiles in early infarct development may give an insight on the fate of compromised tissue. Here we used Mass Spectrometry Imaging to identify lipids at 4, 8 and 24 hours after ischemic stroke in mice, induced by transient middle cerebral artery occlusion (tMCAO). Combining linear transparency overlay, a clustering pipeline and spatial segmentation, we identified three regions: infarct core, penumbra (i.e. comprised tissue that is not yet converted to core), and surrounding healthy tissue. Phosphatidylinositol 4-phosphate (m/z = 965.5) became visible in the penumbra 24 hours after tMCAO. Infarct evolution was shown by 2D-renderings of multiple phosphatidylcholine (PC) and Lyso-PC isoforms. High-resolution Secondary Ion Mass Spectrometry, to evaluate sodium/potassium ratios, revealed a significant increase in sodium and a decrease in potassium species in the ischemic area (core and penumbra) compared to healthy tissue at 24 hours after tMCAO. In a transgenic mouse model with an enhanced susceptibility to ischemic stroke, we found a more pronounced discrimination in sodium/potassium ratios between penumbra and healthy regions. Insight in changes in lipid profiles in the first hours of stroke may guide the development of new prognostic biomarkers and novel therapeutic targets to minimize infarct progression