Imaging mass spectrometry is an emerging technique of great potential for investigating the chemical architecture in biological matrices. Although the potential for studying neurobiological systems is evident, the relevance of the technique for application in neuroscience is still in its infancy. In the present Review, a principal overview of the different approaches, including matrix assisted laser desorption ionization and secondary ion mass spectrometry, is provided with particular focus on their strengths and limitations for studying different neurochemical species in situ and in vitro. The potential of the various approaches is discussed based on both fundamental and biomedical neuroscience research. This Review aims to serve as a general guide to familiarize the neuroscience community and other biomedical researchers with the technique, highlighting its great potential and suitability for comprehensive and specific chemical imaging.
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.
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