Imaging mass spectrometry: fundamentals and applications to drug discovery
ABSTRACT Imaging mass spectrometry (IMS) encompasses a variety of techniques that enable the chemical imaging of analytes, which range in size from atoms and small molecules to intact proteins, directly from biological tissues. IMS is transforming specific areas in biological research with its unique combination of chemical and spatial information. Innovations in instrumentation and imaging protocols will make this approach invaluable at many stages of the drug discovery process, including pharmacological target screening and evaluating the distribution of drug and drug metabolites in cells and tissues. The fundamentals and unique methodology of IMS are discussed, along with exciting new applications to drug discovery science.
- SourceAvailable from: Gwendolyn Barceló-Coblijn[Show abstract] [Hide abstract]
ABSTRACT: These are definitively exciting times for membrane lipid researchers. Once considered just as the cell membrane building blocks, the important role these lipids play is steadily being acknowledged. The improvement occurred in mass spectrometry techniques (MS) allows the establishment of the precise lipid composition of biological extracts. However, to fully understand the biological function of each individual lipid species, we need to know its spatial distribution and dynamics. In the past 10 years, the field has experienced a profound revolution thanks to the development of MS-based techniques allowing lipid imaging (MSI). Images reveal and verify what many lipid researchers had already shown by different means, but none as convincing as an image: each cell type presents a specific lipid composition, which is highly sensitive to its physiological and pathological state. While these techniques will help to place membrane lipids in the position they deserve, they also open the black box containing all the unknown regulatory mechanisms accounting for such tailored lipid composition. Thus, these results urges to different disciplines to redefine their paradigm of study by including the complexity revealed by the MSI techniques.Frontiers in Physiology 02/2015; 6. DOI:10.3389/fphys.2015.00003
- [Show abstract] [Hide abstract]
ABSTRACT: Mass spectrometry imaging (MSI) by laser ablation electrospray ionization (LAESI) enables the lateral mapping of molecular distributions in untreated biological tissues. However, direct sampling and ionization by LAESI-MSI limits the differentiation of isobaric ions (e.g., structural isomers) in a complex sample. Ion mobility separation (IMS) of LAESI-generated species is sufficiently fast to be integrated with the MSI experiments. Here, we present an imaging technique based on a novel combination of LAESI-MSI with IMS that enables in vivo and in situ imaging with enhanced coverage for small metabolites. Ionized molecules produced at each pixel on the tissue were separated by a traveling wave IMS and analyzed by a high performance quadrupole time-of-flight mass spectrometer. Plant (Pelargonium peltatum leaves) and animal tissues (frozen mouse brain sections) were imaged under atmospheric pressure. In LAESI-IMS-MSI, a multidimensional dataset of m/z, drift time (DT), ion intensity, and spatial coordinates was collected. Molecular images for the P. peltatum leaf illustrated that the distributions of flavonoid glycoside ions are aligned with a vein pattern in the tissue. Differentiation of isobaric ions over DT reduced the chemical interferences and allowed separate imaging of these ions. Molecular images were constructed for selected ions in the sagittal sections of the mouse brain, and isobaric species were distinguished by differences in drift times corresponding to distinct molecular structures or conformations. We demonstrated that IMS enhanced the metabolite coverage of LAESI in biological tissues and provided new perspective on MSI for isobaric species.International Journal of Mass Spectrometry 02/2015; 377:681-689. DOI:10.1016/j.ijms.2014.06.025 · 2.23 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Mass spectrometry imaging (MSI) as an analytical tool for bio-molecular and bio-medical research targets accurate compound localization and identification. In terms of dedicated instrumentation, this translates into the demand for more detail in the image dimension (spatial resolution) and in the spectral dimension (mass resolution and accuracy), preferably combined in one instrument. At the same time, large area biological tissue samples require fast acquisition schemes, instrument automation and a robust data infrastructure. This review discusses the analytical capabilities of an "ideal" MSI instrument for bio-molecular and bio-medical molecular imaging. The analytical attributes of such an ideal system are contrasted with technological and methodological challenges in MSI. In particular, innovative instrumentation for high spatial resolution imaging in combination with high sample throughput is discussed. Detector technology that targets various shortcomings of conventional imaging detector systems is highlighted. The benefits of accurate mass analysis, high mass resolving power, additional separation strategies and multimodal three-dimensional data reconstruction algorithms are discussed to provide the reader with an insight in the current technological advances and the potential of MSI for bio-medical research.Journal of proteomics 03/2012; 75(16):5077-92. DOI:10.1016/j.jprot.2012.03.022 · 3.93 Impact Factor