High Mass-Resolution MALDI-imaging MS for Drug Metabolism in Tissue Using the JMS-S3000 March 5, 2020 Application Note, MALDI Imaging, Mass Spectrometry (MS) 0 Introduction Imaging by using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-Imaging) has been expanded during the last decade into biological applications in order to assess the distribution of proteins, peptides, lipids, drugs, and metabolites in tissue specimens. For a drug metabolism analysis, MALDI-Imaging has an advantage in that it can visualize the distributions of drugs and metabolites without using radio isotopes which are used for whole body autoradiography. In MALDI-Imaging measurements, a laser is used to irradiate each point across a sample surface in order to acquire a mass spectrum for a given location. By combining the mass spectra with their two-dimensional position information, localization of compounds with inherent molecular weights can be visualized or the mass spectra for certain regions of interests (ROIs) can be created. The JMS-S3000 SpiralTOF is a MALDI-TOFMS, which utilizes the JEOL patented spiral ion optics system. It has a 5-10 times longer flight path than the typical reflectron type MALDI-TOFMS. As a result, it can achieve high mass-resolution to separate peaks that have the same nominal mass but have different exact masses (isobaric separation). This feature is particularly effective for MALDI-Imaging for drug metabolism, which typically consist of relatively low molecular weight compounds which are often interfered with by matrix compounds and/or surface contaminants. For full details: Attached files often contain the full content of the item you are viewing. Be sure and view any attachments. Apps Note Drug Metabolism in Tissue.pdf 707.08 KB Related Articles High Mass Resolution MALDI-imaging MS Using JMS-S3000 SpiralTOF and msMicroImager Imaging mass spectrometry using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-Imaging) has been expanded during the last decade in biological applications, to assess the distribution of proteins, peptides, lipids, drugs, and metabolites in a tissue specimen. In MALDI-Imaging measurements, a laser irradiation point was scanned on a sample surface to acquire a mass spectrum at each point. Analyzing the mass spectra with two-dimensional position information, localization of compounds with inherent molecular weights can be visualized or the mass spectra for certain regions of interests (ROIs) can be created. The JMS-S3000 SpiralTOF (Fig. 1) is a MALDI-TOFMS, which utilizes the JEOL patented spiral ion optical system. It has a 5-10 times longer flight path than the typical reflectron type MALDI-TOFMS. As a result, it can achieve high mass-resolution to separate peaks that have the same nominal mass but have different exact masses (isobaric separation). On the other hand, there are some issues for analyzing high mass resolution and high lateral resolution MALDI-Imaging raw data with common imaging software options such as Biomap. High Mass Resolution MALDI-Imaging MS: High Stability of Peak Position during Imaging MS Measurement Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-Imaging MS) is a powerful tool for the biochemical analyses of surfaces. Previously, this technique has been used to determine the spatial distribution of hundreds of unknown compounds in thinly sliced tissue sections. The mass spectral images are generated by changing the laser irradiation point at regular intervals across the sample surface and collecting a mass spectrum for each point. Time-of-flight mass spectrometers (TOFMS) are widely used as the mass analyzer for MALDI-Imaging MS because they are well matched for the MALDI ionization process. However, the fine structure of the matrix crystals and small irregularities in the tissue surface flatness can cause peak drift in the collected mass spectra that is caused by slight differences in the starting point of the flight path for the ions at each laser irradiation point. As a result, the typical reflectron type TOFMS systems have a difficult time achieving high mass resolution from spot to spot over a thinly sliced biological surface. Conversely, the JEOL JMS-S3000 “SpiralTOFTM”, which has 5-10 times longer flight path than the reflectron type TOF, is able to reduce the effect of this mass drift to achieve high mass resolution and high mass accuracy. In this work, we report the advantages of using the SpiralTOF for MALDI-Imaging MS analyses of lipids in a mouse brain tissue section. MALDI-Imaging MS of Lipids on Mouse Brain Tissue Sections Using Negative Ion Mode The main biological functions of lipids include energy storage, signaling, and acting as structural components of cell membranes. Not only their chemical composition and structures but also the distributions in biological body are important for biochemistry. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-Imaging MS) is a powerful tool for the biochemical analyses of surfaces. Different lipid types are observed in positive or negative-ion MALDI mass spectra, depending on the presence of polar functional groups. Phosphatidyl cholines and galactosyl ceramides were mainly observed in the MALDI-Imaging MS of positive ion mode using JMS-S3000 SpiralTOF[1]. In this work, we report the use of the SpiralTOF for negative-ion MALDI-Imaging MS of sulfatides. High-resolution, accurate mass data and MS/MS data obtained under high-energy CID conditions provide information about structures, elemental compositions, and localization of many types of sulfatides. Tissue imaging with high mass-resolving power and high-energy CID The JMS-S3000 is based on JEOL's proprietary SpiralTOF ion optic system that offers the highest resolving power available in a MALDI-TOF mass spectrometer. The unique properties of the SpiralTOF provide a new level of performance in MALDI imaging. High Mass Resolution MALDI-MS Imaging Part II: Using the "MALDIVision" from PREMIER Biosoft Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MS Imaging) is a powerful tool for the biochemical analyses of surfaces. Previously, this technique has been used to determine the spatial distribution of hundreds of unknown compounds in thinly sliced tissue sections. The mass spectral images are generated by changing the laser irradiation point at regular intervals across the sample surface and collecting a mass spectrum for each point. Time-of-flight mass spectrometers (TOFMS) are widely used as the mass analyzer for MALDI-MS Imaging because they are well matched for the MALDI ionization process. Ultra-high mass resolution achieving isobaric peak separation is important for lipid profiling using MALDI-Imaging [1, 2]. However, the fine structure of the matrix crystals and small irregularities in the tissue surface flatness can cause peak drift in the collected mass spectra that is caused by slight differences in the starting point of the flight path for the ions at each laser irradiation point. As a result, the typical reflectron type TOFMS systems have a difficult time achieving high mass resolution from spot to spot over a thinly sliced biological surface. Analysis of organic compounds on an acrylic plate using JMS-S3000 SpiralTOF™ - MSTips - 251 Industrial materials are often evaluated by surface analysis instruments that provide information on surface elements, bonding states, and functional groups. However, there are limited options for surface analysis techniques that provide molecular weight and molecular structure information for organic compounds present on surfaces. Matrix Assisted Laser Desorption Ionization - Time of Flight Mass Spectrometry (MALDI-TOFMS) is a soft ionization technique that can be used to analyze surfaces in order to estimate elemental compositions with accurate mass measurements, obtain structural information by using MS/MS, and map surface compounds by using MS imaging. MALDI-TOFMS uses a high voltage on the target plate to accelerate the ions into the TOFMS analyzer. Therefore, the target plates are conductive and are typically made of stainless steel. MALDI imaging mass spectrometry is widely used for analyzing organic substances on frozen tissue sections. In this case, a frozen tissue section with a thickness of about 10 μm is placed on a conductive glass slide coated with an indium tin oxide (ITO) film. However, for the analysis of industrial products, the target organic compounds are on nonconductive substrates such as resins with millimeter thicknesses. MALDI-TOFMS surface measurements using nonconductive substrates lead to a reduction in mass resolution and a significant decrease in ion intensity due to surface charging. This problem can be solved by pretreating the surface with gold vapor deposition in order to change it from nonconductive to conductive. This method was previously shown to work well in MSTips No. 204 in which the gold vapor deposition method was applied to the MALDI-MS imaging analysis of inks on paper. In this report, we used gold vapor deposition to look at samples on the surface of a 1 mm thick acrylic plate. Showing 0 Comment Comments are closed.