Shimadzu’s novel Imaging Mass Microscope, iMScope, enables optically observed samples to be analyzed by mass spectrometry directly in the one instrument.

-Application in disease biomarker research and biological function studies-

Shimadzu Corporation has just introduced the novel imaging mass microscope, iMScope. The iMScope is equipped with an optical microscope, which allows the observation of high resolution morphological images; and a hybrid ion trap time of flight mass spectrometer which identifies and visualizes the distribution of specific molecules in a sectioned sample. Proprietary ultra focusing laser optics and the highly reproducible 3 dimensional automated sample transfer stage results in the world's best spatial mass spectrometry resolution of 5 µm * enabling visualization of the distribution of molecules at the sub-cellular level. The iMScope is capable of analyzing living cells or tissue samples by atmospheric pressure MALDI. By superimposing the two images obtained based on these different principles, Shimadzu has created a significant new research tool, the imaging mass microscope. Applications include disease biomarker research and functional biology research.

* Worlds finest spatial resolution in imaging mass spectrometry using matrix assisted laser desorption ionization (MALDI-TOF) mass spectrometer commercially available.

The iMScope will make its debut at both KSBMB 2013, Korean Society of Biochemistry and Molecular Biology (May 14-16) and ASMS 2013, American Society of Mass Spectrometry (June 9-13 in Minneapolis) in conjunction with the new iMLayer, matrix sample preparation device for tissue imaging.

Background to Development

The positional information of molecules is lost in traditional mass spectrometric analysis, where sample extraction and homogenization is needed for sample pre-treatment. Consequently, it is impossible to know where a specific molecule is located or what kinds of molecules are localized in an interesting region. The Imaging mass microscope, iMScope, finally meets the demand of researchers, to analyze what they see and identify the significant molecules in the field of view.

The iMScope laser irradiates the sectioned sample at each sampling point and analyzes ionized molecules by the mass spectrometer. The 3-dimensional distribution of specific molecules is visualized by combining the positional information of each mass spectrum and the relative amounts of specific ions in the spectrum. This can, for example, pinpoint and map the distribution of disease-related molecules, and their location in a specific part of the tissue section. In addition, the relative abundance of specific molecules, e.g.: drugs and their metabolites localized in different tissues can be resolved and compared.

By superimposing the optical image and the mass spectral information, the iMScope now makes it possible to identify various substances directly in both tissue samples and manufactured devices. It expands potential research opportunities to a diversity of fields, such as the development of early stage cancer indicators with biomarkers in cancer tissue, as a new pharmacokinetics tool monitoring drug metabolism, and advancing the breeding of agricultural and horticultural products by locating the distribution of key compounds for enhancing human health. In industry it is perfect for defect analysis of electronic components and synthetic polymer materials.

Hamamatsu University of Medicine mainly contributed to develop the prototype, with financial support from the "Development of Systems and Technology for Advanced Measurement and Analysis" program, through the Japan Science and Technology Agency. And, Shimadzu Corporation commercialized the instrument. In the commercialization phase, Keio University joined the team and contributed to develop a more user friendly product.

Features of this system

1. High spatial resolution – Achieving the world finest spatial resolution 5 μm.
  Our original ultra focusing laser optics and high precision 3 dimensional automated sample transfer stage achieves the world best spatial resolution of 5 µm mass images. With this resolution, visualization of the distribution of molecules in micro tissue like the pigmentation layer of the retina, whose size is smaller than 10 µm, is possible. The iMLayer, automated sample treatment (matrix deposition) system, released at the same time, can prepare samples for high spatial resolution imaging mass spectrometry with simple operation.
2. Atmosphere MALDI - Enables to analyze straightly optical microscopic “observing” samples.
  The iMScope can analyze straightly optical microscopic observing samples by adopting atmosphere MALDI. In comparison with vacuum MALDI, atmospheric pressure MALDI not only be delivers shorter analysis times, but also determines volatiles and biomolecules in tissue that is much more akin to its living state.

Imaging MS Solution, the dedicated software for iMScope, conveniently sets all operational parameters on the optical microscope image. Additionally, many method parameters for typical targets are ready provided as default method files. Hence, users can quickly perform imaging mass spectrometry without difficult parameter setting, similar to just observing samples by optical microscopy.
3. High speed 2D microscopic/MALDI imaging – Achieving 100 times faster than existing method.
  A high speed Nd:YAG laser ionizes molecules at a 1 kHz frequency. Shimadzu’s original ion optics and fast electronics acquires and analyses the ion signals, accumulated over multiple laser shots. These novel technologies have resulted in 100 fold faster high throughput in imaging mass spectrometry than the norm in existing MALDI model in our portfolio.

For example, a previous model took about 10 hours to acquire mass images of 2.5 x 2.5 mm2 with a 10 micron resolution. However, iMScope completes the same experiment within 3 hours. When comparing controls and samples, eg: normal and cancerous tissues, at least two mass images should be acquired. In this case, iMScope can finish all measurements within 6 hours. So practically if researchers prepare their sample during the day time and start their imaging mass spectrometry experiment at the end of the day, they can wake up to their mass images next morning. The ultra fast imaging mass spectrometry performance of the iMScope significantly accelerates your research.

* “iMScope” is the mintage from “Imaging Mass microScope”
* Sales area: All areas excluding EU nations and North America

Figure: Lipid distribution of mouse pigment layer of the retina with 10 μm spatial resolution. Only 10 μm spatial resolution images or better can distinguish lipid multi layers.

* The mass images with 20 μm, 50 μm and 100 μm space resolutions are simulated from the mass image with 10 μm space resolution.


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