Imaging Mass Microscope iMScope QT

Importance of the topic

Mass spectrometry imaging (MSI) has become an invaluable tool in analytical chemistry, bridging the gap between molecular analysis and spatial localization in biological and material samples. By combining morphological insights from optical microscopy with molecular information from mass spectrometry, researchers can visualize the distribution of compounds with high sensitivity and resolution, supporting developments in drug discovery, pathology, and biomarker identification.

Study objectives and overview

This article presents the design and performance features of the iMScope QT, Shimadzu’s flagship imaging mass microscope equipped with a quadrupole time-of-flight mass spectrometer (QTOFMS). The primary goals are to demonstrate advances in imaging speed, spatial and mass resolution, automation of sample preparation, and quantification capabilities integrated within a single platform capable of both MSI and LC–MS analyses.

Methodology and instrumentation

• Pretreatment: Automated matrix application using iMLayer AERO spray system and iMLayer vapor deposition to ensure reproducible crystal formation for MALDI imaging.
• Imaging acquisition: High spatial resolution imaging (down to 5 μm pitch) with rapid laser scanning combined with optical observation for precise targeting.
• Data analysis: IMAGEREVEAL MS software facilitates differential and similarity-based image analysis, enabling detection of region-specific molecules and correlation with reference distributions.
• Quantification: Seamless switching to LCMS QTOF allows extraction of dissected tissue regions via laser microdissection, followed by quantitative LC–MS analysis and composition estimation using LabSolutions Insight Explore.

Main results and discussion

• High-resolution MSI of mouse cerebellum and whole-brain sections achieved over hundreds of thousands of pixels within a few hours, illustrating both throughput and detail.
• Combined MS and optical images provided clear molecular maps matched to histological features, revealing distribution patterns of lipids, pharmaceuticals, and metabolites.
• Temperature-controlled QTOFMS maintained sub-1 ppm mass accuracy over 60 hours under varying laboratory conditions, ensuring data reliability.
• Oxygen Attachment Dissociation (OAD) fragmentation enabled structural elucidation of isomeric fatty acids by targeting C=C bonds, offering novel insights into lipidomics applications.

Benefits and practical applications

• Integrated platform reduces sample handling and analysis time by unifying imaging and quantification workflows.
• Automated pretreatment systems improve reproducibility and spatial resolution in MALDI MSI without requiring extensive operator expertise.
• High mass accuracy and specific fragmentation techniques widen the scope for detailed structural analysis of complex biomolecules.
• Applicable to pharmaceutical distribution studies, pathology, metabolomics, and materials science, enhancing both qualitative and quantitative assessment.

Future trends and applications

With continued improvements in laser technology, detector sensitivity, and data processing algorithms, MSI platforms like the iMScope QT are expected to push spatial resolution further towards the cellular and subcellular scale. Integration with multi-omics approaches and real-time imaging modalities promises comprehensive molecular histology, while AI-driven data analysis will streamline interpretation and biomarker discovery.

Conclusion

The iMScope QT offers a comprehensive solution for high-performance mass spectrometry imaging, combining optical microscopy, automated sample preparation, accurate mass analysis, and seamless integration with quantitative LC–MS. Its versatility and robustness address key challenges in spatially resolved molecular analysis and open new avenues across research and clinical diagnostics.

Used Instrumentation

• iMScope QT imaging mass microscope with integrated optical microscope and QTOFMS
• LCMS QTOF liquid chromatograph mass spectrometer
• iMLayer AERO automatic MALDI matrix sprayer
• iMLayer matrix vapor deposition system
• OAD-TOF optional Oxygen Attachment Dissociation source
• IMAGEREVEAL MS data analysis software
• LabSolutions Insight and LabSolutions Insight Explore