Life science
Medical & healthcare, Bio-imaging, Material analysis

Research on mass spectrometry imaging technique using picoliterliquid and its application to human disease tissues
Department of Physics, Graduate School of Science
Associate Professor Yoichi Otsuka
Researchmap https://researchmap.jp/yoichiotsuka?lang=en

Life science

Abstract
Mass spectrometry imaging, which extracts and ionizes various components in a sample and performs mass spectrometry,can visualize the distribution of multiple chemical components ina sample in a single measurement. We have been developing aunique extraction and ionization method called "tapping-mode
scanning probe electrospray ionization (t-SPESI)" using a vibrating
capillary probe and picoliter liquid. In order to stabilize the measurement of real samples with non-flat surfaces, we developed themeasurement technique of probe vibration amplitude and the amplitude feedback control. This enabled simultaneous acquisitionof high-spatial-resolution mass spectrometry imaging and surface
topography imaging. We have also succeeded in visualizing thevarious distributions of lipid components in human heart disease
tissues through collaborative research with the graduate school ofmedicine and engineering, Osaka University.

▍ Significance of the research and Future perspective
This technique, which enables high-spatial-resolution imaging of
biological tissue sections without pretreatment, is effective for visualizing a variety of chemical information in diseased tissues. In thefuture, we will continue our research on multi-dimensional chemical
distribution information measurement and feature extraction methods for human disease tissues. We expect that this technology willcontribute to the elucidation of pathological conditions and be applied to diagnostic techniques.

▍ Background & Results
In the cells that constitute our bodies, it is known that the chemical reactions necessary for life activities proceed through theinteraction of various molecules with different molecular weights
and chemical properties, such as lipids, metabolites, and proteins.
Imaging technology to investigate the distribution of complex
chemical species in biological tissues is important for detailed understanding and diagnosis of disease states in biological tissues,
where various cells form a network.
t-SPESI can rapidly extract and ionize chemical components
contained in a localized region of a sample by intermittently supplying a picoliter of solvent with high voltage applied to the sample
through a fast vibrating capillary probe ("probe"). Electrospray ionization is used for ionization, and biomolecules are changed into
gas-phase ions without breaking their structures. By scanning theprobe in a two-dimensional direction with respect to the sample
surface, we can obtain mass spectra associated with the coordinate information of a sample and visualize the distribution of specific chemical components in a sample.
We integrated the elemental technology of atomic force microscopy, which can measure the unevenness of a sample at the nanoscale, with t-SPESI. Using this technique, we were able to image
multiple lipids in a mouse brain tissue section with a spatial resolution of 6.5 micrometers, and showed that it is possible to classify
brain structures based on differences in the mass spectral patternsof multiple lipids.
As a medical application of t-SPESI, we are also conducting
collaborative research on human disease tissues. As a result ofmeasurement of cardiac tissue donated by a patient with dilated
cardiomyopathy, we found that multiple lipids were localized in thetissue, indicating that the type and distribution of lipids can be precisely measured.

P a t e n t
Otsuka, Yoichi; Kamihoriuchi, Bui; Takeuchi, Aya et al. High spatial resolution multimodal imaging by tapping-mode scanning probe electrospray ionization
with feedback control, Anal. Chem. 2021; 93: 2263–2272. doi: 10.1021/acs.analchem.0c04144
Otsuka, Yoichi; Satoh, Shuya; Naito, Junpei et al. Visualization of cancer-related chemical components in mouse pancreas tissue by tapping-mode scanning probe electrospray ionization mass spectrometry, J. Mass Spectrom. 2015; 50; 1157-1162. doi: 10.1002/jms.3634
UR
L https://resou.osaka-u.ac.jp/ja/research/2021/20210114_1
K e y w o r d mass spectrometry, bioinformatics, imaging, extraction ionization, multidimensional information

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