Research

Tapping-mode Scanning Probe Electrospray Ionization (t-SPESI) for Mass Spectrometry Imaging

　There is a demand for technology that comprehensively captures the distribution of multiple chemical components within substances across a wide range of applications, such as cancerous regions in biological tissues and the distribution of additives in polymer materials. Mass Spectrometry Imaging (MSI) is one such technology that achieves this.

　MSI enables visualization of the two-dimensional distribution of chemical species within a sample by combining two technologies: (1) sampling and ionizing chemical species within a micro-region of the material for component analysis using a mass spectrometer, and (2) scanning the analysis area across the sample surface.

　The tapping-mode scanning probe electrospray ionization (t-SPESI) method we are developing enables visualization of chemical species distribution under atmospheric conditions without requiring sample surface treatment. When a high-voltage-applied solvent is locally supplied to the sample surface via a oscillating capillary probe, a solvent bridge (liquid bridge) forms between the probe and the sample, extracting the sample components. Subsequently, as the probe moves, the extracted solution is lifted and supplied to the electrospray ionization (ESI) source. ESI enables ionization of biomolecules such as lipids and proteins without degrading them. The development of core technologies for high-spatial-resolution MSI has led to the demonstration of single-cell MSI, enabling visualization of component distribution within individual cells. 

　The oscillating probe of t-SPESI not only spatially and temporally separates and rapidly performs the extraction, transport, and ESI processes, but also incorporates a function to detect the height of the sample surface. Feedback control of the oscillation amplitude dynamically compensates for the influence of sample surface topography on extraction-ionization instability. This multifunctionality of the oscillating probe represents a fundamentally different characteristic from conventional continuous extraction ambient ionization methods.

　We will continue advancing our research by pursuing both instrument development and application to diseased tissues. We will tackle challenges in refining the extraction area, enhancing sensitivity, and stabilizing the measurement system. We aim to visualize the heterogeneity of cellular networks in diseased tissues with high precision and contribute to life sciences.

Introduction of t-SPESI development (PDF) :
Yoichi Otsuka, Advances in tapping-mode scanning probe electrospray ionization (t-SPESI): Instrumental development for high-spatial-resolution ambient mass spectrometry imaging, International Journal of Mass Spectrometry (2026).

Development of Nanoscale Electrical Measurement for Molecular Electronics

Understanding the electrical properties of molecules in nanoscale is needed for the research of molecular electronics. We have been working on the developments of measurement techniques. Here, we introduce two representative techniques.

One is the electrical measurement technique by atomic force microscope (AFM). Point-contact current imaging atomic force microscope (PCI-AFM) enables us to obtain the relationship between the nanostructure and the electrical conductivity.

The other is the fabrication technique of nanogap electrodes for the top-contacted geometry without wet processes. It is possible to make nanogap electrodes onto the molecules which are immobilized on a flat substrate beforehand.

Outline PDF