Advances in tapping-mode scanning probe electrospray ionization (t-SPESI): Instrumental development for high-spatial-resolution ambient mass spectrometry imaging

Abstract

Mass spectrometry imaging (MSI) is an essential technique for visualizing the distribution of molecules in biological tissues. Ambient sampling ionization-based MSI has attracted attention for its ability to analyze samples directly; however, ​improving spatial resolution remains a major technical challenge. Young Scientist developed a tapping-mode scanning probe electrospray ionization (t-SPESI) method that uniquely combines the core technologies of electrospray ionization (ESI) and atomic force microscopy (AFM). By using an oscillating capillary probe to periodically supply minute amounts of solvent to the sample surface, t-SPESI enables spatiotemporal separation of the extraction and ionization processes, allowing rapid, soft ionization of analytes in micro-regions of the sample. In addition, the oscillating probe senses the sample surface, minimizing the influence of surface topography on extraction and ionization during MSI. Young Scientist has further advanced high-spatial-resolution t-SPESI-MSI through the development of feedback-control methods, probe fabrication techniques, and miniaturization of t-SPESI units. This paper provides an overview of the progress made in the development of t-SPESI instrumentation and highlights MSI results obtained from tissues and single cells.