Next Generation of Mass Spectrometry Imaging: from Micrometer to Subcellular Resolution

Abstract

Developing an imaging method with micrometer-to-subcellular resolution is of great significance for visualizing biological samples of different sizes. The label-free and high-throughput mass spectrometry imaging (MSI) technology has shown potential in the implementation of this view. Despite many improvements in MSI witnessed over the past decades, it remains a challenge to achieve a flexible resolution from micrometer down to subcellular level with high detection sensitivity. In this Perspective, we focus on the recent development of MSI techniques based on different ionization resources. Furthermore, several designs of instruments and applications in bioimaging have been reviewed and compared. Additionally, we proposed the perspectives and challenges for MSI methods, including pursuing the matrix free and multiscale resolution with high detection sensitivity and deeply combining machine learning in omics research.

AI-assisted mass spectrometry imaging with in situ image segmentation for subcellular metabolomics analysis

“…Recently, our group has developed an MSI technique with an optimal ∼300 × 300 × 25 nm 3 spatial resolution for in-depth anatomical profiling of single cells. 31,32 It revealed the action mechanisms of anticancer drugs that affect the expression level of partial endogenous metabolites in the nucleus. Moreover, the metabolomics analysis of cell membranes was successfully performed without signal interference from the cytoplasm.…”