Biomolecular localization and heterogeneity are factors important for signaling and structure in multicellular organisms. Current understandings of metabolic heterogeneity utilize bulk approaches. However, these approaches lack the ability to retain the spatial distribution of metabolites. Mass spectrometry imaging (MSI) can be employed as an alternative, label-free technique which retains this distribution; however, many commercial instruments lack the capabilities for high resolution imaging, with specialized instrumentation remaining unattainably expensive for many research labs. To address this issue, advancements in sample preparation allow for increased spatial resolution to be observed without the need to modify existing instruments or purchase new ones. One such method being. Tissue expansion MSI (TEMI), which embeds tissue samples in a hydrogel, allowing expansion of the tissue sample while retaining the native distribution of metabolites. Through TEMI, researchers were able to achieve an effective resolution of 3 µM while using a commercial instrument to reveal metabolic heterogeneity between layers of the cerebellum and identify individual cells¹. This demonstrates that, through tissue expansion sample preparation, higher resolution MSI is achievable without a need for new instrumentation.

1. Zhang, H., Ding, L., Hu, A. et al. TEMI: tissue-expansion mass-spectrometry imaging. Nat Methods 22, 1051–1058 (2025).      https://doi.org/10.1038/s41592-025-02664-9