Citation: Xiaopin Lai, Hao Xu, Xing Chen, Jiayi Ke, Shu-Hai Lin. From innovation to application: Pioneering advances in mass spectrometry imaging for spatially resolved single-cell omics[J]. Chinese Chemical Letters, ;2026, 37(6): 111932. doi: 10.1016/j.cclet.2025.111932 shu

From innovation to application: Pioneering advances in mass spectrometry imaging for spatially resolved single-cell omics

State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen 361102, China

shuhai@xmu.edu.cn

Received Date: 21 February 2025
Revised Date: 18 July 2025
Accepted Date: 30 September 2025
Available Online: 1 October 2025

Figures(5)

Mass spectrometry imaging (MSI) is a rapidly advancing field in omics research, offering spatially resolved localization of biomolecules such as metabolites, lipids, and proteins within tissue sections. Recent advancements in high-resolution MSI instrumentation have significantly enhanced the visualization of cellular structures, enabling molecular mapping at the single-cell level. Current single-cell MSI techniques can be broadly categorized into label-free approaches and multiplexed antibody-based strategies, both of which are continuously evolving to support comprehensive molecular profiling with subcellular precision. These technologies have become particularly valuable in cancer and neurodegenerative disease research, where they facilitate the characterization of cellular heterogeneity, metabolic reprogramming, and microenvironmental changes associated with disease progression. To meet the increasing demands of high-content spatial biology, multiple single-cell MSI platforms have been employed to detect low-abundance molecules, distinguish phenotypically distinct cell populations, and uncover region-specific molecular alterations in complex tissues. Moreover, emerging capabilities such as three-dimensional MSI are further extending the potential of this technology to reconstruct tissue biochemical architecture and capture spatially resolved molecular dynamics. In this review, we highlight pioneering advancements in single-cell MSI techniques and their applications in cancer and neurodegenerative disease research, with a particular emphasis on their role in elucidating disease mechanisms at the cellular level. We also discuss current challenges and future perspectives for expanding the utility of single-cell MSI in subcellular imaging and deeper biological discoveries.
- Single-cell omics,
- Mass spectrometry imaging,
- Label-free detection,
- Multiplexed imaging,
- Tumor microenvironment,
- Neurodegenerative disease
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