Advancing tissue analysis: Integrating mass tags with mass spectrometry imaging and immunohistochemistry

In biological and biomedical research, it's a crucial task to detect or quantify proteins or proteomes accurately across multiple samples. Immunohistochemistry (IHC) and spatial proteomics based on mass spectrometry imaging (MSI) are used to detect proteins in tissue samples. IHC can detect precisely but has a limited throughput, whereas MSI can simultaneously visualize thousands of specific chemical components but hindered by detailed protein annotation. Thereby, the introduction of mass tags may be adopted to expand the potential for integrating MSI and IHC. By enriching optical information for IHC and enhancing MS signals, mass tags can boost the accuracy of qualitative, localization, and quantitative detection of specific proteins in tissue sections, thereby widening the scope of protein detection and annotation results. Consequently, more comprehensive information regarding biological processes and disease states can be obtained, which aids in understanding complex biological processes and disease mechanisms and provides additional perspectives for clinical diagnosis and treatment. In the current review, we aim to discuss the role of different mass tags (e.g., mass tags based on inorganic molecules and organic molecules) in the combined application of MSI and IHC.