Mass spectromety imaging can map the molecular distribution of species directly from biological tissues.  Combining this with top-down MS provides for the molecular classification of the tissue and identification of protein biomarkers, potentially yielding considerable diagnostic and prognostic value.

Recent Publications

4238047 {4238047:CMXI94QX},{4238047:CK64WEFM},{4238047:5E6JMLWF},{4238047:IFUMBDG8},{4238047:QKLELRJ6},{4238047:FENAHJTQ} 1 annual-reviews-author-date 50 date desc 1 title 49 https://proteoforms.org/wp-content/plugins/zotpress/
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Yang M, Tang X, Laskin J. 2027. Imaging of proteoforms in biological tissues with high spatial resolution using nano-DESI mass spectrometry. International Journal of Mass Spectrometry. 531:117698
Iqfath M, Swansiger AK, Yang M, Miller L, Moore AM, et al. 2026. Quantitative Mass Spectrometry Imaging of Intact Proteins in Tissues. Anal. Chem.
Sun Y, Liu D, Liang Y, Yang X, Liu X, et al. 2025. High-Throughput Proteoform Imaging for Revealing Spatial-Resolved Changes in Brain Tissues Associated with Alzheimer's Disease. Advanced Science. n/a(n/a):2416722
McGee JP, Su P, Durbin KR, Hollas MAR, Bateman NW, et al. 2023. Automated imaging and identification of proteoforms directly from ovarian cancer tissue. Nat Commun. 14(1):6478