内容简介：

Biological systems are highly organized arrangements of heterogeneous populations of cells that coordinate and intercommunicate to carry out their functions properly. Spatially resolved omics at the single-cell level is an increasingly attractive strategy for delineating cell-to-cell variants under normal regulatory processes and disease-specific discoordination. Apart from the multiple spectroscopic technologies, mass spectrometry imaging (MSI) has shown the most advances for single-cell omics by simultaneously detecting multiple unlabeled biomolecules. However, many challenges remain in the applications of MSI. First, despite the appreciation of metabolic reprogramming/signaling as early and consequential responses to dynamic changes, spatial lipidomic/metabolomic is still underdeveloped owing to the difficulty to preserve the transient and dynamic flux of smaller molecules and the lack of biological approach to tag metabolites. Second, incompatibility of sample preparation makes it nearly impossible to integrate different omics in a single sample, let alone spatially colocalize them at the single-cell level. Third, current MSI tools (e.g., MALDI, SIMS, LAESI, DESI and LESA) compromise between the molecular coverage and spatial resolution, which has hindered their utilization in lipidomic/metabolomic imaging at subcellular resolution. New analytical tools and methods are needed to target single cells under minimally disturbed conditions to probe the intricate molecular network.

I herein present a new tool, an unconventional buncher-ToF-SIMS instrument coupled with a novel desorption/ionization source high energy GCIB to approach the frozen-hydrated biological systems at the spatial resolution of 1 μm. In the past five years, I have developed a high energy GCIB operating with mixed gases (e.g., HCl infused Ar), CO₂ or H₂O, which offers improved spatial resolution, chemical sensitivity (up to ~200 fold increase), reduced matrix effects, and extended mass detection ranges (up to m/z 6000). To illustrate the capabilities, I would showcase the studies in single-cell spatial metabolomics for visualizing the active purinosome in HeLa cells and cell-type-specific metabolomics/lipidomics for dissecting tumors microenvironment. Through chemical tuning, the capability of (H₂O)_n-GCIB has been further expanded to generate the multiple charged protein/peptide ions, which facilitates simultaneous imaging of different omics in a single acquisition. The unique instrumentation, GCIB-SIMS allows comprehensive imaging of multiomics in biological systems at near-nature state with subcellular resolution, unwinding the molecular/cellular heterogeneity and phenotypes to infer the physiological states of an organism in health and disease.