3D single-cell spatial biology using giant cluster ion beam secondary ion mass spectrometry
Description:
Tissue is highly organized with diverse cells. Together with cellular chemical flux, the multilevel heterogeneities drive the biological function/discoordination. This spatial complexity is often ignored by traditional assays. Mass spectrometry imaging holds the potential to visualize the spatial correlations in tissue content. However, it is challenging to achieve high spatial resolution and chemical sensitivity. Moreover, multiomics in a single sample is impossible due to the difficulty of preserving transient molecules and the incompatibility of sample preparation. To overcome these analytical hurdles, we developed water cluster ion beam secondary ion mass spectrometry ((H2O)n-GCIB-SIMS) and a multimodal imaging pipeline. (H2O)n-GCIB, operating at high energy of 70 kV, images the intact biomolecules (~m/z 10,000) with enhanced sensitivity and reduced chemical damage at 1 µm resolution. With multimodal SIMS, it is now possible to integrate spatial omics in the same tissue with subcellular resolution. The cryogenic workflow is adapted to reveal pristine chemical gradients, which are otherwise difficult to preserve. AI-aided computational processing then integrates the omics in different cell types for further discriminant analyses. This new development provides new insights into tissue architecture/microenvironment. On breast cancer tissue, the key metabolites and 12 cell types/pathways are visualized, indicating the anticorrelation of macrophages and infiltrating immune cells and the antioxidation mechanism of cancer cells. On liver tissue, distinct lipid clusters colocalize with periportal and pericentral proteins, and metabolic and lipidomic signatures vary in different liver cells. The discriminant analysis further classifies the cell types by metabolites and lipids that are beyond protein markers. Multimodal SIMS imaging opens broad applications to explore cellular/biomolecular interactions in health/disease and aids the discovery of new therapeutic targets.
Speaker: Hua Tian - Environmental and Occupational Health, Pitt Public Heath; Children’s Nuronscinece Insititute, School of Medicine, University of Pittsburgh
Tian earned her Ph.D. at The University of Manchester in Vickerman lab, focusing on biological imaging using SIMS. She then did a postdoc at Pennsylvania State University in Winograd lab, developing the high-resolution GCIB such as water cluster ion beam to enhance chemical sensitivity and spatial resolution, and the methodologies to integrate the multiomics in the single cell. She moved to the University of Pittsburgh as Visiting Associate Professor. Hua has published papers in high-profile journals such as Science, Angewandte Chemie, and Analytical Chemistry, with several being selected as "Very Important Paper" and "ACS Editors' Choice". Tian’s work has been interviewed and reported by Nature Methods and Nature Chemical Biology and attracted funding from the NIH Human Biomolecular Atlas Program with Tian as PI and Co-PI. She has also been recognised as 'Rising Star' at the International SIMS conference.
Co-Authors
3D single-cell spatial biology using giant cluster ion beam secondary ion mass spectrometry
Category
2023 Call for Invited Abstracts
Description
Session Number: Waters-04
Session Type: Award Abstract
Session Date: Monday 3/20/2023
Session Time: 1:30 PM - 4:50 PM
Room Number: 126A
Track: Bioanalytics & Life Sciences
Category: Bioanalytical, Mass Spectrometry, Surface Analysis/Imaging
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