Bruker timsTOF fleX MALDI-2 - This proposal requests funding for a Bruker timsTOF fleX MALDI-2 mass spectrometer to support spatial single-cell omics research at Stanford University. The instrument will be placed at the Stanford Center for Genomics and Personalized Medicine (SCGPM) Genome Sequencing Service Center (GSSC). Increasing evidence from single-cell studies reveals that spatial distribution of biomolecules is crucial for understanding tissue complexity,cell to cell communication and their interaction with microenvironments. Although our facility has a robust selection of mass spectrometers for bulk omics studies, spatial single cell omics requires specialized equipment. Currently, our facility excels in supporting spatial single cell transcriptomics and proteomics, technologies widely available to our researchers. The crucial missing piece is an instrument capable of studying spatial distribution of small molecules at single cell resolution. A comprehensive understanding of cellular heterogeneity and the microenvironment requires not just RNA and protein expression, but also the distribution of small molecules such as metabolites, lipids and glycans. Correlating small molecule distribution with gene and protein expression helps establish crucial links between genetic instructions and their functional consequences. The proposed instrument offers unmatched single-cell resolution for analyzing the spatial distribution of small molecules, complementing existing spatial transcriptomics and proteomics studies. This cutting-edge instrument will offer several unique features: (1) Un-paralleled spatial resolution to single cells for tissue imaging; (2) Fast data acquisition speed which is essential for imaging large tissue areas and high throughput screening; (3) Streamlined workflow for easy operation, data visualization and analysis. Access to this instrument will facilitate multiple levels of translational and basic science research. This includes constructing molecular maps of human tissues at single-cell resolution, conducting in situ tissue glycomics analysis for biomarker discovery and disease mechanism investigation in various types of cancer, and investigating how the alternation of small molecules contributes to lung and cardiovascular disease, cancer development, aging, and more. Progress on this broad array of projects will be catalyzed by the effective usage of the new instrument through close cooperation among the user groups. By serving a highly productive interdisciplinary group of NIH-funded investigators, the proposed instrument will enhance existing research programs while encouraging new projects and collaborations to emerge and be funded.
