Journal
SCIENCE ADVANCES
Volume 5, Issue 10, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.aax5851
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Funding
- Damon Runyon Cancer Research Foundation [DRG-2017-09]
- EMBO Long-Term fellowship [ALTF 1128-2016]
- NIH [5-T32-AI07290-33, 5R01CA18390402, 1DP2OD022550, 1-R00-GM104148, 5U19AI116484, U19 AI104209]
- NSF [2017242837]
- DoD [W81XWH-14-1-0180]
- Udall [NS062684]
- Bill and Melinda Gates Foundation
- Translational Research Award from the Stanford Cancer Institute
- [1-DP5-OD019822]
- [1R01AG056287]
- [1R01AG057915]
- [R01 AR067145]
- [R01 AI32494]
- [1U24CA224309]
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Understanding tissue structure and function requires tools that quantify the expression of multiple proteins while preserving spatial information. Here, we describe MIBI-TOF (multiplexed ion beam imaging by time of flight), an instrument that uses bright ion sources and orthogonal time-of-flight mass spectrometry to image metal-tagged antibodies at subcellular resolution in clinical tissue sections. We demonstrate quantitative, full periodic table coverage across a five-log dynamic range, imaging 36 labeled antibodies simultaneously with histochemical stains and endogenous elements. We image fields of view up to 800 mu m x 800 mu m at resolutions down to 260 nm with sensitivities approaching single-molecule detection. We leverage these properties to interrogate intrapatient heterogeneity in tumor organization in triple-negative breast cancer, revealing regional variability in tumor cell phenotypes in contrast to a structured immune response. Given its versatility and sample back-compatibility, MIBI-TOF is positioned to leverage existing annotated, archival tissue cohorts to explore emerging questions in cancer, immunology, and neurobiology.
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