MIBI-TOF: A multiplexed imaging platform relates cellular phenotypes and tissue structure

被引：283

作者：

Keren, Leeat ^{[1
]}

Bosse, Marc ^{[1
]}

Thompson, Steve ^{[1
]}

Risom, Tyler ^{[1
]}

Vijayaragavan, Kausalia ^{[1
]}

McCaffrey, Erin ^{[1
,2
]}

Marquez, Diana ^{[1
]}

Angoshtari, Roshan ^{[1
]}

Greenwald, Noah F. ^{[1
,3
]}

Fienberg, Harris ^{[1
]}

Wang, Jennifer ^{[1
]}

Kambham, Neeraja ^{[1
]}

Kirkwood, David ^{[1
]}

Nolan, Garry ^{[4
]}

Montine, Thomas J. ^{[1
]}

Galli, Stephen J. ^{[1
]}

West, Robert ^{[1
]}

Bendall, Sean C. ^{[1
]}

Angelo, Michael ^{[1
]}

机构：

[1] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA

[2] Stanford Univ, Sch Med, Immunol Program, Stanford, CA 94305 USA

[3] Stanford Univ, Sch Med, Canc Biol Program, Stanford, CA 94305 USA

[4] Stanford Univ, Dept Microbiol & Immunol, Stanford, CA 94305 USA

来源：

SCIENCE ADVANCES | 2019年 / 5卷 / 10期

关键词：

BETA-CATENIN; SUBCELLULAR RESOLUTION; MASS CYTOMETRY; IMMUNE; CANCER; RNA; IMMUNOHISTOCHEMISTRY; EMISSION; PROTEINS; CELLS;

D O I：

10.1126/sciadv.aax5851

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

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.

引用

页数：16

共 53 条

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