MIBI-TOF: A multiplexed imaging platform relates cellular phenotypes and tissue structure
MIBI-TOF: A multiplexed imaging platform relates cellular phenotypes and tissue structure
复制标题
DOI：
10.1126/sciadv.aax5851
复制
发表时间：
2019-10-01
期刊：
影响因子：
13.6
通讯作者：
Angelo, Michael
中科院分区：
文献类型：
--
作者：
Keren, Leeat;Bosse, Marc;Angelo, Michael
了解组织结构和功能需要在保留空间信息的同时量化多种蛋白质表达的工具。在这里，我们描述了MIBI-TOF（多路复用离子束飞行时间成像），一种仪器，使用明亮的离子源和正交飞行时间质谱成像金属标记的抗体在临床组织切片亚细胞分辨率。我们证明了定量，全周期表覆盖范围在五个对数的动态范围内，同时与组织化学染色和内源性元素成像36标记抗体。我们的图像视野高达800亩米× 800亩米分辨率下降到260纳米的灵敏度接近单分子检测。我们利用这些特性来询问三阴性乳腺癌中肿瘤组织的患者内异质性，揭示与结构化免疫反应相反的肿瘤细胞表型的区域变异性。鉴于其多功能性和样本回兼容性，MIBI-TOF定位于利用现有的注释、存档组织队列来探索癌症、免疫学和神经生物学中的新问题。
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.