CyTOF ICP-TOF-MS Model C5

描述(由申请人提供)：纪念斯隆-凯特琳癌症中心(MSKCC)的研究团体要求使用DVS Sciences制造的CyTOF质量细胞仪(即Time of Flight)，以研究癌症生物学和免疫学中的表型变异性和异型相互作用。CyTOF是传统流式细胞术的扩展，抗体用螯合金属同位素标记，并通过质量细胞仪进行定量，从而绕过了荧光发射的限制，即不能测量每个单个细胞超过10个左右的参数。CyTOF方法使每个单个细胞能够获得30+个参数，具有100个参数分辨率的潜力。将CyTOF整合到该中心的技术平台库中将为研究人员提供一种新兴技术，该技术能够改变我们对复杂信号事件的理解，这些事件影响细胞增殖、分化和生存决定，影响治疗后正常/癌细胞的适应，以及肿瘤间和瘤内的异质性。MSKCC的一组研究人员联合起来，对哺乳动物细胞进行单细胞异质性分析。该小组的研究兴趣广泛：S.Lowe研究肿瘤抑制因子和肿瘤维持网络；G.Altan-Bonnet开发新的计算建模方法来分析淋巴细胞的表型变异性；J.Joyce专注于肿瘤微环境；J.Massague研究涉及潜在转移的调节网络；S.Rudensky研究复杂炎症和肿瘤环境中的调节T细胞功能；M.van den Brink探索异基因造血干细胞移植后的免疫恢复和反应。其他小组(Benezra、Levine、Park、Rosen、Sander、Windel)研究肿瘤生物学或治疗反应的各个方面。所有这些小组都有兴趣测试单细胞分辨率的极限，以更好地分析免疫/癌细胞的表型可变性如何驱动系统的生物学。此外，具有多参数单细胞分辨率的测量对于剖析这些种群内的异型细胞-细胞相互作用至关重要。CyTOF是提供必要分辨率的关键技术。值得注意的是，MSKCC研究小组已经在使用基于荧光的流式细胞术(项目I-IV)的单细胞磷酸图谱方面积累了广泛的专业知识，并在细胞飞行时间技术(项目I)方面积累了一些经验。此外，MSKCC的基础设施非常适合结合质量细胞学，具有完善的核心结构，包括将操作机器的流式细胞仪核心，将协助新的抗体结合物的抗体核心，非常适合帮助分析细胞间歇研究产生的复杂数据集的生物信息学核心，以及将促进该技术在患者材料上的应用的组织采购核心。由于这项技术是新技术，因此没有其他来源或替代它的能力。

DESCRIPTION (provided by applicant): The research community at Memorial Sloan Kettering Cancer Center (MSKCC) is requesting a CyTOF mass cytometer (i.e. Cytometer via Time of Flight) manufactured by DVS Sciences to study phenotypic variability and heterotypic interactions in cancer biology and in immunology. CyTOF is an extension of traditional flow cytometry in which antibodies are tagged with chelated metal isotope and quantified by mass cytometry, thus circumventing the limitations of fluorescence emission that precludes measuring more than 10 or so parameters per single cell. The CyTOF methodology enables the acquisition of 30+ parameters per individual cell with a potential for 100 parameter-resolution. Incorporation of CyTOF into the Center's repertoire of technology platforms will provide investigators with an emerging technology that has the ability to transform our understanding of the complex signaling events that influence cell proliferation, differentiation and survival decisions, adaptaton of normal/cancer cells following therapy, and inter- and intra-tumoral heterogeneity. A team of researchers at MSKCC coalesced to apply single-cell heterogeneity analysis for mammalian cells. This group's research interests are diverse: S. Lowe studies tumor-suppressor and tumor maintenance networks; G. Altan-Bonnet develops new computational modeling methodologies to analyze lymphocytes' phenotypic variability; J. Joyce focuses on the tumor microenvironment; J. Massague studies regulatory networks involved in latent metastasis; S. Rudensky investigates regulatory T cell functions in complex inflammatory and tumor environments and M. van den Brink explores immune recovery and response to allogeneic hematopoietic stem cell transplantation. Other groups (Benezra, Levine, Park, Rosen, Sander, Wendel) study various aspects of tumor biology or therapy response. All these groups share an interest in testing the limits of single-cell resolution to better analyze how the phenotypic variability of immune/cancer cells drives the biology of the system. Moreover, measurements with multi-parametric single-cell resolution are critical to dissect heterotypic cell-cell interactions within these populations. CyTOF is the key technology that will deliver the necessary resolution. Of note, the MSKCC research team has already accumulated extensive expertise in single-cell phospho-profiling using fluorescence-based flow cytometry (Project I-IV), as well as some experience with the CyTOF technology (Project I). Moreover, the infrastructure at MSKCC is well-suited to incorporate mass cytometry, having a well-established core structure, including a flow cytometry core that will operate the machine, and antibody core that will assist with new antibody conjugations, a bioinformatics core that is well-suited to help analyze complex data sets arising from CyTOF studies, and a tissue procurement core that will facilitate the application of the technology on patient material. As the technology is new, there is no other source or alternative for its capabilities.