Tellurium reagents for mass cytometry

生物系统异常复杂。为了了解影响疾病的生化过程，需要了解生物样本中存在的细胞类型和每个细胞的活动。质量细胞术是一种新的分析方法，适合于这种具有挑战性的测量。质量细胞术有可能允许在异质细胞群的细胞水平上同时定量大约100个参数。因此，使用细胞计数技术可以从单个血液或活检样本中提取比以往更多的信息。发挥细胞分析潜力的关键是开发新的试剂来补充这项技术。每种不同的细胞计数试剂需要含有不同的重元素同位素。针对镧系金属，我们已经开发了化学技术，将30多种不同的重同位素添加到细胞计数试剂中。本提案的重点是扩大可用于质量细胞术的重同位素库，以及增加可通过质量细胞术靶向的信息类型。我们将通过发展化学来将碲同位素引入细胞计数试剂来实现这一目标。碲的使用将为大规模细胞术提供五种额外的重同位素，更重要的是，化学设计允许生成功能探针，可以测量单个细胞的代谢。化学将通过合成探针来测量细胞摄取糖的速率和测量细胞可用的氧气量来展示。

Biological systems are exceptionally complex. To understand the biochemical processes that influence diseases information about the cell types present and the activities of each cell in a biological sample is required. Mass cytometry is a new analysis method that is suited to this type of challenging measurement. Mass cytometry has the potential to allow simultaneous quantification of approximately 100 parameters at the cellular level in heterogeneous cell populations. Thus, using mass cytometry more information than ever before can be extracted from a single blood or biopsy sample. The key to reaching the potential of mass cytometric analysis is the development of new reagents that complement the technique. Each different mass cytometry reagent needs to contain a different heavy elemental isotope. Targeting the lanthanide metals we have developed chemistry to append over 30 different heavy isotopes to mass cytometry reagents. This proposal focuses on expanding the repertoire of heavy isotopes that can be used for mass cytometry as well as to increase the types of information that can targeted by mass cytometry. We will do this by developing chemistry to introduce tellurium isotopes into mass cytometry reagents. The use of tellurium will provide five additional heavy isotopes for use in mass cytometry and more importantly the chemistry is designed to allow the generation of functional probes that can measure the metabolism of single cells. The chemistry will be show cased through the synthesis of probes to measure the rate of sugar uptake by cells and to measure the amount of oxygen available to the cells.