Next generation reagents for mass cytometry and imaging mass cytometry

该项目的目的是开发更好的工具，帮助生物学和生物医学领域的科学家研究生物样本。质量细胞术是加拿大开发的一项技术，由加拿大马卡姆州的Fluidigm Canada制造，使这些科学家能够同时测量和量化细胞上的许多生物标记物并发布样本。生物标记物是表达在细胞表面或细胞内的蛋白质和其他生物分子。它们传递关于细胞类型、行为和功能的信息，以及细胞的疾病状态。质量细胞术使用基于重金属同位素标记的抗体的试剂来检测单个细胞上表达的蛋白质和其他生物标记物。在质量细胞术中，细胞被注入原子质谱仪的等离子体炬中，在那里细胞被蒸发、雾化和电离，产生附着在每个细胞上的金属离子云。然后对这些离子进行质谱分析。质量细胞术使人们能够以高通量(高达1000个细胞/秒)检查单个细胞。它最大的优点是可以同时测量每个细胞比使用荧光试剂的流式细胞术多得多的生物标记物。在目前的技术中，人们可以以每秒500到1000个细胞的速度测量每个细胞的~50个生物标记物。我们建议创造新的试剂，将这一数字增加到每个细胞80多个生物标记物。为了识别表达水平非常低的蛋白质，我们将创建一套不同的试剂，将信号强度提高10到100倍。这项新技术将增强我们研究生物学和疾病过程的能力，并可能在未来加强对疾病的早期诊断。

The purpose of this project is to develop better tools to help scientists in biology and the biomedical area study biological samples. Mass cytometry is a technology developed in Canada and manufactured by Fluidigm Canada in Markham ON that enables these scientists to measure and quantify many biomarkers simultaneously on cells and issue samples. Biomarkers are proteins and other biomolecules expressed on the surface of cells or inside the cells. They convey information about cell type, behavior and function as well as the disease state of a cell. Mass cytometry employs reagents based on antibodies labeled with heavy metal isotopes to detect proteins and other biomarkers expressed on individual cells. In mass cytometry, the cells are injected into the plasma torch of an atomic mass spectrometer, where the cells are vaporized, atomized and ionized to generate a cloud of the metal ions that were attached to each cell. These ions are then analyzed by mass spectrometry. Mass cytometry enables one to examine individual cells at high throughput (up to 1000 cells/sec). Its greatest strength is that it can simultaneously measure many more biomarkers per cell than flow cytometry, which employs fluorescent reagents. In current technology, one can measure ~50 biomarkers per cell at 500 to 1000 cells per second. We propose to create new reagents that will increase this number to more than 80 biomarkers per cell. To identify proteins expressed at very low levels, we will create a different set of reagents that will increase signal intensity by 10 to 100 times. This new technology will enhance our ability to study biological and disease processes, and may in the future enhance early diagnosis of disease.