Mikes Jaromir, Olin Axel, Lakshmikanth Tadepally, Chen Yang, Brodin Petter
Science for Life Laboratory, Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
Department of Newborn Medicine, Karolinska University Hospital, Stockholm, Sweden.
Methods Mol Biol. 2019;1989:111-123. doi: 10.1007/978-1-4939-9454-0_8.
Mass cytometry is a powerful technology for high-dimensional single-cell measurements in millions of individual cells. Antibodies and other detection probes are coupled to elemental tags, each with a unique mass and detectable at single-cell resolution using an ICP-MS type of instrument. Given the sensitivity of the detection system, any free metal ions must be carefully removed through multiple rounds of washing in order to prevent background signal. This results in significant loss of cells. Together with cells lost during acquisition, the final data can represent as little as 10% of the starting material, seriously limiting the amount of information that can be extracted from small samples. Furthermore, complex staining protocols introduce experimental variations that limit comparisons across experiments. Here we present a cell processing and staining procedure for mass cytometry fully automated using a liquid handling robotic system and we present measures taken to optimize all steps of the protocol. These advances are applicable to both manual and automated protocols and provide a six-fold higher cell yield as compared to a standard protocol. With this increased yield and improved reproducibility this protocol now allows us to perform mass cytometry analysis using as little as 100 μL of whole blood as starting material.
质谱流式细胞术是一种用于对数百万个单个细胞进行高维单细胞测量的强大技术。抗体和其他检测探针与元素标签偶联,每个标签都有独特的质量,并可使用电感耦合等离子体质谱仪类型的仪器以单细胞分辨率进行检测。鉴于检测系统的灵敏度,必须通过多轮洗涤仔细去除任何游离金属离子,以防止背景信号。这会导致大量细胞损失。加上采集过程中损失的细胞,最终数据可能仅占起始材料的10%,严重限制了从小样本中可提取的信息量。此外,复杂的染色方案会引入实验变量,限制不同实验之间的比较。在这里,我们展示了一种使用液体处理机器人系统实现完全自动化的质谱流式细胞术细胞处理和染色程序,并展示了为优化该方案的所有步骤而采取的措施。这些进展适用于手动和自动化方案,与标准方案相比,细胞产量提高了六倍。有了这种提高的产量和更好的重现性,现在该方案使我们能够使用低至100微升全血作为起始材料进行质谱流式细胞术分析。