Nassar Ala F, Wisnewski Adam V, Raddassi Khadir
School of Medicine, Department of Internal Medicine, Yale University, 300 Cedar St./TAC s416, New Haven, CT, 06510, USA.
Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, CT, 06269, USA.
Anal Bioanal Chem. 2017 Mar;409(9):2363-2372. doi: 10.1007/s00216-017-0182-4. Epub 2017 Jan 26.
Analysis of multiplexed assays is highly important for clinical diagnostics and other analytical applications. Mass cytometry enables multi-dimensional, single-cell analysis of cell type and state. In mass cytometry, the rare earth metals used as reporters on antibodies allow determination of marker expression in individual cells. Barcode-based bioassays for CyTOF are able to encode and decode for different experimental conditions or samples within the same experiment, facilitating progress in producing straightforward and consistent results. Herein, an integrated protocol for automated sample preparation for barcoding used in conjunction with mass cytometry for clinical bioanalysis samples is described; we offer results of our work with barcoding protocol optimization. In addition, we present some points to be considered in order to minimize the variability of quantitative mass cytometry measurements. For example, we discuss the importance of having multiple populations during titration of the antibodies and effect of storage and shipping of labelled samples on the stability of staining for purposes of CyTOF analysis. Data quality is not affected when labelled samples are stored either frozen or at 4 °C and used within 10 days; we observed that cell loss is greater if cells are washed with deionized water prior to shipment or are shipped in lower concentration. Once the labelled samples for CyTOF are suspended in deionized water, the analysis should be performed expeditiously, preferably within the first hour. Damage can be minimized if the cells are resuspended in phosphate-buffered saline (PBS) rather than deionized water while waiting for data acquisition.
多重分析对于临床诊断和其他分析应用非常重要。质谱流式细胞术能够对细胞类型和状态进行多维度单细胞分析。在质谱流式细胞术中,用作抗体报告分子的稀土金属可用于确定单个细胞中的标志物表达。基于条形码的CyTOF生物分析方法能够对同一实验中的不同实验条件或样本进行编码和解码,有助于产生直接且一致的结果。本文描述了一种用于临床生物分析样本的与质谱流式细胞术结合使用的条形码自动化样本制备综合方案;我们提供了条形码方案优化工作的结果。此外,我们还提出了一些需要考虑的要点,以尽量减少定量质谱流式细胞术测量的变异性。例如,我们讨论了在抗体滴定过程中具有多个细胞群体的重要性,以及标记样本的储存和运输对CyTOF分析染色稳定性的影响。标记样本在冷冻或4℃储存并在10天内使用时,数据质量不受影响;我们观察到,如果在运输前用去离子水洗涤细胞或在较低浓度下运输,细胞损失会更大。一旦用于CyTOF的标记样本悬浮在去离子水中,应尽快进行分析,最好在第一小时内进行。如果在等待数据采集时将细胞重悬于磷酸盐缓冲盐水(PBS)而非去离子水中,则可以将损伤降至最低。