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单细胞质谱分析方法研究进展

谭思源 李曼莉 傅博强 戴新华 龚晓云

谭思源,李曼莉,傅博强,等. 单细胞质谱分析方法研究进展[J]. 计量科学与技术,2021, 65(5): 20-29, 13 doi: 10.12338/j.issn.2096-9015.2020.9021
引用本文: 谭思源,李曼莉,傅博强,等. 单细胞质谱分析方法研究进展[J]. 计量科学与技术,2021, 65(5): 20-29, 13 doi: 10.12338/j.issn.2096-9015.2020.9021
TAN Siyuan, LI Manli, FU Boqiang, DAI Xinhua, GONG Xiaoyun. Recent Advances in Single-Cell Mass Spectrometry Methods[J]. Metrology Science and Technology, 2021, 65(5): 20-29, 13. doi: 10.12338/j.issn.2096-9015.2020.9021
Citation: TAN Siyuan, LI Manli, FU Boqiang, DAI Xinhua, GONG Xiaoyun. Recent Advances in Single-Cell Mass Spectrometry Methods[J]. Metrology Science and Technology, 2021, 65(5): 20-29, 13. doi: 10.12338/j.issn.2096-9015.2020.9021

单细胞质谱分析方法研究进展

doi: 10.12338/j.issn.2096-9015.2020.9021
基金项目: 国家自然科学基金资助项目(21605135);国家自然科学基金资助项目(21927812)
详细信息
    作者简介:

    谭思源(1993-),中国计量科学研究院博士后,研究方向:单细胞质谱离子源研发,邮箱:tansy@nim.ac.cn

    通讯作者:

    龚晓云(1988-),中国计量科学研究院副研究员,研究方向:质谱离子源研发,邮箱:gxy@nim.ac.cn

Recent Advances in Single-Cell Mass Spectrometry Methods

  • 摘要: 细胞个体间的异质性对于生物体内各类生理功能的顺利完成十分重要。从单细胞尺度上对生物分子进行准确测量有助于获得在组织整体测量水平上被掩盖的微观生物学机制。由于单细胞中物质组成复杂、含量极低、不同组分的浓度差异显著,导致单细胞内生物分子的测量难度极大。质谱技术凭借其高灵敏度、高特异性、准确定量能力以及强大的化合物结构解析能力,近年来在单细胞分析领域获得广泛关注。目前,单细胞质谱分析方法的研究主要集中在离子化技术和相应的样品前处理方法上。根据离子化技术的不同,可将主流的质谱单细胞分析方法分为以下四类:纳升电喷雾离子化质谱法、激光解吸附离子化质谱法、二次离子质谱法和电感耦合等离子体质谱法。本文对近5年来基于上述四种离子化技术的单细胞质谱分析方法进行了归纳和评述,并对单细胞质谱分析方法在未来的计量科学发展进行了展望。
  • 图  1  单细胞内多组学分析研究

    Figure  1.  Multi-omics analysis in single cell

    图  2  单细胞局部电渗析采样及质谱分析流程图[12]

    Figure  2.  Schematic illustration of single-cell local electroosmotic sampling and mass spectrometry analysis [12]

    图  3  单细胞液滴微萃取和Pico-ESI-MS分析流程图[23]

    Figure  3.  Schematic illustration of single-cell droplet microextraction and Pico-ESI-MS analysis [23]

    图  4  单细胞采样和高效CE-nanoESI-MS分析流程图[31]

    Figure  4.  Schematic illustration of single-cell sampling and high performance CE-nanoESI-MS analysis [31]

    图  5  用于单细胞成像的VUVDI-MS平台[35]

    Figure  5.  The VUVDI-MS platform for single-cell imaging [35]

    图  6  用于单细胞成像的t-MALDI-2示意图[37]

    Figure  6.  Schematic illustration of t-MALDI-2 platform for single-cell imaging [37]

    图  7  单细胞MALDI-MS/ICC分析流程图[40]

    Figure  7.  Schematic illustration of single-cell MALDI-MS/ICC analysis [40]

    图  8  可视化TOF-SIMS的单细胞蛋白质和脂质分析[48]

    Figure  8.  Single-cell protein and lipid analysis based on visualized TOF-SIMS [48]

    图  9  三维OrbiSIMS质谱装置及成像分析[45]

    Figure  9.  Three-dimensional OrbiSIMS mass spectrometry device and imaging analysis [45]

    图  10  亚细胞药物与代谢物的nanoSIMS绝对定量分析[49]

    Figure  10.  Absolute quantitative analysis of subcellular drugs and metabolites based on NanoSIMS [49]

    图  11  LA-ICP-MS法测量不同单细胞中蛋白含量[59]

    Figure  11.  LA-ICP-MS method for measuring protein content in different single cells [59]

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