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

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

中国计量科学研究院，北京 100029

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

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出版历程
- 网络出版日期: 2021-05-10
- 刊出日期: 2021-06-24

Recent Advances in Single-Cell Mass Spectrometry Methods

National Institute of Metrology, Beijing 100029, China

摘要

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。
- 质谱 /
- 单细胞分析 /
- 离子化 /
- 纳升电喷雾离子化 /
- 激光解吸附离子化 /
- 二次离子质谱 /
- 电感耦合等离子体质谱
Abstract: The heterogeneity between individual cells is essential for the realization of various biological functions. Accurate measurement of biomolecules at the single-cell scale is beneficial to obtain microcosmic biological mechanisms that are scarcely acquired at the tissue scale. However, the measurement of biomolecules in single cells is extremely difficult due to the complex composition in individual cells, the extremely low content of substances, and the significant differences in concentration of different components. With its high sensitivity, high specificity, accurate quantitation, and structural identification capabilities, mass spectrometry technology has attracted much attention in single-cell analysis field in recent years. At present, research on single-cell mass spectrometry methods has focused on the development of ionization techniques and corresponding sample pre-treatment methods. From the perspectives of ionization techniques, there are mainly four categories: nano-electrospray ionization mass spectrometry (nanoESI-MS), laser desorption ionization mass spectrometry (LDI-MS), secondary ion mass spectrometry (SIMS) and inductively coupled plasma mass spectrometry (ICP-MS). This review summarizes the recent developments of these methods and their future trends in metrology field.
- mass spectrometry /
- single-cell analysis /
- ionization /
- nano-electrospray ionization /
- laser desorption ionization /
- secondary ion mass spectrometry /
- inductively coupled plasma mass spectrometry

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图 1 单细胞内多组学分析研究

Figure 1. Multi-omics analysis in single cell

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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]

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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]

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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]

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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]

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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]

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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]

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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]

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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]

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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]

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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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