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化学进展 2021, Vol. 33 Issue (1): 97-110 DOI: 10.7536/PC200458 前一篇   后一篇

• 综述 •

二次离子质谱生物成像

蔡乐斯1, 夏梦婵1, 李展平1,2,*(), 张四纯1,*(), 张新荣1   

  1. 1 清华大学化学系 北京 100084
    2 有机光电子与分子工程教育部重点实验室 北京 100084
  • 收稿日期:2020-04-19 修回日期:2020-05-06 出版日期:2021-01-24 发布日期:2020-10-15
  • 通讯作者: 李展平, 张四纯
  • 作者简介:
    * Corresponding author e-mail: (Zhanping Li);sczhang@mail.tsinghua.edu.cn(Sichun Zhang)
  • 基金资助:
    国家自然科学基金项目(21974078); 国家自然科学基金项目(21727813); 国家自然科学基金项目(21621003); 国家重点研发计划(2018YFA0702600)
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Bioimaging By Secondary Ion Mass Spectrometry

Lesi Cai1, Meng-Chan Xia1, Zhanping Li1,2,*(), Sichun Zhang1,*(), Xinrong Zhang1   

  1. 1 Department of Chemistry, Tsinghua University,Beijing 100084, China
    2 Key Laboratory of Organic Optoelectronics & Molecular Engineering of the Ministry of Education, Tsinghua University,Beijing 100084, China
  • Received:2020-04-19 Revised:2020-05-06 Online:2021-01-24 Published:2020-10-15
  • Contact: Zhanping Li, Sichun Zhang
  • Supported by:
    21621003; the National Key R&D Program of China(2018YFA0702600)

二次离子质谱作为目前空间分辨率最高的质谱成像技术,以其免标记、高灵敏、多组分检测优势和亚微米级高空间分辨成像优势为诸多生命科学问题的研究提供了全新的分析手段,在基础细胞生物学、组织生理病理学、生物医药与临床医学等领域的研究中得到了广泛应用。本文综述了二次离子质谱在生物组织、细胞、仿生生物膜等体系中的质谱成像研究进展。

关键词： 二次离子质谱, 质谱成像, 生物分析, 单细胞分析, 生命科学

Secondary ion mass spectrometry(SIMS), as the highest spatial resolution mass spectrometry imaging technique, holds label-free, high sensitivity, multi-component detection advantages and sub-micron high spatial resolution imaging advantage, providing new analysis method to study life science problems. SIMS has been widely used in cell biology, tissue pathological physiology, biological medicine, clinical medicine and other fields. This paper reviews the progress of SIMS imaging in biological tissue, cell, bionic biofilm and other bio-samples.

Contents

1 Introduction

2 SIMS chemical imaging at tissue level

2.1 Chemical imaging of animal tissue section

2.2 Chemical imaging of plant tissue section

2.3 Chemical imaging of bionic biofilm

3 SIMS chemical imaging at single-cell level

3.1 Endogenous substances analysis

3.2 Exogenous substance analysis

3.3 Cell classification based on SIMS fingerprint

4 SIMS chemical imaging of other bio-samples

5 Conclusion and outlook

Key words: SIMS, mass spectrometry imaging, bio-analysis, single-cell analysis, life science
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图1 3D OrbiSIMS仪器结构示意图[8]
Fig. 1 Schematic diagram of the 3D OrbiSIMS[8]
图2 二次离子质谱的动物组织化学成像: (a)鼠脑切片的TOF-SIMS化学成像[63] ;(b)TOF-SIMS对非酒精性脂肪变性肝脏的化学成像[66] ;(c)骨骼肌中脂质的TOF-SIMS成像[68]
Fig. 2 Chemical imaging of animal tissue sections by SIMS: (a) TOF-SIMS chemical imaging of rat brain section[63] .(b) Chemical imaging of non-alcoholic steatosis liver by TOF-SIMS[66] .(c) TOF-SIMS imaging of lipids in skeletal muscle section[68]
图3 二次离子质谱的植物组织化学成像: (a)豆茎组织切片的Cryo-TOF-SIMS化学成像[75] ;(b)杨树枝干上应拉木组织的纤维素和木质素的SIMS 3D成像[80]
Fig. 3 Chemical imaging of tissue sections by SIMS: (a) Cryo-TOF-SIMS chemical imaging of surface of a bean stem cross section[75] .(b) 3D TOF-SIMS imaging of cellulose and lignin in poplar branches tension wood section[80]
图4 TOF-SIMS单细胞化学成像研究。 (a)四膜虫配对过程中的脂质变化的TOF-SIMS化学成像研究[98] ;(b)维生素E在神经元中的亚细胞区域富集TOF-SIMS成像[99]
Fig. 4 TOF-SIMS chemical imaging at single-cell level: (a) TOF-SIMS chemical imaging of lipid changes during the pairing of tetrahymena[98] .(b) TOF-SIMS chemical imaging of Vitamin E enriched in subcellular regions of a neuron[99]
图5 TOF-SIMS 3D化学成像。 (a)冷冻脆断制样的甲状腺癌细胞的高分辨率化学3D成像[56] ;(b)ZCorrectorGUI校正的3D-TOF-SIMS细胞成像[101]
Fig. 5 3D chemical imaging by TOF-SIMS:(a) High-resolution chemical 3D imaging of high pressure frozen, freeze-fractured, and freeze-dried thyroid tumor cells[56] .(b) ZCorrectorGUI corrected 3D TOF -SIMS cell imaging of a NIH/3T3 cell[101]
图6 细胞中外源性物质的SIMS化学成像: (a) 15N多肽标记HeLa细胞的Nano-SIMS成像[55] ;(b)Nano-SIMS用于细胞中的药物碘信号与黑色素信号的共定位分布成像[108] ;(c)NR8383巨噬细胞中脱乙基胺碘酮的TOF-SIMS 3D化学成像[111]
Fig. 6 SIMS chemical imaging of exogenous substances in cells: (a) Nano-SIMS imaging of HeLa cell with 15N-labeled peptide[55] .(b) Nano-SIMS was used to image the co-location distribution of drug iodine signal and melanin signal in cells[108] .(c) TOF-SIMS 3D chemical imaging of desethylamiodarone in R8383 macrophages[111]
图7 基于SIMS指纹图谱的细胞分型研究: (a)TOF-SIMS数据结合多变量分析手段用来识别从小鼠骨髓中分离出的单个造血细胞分化状态[127] ;(b)小鼠成纤维细胞NIH 3T3培养大鼠原代食管上皮细胞REEC的SIMS分型[96] ;(c)基于TOF-SIMS脂质指纹图谱的8种乳腺癌细胞系PCA分型结果[129]
Fig. 7 Cell typing based on SIMS fingerprint: (a) TOF-SIMS data combined with multivariate analysis were used to identify the differentiation status of individual hematopoietic cells isolated from mouse bone marrow[127] .(b) SIMS typing of mouse fibroblast NIH 3T3 cultured rat primary esophageal epithelial cells REEC[96] .(c) PCA typing results of 8 breast cancer cell lines based on TOF-SIMS lipid fingerprint[129]
图8 TOF-SIMS在刑侦科学中的应用:指纹残留物的化学成像[22]
Fig. 8 Application of TOF-SIMS in forensic science: chemical imaging of fingerprint residues[22]
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摘要

二次离子质谱生物成像