二次离子质谱-激光扫描共聚焦显微镜联用对单细胞显微成像-原理及应用  

Correlated Secondary Ion Mass Spectrometry-Laser Scanning Confocal Microscopy Imaging for Single Cell-Principles and Applications

作　　者：邵长芳 赵耀[2] 吴魁[2] 贾菲菲 罗群[2,3] 刘哲 汪福意[2,3] SHAO Chang-Fang;ZHAO Yao;WU Kui;JIA Fei-Fei;LUO Qun;LIU Zhe;WANG Fu-Yi(Institute of Anticancer Agents Development and Theranostic Application,the Key Laboratory of Life-Organic Analysis andKey Laboratory of Pharmaceutical Intermediates and Analysis of Natural Medicine,Department of Chemistry andChemical Engineering,Qufu Normal University,Qufu 273165,China;Beijing National Laboratory for Molecular Sciences,National Centre for Mass Spectrometry in Beijing,CAS Key Laboratoryof Analytical Chemistry for Living Biosystems,Institute of Chemistry,Chinese Academy of Sciences,Beijing 100190,China)

机构地区：[1]曲阜师范大学抗癌药物开发与诊疗应用研究所,山东省生命有机分析重点实验室,山东省绿色天然产物及医药中间体开发重点实验室,化学与化工学院,曲阜师范大学,曲阜273165 [2]北京分子科学国家实验室,北京国家质谱中心,活体分析化学中国科学院重点实验室,中国科学院化学研究所,北京100190 [3]中国科学院大学,北京100149

出　　处：《分析化学》2018年第7期1005-1016,共12页Chinese Journal of Analytical Chemistry

基　　金：文系国家自然科学基金项目(Nos.91543101,21671118,21790390,21790392,21575145,21621062)、泰山学者项目和中国科学院青年创新促进会(No.2017051)资助

摘　　要：二次离子质谱(SIMS)分析主要用于半导体、地质等领域材料表面分析,随着科学仪器技术的发展,近年来,SIMS在生命科学领域中得到了越来越广泛的应用。SIMS可以实现对样品表面的质谱分析、化学成像以及深度剖析。三维SIMS成像分析的横向分辨率可达80~100 nm,纵向分辨率1~5 nm。但是,由于缺少特异性指示亚细胞结构的碎片离子,单细胞SIMS成像分析仍然面临着诸多挑战。激光扫描共聚焦显微成像(LSCM)作为一种单细胞成像技术已日趋成熟,可以对单细胞中的荧光分子或者对荧光标记的目标分子、细胞器成像,获得高分辨率亚细胞结构成像图。因而,LSCM在单细胞形貌分析上的优势和SIMS在单细胞化学成像方面的优势可以有效互补,其联合应用能显著提升单细胞分析的应用范围、深度和结果的准确性。本文重点介绍SIMS成像以及SIMS-LSCM联用成像在单细胞成像研究中的应用进展,在总结、评述该领域代表性工作的同时,对SIMS-LSCM联用成像在化学和生命科学研究,特别是在细胞生物学和药物发现领域的应用前景进行了展望。Secondary ion mass spectrometry （SIMS） as a powerful surface analysis technique has been widelyapplied in semiconductor industry and geology research. Recently, with the development of instrumentaltechnology, SIMS is attracting more and more attention in life sciences. SIMS can provide surface MS spectra,2D/ 3D chemical images and depth profiling of substances simultaneously. The minimal lateral resolution of 2DSIMS imaging is 80 to 100 nm, and the longitudinal resolution of 3D SIMS imaging is about 1 - 5 nm.However, due to lack of specific ions to render the structures of organelles, SIMS imaging for single cells stillhas great challenges. Optical microscopy, in particular laser scanning confocal microscopy （LSCM）, has beenemerged to be an indispensable technique for single cell imaging and can obtain high spatial 2D/ 3D imaging tovisualize the structures of organelles. Thus, the combinational use of SIMS and LSCM, which takes advantagesof SIMS for molecular imaging and LSCM for morphological imaging, has greatly extended the application ofSIMS imaging and ensured its accuracy at single cells level, providing novel insights into better understandingof the biological events inside cells. In this review, we focus on the development and application of SIMSimaging and the correlated SIMS and LSCM imaging in the research of cell biology and drug discovery. Weanticipate that the combinational use of SIMS and LSCM imaging has promising future in biomedicine and lifesciences.

关 键 词：二次离子质谱成像 激光扫描共聚焦显微成像 联用成像 单细胞成像 细胞生物学 评述 

分 类 号：O657.63[理学—分析化学] Q2-33[理学—化学]