Mass spectrometric profiling of intact biological tissue by using desorption electrospray ionization
Mass spectrometric profiling of intact biological tissue by using desorption electrospray ionization
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DOI：
10.1002/anie.200502362
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发表时间：
2005-01-01
影响因子：
16.6
通讯作者：
Caprioli, RM
中科院分区：
文献类型：
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作者：
Wiseman, JM;Puolitaival, SM;Caprioli, RM
在飞行时间二次离子质谱仪(TOF-SIMS)[1]和基质辅助激光解吸/电离(MALDI)的基础上，成像质谱学已经成为一种强大的技术。然而，到目前为止，生物组织的质谱学分析一直局限于需要样品制备的技术，之后样品被限制在仪器的高真空区，因此这种方法无法进行进一步的物理或化学操作。在这里，生物组织的直接化学图谱是在常压环境条件下通过解吸电喷雾电离质谱仪(DESI-MS)实现的，[4]这是一种从质谱仪外的表面产生离子的新的、通用的方法。利用DESI-MS对生物组织中的脂类进行分析，几乎可以瞬间提供高度敏感和特定的化学信息。这种能力通过一些例子来说明，在这些例子中，小鼠胰腺、大鼠脑和转移性人肝腺癌组织的磷脂分布无需任何样品处理。生物膜是细胞分化和增殖的重要介质；前者在肿瘤形成中起重要作用，后者在肿瘤进展中起重要作用。磷脂在维持细胞结构完整性方面发挥着重要的作用，它通过形成膜上特有的双层结构，并在重要的细胞事件中发挥关键的中介作用，例如细胞信号传递和所谓的脂筏上的蛋白质分选。因此，细胞膜的化学和物理性质由磷脂成分决定。组织磷脂组成的改变已被报道用于某些疾病，包括癌症和阿尔茨海默病。[5]重要的是，某些磷脂及其酶副产物的丰富与某些组织的恶变有关。[6]这些发现强调了测定生物组织中磷脂组成的重要性，这些信息可以作为疾病和非疾病的预后变量。组织的质谱学已被广泛用于研究脂质(如磷脂)，[7]，尽管不是在环境条件下。MALDI-TOF已被用于分析晶状体组织中的脂类[8]，并已成为描绘生物组织中肽和蛋白质的空间分布的一种特别有效的技术。[3，9]另一种分子成像方法，TOF-SIMS，已被用于通过监测m/z 184处的磷胆碱头基来研究四膜虫交配接头中的磷胆碱分布。[10]在另一篇报道中，对小鼠脑切片中的脂类进行了TOF-SIMS成像，并对各种硫脂以及磷脂酰肌醇、磷脂酰胆碱和胆固醇、[11]DESI属于喷雾电离方法家族，如电喷雾电离(ESI)，[12]和解吸电离方法家族。[13]DESI允许直接和快速地分析表面，而不需要准备样品或将样品引入真空系统。[4]该方法已被应用于许多类化合物的痕量水平的分析，包括肽、蛋白质、核苷酸、硝基芳香化合物和其他。
Imaging mass spectrometry has emerged as a powerful technique based on time-of-flight secondary-ion mass spectrometry (TOF-SIMS)[1] and matrix-assisted laser desorption/ionization (MALDI).[2, 3] However, until now, the massspectrometric analysis of biological tissues has been limited to techniques that require sample preparation after which the sample is confined to the high-vacuum region of the instrument, thus making this approach inaccessible to further physical or chemical manipulations. Herein, direct chemical profiling of biological tissues is achieved under ambient conditions at atmospheric pressure by desorption electrospray ionization mass spectrometry (DESI-MS),[4] which is a new and versatile method for the creation of ions from surfaces outside of the mass spectrometer. The profiling of lipids in biological tissues by using DESI-MS provides highly sensitive and chemically specific information almost instantaneously. This capability is illustrated by examples in which phospholipid profiles of mouse pancreas, rat brain, and metastatic human-liver adenocarcinoma tissues are obtained without any sample pretreatment. Biological membranes serve as crucial mediators in cellular differentiation and proliferation; the former being important in tumor formation, the latter in tumor progression. Phospholipids play important roles in maintaining the structural integrity of the cell by forming of the characteristic bilayer of the membrane and by serving as key mediators in important cellular events, for example, cell signaling and protein sorting on so-called lipid rafts. As such, the chemical and physical properties of the cell membrane are determined by the phospholipid composition. Alterations in the phospholipid composition of tissues have been reported for certain diseases, including cancer and Alzheimer s disease.[5] Importantly, the abundance of certain phospholipids and their enzymatic by-products has been associated with malignant transformations in some tissues.[6] These findings emphasize the importance of the determination of the composition of phospholipids in biological tissues, information which may serve as prognostic variables in diseased and nondiseased tissues.Mass spectrometry has been used extensively to investigate lipids (eg, phospholipids),[7] although not under ambient conditions. MALDI-TOF has been used for the analysis of lipids in lens tissue [8] and has emerged as a particularly powerful technique for profiling the spatial distributions of peptides and proteins in biological tissues.[3, 9] An alternative molecular imaging method, TOF-SIMS, has been applied to the investigation of the phosphocholine distribution in Tetrahymena mating junction by monitoring the phosphocholine head group at m/z 184.[10] In another report, TOF-SIMS imaging of lipids in mouse-brain sections was performed and various sulfatides, as well as phosphatidylinositol, phosphatidylcholine, and cholesterol, were identified and their spatial distributions determined.[11] DESI belongs to the family of spray ionization methods, such as electrospray ionization (ESI),[12] as well as to the family of desorption ionization methods.[13] DESI allows direct and rapid analysis of surfaces without sample preparation or the need to introduce the sample into a vacuum system.[4] The methodology has been applied to the analysis of trace levels of many classes of compounds, including peptides, proteins, nucleotides, nitroaromatic compounds, and others.[14] Semiquantitative results have been obtained from