Department of Chemistry, University of Montreal, Montreal, Quebec, Canada.
Anal Chem. 2012 Feb 21;84(4):2048-54. doi: 10.1021/ac2033547. Epub 2012 Feb 8.
Matrix sublimation has demonstrated to be a powerful approach for high-resolution matrix-assisted laser desorption ionization (MALDI) imaging of lipids, providing very homogeneous solvent-free deposition. This work presents a comprehensive study aiming to evaluate current and novel matrix candidates for high spatial resolution MALDI imaging mass spectrometry of lipids from tissue section after deposition by sublimation. For this purpose, 12 matrices including 2,5-dihydroxybenzoic acid (DHB), sinapinic acid (SA), α-cyano-4-hydroxycinnamic acid (CHCA), 2,6-dihydroxyacetphenone (DHA), 2',4',6'-trihydroxyacetophenone (THAP), 3-hydroxypicolinic acid (3-HPA), 1,8-bis(dimethylamino)naphthalene (DMAN), 1,8,9-anthracentriol (DIT), 1,5-diaminonapthalene (DAN), p-nitroaniline (NIT), 9-aminoacridine (9-AA), and 2-mercaptobenzothiazole (MBT) were investigated for lipid detection efficiency in both positive and negative ionization modes, matrix interferences, and stability under vacuum. For the most relevant matrices, ion maps of the different lipid species were obtained from tissue sections at high spatial resolution and the detected peaks were characterized by matrix-assisted laser desorption ionization time-of-flight/time-of-flight (MALDI-TOF/TOF) mass spectrometry. First proposed for imaging mass spectrometry (IMS) after sublimation, DAN has demonstrated to be of high efficiency providing rich lipid signatures in both positive and negative polarities with high vacuum stability and sub-20 μm resolution capacity. Ion images from adult mouse brain were generated with a 10 μm scanning resolution. Furthermore, ion images from adult mouse brain and whole-body fish tissue sections were also acquired in both polarity modes from the same tissue section at 100 μm spatial resolution. Sublimation of DAN represents an interesting approach to improve information with respect to currently employed matrices providing a deeper analysis of the lipidome by IMS.
基质升华已被证明是一种用于高分辨率基质辅助激光解吸电离（MALDI）成像脂质的强大方法，可实现非常均匀的无溶剂沉积。本工作全面研究了当前和新型基质候选物，用于通过升华沉积后从组织切片中进行高空间分辨率 MALDI 成像质谱分析脂质。为此，我们研究了 12 种基质，包括 2,5-二羟基苯甲酸（DHB）、香豆素酸（SA）、α-氰基-4-羟基肉桂酸（CHCA）、2,6-二羟基苯乙酮（DHA）、2',4',6'-三羟基苯乙酮（THAP）、3-羟基吡啶甲酸（3-HPA）、1,8-双（二甲氨基）萘（DMAN）、1,8,9-蒽三醇（DIT）、1,5-二氨基萘（DAN）、对硝基苯胺（NIT）、9-氨基吖啶（9-AA）和 2-巯基苯并噻唑（MBT），用于在正离子和负离子模式下检测脂质的效率、基质干扰以及在真空中的稳定性。对于最相关的基质，我们从组织切片中以高空间分辨率获得了不同脂质种类的离子图谱，并通过基质辅助激光解吸电离飞行时间/飞行时间（MALDI-TOF/TOF）质谱对检测到的峰进行了表征。DAN 首次被提议用于升华后的成像质谱（IMS），它具有高效性，在高真空稳定性和低于 20 μm 的分辨率能力下，在正、负两种极性下都能提供丰富的脂质特征。利用 10 μm 的扫描分辨率生成了成年小鼠大脑的离子图像。此外，还从相同组织切片中以 100 μm 的空间分辨率在正、负两种极性模式下获取了成年小鼠大脑和全鱼组织切片的离子图像。DAN 的升华代表了一种改善信息的有趣方法，相对于目前使用的基质，它提供了通过 IMS 对脂质组进行更深入的分析。
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