Resolving the Complexity of Spatial Lipidomics Using MALDI TIMS Imaging Mass Spectrometry
Resolving the Complexity of Spatial Lipidomics Using MALDI TIMS Imaging Mass Spectrometry
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DOI：
10.1021/acs.analchem.0c02520
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发表时间：
2020-10-06
影响因子：
7.4
通讯作者：
Spraggins, Jeffrey M.
中科院分区：
文献类型：
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作者：
Djambazova, Katerina, V;Klein, Dustin R.;Spraggins, Jeffrey M.
脂质是一类结构多样的分子，具有重要的生物学功能，包括细胞信号传导和能量储存。基质辅助激光解吸/电离（MALDI）成像质谱（IMS）允许直接映射组织中的生物分子。充分表征脂质的结构多样性仍然是一个挑战，由于同量异位素和异构体的存在，这大大复杂的数据解释时，只有m/z信息是可用的。整合离子迁移率分离有助于解卷积这些复杂的混合物，并解决脂质IMS的挑战。在这里，我们证明了具有捕获离子迁移谱（TIMS）的MALDI四极杆飞行时间（Q-TOF）质谱仪在IMS实验期间能够使峰值容量增加>250%。证明了脂质异构体标准品（包括sn骨架异构体、酰基链异构体以及双键位置和立体异构体）的MALDI TIMS-MS分离。作为概念的证明，使用来自全身小鼠幼仔的组织切片进行具有不同空间分布的脂质异构体的原位分离和成像。
Lipids are a structurally diverse class of molecules with important biological functions including cellular signaling and energy storage. Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) allows for direct mapping of biomolecules in tissues. Fully characterizing the structural diversity of lipids remains a challenge due to the presence of isobaric and isomeric species, which greatly complicates data interpretation when only m/z information is available. Integrating ion mobility separations aids in deconvoluting these complex mixtures and addressing the challenges of lipid IMS. Here, we demonstrate that a MALDI quadrupole time-of-flight (Q-TOF) mass spectrometer with trapped ion mobility spectrometry (TIMS) enables a >250% increase in the peak capacity during IMS experiments. MALDI TIMS-MS separation of lipid isomer standards, including sn backbone isomers, acyl chain isomers, and double-bond position and stereoisomers, is demonstrated. As a proof of concept, in situ separation and imaging of lipid isomers with distinct spatial distributions were performed using tissue sections from a whole-body mouse pup.