Department of Chemistry, Vanderbilt University, 7330 Stevenson Center, Station B 351822, Nashville, Tennessee 37235, United States.
Mass Spectrometry Research Center, Vanderbilt University, 465 21st Avenue S #9160, Nashville, Tennessee 37235, United States.
Anal Chem. 2020 Oct 6;92(19):13290-13297. doi: 10.1021/acs.analchem.0c02520. Epub 2020 Sep 9.
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 / 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 backbone isomers, acyl chain isomers, and double-bond position and stereoisomers, is demonstrated. As a proof of concept, separation and imaging of lipid isomers with distinct spatial distributions were performed using tissue sections from a whole-body mouse pup.
脂质是一类结构多样的分子，具有重要的生物学功能，包括细胞信号转导和能量储存。基质辅助激光解吸/电离（MALDI）成像质谱（IMS）允许直接在组织中绘制生物分子图谱。由于存在等质异位和同构体，完全表征脂质的结构多样性仍然是一个挑战，因为仅提供 / 信息时，这极大地复杂化了数据解释。整合离子淌度分离有助于解析这些复杂混合物，并解决脂质 IMS 的挑战。在这里，我们证明了带有俘获离子淌度谱（TIMS）的 MALDI 四极杆飞行时间（Q-TOF）质谱仪能够在 IMS 实验期间将峰容量增加超过 250%。展示了脂质异构体标准品的 MALDI TIMS-MS 分离，包括 骨架异构体、酰基链异构体以及双键位置和立体异构体。作为概念验证，使用来自全身体内小鼠幼仔的组织切片进行了具有不同空间分布的脂质异构体的分离和成像。
