Fast and broad-coverage lipidomics enabled by ion mobility-mass spectrometry,Analyst

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Fast and broad-coverage lipidomics enabled by ion mobility-mass spectrometry
Analyst ( IF 3.6 ) Pub Date : 2024-08-20 , DOI: 10.1039/d4an00751d
Yuping Cai ₁ , Xi Chen _{1,

2} , Fandong Ren ₁ , Hongmiao Wang _{1,

2} , Yandong Yin ₁ , Zheng-Jiang Zhu _{1,

3}

Affiliation

Aberrant lipid metabolism has been widely recognized as a hallmark of various diseases. However, the comprehensive analysis of distinct lipids is challenging due to the complexity of lipid molecular structures, wide concentration ranges, and numerous isobaric and isomeric lipids. Usually, liquid chromatography-mass spectrometry (LC-MS)-based lipidomics requires a long time for chromatographic separation to achieve optimal separation and selectivity. Ion mobility (IM) adds a new separation dimension to LC-MS, significantly enhancing the coverage, sensitivity, and resolving power. We took advantage of the rapid separation provided by ion mobility and optimized a fast and broad-coverage lipidomics method using the LC-IM-MS technology. The method required only 8 minutes for separation and detected over 1000 lipid molecules in a single analysis of common biological samples. The high reproducibility and accurate quantification of this high-throughput lipidomics method were systematically characterized. We then applied the method to comprehensively measure dysregulated lipid metabolism in patients with colorectal cancer (CRC). Our results revealed 115 significantly changed lipid species between preoperative and postoperative plasma of patients with CRC and also disclosed associated differences in lipid classes such as phosphatidylcholines (PC), sphingomyelins (SM), and triglycerides (TG) regarding carbon number and double bond. Together, a fast and broad-coverage lipidomics method was developed using ion mobility-mass spectrometry. This method is feasible for large-scale clinical lipidomic studies, as it effectively balances the requirements of high-throughput and broad-coverage in clinical studies.

中文翻译：

通过离子淌度质谱法实现快速且覆盖度广的脂质组学

异常的脂质代谢已被广泛认为是各种疾病的标志。然而，由于脂质分子结构复杂、浓度范围宽以及同量异位和异构体脂质众多，因此对不同脂质的综合分析具有挑战性。通常，基于液相色谱-质谱（LC-MS）的脂质组学需要很长时间进行色谱分离才能实现最佳分离和选择性。离子淌度（IM）为 LC-MS 增加了一个新的分离维度，显著提高了覆盖率、灵敏度和分离能力。我们利用离子淌度提供的快速分离，并使用LC-IM-MS技术优化了快速、覆盖度广的脂质组学方法。该方法仅需 8 分钟即可完成分离，在普通生物样品的单次分析中可检测到 1000 多个脂质分子。系统表征了这种高通量脂质组学方法的高重现性和准确定量。然后，我们应用该方法全面测量结直肠癌（CRC）患者脂质代谢失调的情况。我们的结果显示，CRC 患者术前和术后血浆之间的 115 种脂质种类发生显著变化，还揭示了磷脂酰胆碱（PC）、鞘磷脂（SM）和甘油三酯（TG）等脂质类别在碳数和双键方面的相关差异。总之，使用离子淌度质谱法开发了一种快速且覆盖度广的脂质组学方法。该方法对于大规模临床脂质组学研究是可行的，因为它有效地平衡了临床研究中高通量和广泛覆盖的要求。

更新日期：2024-08-20

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