An Ultrasensitive Mass Spectrometry Platform for Comprehensive Analysis of Lipids

说明(申请人提供)：脂类的特定功能与其化学和物理性质有关，并取决于特定的分子结构。尽管技术的进步使得质谱学(MS)成为生物分子分析的基本工具，但明确的脂类位置和立体异构体的指定仍然是一项具有根本挑战性的任务。该项目的主要目标是开发一个基于MS的仪器平台，能够在复杂的脂体样品中阐明脂类结构 高通量方式，并具有显著提高的灵敏度和特异度。这个分析平台将主要基于一个经过改装的三重四极杆质谱仪，具有高效臭氧诱导解离(OZID)识别脂类双键位置异构体的能力。将基于电动离子漏斗的MS接口技术和高分辨率场不对称波形离子迁移谱(FAIMS)技术相结合，将显著提高其灵敏度、动态范围和测量特异度。这个FAIMS/OzID MS仪器平台的应用将通过分析一个2型糖尿病队列的人血浆样本来展示，以实现对脂质生物标记物的明确和完整的结构阐明。由此产生的仪器平台有望在完整脂质的结构鉴定方面有广泛的应用，并将有助于发现和 验证脂类生物标记物在生物医学中的应用，并提供对不同脂类的功能作用的洞察。

DESCRIPTION (provided by applicant): The specific functions of lipids are related to their chemical and physical properties and depend on specific molecular structures. Despite technological advancements that have made mass spectrometry (MS) an essential tool for biomolecule analysis, unequivocal assignment of lipid positional and stereo isomers remains a fundamentally challenging task. The primary goal of this project is to develop a MS- based instrument platform that is capable of elucidating lipid structures in complex lipidomic samples in a high throughput manner and with significantly improved sensitivity and specificity. This analytical platform will be primarily based on a triple quadrupole mass spectrometer modified to have the capability of high efficiency ozone induced dissociation (OzID) for lipids double bond positional isomer identification. Its sensitivity, dynamic range and measurement specificity will be significantly enhanced by integrating with electrodynamic ion funnel-based MS interface technology and high resolution field asymmetric waveform ion mobility spectrometry (FAIMS) technology. The applications of this FAIMS/OzID MS instrument platform will be demonstrated by analyzing human plasma samples of a type 2 diabetes cohort to achieve unambiguous and complete structural elucidation of lipid biomarkers. The resulting instrument platform is expected to have broad applications in structural identification of intact lipids and will aid discovery and verification of lipid biomarkers in biomedical applications in addition to providing insights into functional roles of diverse lipid species.