An Ultrasensitive Mass Spectrometry Platform for Comprehensive Analysis of Lipids

描述（由申请人提供）：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。尽管技术进步使质谱（MS）成为生物分子分析的重要工具，但脂质位置和立体异构体的明确分配仍然是一项具有根本性挑战性的任务。本项目的主要目标是开发一个基于质谱的仪器平台，该平台能够阐明复杂脂质组学样品中的脂质结构

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.