Advion Triversa Nanomate/ABSciex Nanospray III Ion Source for Targeted Lipidomics

用于靶向脂质组学的 Advion Triversa Nanomate/ABSciex Nanospray III 离子源

• 批准号: 8051194
• 负责人: ANDREW J MORRIS
• 金额: $ 10.57万
• 依托单位: UNIVERSITY OF KENTUCKY
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8051194
• 关键词: Address; Arachidonic Acids; Area; Biological; Cardiovascular Diseases; Carnitine; Ceramides; Cholesterol Esters; Column Chromatography; Data Analyses; Detection; Diabetes Mellitus; Energy Metabolism; Fatty Acids; Functional disorder; Funding; Genomics; Glycerides; High Pressure Liquid Chromatography; Human; Hybrids; Infusion procedures; Ions; Kentucky; Laboratories; Lipids; Liquid Chromatography; Malignant Neoplasms; Mass Spectrum Analysis; Membrane; Methods; Molecular; Monitor; Obesity; Phospholipids; Play; Process; Proteomics; Reaction; Research; Role; Sampling; Scanning; Series; Signal Transduction; Signaling Molecule; Sphingomyelins; Sterols; System; Time; Universities; Width; instrument; ion source; ionization; lipid metabolism; mass analyzer; mass spectrometer; metabolomics; operation; oxidized lipid; peptide hormone; research study; tandem mass spectrometry; tool

DESCRIPTION (provided by applicant): Lipids are intermediates in energy metabolism, structural components of biological membranes and as intra- and extra- cellular signals. Aberrant lipid metabolism plays a central role human pathophysiologies, including cardiovascular disease, obesity, diabetes, and cancer Systems-level analysis of lipids has lagged behind rapid progress in genomics and proteomics. Newly developed analytical approaches using tandem liquid chromatography and multi- dimensional mass spectrometry have spawned the field of "lipidomics"- a focused area of metabolomics that concerns the systems-level analysis of lipids and lipid-dependent processes. As a component of a core laboratory of our Center for Research on Obesity and Cardiovascular Disease, the University of Kentucky operates an ABSciex 4000 Q-Trap hybrid triple quadrupole linear ion trap mass spectrometer which is used primarily for analysis of lipids and lipid-related molecules including glycero and sphingo phospholipids, fatty acids, ceramides, sphingomyelins, sterols and cholesterol esters, di and tri glycerides, acyl carnitines, oxidized lipids and their reaction products, peptide hormones, arachidonic acid derived signaling molecules and their metabolites by HPLC, electospray ionization (ESI) selective reaction monitoring mode tandem mass spectrometry. In addition to its ability to operate as a component of a triple quadrupole mass spectrometer, the Q3 mass analyzer of this instrument can function as a linear ion trap conferring significant additional capabilities to the instrument that make it an extremely powerful tool for metabolite identification. While the HPLC configuration for sample separation and introduction using a high flow Turbo V ESI ion source is ideal for analyte quantitation by selective reaction monitoring, this arrangement is not compatible with newly developed powerful strategies for lipid profiling. This is because it is often difficult (or not possible) to separate the sometimes greater than 30-50 distinct lipid molecular species within a given class by column chromatography so narrow peak widths limit the time the instrument has to conduct scans to identify components of closely eluting lipid species. Methods that address this limitation mandate direct sample infusion allowing the instrument to identify lipid species conducting a series of lipid class specific precursor ion or neutral loss scans. Because of issues of sensitivity, sample availability and analyte abundance, detection of lipids in these experiments is greatly enhanced by low flow (10-200 nl/min) infusion of small volumes of concentrated samples. The purpose of the present application is to request funds to upgrade the instrument with an Advion Nanomate Triversa automated chip infusion system and an ABI Nanospray III ion source. This upgrade will allow us to use our instrument for lipid profiling studies by automated nanospray ESI mass spectrometry using these newly developed platforms for instrument operation and data analysis.

描述（由申请人提供）：脂质是能量代谢中的中间体，生物膜的结构成分以及作为内部和外细胞信号。异常的脂质代谢在人类病理生理中起着核心作用，包括心血管疾病，肥胖，糖尿病和癌症系统水平的脂质分析落后于基因组学和蛋白质组学方面的快速进步。使用串联液相色谱和多维质谱法的新开发的分析方法催生了“脂质组学”的领域，这是一个集中的代谢组学领域，涉及脂质和脂质依赖性过程的系统级分析。作为我们肥胖和心血管疾病研究中心的核心实验室的组成部分，肯塔基大学运营了腹肌4000 Q-TRAP混合三倍四极杆线性离子陷阱质谱仪，主要用于分析脂质和脂质相关的分子，包括glycero and Sphingsos sercringo phlyceros，磷酸化磷酸化，鞘氨质蛋白，固醇和胆固醇酯，DI和三甘油酯，酰基肉碱，氧化的脂质及其反应产物，肽激素，蛛网膜酸得出的信号传导分子及其代谢物及其代谢产物通过HPLC，pelesospray iipare（ESI）选择性反应反应反应模式质量质量图。除了它作为三倍四极杆质谱仪的组成部分的能力外，该仪器的Q3质量分析仪还可以充当线性离子陷阱，从而赋予该仪器的显着附加功能，从而使其成为代谢物识别非常强大的工具。虽然使用高流量涡轮增压源用于样品分离和引入的HPLC配置是通过选择性反应监测的分析物定量的理想选择，但这种布置与新开发的脂质分析的强大策略不兼容。这是因为通常很难（或不可能）将有时大于30-50个不同的脂质分子物种在给定类别中通过柱色谱法分离，因此狭窄的峰宽度限制了仪器必须进行扫描以识别紧密洗脱脂质物种的成分的时间。解决此限制的方法授权直接输注，从而允许仪器识别进行一系列脂质类特异性前体离子或中性损失扫描的脂质物种。由于敏感性，样品可用性和分析物丰度的问题，由于低流量（10-200 nl/min）输注少量浓缩样品，这些实验中脂质的检测大大增强了。本申请的目的是要求资金使用纳米酸盐Triversa自动化芯片输液系统和ABI Nanospray III ION源来升级该工具。此升级将使我们能够使用这些新开发的仪器质谱法进行自动化的纳米喷雾ESI质谱法进行脂质分析研究，以进行仪器操作和数据分析。