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.

Public Health Relevance

Dysregulated lipid metabolism is associated with a variety of pathological conditions, such as diabetes mellitus, cancer and infectious diseases. The proposed research will build a new instrument platform to aid the unambiguous identification of lipid biomarkers of diseases and improve our understanding of the functional roles of diverse lipids in the disease process.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21GM104678-02
Application #
8518417
Study Section
Special Emphasis Panel (ZRR1-BT-7 (01))
Program Officer
Friedman, Fred K
Project Start
2012-08-01
Project End
2015-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
2
Fiscal Year
2013
Total Cost
$199,626
Indirect Cost
$79,001
Name
Battelle Pacific Northwest Laboratories
Department
Type
DUNS #
032987476
City
Richland
State
WA
Country
United States
Zip Code
99352