We propose to construct and develop an enabling, cutting-edge gas-chromatography/mass spectrometer instrument (GC/MS) based on the recently introduced Orbitrap mass analyzer. By combining ultra-high resolving power and mass accuracy measurement with tandem MS capabilities, the proposed system will bridge a fundamental technology gap in small molecule analysis. This instrument will greatly facilitate identification of unknown species when standard GC-electron impact (EI) fragmentation and mass spectral matching strategies fail;surpassing current high end GC-MS systems such as GC-time-of-flight (TOF) - by offering greater mass accuracy, dynamic range, and added MS/MS capabilities. We provide preliminary data utilizing a standard linear ion trap Orbitrap hybrid demonstrating practical feasibility and utility. That system, however, is not optimal for routine use and has not yet realized the potential for MS/MS coupled to GC. The proposed GC-Orbitrap system will have a transformative impact on multiple fields, especially metabolomics (the set of small molecules present in a biological system, i.e., <1000 Da), but also environmental toxin identification (e.g., pesticides, persistent organic pollutants, disinfection by-products, etc.), doping, petroleum and biofuel analysis, among many others. !

Public Health Relevance

A cutting-edge gas-chromatography/mass spectrometer (GC/MS), based on the recently introduced Orbitrap mass analyzer, is being developed. By combining ultra-high resolving power and mass accuracy measurement with tandem MS capabilities, a fundamental technology gap in small molecule analysis will be bridged, a means to identify metabolites that cannot be identified by standard GC- mass spectral matching strategies. The identification of metabolites is critical to developing a complete understanding of cellular function.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM107199-01
Application #
8560146
Study Section
Instrumentation and Systems Development Study Section (ISD)
Program Officer
Sheeley, Douglas
Project Start
2013-09-10
Project End
2016-05-31
Budget Start
2013-09-10
Budget End
2014-05-31
Support Year
1
Fiscal Year
2013
Total Cost
$222,619
Indirect Cost
$70,619
Name
University of Wisconsin Madison
Department
Biochemistry
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Peterson, Amelia C; Balloon, Allison J; Westphall, Michael S et al. (2014) Development of a GC/Quadrupole-Orbitrap mass spectrometer, part II: new approaches for discovery metabolomics. Anal Chem 86:10044-51
Peterson, Amelia C; Hauschild, Jan-Peter; Quarmby, Scott T et al. (2014) Development of a GC/Quadrupole-Orbitrap mass spectrometer, part I: design and characterization. Anal Chem 86:10036-43
Lemke, Rachelle A S; Peterson, Amelia C; Ziegelhoffer, Eva C et al. (2014) Synthesis and scavenging role of furan fatty acids. Proc Natl Acad Sci U S A 111:E3450-7