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. !
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.
|Kwiecien, Nicholas W; Bailey, Derek J; Rush, Matthew J P et al. (2015) High-resolution filtering for improved small molecule identification via GC/MS. Anal Chem 87:8328-35|
|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|
|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|
|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|