Ion Mobility Mass Spectrometry (IMMS) is an emerging analytical technique with the potential capability of detecting, quantifying and identifying thousands of compounds in a complex mixture in fractions of a second. While IMMS has been applied primarily to the proteome, this grant application proposes to develop and evaluate its potential to measure and monitor the metabolome. Using both electro spray ionization and matrix assisted laser desorption ionization to create peptide and protein ions in the gas phase, IMS separates isomeric peptides and protein conformations before mass spectral analysis. This separation mechanism is based on ion-molecule collisions as an ion migrates through a neutral buffer gas in an electric field. The time an ion takes to transverse the buffer gas region is related to its size and shape. In IMS instruments currently used for peptide and protein separations, ion migration through the buffer gas occurs at a reduced pressures (typically 10 torr) with a typical separation efficiency of about 2000 theoretical plates. For application to metabolomics, we propose to use ion mobility separations at atmospheric pressures or greater, increasing the separation efficiency to more than 300,000 theoretical plates and improving significantly the two-dimensional resolving power of IMMS. In addition to separation efficiency, separation range and selectivity will be enhanced. Using IMS parameters of temperature, pressure, buffer gas, and voltage, the separation range will be extended to achieve maximal peak capacity and the separation selectivity will be optimized for maximal resolution of a metabolome. IMMS will also be interfaced to both gas chromatography and liquid chromatography to provide maximal metabolite quantification and provide three dimensional separations. With IMMS, both pattern recognition algorithms to identify modification in an entire metabolome as well as identification and quantification of individual metabolites is possible.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21DK070274-02
Application #
6952355
Study Section
Special Emphasis Panel (ZRG1-EMNR-J (50))
Program Officer
Castle, Arthur
Project Start
2004-09-30
Project End
2006-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
2
Fiscal Year
2005
Total Cost
$606,081
Indirect Cost
Name
Washington State University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
041485301
City
Pullman
State
WA
Country
United States
Zip Code
99164
Kaplan, Kimberly A; Chiu, Veronica M; Lukus, Peter A et al. (2013) Neuronal metabolomics by ion mobility mass spectrometry: cocaine effects on glucose and selected biogenic amine metabolites in the frontal cortex, striatum, and thalamus of the rat. Anal Bioanal Chem 405:1959-68
Kaplan, Kimberly; Graf, Stephan; Tanner, Christian et al. (2010) Resistive glass IM-TOFMS. Anal Chem 82:9336-43
Dwivedi, Prabha; Puzon, Geoffery; Tam, Maggie et al. (2010) Metabolic profiling of Escherichia coli by ion mobility-mass spectrometry with MALDI ion source. J Mass Spectrom 45:1383-93
Fernández-Maestre, Roberto; Wu, Ching; Hill, Herbert H (2010) Using a Buffer Gas Modifier to Change Separation Selectivity in Ion Mobility Spectrometry. Int J Mass Spectrom 298:2-9
Dwivedi, Prabha; Schultz, Albert J; Hill, Herbert H (2010) Metabolic Profiling of Human Blood by High Resolution Ion Mobility Mass Spectrometry (IM-MS). Int J Mass Spectrom 298:78-90
Kaplan, Kimberly; Dwivedi, Prabha; Davidson, Sean et al. (2009) Monitoring dynamic changes in lymph metabolome of fasting and fed rats by electrospray ionization-ion mobility mass spectrometry (ESI-IMMS). Anal Chem 81:7944-53
Huang, Yan; Xun, Randy; Chen, Guanjun et al. (2008) Maintenance role of a glutathionyl-hydroquinone lyase (PcpF) in pentachlorophenol degradation by Sphingobium chlorophenolicum ATCC 39723. J Bacteriol 190:7595-600
Kanu, Abu B; Dwivedi, Prabha; Tam, Maggie et al. (2008) Ion mobility-mass spectrometry. J Mass Spectrom 43:1-22
Dwivedi, Prabha; Bendiak, Brad; Clowers, Brian H et al. (2007) Rapid resolution of carbohydrate isomers by electrospray ionization ambient pressure ion mobility spectrometry-time-of-flight mass spectrometry (ESI-APIMS-TOFMS). J Am Soc Mass Spectrom 18:1163-75
Tang, Xiaoting; Bruce, James E; Hill Jr, Herbert H (2007) Design and performance of an atmospheric pressure ion mobility Fourier transform ion cyclotron resonance mass spectrometer. Rapid Commun Mass Spectrom 21:1115-22

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