Significant increase in the efficiency and speed of electron transfer dissociation (ETD) in tandem mass spectrometry (MS) will have a profound impact on its applications to the entire analytical field of characterization of posttranslational modifications (PTM) in proteins. At present, the applicability of ETD-based MS analysis as a unique analytical tool specifically targeting PTM is limited by its low speed and by inability of ETD to efficiently dissociate proteins or peptides with low charge density. We plan to build a novel ETD ion source generating an energetic beam of negative ions to significantly improve efficiency and speed of PTM detection of both proteins and peptides. To demonstrate high rate of MS/MS analysis based on ETD, we plan to utilize capabilities of house-built desktop FTMS instrument equipped with multi-electrode detection system, and record MS/MS mass spectra obtained from fast ETD process with high mass resolution and in a short time.

Public Health Relevance

Utilizing complementary fragmentation methods is a broadly used approach in mass-spectrometry based analysis of complex protein mixtures providing reliable identification of posttranslation modifications in proteins. We plan to develop a novel source providing fast fragmentation that will substantially improve and accelerate characterization of posttranslation modifications in proteins analyzed in tandem mass spectrometers. The source can be easily incorporated into a design of a variety of tandem mass spectrometers. This will allow much better detection of disease-specific biomarkers from biological fluids or tissues.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43GM103358-01
Application #
8315467
Study Section
Special Emphasis Panel (ZRG1-IMST-G (10))
Program Officer
Sheeley, Douglas
Project Start
2012-08-10
Project End
2014-08-09
Budget Start
2012-08-10
Budget End
2014-08-09
Support Year
1
Fiscal Year
2012
Total Cost
$413,605
Indirect Cost
Name
Masstech, Inc.
Department
Type
DUNS #
123310083
City
Columbia
State
MD
Country
United States
Zip Code
21046
Gimelshein, Natalia; Gimelshein, Sergey; Lilly, Taylor et al. (2014) Numerical modeling of ion transport in an ESI-MS system. J Am Soc Mass Spectrom 25:820-31