Electron Capture Dissociation in Multipole Ion Guides

Award Information
Agency:
Department of Health and Human Services
Branch
n/a
Amount:
$100,000.00
Award Year:
2004
Program:
SBIR
Phase:
Phase I
Contract:
1R43RR019176-01
Award Id:
70784
Agency Tracking Number:
RR019176
Solicitation Year:
n/a
Solicitation Topic Code:
n/a
Solicitation Number:
n/a
Small Business Information
29 BUSINESS PARK DRIVE, BRANFORD, CT, 06405
Hubzone Owned:
N
Minority Owned:
N
Woman Owned:
N
Duns:
n/a
Principal Investigator:
DAVID WELKIE
(203) 488-8899
DWELKIE@AOB.COM
Business Contact:
(203) 488-8899
Research Institute:
n/a
Abstract
DESCRIPTION (provided by applicant): Mass spectrometry has become an essential analytical tool for clinical diagnostics, drug discovery, and similar biomedical research areas, due in large part to its ability to elucidate the structure of biological molecules. Such information is commonly derived from analysis of fragment ions produced by 'collision-activated dissociation' (CAD), which relies on collisions between ions and gas molecules to rupture chemical bonds of the ions due to vibrational excitations. However, the energy available in CAD is distributed among the vibrational degrees of freedom of a molecule, so the CAD process becomes increasingly inefficient for larger molecules. This is especially problematic for protein analysis, in which cleavage occurs preferentially at a limited number of characteristically weak bonds, resulting in incomplete sequence information. A completely different mechanism for fragmentation has been discovered, arising from the interaction of low energy electrons with multiply-protonated molecules, and is referred to as 'electron capture dissociation' (ECD). With ECD, the energy for fragmentation derives from electronic state interactions rather than vibrational excitation, resulting in a larger variety of cleavage sites than CAD. Thus, ECD fragmentation information greatly expands and complements that from CAD. To date, however, ECD has only been effectively incorporated in high-priced Fourier transform mass spectrometers with constrained throughput, and limited availability to the larger research community due to the high cost and complexity of operation. The thrust of this project is to investigate several proposed design approaches for integrating ECD into a multipole ion guide configuration similar to that used in commonly available, high-throughput triple-quadrupole and quadrupole/time-of-flight mass spectrometers. The main objectives are: to investigate the feasibility of the proposed design approaches for providing an environment within a quadrupole ion guide configuration in which an abundance of electrons of low energy can be produced and manipulated so as to efficiently and effectively interact with ions traversing the ion guide; to efficiently collect and mass analyze the resulting fragment ions; and to evaluate the information content of the resulting ECD fragment ion spectra in relation to that from CAD.

* information listed above is at the time of submission.

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