The use of ion formation methods such as matrix-assisted laser desorption/ionization (MALDI) in tandem with mass spectrometry (MS) has revolutionized the characterization of biologically significant molecules. MS has now become an indispensable technique for the analysis of large molecules such as lipids, peptides, proteins and nucleic acids. The ToF mass analyzer is widely used because of its simplicity, quasi-parallel detection and theoretically unlimited mass range. One historical drawback to the use of ToF is poor mass peak resolving power. The ability to resolve mass peaks is critical to the success of using accurate mass measurement to assign peak composition and structure. We feel the best approach to improving MALDI mass resolution is to decouple the ionization and extraction from acceleration and mass analysis by adding an interstitial collisional cooling stage. The proposed instrument design should markedly improve the resolution of MALDI mass spectra. To further improve resolution and timing accuracy and mass measurement accuracy, we will use the IOnwerks multi-channel time-to-digital converter (TDC). The combination of multi-pixel detector and multi-channel TDC will increase the dynamic range of the TDC data recorder to the point that it should compete with transient digitizers, but provide superior timing resolution.

Proposed Commercial Applications

MALDI mass spectrometry is widely and effectively used in all aspects of biomolecule characterization. Should Phase I be successful, we will provide an instrument with mass resolution and mass accuracy superior to currently available instrumentation. We envision that the instrument will be immediately marketable to the biotechnology and pharmaceutical industries with applications as wide ranging as research scale protein scale protein assay to small scale clinical diagnosis.

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 #
1R43GM057736-01
Application #
2649433
Study Section
Special Emphasis Panel (ZRG3-SSS-6 (01))
Project Start
1998-04-01
Project End
1999-03-31
Budget Start
1998-04-01
Budget End
1999-03-31
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Ionwerks, Inc.
Department
Type
DUNS #
154074553
City
Houston
State
TX
Country
United States
Zip Code
77002
Chifotides, Helen T; Koomen, John M; Kang, Mijeong et al. (2004) Binding of DNA purine sites to dirhodium compounds probed by mass spectrometry. Inorg Chem 43:6177-87
Woods, Amina S; Fuhrer, Katrin; Gonin, Marc et al. (2003) Angiotensin II-acetylcholine noncovalent complexes analyzed with MALDI-ion mobility-TOF MS. J Biomol Tech 14:1-8
Koomen, John M; Russell, William K; Tichy, Shane E et al. (2002) Accurate mass measurement of DNA oligonucleotide ions using high-resolution time-of-flight mass spectrometry. J Mass Spectrom 37:357-71
Koomen, John M; Ruotolo, Brandon T; Gillig, Kent J et al. (2002) Oligonucleotide analysis with MALDI-ion-mobility-TOFMS. Anal Bioanal Chem 373:612-7
Gillig, K J; Ruotolo, B; Stone, E G et al. (2000) Coupling high-pressure MALDI with ion mobility/orthogonal time-of-flight mass spectrometry. Anal Chem 72:3965-71