Don Douglas

The last few decades have seen dramatic growth of mass spectrometry into new application areas. Most notable among these have been the applications to biomolecules, particularly peptides and proteins. Research in this group centers on the development of new techniques in mass spectrometry and new instrumentation and for such applications.

Electrospray ionization sources can produce gas-phase ions of proteins at atmospheric pressure directly from proteins in solution. The ionization process is sufficiently gentle that proteins up to a molecular weight of at least 500,000 can be ionized. In many cases noncovalent complexes between proteins and other proteins, or between proteins and small molecules, can be observed in mass spectra. Little is known about the structure of these gas-phase ions or complexes. Research here is directed towards new methods and new instrumentation to study the structures of these ions and to determine the relationships of these structures, if any, to those of proteins in solution. Collision cross sections are measured to give an estimate of ion "size". Gas-phase hydrogen/deuterium exchange is used to probe protein conformation, and tandem mass spectrometry is used to determine relative binding strengths of gas-phase noncovalent complexes. This work is done in collaboration with protein chemists in the Department of Chemistry and Department of Biochemistry at UBC.

Instrumentation for mass spectrometry continues to evolve rapidly. Work in this lab is directed towards developing improved linear quadrupole ion trap mass spectrometers. A linear quadrupole mass filter is operated at very low resolution and stopping potentials are applied to electrodes at the ends of the quadrupole. As a result, ions with a broad range of mass to charge ratios can be confined in the trap, manipulated, and then ejected in a mass selective manner to produce a mass spectrum. Current work is directed to understanding and reducing so called "space charge" effects in such traps. If too many ions are introduced to a trap, the Coulombic repulsion between the ions ("space charge") changes the character of the ion motion. The net result is changes of the apparent masses of ions and a loss of mass resolution in mass spectra. This work is sponsored through an NSERC-SCIEX Industrial Research Chair. As a result, there are opportunities for consultation and co-operation with researchers at AB SCIEX, a major manufacturer of mass spectrometers located near Toronto.