Bruce A. Thomson

A segmented radiofrequency-only quadrupole collision cell for measurements of ion collision cross section on a triple quadrupole mass spectrometer

The gas collision cell of a triple quadrupole mass spectrometer has been modified to consist of ten short quadrupole rod segments that allow an axial field to be applied to the cell in order to make measurements of ion mobility. The radiofrequency (rf)-quadrupole field provides effective radial confinement that greatly reduces diffusional losses at low pressure. The mobilities of mass-selected ions from an ionspray source have been measured at a pressure of 8 × 10−3 torr at electric fields of 0. 1 to 3 V/cm, and used to calculate the collision cross sections of the ions. The measured cross sections compare well with those measured by other techniques.

Analytical performance of a high-pressure radio frequency-only quadrupole collision cell with an axial field applied by using conical rods

The effect on triple-quadrupole performance of applying an axial field, in an rf-only quadrupole collision cell operated at pressures sufficiently high that collisional focusing is operating, has been investigated. The advantages of such cells have been shown previously to include increased transmission and much improved resolution in fragment ion spectra relative to the performance of collision cells operating at lower gas pressures. The disadvantages of high-pressure collision cells all derive from the relatively long transit times for the ions, which can be long relative to characteristic times for scanning the first mass filter (precursor ion selector) or for switching its setting in multiple reaction monitoring (MRM) cycles. The present work describes experiments on a high-pressure cell in which an axial field is created through use of conical rather than cylindrical or hyperbolic rods. In addition, results of computations of the electric fields within such a cell, and of ion trajectories through it, are presented. It is shown that application of axial fields of the order of 0. 1 V/cm can remove all hysteresis effects associated with the long ion transit times, and thus provide excellent performance in quantitation work using MRM, as well as in other scan modes. Furthermore, the advantages of collisional focusing in quadrupole collision cells are shown to be unimpaired by these low axial fields.

Determination of drugs in biological samples by thin-layer chromatography-tandem mass spectrometry.

In this work thin-layer chromatography-tandem mass spectrometry (TLC-MS-MS) allowed detection and confirmation of caffeine and nicotine in human urine and of butorphanol, betamethasone, and clenbuterol in equine urine. In most cases of trace analysis of labile compounds the drugs could not be identified unless they were developed on a TLC plate, scraped from the plate and the TLC scrape eluted with a suitable organic solvent prior to MS-MS. Usually a sample prepared in this way still had several components in it, but was sufficiently cleaned up to allow collision-induced dissociation (CID) experiments to unequivocally identify the drug. In contrast, trace levels of labile drugs could not be identified by CID experiments either directly from the raw urine extracts or by thermally desorbing them from the TLC scrape.

Atmospheric pressure ionization and liquid chromatography/mass spectrometry—together at last

The evolution of atmospheric pressure ionization techniques which are now routinely applied as liquid chromatograph/mass spectrometer (LC/MS) interfaces is described. Electrospray and related methods, as well as atmospheric pressure chemical ionization combined with the heated nebulizer interface, both began as specialized ionization techniques which became much more widely accepted when combined with tandem mass spectrometry. Today, both are widely used for quantitative and qualitative LC/MS and LC/MS/MS analyses. Important events in the development of these methods are described, along with key elements in the evolution of the ion source-to-vacuum interface techniques that contributed to their success.

Solid phase microextraction with matrix assisted laser desorption/ionization introduction to mass spectrometry and ion mobility spectrometry

Solid phase microextraction (SPME) with matrix assisted laser desorption/ionization (MALDI) introduction was coupled to mass spectrometry and ion mobility spectrometry. Nicotine and myoglobin in matrix 2,5-dihydroxybenzonic acid (DHB), enkephalin and substance P in alpha-cyano-4-hydroxy cinnaminic acid were investigated as the target compounds. The tip of an optical fiber was silanized for extraction of the analytes of interest from solution. The optical fiber thus served as the sample extraction surface, the support for the sample plus matrix, and the optical pipe to transfer the laser energy from the laser to the sample. The MALDI worked under atmospheric pressure, and both an ion mobility spectrometer and a quadrupole/time-of-flight mass spectrometer were used for the detection of the SPME/MALDI signal. The spectra obtained demonstrate the feasibility of the SPME with MALDI introduction to mass spectrometry instrumentation.

Infrared irradiation in the collision cell of a hybrid tandem quadrupole/time-of-flight mass spectrometer for declustering and cleaning of nanoelectrosprayed protein complex ions.

Herein we report the performance of a hybrid quadrupole time-of-flight tandem mass spectrometer with an improved designed for coaxial infrared laser introduction for the characterization and dissociation of large protein complex ions and their aggregates formed under nanoelectrospray ionization. The major improvement from the original design (Raspopov, S. A.; El-Faramawy, A.; Thomson, B. A.; Siu, K. W. M. Anal. Chem. 2006, 78, 4572-4577) involves the use of a hollow silica waveguide and physical isolation of the infrared laser. Large model protein complex ions and their aggregates examined include alcohol dehydrogenase, avidin, GroEL, and others. Gentle heating of these complexes with the infrared laser facilitated declustering and resulted in better resolved mass spectral peaks and more accurate molecular-weight measurements.

Development of a Branched Radio-Frequency Ion Trap for Electron Based Dissociation and Related Applications

Collision-induced dissociation (CID) is the most common tool for molecular analysis in mass spectrometry to date. However, there are difficulties associated with many applications because CID does not provide sufficient information to permit details of the molecular structures to be elucidated, including post-translational-modifications in proteomics, as well as isomer differentiation in metabolomics and lipidomics. To face these challenges, we are developing fast electron-based dissociation devices using a novel radio-frequency ion trap (i.e., a branched ion trap). These devices have the ability to perform electron capture dissociation (ECD) on multiply protonated peptide/proteins; in addition, the electron impact excitation of ions from organics (EIEIO) can be also performed on singly charged molecules using such a device. In this article, we review the development of this technology, in particular on how reaction speed for EIEIO analyses on singly charged ions can be improved. We also overview some unique, recently reported applications in both lipidomics and glycoproteomics.

Julio Victor Iribarne, November 11, 1916–November 15, 2012

J ulio Iribarne, known in our field for developing the theory of ion evaporation, died recently at the age of 96. Ion evaporation is one of the two proposed explanations for the process of ion emission from charged droplets at atmospheric pressure. Originally published in two papers in 1976 and 1979, the theory was largely unrecognized in the mass spectrometry community until the explosion of interest in electrospray ionization in the late 1980s. Julio developed the theory to explain observations arising from my Ph.D. work in his lab in the Department of Physics at the University of Toronto. This work was directed at understanding what happens to the charges on cloud droplets when they evaporate, and it built on earlier work by Chapman and others who had noted that small, high mobility charge carriers were created. Our experiments using ion mobility and mass spectrometry identified the small ions that remained in the air when droplets evaporated. Rather than accept the previous explanations that these were simply residues of evaporated droplets, Julio proposed that ion emission from a charged droplet could be an activated process that competed with Rayleigh instability in certain regimes, and he developed a relatively simple but rigorous theory to support this idea. Julio, originally trained as a chemist, also recognized the potential analytical applications of this technique, and initiated some experiments with some small biomolecules to prove that these too could be emitted from charged droplets. Unfortunately, he did not consider trying to apply this method to proteins or larger biomolecules, and so the method did not attract much attention as an analytical technique, even when it was coupled to liquid chromatography. It was John Fenn who recognized the similarities of ion evaporation and electrospray methods, and he brought Julio’s work and the theory to the attention of the mass spectrometry community. Offered as a competing explanation to the charge residue theory of Malcolm Dole, the two theories have been debated and discussed for many years without complete resolution, but with the recognition that the truth is probably somewhere between. Julio was born in Argentina in 1916, and after obtaining his doctorate in chemistry at the University of Buenos Aires in 1942, he held a variety of research and teaching positions at the university. From 1957 to 1966 he was head of the Institute of Atmospheric Physics at the National Meteorological Service in Argentina. There, he oversaw some of the earliest cloud-seeding experiments. In 1966, his dissatisfaction with the political situation in Argentina led him to emigrate to Toronto, where he assumed a position in the atmospheric physics group in the physics department, coauthoring two textbooks: Atmospheric Thermodynamics in 1973 and Atmospheric Physics in 1980. His interest in microphysical processes in clouds, and cloud electrification, led to a number of challenging experiments in droplet/ droplet and droplet/ice collisions to measure and model the shearing processes that produce charge separation and electrified droplets. That theme led to the project on droplet evaporation, a project that he suggested to me and that led to the theory of ion evaporation. After formal retirement in 1982, Julio continued research in a completely different area. Together with his wife Agripina, a chemical engineer, he studied the chemistry of residues from combustion of coal in fluidized beds, continuing even with a lab in his home until the age of 87 and publishing some 22 papers in this field. Along with his varied scientific contributions, Julio was a gifted amateur violinist throughout his life, eventually finding time to study chamber music seriously at the university after his retirement. Widely read in three languages, he was particularly fond of French literature, poetry, and culture, as well as good food and un buen venito. A modest man and a gentleman in the true sense of the word, his collaborative approach to supervising the work of graduate students was fondly recalled at his memorial.