FOURIER TRANSFORM ION CYCLOTRON RESONANCE (FT-ICR) MASS SPECTROMETRY
My research consists of the continuing development of new theory, techniques, and analytical/biological/environmental applications of Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry. We were the first to apply Fourier transform techniques to mass spectrometry, and more than 575 FT-ICR mass spectrometry systems based on our patents and papers have been bought or built worldwide. At our National NSF High-Field FT-ICR Mass Spectrometry Facility at the National High Magnetic Field Laboratory, we have built 7, 7, 9.4, 9.4, and 14.5 tesla FT/ICR instruments. Our instruments hold the world records for mass resolution and mass accuracy (e.g., see Figure), and attract hundreds of users and collaborators from all over the world.
We continue to push the FT-ICR technique to its ultimate limits for mass resolution, mass range, and sensitivity. Our stored-waveform inverse Fourier transform ("SWIFT") excitation/detection scheme offers ultrahigh-resolution MS/MS with a single spectrometer as well as truly simultaneous multiple-ion monitoring. We use electrospray ionization, field desorption/ionization, and atmospheric pressure photoionization to produce mass spectra of substances with little or no volatility (e.g., biopolymers, drugs). We are developing robotic sample handling for generation and introduction of biologically interesting ions (e.g., oligosaccharides, phospholipids, peptides/proteins, RNA/DNA) into an ICR ion trap for ultrahigh-resolution MS or MS/MS analysis. We optimize MS/MS (electron capture dissociation, infrared multiphoton dissociation) methods to identify the primary amino acid sequence as well as the site(s) and nature (e.g., phosphorylation, glycosylation) of protein posttranslational modifications. Applications include discovery and characterization of disease biomarkers (e.g., Alzheimer's, kidney diseases).
FT-ICR MS allows us to identify up to 20,000 components in a mixture without prior separation (GC, LC , gels), thereby changing the whole approach to mixture analysis. For each component, the elemental composition reveals the heteroatom content (numbers of N, S, O atoms), number of rings plus double bonds, and degree of alkylation, from which we correlate and ultimately predict the origin, properties, and behavior of petroleum crude oil and its distillates, as well as other complex mixtures (e.g., vegetable oils, wine). We are developing new numerical and graphical methods to recognize patterns in the enormous volume of data made available by FT-ICR MS (up to 4 Mwords per spectrum).
We monitor H/D exchange by mass spectrometry to identify surface-exposed residues in proteins and protein complexes. When two proteins stick to each other, we can identify amino acid residues at the contact surface between the two proteins, as prospective drug targets. Applications range from drug screening to the mechanism of self-assembly of the protein "capsid" that envelops and protects RNA in the AIDS virus.
