Fourier transform ion cyclotron resonance mass spectrometry
Protein structure and folding in solution and gas phase
Non-covalent bonding in biological macromolecules
Mixture analysis by ultrahigh-resolution mass spectrometry
Ultrasensitive mass analysis (at level of a single biological cell)
Environmental mass spectrometry
Optical spectroscopy of mass-selected trapped ions

Marshall Research Group

    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.

9.4 Tesla FT-ICR Mass Spectrometer

    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.

Marshall, A. G.; Hendrickson, C. L.; Jackson, G. S. "Fourier Transform Ion Cyclotron Resonance Mass Spectrometry: A Primer", Mass Spectrom. Rev. 1998, 17, 1-35.

He, F.; Hendrickson, C. L.; Marshall, A. G. "Unequivocal Determination of Metal Atom Oxidation State in Naked Heme Proteins: Fe(III)Myoglobin, Fe(III)Cytochrome c, Fe(III)Cytochrome b5, and Fe(III)Cytochrome b5 L47R," J. Am. Soc. Mass Spectrom. 2000, 11, 120-126.

Marshall, A. G. "Milestones in Fourier Transform Ion Cyclotron Resonance Mass Spectrometry Technique Development," Int. J. Mass Spectrom. 2000, 200, 331-356.

Wang, Y.; Hendrickson, C. L.; Marshall, A. G. "Direct Optical Spectroscopy of Gas-Phase Molecular Ions Trapped and Mass-Selected by Ion Cyclotron Resonance: Laser-Induced Fluorescence Excitation Spectrum of Hexafluorobenzene (C₆F₆⁺)," Chem. Phys. Lett. 2001, 334, 69-75.

He, F.; Hendrickson, C. L.; Marshall, A. G. "Baseline Mass Resolution of Peptide Isobars: A Record for Molecular Mass Resolution," Anal. Chem. 2001, 73, 647-650.

Qian, K.; Rodgers, R. P.; Hendrickson, C. L.; Emmett, M. R.; Marshall, A. G. "Reading Chemical Fine Print:  Resolution and Identification of 3000 Nitrogen-Containing Aromatic Compounds from a Single Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrum of Heavy Petroleum Crude Oil," Energy & Fuels 2001, 15, 492-498.

Rodgers, R. P.; Blumer, E. N.; Freitas, M. A.; Marshall, A. G. "Compositional Analysis for Identification of Arson Accelerants by Electron Ionization Fourier Transform Ion Cyclotron Resonance High-Resolution Mass Spectrometry,î J. Forensic Sci. 2001, 46, 268-279.

HÂkansson, K.; Cooper, H. J.; Emmett, M. R.; Costello, C. E.; Marshall, A. G.; Nilsson, C. L. "Electron Capture Dissociation and Infrared Multiphoton Dissociation MS/MS of an N-Glycosylated Tryptic Peptide to Yield Complementary Sequence Information," Anal. Chem. 2001, 73, 4530-4536.

Hughey, C. A.; Hendrickson, C. L.; Rodgers, R. P.; Marshall, A. G. "Elemental Composition Analysis of Processed and Unprocessed Diesel Fuel by Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry," Energy & Fuels 2001, 15, 1186-1193.

Hughey, C. A.; Hendrickson, C. L.; Rodgers, R. P.; Marshall, A. G.; Qian, K. "Kendrick Mass Defect Spectroscopy: A Compact Visual Analysis for Ultrahigh-Resolution Broadband Mass Spectra," Anal. Chem. 2001, 73, 4676-4681.

Marshall, A. G.; Hendrickson, C. L. "Fourier Transform Ion Cyclotron Resonance Detection: Principles and Experimental Configurations," Int. J. Mass Spectrom. 2002, 215, 59-75.

Wu, Z.; Hendrickson, C. L.; Rodgers, R. P.; Marshall, A. G. "Compositional Analysis of Military Explosives by Electrospray Ionization Fourier Transform Negative Ion Cyclotron Resonance Mass Spectrometry," Anal. Chem. 2002, 74, 1879-1883.

Marshall, A. G.; Hendrickson, C. L.; Shi. S. D.-H. "Scaling MS Plateaus with FTICR MS," Anal. Chem. 2002, 74, 252A-259A.

Hughey, C. A.; Rodgers, R. P.; Marshall, A. G. "Resolution of 11,000 Compositionally Distinct Components in a Single Electrospray Ionization Fourier Transform Ion Cyclotron Resonance Mass Spectrum of Crude Oil," Anal. Chem. 2002, 74, 4145-4149.

"Structural Analysis of 2D-Gel-Separated Glycoproteins from Human Cerebrospinal Fluid by Tandem High Resolution Mass Spectrometry," Håkansson, K.; Emmett, M. R.; Marshall, A. G.; Davidsson, P.; Nilsson, C. L. J. Proteome Res. 2, 581-588 2003.

"Glycoproteomics of Cerebrospinal Fluid in Neurodegenerative Disease," Sihlbom, C.; Davidsson, P.; Emmett, M. R.; Marshall, A. G.; Nilsson, C. L. Int. J. Mass Spectrom.. 234, 145-152 2004.

"Petroleomics: The Next Grand Challenge for Chemical Analysis," Marshall, A. G.; Rodgers, R. P. Acc. Chem. Res. 37, 53-59 2004.

"The Role of Electron Capture Dissociation in Biomolecular Analysis," Cooper, H. J.; Håkansson, K.; Marshall, A. G. Mass Spectrom. Rev. 24, 201-222 2005.

For a complete, continuously updated, publication list and other information, visit the ICR Program web page.