Analytical Method Development
The ICR facility leads the world in instrument and technique development as well as pursuing novel applications of FT-ICR mass spectrometry.
21 Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometer: A National Resource for Ultrahigh Resolution Mass Analysis Hendrickson, C.L.; Quinn, J.P.; Kaiser, N.K.; Smith, D.F.; Blakney, G.T.; Chen, T.; Marshall, A.G.; Weisbrod, C.R. and Beu, S.C. Journal of the American Society for Mass Spectrometry, 26, 9, 1626-1632 (2015)
Ultrahigh Resolution Ion Isolation by Stored Waveform Inverse Fourier Transform 21 T Fourier Transform Ion Cyclotron Resonance Mass Spectrometry Smith, D.F.; Blakney, G.T.; Beu, S.C.; Anderson, L.C.; Weisbrod, C.D.; Hendrickson, C.L. Analytical Chemistry, 92, 4, 3213-3219 (2020) - Data Set
Increased Single-Spectrum Top-Down Protein Sequence Coverage in Trapping Mass Spectrometers with Chimeric Ion Loading Weisbrod, C.; Anderson, L.C.; Greer, J.B.; DeHart, C.J.; Hendrickson, C.L. Analytical Chemistry, 92, 18, 12193-12200 (2020) - Data Set
21 Tesla FT-ICR Mass Spectrometer for Ultrahigh-Resolution Analysis of Complex Organic Mixtures Smith, D.; Podgorski, D.C.; Rodgers, R.P.; Blakney, G.T.; Hendrickson, C.L. Analytical Chemistry, 90, 3, 2041-2047 (2018) - Data Set
Front-End Electron Transfer Dissociation Coupled to a 21Tesla FT-ICR Mass Spectrometer for Intact Protein Sequence Analysis Weisbrod, C.R.; Kaiser, N.K.; Syka, J.E.P.; Early, L.; Mullen, C.; Dunyach, J.J.; English, A.M.; Anderson, L.C.; Blakney, G.T.; Shabanowitz, J.; Hendrickson, C.L.; Marshall, A.G. and Hunt, D.F. Journal of the American Society for Mass Spectrometry, 28, 9, 1787-1795 (2017)
Tailored Ion Radius Distribution for Increased Dynamic Range in FT-ICR Mass Analysis of Complex Mixtures Kaiser, N.K.; McKenna, A.M.; Savory, J.J.; Hendrickson, C.L. and Marshall, A.G. Analytical Chemistry, 85, 1, 265-272 (2013)
A Novel 9.4 Tesla FT-ICR Mass Spectrometer with Improved Sensitivity, Mass Resolution, and Mass Range Kaiser, N.K.; Quinn, J.P.; Blakney, G.T.; Hendrickson, C.L. and Marshall, A.G. Journal of the American Society for Mass Spectrometry, 22, 1343-1351 (2011)
Parts-Per-Billion Fourier Transform Ion Cyclotron Resonance Mass Measurement Accuracy with a 'Walking' Calibration Equation Savory, J.J.; Kaiser, N.K.; McKenna, A.M.; Xian, F.; Blakney, G.T.; Rodgers, R.P.; Hendrickson, C.L. and Marshall, A.G. Analytical Chemistry, 83, 1732-1736 (2011)
The biological applications group provides service operations for biomolecular analyses that require ultrahigh resolution and high mass accuracy achieved by high-field FT-ICR MS. Most applications center on intact protein, or “top-down” proteomic analysis, which provides a truly molecular-level understanding of structure-function relationships. Top-down mass spectrometry requires high detection sensitivity, mass resolving power, mass measurement accuracy, and multiple dissociation modalities, which leverage the unique capabilities of the 14.5 and 21 T FT-ICR instruments. Experiments are performed by direct infusion, or with online reversed-phase liquid chromatography, with support staff able to provide a limited slate of sample preparation services to users, including protein extraction, affinity purification, fractionation, and clean-up.
PEPPI-MS: Polyacrylamide Gel-based Prefractionation for Analysis of Intact Proteoforms and Protein Complexes by Mass Spectrometry Takemori, A.; Butcher, D.S.; Harman, V.M.; Brownbridge, P.; Shima, K.; Higo, D.; Ishizaki, J.; Hasegawa, H.; Suzuki, J.; Yamashita, M.; Loo, J.A.; Ogorzalek, R.R.; Beynon, R.J.; Anderson, L.C.; Takemori, N. Journal of Proteome Research, 19, 9, 3779-3791 (2020) - Data Set, ACS LiveSlides
Ultra-High Mass Resolving Power, Mass Accuracy, and Dynamic Range MALDI Mass Spectrometry Imaging by 21 T FT-ICR MS Bowman, A.P.; Blakney, G.T.; Hendrickson, C.L.; Ellis, S.R.; Heeren, R.M.A.; Smith, D.F. Analytical Chemistry, 92, 4, 3133-3142 (2020) - Data Set
Construction of Human Proteoform Families from 21 Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometry Top-Down Proteomic Data Schaffer, L.V.; Anderson, L.C.; Butcher, D.S.; Shortreed, M.R.; Miller, R.M.; Pavelec, C.; Smith, L.M. Journal of Proteome Research, 20, 1, 317-325 (2020) - Data Set
Inter-laboratory Study for Characterizing Monoclonal Antibodies by Top-Down and Middle-Down Mass Spectrometry Srzentić, K.; Fornelli, L.; Tsybin, Y.O.; Loo, J.A.; Seckler, H.; Agar, J.N.; Anderson, L.C.; Bai, D.L.; Beck, A.; Brodbelt, J.S.; van der Burgt, Y.E.M.; Chamot-Rooke, J.; Chatterjee, S.; Chen, Y.; Clark, D.J.; Danis, P.O.; Diedrich, J.K.; D'Ippolito, R.A.; Dupré, M.; Gasilova, N.; Ge, Y.; Goo, Y.A.; Goodlett, D.R.; Greer, S.M.; Haselmann, K.F.; He, L.; Hendrickson, C.L.; Hinkle, J.D.; Holt, M.; Hughes, S.; Hunt, D.F.; Kelleher, N.L.; Kozhinov, A.N.; Lin, Z.; Malosse, C.; Marshall, A.G.; Menin, L.; Millikin, R.J.; Nagornov, K.O.; Nicolardi, S.; Pa a-Tolić, L.; Pengelley, S.; Quebbemann, N.R.; Resemann, A.; Sandoval, W.; Sarin, R.; Schmitt, N.D.; Shabanowitz, J.; Shaw, J.B.; Shortreed, M.R.; Smith, L.M.; Sobott, F.; Suckau, D.; Toby, T.; Weisbrod, C.; Wildburger, N.C.; Yates, J.R.; Yoon, S.H.; Young, N.L.; Zhou, M. Journal of the American Society for Mass Spectrometry, 31, 9, 1783-1802 (2020)
Top-down proteomics A Near-future Technique for Clinical Diagnosis He, L.; Rockwood, A.L.; Agarwal, A.M.; Anderson, L.C.; Weisbrod, C.; Hendrickson, C.L.; Marshall, A.G. Annals of Translational Medicine, 8, 4, 136 (2020)
Classification of Plasma Cell Disorders by 21 Tesla Fourier Transform Ion Cyclotron Resonance Top-Down and Middle-Down MS/MS Analysis of Monoclonal Immunoglobulin Light Chains in Human Serum He, L.; Anderson, L.C.; Barnidge, D.R.; Murray, D.L.; Dasari, S.; Dispenzieri, A.; Hendrickson, C.L.; Marshall, A.G. Analytical Chemistry, 91, 5, 3263-3269 (2019)
Diagnosis of Hemoglobinopathy and β-Thalassemia by 21-Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Tandem Mass Spectrometry of Hemoglobin from Blood He, L.; Rockwood, A.L.; Agarwal, A.M.; Anderson, L.C.; Weisbrod, C.; Hendrickson, C.L.; Marshall, A.G. Clinical Chemistry, 65, 8, 986-994 (2019)
Protein de novo Sequencing by Top-down and Middle-down MS/MS: Limitations Imposed by Mass Measurement Accuracy and Gaps in Sequence Coverage He, L.; Weisbrod, C.R.; Marshall, A.G. International Journal of Mass Spectrometry, 427, 107-113 (2018)
Top Down Tandem Mass Spectrometric Analysis of a Chemically Modified Rough-Type Lipopolysaccharide Vaccine Candidate Oyler, B.L.; Khan, M.M.; Smith, D.F.; Harberts, E.M.; Kilgour, D.P.A.; Ernst, R.K.; Cross, A.S.; Goodlett, D.R. Journal of the American Society for Mass Spectrometry, 29, 6, 1221-1229 (2018)
Identification and Characterization of Human Proteoforms by Top-Down LC-21 Tesla FT-ICR Mass Spectrometry Anderson, L.C.; DeHart, C.J.; Kaiser, N.K.; Fellers, R.T.; Smith, D.F.; Greer, J.B.; LeDuc, R.D.; Blakney, G.T.; Thomas, P.M.; Kelleher, N.L.; Hendrickson, C.L. Journal of Proteome Research, 16, 2, 1087-1096 (2017) - Data Set 1
Additionally, the facility provides state-of-the art instrumentation for rapid MALDI FT-ICR mass spectral imaging, a technique used to simultaneously visualize the spatial distributions of thousands of molecules in samples and tissues. Mass spectrometry imaging (MSI) is a spatial analytical technique that allows the molecular composition of analytes be assigned to a localised position within a given sample. Samples usually consist of biological tissue such as animal, plant or bacterial colonies. One of the most popular MSI techniques is matrix assisted laser desorption ionisation (MALDI)-MSI, in which a laser is used to ablate and ionise the surface of a sample, producing a molecular ions that can be mapped to their position, and give you molecular ion heat map distributions. Researchers can then distinguish where a molecule of interest is present within their sample by looking at their 2D image.
A wide range of interesting molecules can be assessed using MALDI imaging, including lipids, peptides, pharmaceuticals, metabolites and proteins. By analysing these various analytes of interest and assigning them spatially, studies including pharmacokinetic and pharmacodynamic observations and toxicology associations can be determined, without the use of labels in the experiments. Image co-registration can be also be performed using other recognised imaging techniques including tissue staining.
MSI has a vast width of applications that can also be aided by specific sample preparation techniques that will affect the outcome (Goodwin, 2012). This can include sample collection, Employing and developing sample preparation techniques can enhance these capabilities, with examples such as on-tissue chemical derivatisation (Smith, et al. 2020), single cell imaging (Neumann, et al. 2019) and N-glycan imaging (McDowell, et al. 2021).
Goodwin RJA. Sample preparation for mass spectrometry imaging: small mistakes can lead to big consequences. J Proteomics. 2012 Aug 30;75(16):4893-4911. doi: 10.1016/j.jprot.2012.04.012. Epub 2012 Apr 24. PMID: 22554910.
Smith, K.W., Flinders, B., Thompson, P.D., Cruickshank, F.L., Mackay, C.L., Heeren, R.M. and Cobice, D.F., 2020. Spatial localization of vitamin D metabolites in mouse kidney by mass spectrometry imaging. ACS omega, 5(22), pp.13430-13437.
Neumann, E.K., Ellis, J.F., Triplett, A.E., Rubakhin, S.S. and Sweedler, J.V., 2019. Lipid Analysis of 30 000 Individual Rodent Cerebellar Cells Using High-Resolution Mass Spectrometry. Analytical chemistry, 91(12), pp.7871-7878.
McDowell, C.T., Klamer, Z., Hall, J., West, C.A., Wisniewski, L., Powers, T.W., Angel, P.M., Mehta, A.S., Lewin, D.N., Haab, B.B. and Drake, R.R., 2021. Imaging Mass Spectrometry and Lectin Analysis of N-Linked Glycans in Carbohydrate Antigen–Defined Pancreatic Cancer Tissues. Molecular & Cellular Proteomics, 20, p.100012.
Environmental & Geochemical
Traditional tools for routine environmental analysis and forensic chemistry of petroleum have relied almost exclusively on gas chromatography−mass spectrometry (GC-MS), although many compounds in crude oil (and its transformation products) are not chromatographically separated or amenable to GC-MS due to volatility. To enhance current and future studies on the fate, transport, and fingerprinting of oil spills release from anthropogenic or natural release, we apply ultrahigh resolution Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometry to identify compositional changes at the molecular level between native and weathered crude oil samples and reveal enrichment in polar compounds inaccessible by GC-based characterization. The outlined approach provides unprecedented detail with the potential to enhance insight into the environmental fate of spilled oil, improved toxicology, molecular modeling of biotic/abiotic weathering, and comprehensive molecular characterization for petroleum derived releases.
The complexity of natural organic matter (dissolved organic matter, soil organic matter) requires mass resolving power and mass measurement accuracy achievable only by high-field FT-ICR MS. A wide range of researchers from various scientific backgrounds rely of FT-ICR MS to provide molecular-level insight into the global cycling of organic molecules to identify important environmental trends associated with emerging contaminants, carbon/nitrogen cycling, and the impact of climate change across watersheds, wetlands, marine and terrestrial ecosystems and sediments and soils.
The First Decade of Scientific Insights from the Deepwater Horizon Oil Release Kujawinski, E.B.; Reddy, C.M.; Rodgers, R.P.; Thrash, J.C.; Valentine, D.L.; White, H.K. Nature Reviews Earth and Environment, 1, 237-250 (2020)
Expansion of the analytical window for oil spill characterization by ultrahigh resolution mass spectrometry: Beyond gas chromatography Environ. Sci. Technol., 47 (13), 7530-7539 (2013)
Characterization of an Asphalt Binder and Photoproducts by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry Reveals Abundant Water-Soluble Hydrocarbons Niles, S.; Chacon Patino, M.L.; Putnam, S.P.; Rodgers, R.P.; Marshall, A.G. Environmental Science and Technology, 54, 24, 8830-8836 (2020) - Data Set
High-Resolution Mass Spectrometry Identification of Novel Surfactant-Derived Sulfur-Containing Disinfection By-Products from Gas Extraction Wastewater Liberatore, H.K.; Westerman, D.C.; Allen, J.M.; Plewa, M.J.; Wagner, E.D.; McKenna, A.M.; Weisbrod, C.; McCord, J.P.; Liberatore, R.J.; Burnett, D.B.; Cizmas, L.H.; Richardson, S.D. Environmental Science and Technology, 54, 15, 9374-9386 (2020) - Data Set
Stormflows Drive Stream Carbon Concentration, Speciation and Dissolved Organic Matter Composition in Coastal Temperate Rainforest Watersheds Fellman, J.B.; Hood, E.; Behnke, M.I.; Welker, J.M.; Spencer, R.G.M. Journal of Geophysical Research Biogeosciences, 125, e2020JG005804 (2020) - Data Set 1, Data Set 2
Deciphering Dissolved Organic Matter: Ionization, Dopant, and Fragmentation Insights via Fourier Transform-Ion Cyclotron Resonance Mass Spectrometry Kurek, M.R.; Poulin, B.A.; McKenna, A.M.; Spencer, R.G.M. Environmental Science and Technology, 54, 24, 16249-16259 (2020) - Data Set
Molecular Comparison of Solid-Phase Extraction and Liquid/Liquid Extraction of Water-Soluble Petroleum Compounds Produced through Photodegradation and Biodegradation by FT-ICR Mass Spectrometry McKenna, A.M.; Chen, H.; Weisbrod, C.; Blakney, G.T. Analytical Chemistry, 93, 10, 4611-4618 (2021) - Data Set
Mobilization of Aged and Biolabile Soil Carbon by Tropical Deforestation Drake, T.W.; Oost, K.V.; Barthel, M.; Bauters, M.; Hoyt, A.M.; Podgorski, D.C.; Six, J.; Boeckx, P.; Trumbore, S.E.; Ntaboba, L.C.; Spencer, R.G.M. Nature Geoscience, 12, 541-546 (2019) - Data Set 1, Data Set 2
Fate and Transport Processes of Nitrogen in Biosorption Activated Media for Stormwater Treatment at Varying Field Conditions of a Roadside Linear Ditch Wen, D.; Ordonez, D.; McKenna, A.M.; Chang, N.B. Environmental Research, 181, 108915 (2020) - Data Set
Molecular-Level Characterization of Oil-Soluble Ketone/Aldehyde Photo-Oxidation Products by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry Reveals Similarity Between Microcosm and Field Samples Niles, S.; Chacon Patino, M.L.; Chen, H.; McKenna, A.M.; Blakney, G.T.; Rodgers, R.P.; Marshall, A.G. Environmental Science and Technology, 53, 12, 6887-6894 (2019) - Data Set
1.1 Billion Years Old Porphyrins Establish a Marine Ecosystem Dominated by Bacterial Primary Producers Gueneli, N.; McKenna, A.M.; Ohkouchi, N.; Boreham, C.J.; Beghin, J.; Javaux, E.J.; Brocks, J.J. Proceedings of the National Academy of Sciences of the USA (PNAS), 115, 1-9 (2018) - Data Set
High Fire-derived Nitrogen Deposition on Central African Forests Bauters, M.; Drake, T.W.; Verbeeck, H.; Bode, S.; Herve-Fernandez, P.; Zito, P.; Podgorski, D.C.; Boyemba, F.; Makelele, I.; Ntaboba, L.C.; Spencer, R.G.M.; Boeckx, P. Proceedings of the National Academy of Sciences of the USA (PNAS), 115, 3, 549-554 (2018) - Data Set
Organic Coating on Biochar Explains its Nutrient Retention and Stimulation of Soil Fertility Hagemann, N.; Joseph, S.; Schmidt, H.P.; Kammann, C.I.; Harter, J.; Borch, T.; Young, R.B.; Varga, K.; Taherymoosavi, S.; Elliott, K.W.; McKenna, A.; Albu, M.; Mayrhofer, C.; Obst, M.; Conte, P.; Dieguez-Alonso, A.; Orsetti, S.; Subdiaga, E.; Behrens, S.; Kappler, A. Nature Communications, 8, 1, 1089 (2017) - Data Set
4 Years after the Deepwater Horizon Spill: Molecular Transformation of Macondo Well Oil in Louisiana Salt Marsh Sediments Revealed by FT-ICR Mass Spectrometry Chen, H.; Hou, A.; Corilo, Y.; Lin, Q.; Lu, J.; Mendelssohn, I.A.; Zhang, R.; Rodgers, R.P.; McKenna, A.M. Environmental Science and Technology, 50, 17, 9061-9069 (2016) - Data Set
Petrochemical & Sustainable Fuels
Ultrahigh-resolution Fourier transform ion cyclotron resonance mass spectrometry has recently revealed that petroleum crude oil contains heteroatom-containing (N,O,S) organic components having more than 20,000 distinct elemental compositions (CcHhNnOoSs). It is therefore now possible to contemplate the ultimate characterization of all of the chemical constituents of petroleum, along with their interactions and reactivity, a concept we denote as “petroleomics”. Such knowledge has already proved capable of distinguishing petroleum and its distillates according to their geochemical origin and maturity, distillation cut, extraction method, catalytic processing, etc. The key features that have opened up this new field have been (a) ultrahigh-resolution FT-ICR mass analysis, specifically, the capability to resolve species differing in elemental composition by C3 vs SH4 (i.e., 0.0034 Da); (b) higher magnetic field to cover the whole mass range at once; (c) dynamic range extension by external mass filtering; and (d) plots of Kendrick mass defect vs nominal Kendrick mass as a means for sorting different compound “classes” (i.e., numbers of N, O, and S atoms), “types” (rings plusdouble bonds), and alkylation ((-CH2)n) distributions, thereby extending to >900 Da the upper limit for unique assignment of elemental composition based on accurate mass measurement. The same methods are also being applied successfully to analysis of humic and fulvic acids, coals, and other complex natural mixtures, often without prior or on-line chromatographic separation.
Citation: Petroleomics: The Next Grand Challenge for Chemical Analysis, Acc. Chem. Res., 2004, 37, 53-59
Petroleomics: Mass Spectrometry Returns to its Roots
Analytical Chemistry, 77 (1), 20-27 (2005)
Analytical Chemistry, 83, 1616-1623 (2011)
Metal oxide supported Ni-impregnated bifunctional catalysts for controlling char formation and maximizing energy recovery during catalytic hydrothermal liquefaction of food waste. Cheng, F.; Tompsett, G.A.; Alvarez, D.V.F.; Romo, C.I.; McKenna, A.M.; Niles, S.F.; Nelson, R.K.; Reddy, C.M.; Granados-Focil, S.; Paulsen, A.D.; Zhang, R.; Timko, M.T. Sustainable Energy and Fuels, 5, 4, 941-955 (2021) - Data Set
Characterization and Evaluation of Guayule Processing Residues as Potential Feedstock for Biofuel and Chemical Production Cheng, F.; Dehghanizadeh, M.; Audu, M.A.; Jarvis, J.M.; Holguin, O.; Brewer, C.E. Industrial Crops and Products, 150, 112311 (2020) - Data Set
Detailed Chemical Composition of an Oak Biocrude and its Hydrotreated Product Determined by Positive Atmospheric Pressure Photoionization Fourier Transform Ion Cyclotron Resonance Mass Spectrometry Ware, R.; Rodgers, R.P.; Marshall, A.G.; Mante, O.D.; Dayton, D.C.; Verdier, S.; Gabrielsen, J.; Rowland, S.M. Sustainable Energy and Fuels, 4, 2404-2410 (2020) - Data Set
Comprehensive Compositional and Structural Comparison of Coal and Petroleum Asphaltenes Based on Extrography Fractionation Coupled with Fourier Transform Ion Cyclotron Resonance MS and MS/MS Analysis Niles, S.; Chacon Patino, M.L.; Smith, D.F.; Rodgers, R.P.; Marshall, A.G. Energy and Fuels, 34, 2, 1492-1505 (2020) - Data Set
Molecular Characterization of Photochemically Produced Asphaltenes via Photooxidation of Deasphalted Crude Oils Glattke, T.; Chacon Patino, M.L.; Marshall, A.G.; Rodgers, R.P. Energy and Fuels, 34, 11, 14419-14428 (2020) - Data Set
Molecular-Level Characterization of Asphaltenes Isolated from Distillation Cuts McKenna, A.M.; Chacón-Patiño, M.L.; Weisbrod, C.; Blakney, G.T.; Rodgers, R.P. Energy and Fuels, 33, 3, 2018-2029 (2019) - Data Set
Advances in Asphaltene Petroleomics. Part 1: Asphaltenes Are Composed of Abundant Island and Archipelago Structural Motifs Chacon Patino, M.L.; Rowland, S.M.; Rodgers, R.P. Energy and Fuels, 31, 12, 13509-13518 (2017) - Data Set
Advances in Asphaltene Petroleomics. Part 2: A Selective Separation Method that Reveals Fractions Enriched in Island and Archipelago Structural Motifs by Mass Spectrometry Chacon Patino, M.L.; Rowland, S.M.; Rodgers, R.P. Energy and Fuels, 32, 1, 314-328 (2018) - Data Set
Advances in Asphaltene Petroleomics. Part 3. Dominance of Island or Archipelago Structural Motif Is Sample Dependent Chacon Patino, M.L.; Rowland, S.M.; Rodgers, R.P. Energy and Fuels, 32, 9, 9106-9120 (2018) - Data Set
Advances in Asphaltene Petroleomics. Part 4. Compositional Trends of Solubility Subfractions Reveal that Polyfunctional Oxygen-Containing Compounds Drive Asphaltene Chemistry Chacon Patino, M.L.; Smith, D.F.; Hendrickson, C.L.; Marshall, A.G.; Rodgers, R.P. Energy and Fuels, 34, 3, 3013-3030 (2020) - Data Set
Tetramethylammonium hydroxide as a reagent for complex mixture analysis by negative ion electrospray ionization mass spectrometry Energy & Fuels, 85 (16) 7803-7808 (2013)
Silver cationization for rapid speciation of sulfur-containing species in crude oils by positive electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry Energy & Fuels, 28 (1), 447-452 (2014)