Nathan K. Kaiser

A Novel 9.4 Tesla FTICR Mass Spectrometer with Improved Sensitivity, Mass Resolution, and Mass Range

Fourier transform ion cyclotron resonance (FTICR) mass spectrometry provides unparalleled mass measurement accuracy and resolving power. However, propagation of the technique into new analytical fields requires continued advances in instrument speed and sensitivity. Here, we describe a substantial redesign of our custom-built 9.4 tesla FTICR mass spectrometer that improves sensitivity, acquisition speed, and provides an optimized platform for future instrumentation development. The instrument was designed around custom vacuum chambers for improved ion optical alignment, minimized distance from the external ion trap to magnetic field center, and high conductance for effective differential pumping. The length of the transfer optics is 30% shorter than the prior system, for reduced time-of-flight mass discrimination and increased ion transmission and trapping efficiency at the ICR cell. The ICR cell, electrical vacuum feedthroughs, and cabling have been improved to reduce the detection circuit capacitance (and improve detection sensitivity) 2-fold. The design simplifies access to the ICR cell, and the modular vacuum flange accommodates new ICR cell technology, including linearized excitation, high surface area detection, and tunable electrostatic trapping potential.

The Smallest Stable Fullerene, M@C28 (M = Ti, Zr, U): Stabilization and Growth from Carbon Vapor

The smallest fullerene to form in condensing carbon vapor has received considerable interest since the discovery of Buckminsterfullerene, C(60). Smaller fullerenes remain a largely unexplored class of all-carbon molecules that are predicted to exhibit fascinating properties due to the large degree of curvature and resulting highly pyramidalized carbon atoms in their structures. However, that curvature also renders the smallest fullerenes highly reactive, making them difficult to detect experimentally. Gas-phase attempts to investigate the smallest fullerene by stabilization through cage encapsulation of a metal have been hindered by the complexity of mass spectra that result from vaporization experiments which include non-fullerene clusters, empty cages, and metallofullerenes. We use high-resolution FT-ICR mass spectrometry to overcome that problem and investigate formation of the smallest fullerene by use of a pulsed laser vaporization cluster source. Here, we report that the C(28) fullerene stabilized by encapsulation with an appropriate metal forms directly from carbon vapor as the smallest fullerene under our conditions. Its stabilization is investigated, and we show that M@C(28) is formed by a bottom-up growth mechanism and is a precursor to larger metallofullerenes. In fact, it appears that the encapsulating metal species may catalyze or nucleate endohedral fullerene formation.

Closed network growth of fullerenes

Tremendous advances in nanoscience have been made since the discovery of the fullerenes; however, the formation of these carbon-caged nanomaterials still remains a mystery. Here we reveal that fullerenes self-assemble through a closed network growth mechanism by incorporation of atomic carbon and C(2). The growth processes have been elucidated through experiments that probe direct growth of fullerenes upon exposure to carbon vapour, analysed by state-of-the-art Fourier transform ion cyclotron resonance mass spectrometry. Our results shed new light on the fundamental processes that govern self-assembly of carbon networks, and the processes that we reveal in this study of fullerene growth are likely be involved in the formation of other carbon nanostructures from carbon vapour, such as nanotubes and graphene. Further, the results should be of importance for illuminating astrophysical processes near carbon stars or supernovae that result in C(60) formation throughout the Universe.

Electrically compensated Fourier transform ion cyclotron resonance cell for complex mixture mass analysis.

Complex natural organic mixtures such as petroleum require ultrahigh mass spectral resolution to separate and identify thousands of elemental compositions. Here, we incorporate a custom-built, voltage-compensated ICR cell for Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS), based on a prior design by Tolmachev to produce optimal mass resolution. The compensated ICR cell installed in a custom-built 9.4 T FTICR mass spectrometer consists of seven cylindrical segments with axial proportions designed to generate a dc trapping potential that approaches an ideal three-dimensional axial quadrupolar potential. However, the empirically optimized compensation voltages do not correspond to the most quadrupolar trapping field. The compensation electrodes minimize variation in the reduced cyclotron frequency by balancing imperfections in the magnetic and electric field. The optimized voltages applied to compensation electrodes preserve ion cloud coherence for longer transient duration by approximately a factor of 2, enabling separation and identification of isobaric species (compounds with the same nominal mass but different exact mass) common in petroleum, such as C(3) vs SH(4) (separated by 3.4 mDa) and SH(3)(13)C vs (12)C(4) (separated by 1.1 mDa). The improved performance of the ICR cell provides more symmetric peak shape and better mass measurement accuracy. A positive ion atmospheric pressure photoionization (APPI) petroleum spectrum yields more than 26,000 assigned peaks, Fourier-limited resolving power of 800,000 at m/z 500 (6.6 s transient duration), and 124 part per billion root mean square (rms) error. The tunability of the compensation electrodes is critical for optimal performance.

Expansion of the Analytical Window for Oil Spill Characterization by Ultrahigh Resolution Mass Spectrometry: Beyond Gas Chromatography

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 the Macondo well oil released from the 2010 Deepwater Horizon disaster, we created an extensive molecular library of the unadulterated petroleum to compare to a tar ball collected on the beach of Louisiana. 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. Here, we characterize more than 30,000 acidic, basic, and nonpolar unique neutral elemental compositions for the Macondo well crude oil, to provide an archive for future chemical analyses of the environmental consequences of the oil spill.

Unit Mass Baseline Resolution for an Intact 148 kDa Therapeutic Monoclonal Antibody by Fourier Transform Ion Cyclotron Resonance Mass Spectrometry

Fourier transform ion cyclotron resonance mass spectrometry (FTICR MS) provides the highest mass resolving power and mass measurement accuracy for unambiguous identification of biomolecules. Previously, the highest-mass protein for which FTICR unit mass resolution had been obtained was 115 kDa at 7 T. Here, we present baseline resolution for an intact 147.7 kDa monoclonal antibody (mAb), by prior dissociation of noncovalent adducts, optimization of detected total ion number, and optimization of ICR cell parameters to minimize space charge shifts, peak coalescence, and destructive ion cloud Coulombic interactions. The resultant long ICR transient lifetime (as high as 20 s) results in magnitude-mode mass resolving power of ~420,000 at m/z 2,593 for the 57+ charge state (the highest mass for which baseline unit mass resolution has been achieved), auguring for future characterization of even larger intact proteins and protein complexes by FTICR MS. We also demonstrate up to 80% higher resolving power by phase correction to yield an absorption-mode mass spectrum.

A Photocleavable and Mass Spectrometry Identifiable Cross-Linker for Protein Interaction Studies

In this paper, we present the results of proof-of-concept experiments using a novel photocleavable and mass spectrometry identifiable cross-linker pcPIR (photocleavable protein interaction reporter). pcPIR can be dissociated under UV irradiation either off- or online before the introduction to the mass spectrometers. Photo dissociation of cross-linkers is different from either the gas phase or the chemical cleavage of cross-linkers. Different types of cross-links can be identified using the pcPIR mass relationships, where the mass of cross-linked precursor equals the sum of the masses of the released products and reporter. Since pcPIR is cleaved prior to the entrance to the mass spectrometer, the released peptides are available to be sequenced with routine collision-induced dissociation (CID) MS/MS experiments and database search algorithms. In this report, the pcPIR strategy of identifying the cross-linked peptides with on- and off-line photocleavage coupled with novel targeted data dependent LC-MS/MS is demonstrated with the use of standard peptides, bovine serum albumin (BSA), and human hemoglobin tetramer protein complex.

Incorporation of a flared inlet capillary tube on a Fourier transform ion cyclotron resonance mass spectrometer

Flared inlet capillary tubes have been coupled with a Fourier transform ion cyclotron resonance (FT-ICR) mass spectrometer to help the ion transmission from the atmospheric pressure to the first vacuum region. We investigated different types of atmospheric pressure ionization methods using flared inlet tubes. For most of the ionization methods, such as ESI and DESI, increased ion current transmitted from the atmospheric pressure ion source to the first stage vacuum system was observed with the use of our enhanced ion inlet designs. The corresponding ion intensity detected on a FT-ICR mass spectrometer was also observed to increase two- to fivefold using ESI or DESI with the flared tube inlet. Moreover, increased spray tip positional tolerance was observed with implementation of the flared inlet tube. We also include our preliminary results obtained by coupling AP-MALDI with flared inlet tube in this paper. For AP-MALDI, the measured ion current transferred through the flared inlet tube was about 2 to 3 times larger than the ion current through the control non-flared inlet tube.

Bottom-up formation of endohedral mono-metallofullerenes is directed by charge transfer

An understanding of chemical formation mechanisms is essential to achieve effective yields and targeted products. One of the most challenging endeavors is synthesis of molecular nanocarbon. Endohedral metallofullerenes are of particular interest because of their unique properties that offer promise in a variety of applications. Nevertheless, the mechanism of formation from metal-doped graphite has largely eluded experimental study, because harsh synthetic methods are required to obtain them. Here we report bottom-up formation of mono-metallofullerenes under core synthesis conditions. Charge transfer is a principal factor that guides formation, discovered by study of metallofullerene formation with virtually all available elements of the periodic table. These results could enable production strategies that overcome long-standing problems that hinder current and future applications of metallofullerenes.

Metallofullerene and fullerene formation from condensing carbon gas under conditions of stellar outflows and implication to stardust

Significance We experimentally study the processes that result in fullerene formation in oxygen- and hydrogen-rich carbon gas. Metallofullerenes are found to form as readily as empty cages and thus, like fullerenes, should be important constituents of (circum)stellar/interstellar space. Element trapping by metallofullerene formation is shown to be selective and rapid, which can explain long-standing astrophysical puzzles such as the anomalous element enrichment of stardust. Infrared spectroscopic signatures are simulated to provide an observational test for metallofullerenes in space. Further, energetic reactions between larger polycyclic aromatic hydrocarbons (PAHs) and fullerenes are established form stable classes of complex molecules that hold high astrochemical importance. Bottom-up fullerene growth is also demonstrated to result from PAH processing, another potentially important extraterrestrial formation mechanism. Carbonaceous presolar grains of supernovae origin have long been isolated and are determined to be the carrier of anomalous 22Ne in ancient meteorites. That exotic 22Ne is, in fact, the decay isotope of relatively short-lived 22Na formed by explosive nucleosynthesis, and therefore, a selective and rapid Na physical trapping mechanism must take place during carbon condensation in supernova ejecta. Elucidation of the processes that trap Na and produce large carbon molecules should yield insight into carbon stardust enrichment and formation. Herein, we demonstrate that Na effectively nucleates formation of Na@C60 and other metallofullerenes during carbon condensation under highly energetic conditions in oxygen- and hydrogen-rich environments. Thus, fundamental carbon chemistry that leads to trapping of Na is revealed, and should be directly applicable to gas-phase chemistry involving stellar environments, such as supernova ejecta. The results indicate that, in addition to empty fullerenes, metallofullerenes should be constituents of stellar/circumstellar and interstellar space. In addition, gas-phase reactions of fullerenes with polycyclic aromatic hydrocarbons are investigated to probe “build-up” and formation of carbon stardust, and provide insight into fullerene astrochemistry.