Mass Spectrometry Publications

2013

Yang L, Z Zhu, XY Yu, S Thevuthasan, and JP Cowin. 2013. "Performance of a Microfluidic Device for In Situ ToF-SIMS Analysis of Selected Organic Molecules at Aqueous Surfaces." Analytical Methods 5(10):2515-2522. doi:10.1039/c3ay26513g Abstract Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a unique surface analysis technique because it can provide molecular recognition for organic and biological molecules. However, analyzing aqueous solution surfaces by ToF-SIMS is difficult, because ToF-SIMS is a high-vacuum technique, while the vapor pressure of water is about 2.3 kPa at room temperature (20 C). We designed and fabricated a self-contained microfluidic device, enabling in situ analysis of aqueous surfaces by scanning electron microscope (SEM) and ToF-SIMS, which has been briefly reported.1,2 In this study, we report more performance data, focusing on the performance of this device for in situ analysis of organic molecules at aqueous surfaces using ToF-SIMS. Three representative organic compounds (formic acid, glycerol, and glutamic acid) were tested, and their molecular signals were successfully observed. The device can be self-running in vacuum for 8 hours, and SIMS measurements are feasible at any time in this time range. The stability of this device under primary ion beam bombardment is also impressive. High fluence (6 × 1012 ions cm-2 s-1) measurements can be operated continuously for up to 30 minutes without any significant damage to the aperture. However, extra-high fluence measurements (>1 × 1014 ions cm-2 s-1) may lead to liquid bumping in the aperture, and the aqueous solutions may spread out quickly. Signal reproducibility is reasonably good, and relative standard deviation (RSD) for molecular ion signals can be controlled to be smaller than ±15% for consecutive measurements. Measurements at long time intervals (e.g., 60 min) show RSDs of ±40-50%. In addition, the detection limits of formic acid, glycerol, and glutamic acid are estimated to be 0.04%, 0.008%, and 0.002% (weight ratio), respectively.
Kaur M, A Johnson, G Tian, W Jiang, L Rao, A Paszczynski, and Y Qiang. 2013. "Separation Nanotechnology of Diethylenetriaminepentaacetic Acid Bonded Magnetic Nanoparticles for Spent Nuclear Fuel." Nano Energy 2(1):124-132. doi:10.1016/j.nanoen.2012.08.005 Abstract A nanomagnetic separation method based on Diethylenetriaminepentaacetic acid (DTPA) conjugated with magnetic nanoparticles (MNPs) is studied for application in spent nuclear fuel separation. The high affinity of DTPA towards actinides aids in separation from the highly acidic medium of nuclear waste. The solubility and magnetization of particles at low pH is protected by encapsulating them in silica layer. Surface functionalization of silica coated particles with polyamines enhances the loading capacity of the chelators on MNPs. The particles were characterized before and after surface modification using transmission electron microscopy (TEM), helium ion microscopy (HIM), Fourier transform-infrared (FT-IR) spectrometry, and X-ray diffractometry. The coated and uncoated samples were studied using vibrating sample magnetometer (VSM) to understand the change in magnetic properties due to the influence of the surface functionalization. The hydrodynamic size and surface charge of the particles are investigated using Dynamic Light Scattering (DLS). The uptake behavior of Am(III), Pu(IV), U(VI), and Np(V) from 0.1M NaNO3 solution was investigated. The sorption result shows the strong affinity of DTPA towards Am(III) and Pu(IV) by extracting 97% and 80% of actinides, respectively. The high removal efficiency and fast uptake of actinides make the chelator conjugated MNPs an effective method for spent nuclear fuel separation.
Piehowski PD, VA Petyuk, JD Sandoval, KE Burnum, GR Kiebel, ME Monroe, GA Anderson, DG Camp, II, and RD Smith. 2013. "STEPS: A Grid Search Methodology for Optimized Peptide Identification Filtering of MS/MS Database Search Results." Proteomics 13(5):766-770. doi:10.1002/pmic.201200096 Abstract For bottom-up proteomics there are a wide variety of database searching algorithms in use for matching peptide sequences to tandem MS spectra. Likewise, there are numerous strategies being employed to produce a confident list of peptide identifications from the different search algorithm outputs. Here we introduce a grid search approach for determining optimal database filtering criteria in shotgun proteomics data analyses that is easily adaptable to any search. Systematic Trial and Error Parameter Selection - referred to as STEPS - utilizes user-defined parameter ranges to test a wide array of parameter combinations to arrive at an optimal "parameter set" for data filtering, thus maximizing confident identifications. The benefits of this approach in terms of numbers of true positive identifications are demonstrated using datasets derived from immunoaffinity-depleted blood serum and a bacterial cell lysate, two common proteomics sample types.
McDermott JE, J Wang, HD Mitchell, BJM Webb-Robertson, RP Hafen, JA Ramey, II, and KD Rodland. 2013. "Challenges in Biomarker Discovery: Combining Expert Insights with Statistical Analysis of Complex Omics Data." Expert Opinion on Medical Diagnostics 7(1):37-51. doi:10.1517/17530059.2012.718329 Abstract The advent of high throughput technologies capable of comprehensive analysis of genes, transcripts, proteins and other significant biological molecules has provided an unprecedented opportunity for the identification of molecular markers of disease processes. However, it has simultaneously complicated the problem of extracting meaningful signatures of biological processes from these complex datasets. The process of biomarker discovery and characterization provides opportunities both for purely statistical and expert knowledge-based approaches and would benefit from improved integration of the two. Areas covered In this review we will present examples of current practices for biomarker discovery from complex omic datasets and the challenges that have been encountered. We will then present a high-level review of data-driven (statistical) and knowledge-based methods applied to biomarker discovery, highlighting some current efforts to combine the two distinct approaches. Expert opinion Effective, reproducible and objective tools for combining data-driven and knowledge-based approaches to biomarker discovery and characterization are key to future success in the biomarker field. We will describe our recommendations of possible approaches to this problem including metrics for the evaluation of biomarkers.
Song T, CY Ma, IK Chu, CK Siu, and J Laskin. 2013. "Mechanistic Examination of Cβ–Cγ Bond Cleavages of Tryptophan Residues during Dissociations of Molecular Peptide Radical Cations." Journal of Physical Chemistry A 117(6):1059-1068. doi:10.1021/jp303562e Abstract In this study, we used collision-induced dissociation (CID) to examine the gas-phase fragmentations of [GnW]•+ (n = 2-4) and [GXW]•+ (X = C, S, L, F, Y, Q) species. The Cβ–Cγ bond cleavage of a C-terminal decarboxylated tryptophan residue ([M - CO2]•+) can generate [M - CO2 - 116]+, [M - CO2 - 117]•+, and [1H-indole]•+ (m/z 117) species as possible product ions. Competition between the formation of [M - CO2 - 116]+ and [1H-indole]•+ systems implies the existence of a proton-bound dimer formed between the indole ring and peptide backbone. Formation of such a proton-bound dimer is facile via a protonation of the tryptophan γ-carbon atom as suggested by density functional theory (DFT) calculations. DFT calculations also suggested the initially formed ion 2--the decarboxylated species that is active against Cβ–Cγ bond cleavage -can efficiently isomerize to form a more-stable -radical isomer (ion 9) as supported by Rice-Ramsperger-Kassel-Marcus (RRKM) modeling. The Cβ–Cγ bond cleavage of a tryptophan residue also can occur directly from peptide radical cations containing a basic residue. CID of [WGnR]•+ (n = 1-3) radical cations consistently resulted in predominant formation of [M-116]+ product ions. It appears that the basic arginine residue tightly sequesters the proton and allows the charge-remote Cβ–Cγ bond cleavage to prevail over the charge-directed one. DFT calculations predicted the barrier for the former is 6.2 kcal mol -1 lower than that of the latter. Furthermore, the pathway involving a salt-bridge intermediate also was accessible during such a bond cleavage event.
Abramson EH, D Imre, J Beranek, J Wilson, and A Zelenyuk. 2013. "Experimental Determination of Chemical Diffusion within Secondary Organic Aerosol Particles." Physical Chemistry Chemical Physics. PCCP 15(8):2983-2991. doi:10.1039/C2CP44013J Abstract Formation, properties, transformations, and temporal evolution of secondary organic aerosols (SOA) particles strongly depend on particle phase. Recent experimental evidence from a number of groups indicates that SOA is in a semi-solid phase, the viscosity of which remained unknown. We find that when SOA is made in the presence of vapors of volatile hydrophobic molecules the SOA particles absorb and trap them. Here, we illustrate that it is possible to measure the evaporation rate of these molecules that is determined by their diffusion in SOA, which is then used to calculate a reasonably accurate value for the SOA viscosity. We use pyrene as a tracer molecule and a-pinene SOA as an illustrative case. It takes ~24 hours for half the pyrene to evaporate to yield a viscosity of 10^8 Pa s for a-pinene. This viscosity is consistent with measurements of particle bounce and evaporation rates. We show that viscosity of 10^8 Pa s implies coalescence times of minutes, consistent with the findings that SOA particles are spherical. Similar measurements on aged SOA particles doped with pyrene yield a viscosity of 10^9 Pa s, indicating that hardening occurs with time, which is consistent with observed decrease in water uptake and evaporation rate with aging.
Sushko P, L Qiao, ME Bowden, T Varga, GJ Exarhos, FK Urban, III, D Barton, and SA Chambers. 2013. "Multiband Optical Absorption Controlled by Lattice Strain in Thin-Film LaCrO3." Physical Review Letters 110(7):077401. doi:10.1103/PhysRevLett.110.077401 Abstract Experimental measurements and ab initio modeling of the optical transitions in strained G-type antiferromagnetic LaCrO3 resolve two decades of debate regarding the magnitude of the optical band gap and the character of the corresponding transitions in this material. Using time-dependent density functional theory and accounting for thermal disorder effects, we demonstrate that the fourmost prominent low-energy absorption features are due to intra-Cr t2g {eg (2.4, 3.6 eV), inter-Crt2g {t2g (4.4 eV), and inter-ion O 2p { Cr 3d (from ˘5 eV) transitions and show that the excitation energies of the latter type can be strongly affected by the lattice strain.
Merkley ED, ES Baker, KL Crowell, DJ Orton, T Taverner, C Ansong, YM Ibrahim, MC Burnet, JR Cort, GA Anderson, RD Smith, and JN Adkins. 2013. "Mixed-Isotope Labeling with LC-IMS-MS for Characterization of Protein-Protein Interactions by Chemical Cross-Linking ." Journal of the American Society for Mass Spectrometry 24(3):444-449. doi:10.1007/s13361-012-0565-x Abstract Chemical cross-linking of proteins followed by proteolysis and mass spectrometric analysis of the resulting cross-linked peptides can provide insights into protein structure and protein-protein interactions. However, cross-linked peptides are by necessity of low stoichometry and have different physicochemical properties than linear peptides, routine unambiguous identification of the cross-linked peptides has remained difficult. To address this challenge, we demonstrated the use of liquid chromatography and ion mobility separations coupled with mass spectrometry in combination with a heavy-isotope labeling method. The combination of mixed-isotope cross-linking and ion mobility provided unique and easily interpretable spectral multiplet features for the intermolecular cross-linked peptides. Application of the method to two different homodimeric proteins ‒ SrfN, a virulence factor from Salmonella Typhimurium and SO_2176, a protein of unknown function from Shewanella oneidensis‒ revealed several cross-linked peptides from both proteins that were identified with a low false discovery rate (estimated using a decoy approach). A greater number of cross-linked peptides were identified using ion mobility drift time information in the analysis than when the data were summed across the drift time dimension before analysis. The identified cross-linked peptides migrated more quickly in the ion mobility drift tube than the unmodified peptides.
Shvartsburg AA, TA Seim, WF Danielson, III, RV Norheim, RJ Moore, GA Anderson, and RD Smith. 2013. "High-Definition Differential Ion Mobility Spectrometry with Resolving Power up to 500." Journal of the American Society for Mass Spectrometry 24(1):109-114. doi:10.1007/s13361-012-0517-5 Abstract As the resolution of analytical methods improve, further progress tends to be increasingly limited by instrumental parameter instabilities that could be ignored before. This is now the case with differential ion mobility spectrometry (FAIMS), where fluctuations of the voltages and gas pressure have become critical. A new high-definition generator for FAIMS compensation voltage reported here provides a stable and accurate output than can be scanned with negligible steps. This reduces the spectral drift and peak width, thus improving the resolving power (R) and resolution. The gain for multiply-charged peptides that have narrowest peaks is up to ~40%, and R ~ 400 - 500 is achievable using He/N2 or H2/N2 gas mixtures.
Matzke MM, JN Brown, MA Gritsenko, TO Metz, JG Pounds, KD Rodland, AK Shukla, RD Smith, KM Waters, JE McDermott, and BJM Webb-Robertson. 2013. "A Comparative Analysis of Computational Approaches to Relative Protein Quantification Using Peptide Peak Intensities in Label-free LC-MS Proteomics Experiments." Proteomics 13(3-4):493-503. doi:10.1002/pmic.201200269 Abstract Liquid chromatography coupled with mass spectrometry (LC-MS) is widely used to identify and quantify peptides in complex biological samples. In particular, label-free shotgun proteomics is highly effective for the identification of peptides and subsequently obtaining a global protein profile of a sample. As a result, this approach is widely used for discovery studies. Typically, the objective of these discovery studies is to identify proteins that are affected by some condition of interest (e.g. disease, exposure). However, for complex biological samples, label-free LC-MS proteomics experiments measure peptides and do not directly yield protein quantities. Thus, protein quantification must be inferred from one or more measured peptides. In recent years, many computational approaches to relative protein quantification of label-free LC-MS data have been published. In this review, we examine the most commonly employed quantification approaches to relative protein abundance from peak intensity values, evaluate their individual merits, and discuss challenges in the use of the various computational approaches.

Next Displaying results 1 - 10 of 846