A new ion mobility-linear ion trap instrument for complex mixture analysis.

A new instrument that couples a low-pressure drift tube with a linear ion trap mass spectrometer is demonstrated for complex mixture analysis. The combination of the low-pressure separation with the ion trapping capabilities provides several benefits for complex mixture analysis. These include high sensitivity, unique ion fragmentation capabilities, and high reproducibility. Even though the gas-phase separation and the mass measurement steps are each conducted in an ion filtering mode, detection limits for mobility-selected peptide ions are in the tens of attomole range. In addition to ion separation, the low-pressure drift tube can be used as an ion fragmentation cell yielding mobility-resolved fragment ions that can be subsequently analyzed by multistage tandem mass spectrometry (MS(n)) methods in the ion trap. Because of the ion trap configuration, these methods can be comprised of any number (limited by ion signal) of collision-induced dissociation (CID) and electron transfer dissociation (ETD) processes. The high reproducibility of the gas-phase separation allows for comparison of two-dimensional ion mobility spectrometry (IMS)-MS data sets in a pixel-by-pixel fashion without the need for data set alignment. These advantages are presented in model analyses representing mixtures encountered in proteomics and metabolomics experiments.

[1]  Michael A. Buschbach,et al.  High-sensitivity ion mobility spectrometry/mass spectrometry using electrodynamic ion funnel interfaces. , 2005, Analytical chemistry.

[2]  David E. Clemmer,et al.  NAKED PROTEIN CONFORMATIONS : CYTOCHROME C IN THE GAS PHASE , 1995 .

[3]  J P Reilly,et al.  Three-dimensional ion mobility/TOFMS analysis of electrosprayed biomolecules. , 1998, Analytical chemistry.

[4]  S. Valentine,et al.  Development of field modulation in a split-field drift tube for high-throughput multidimensional separations. , 2005, Journal of proteome research.

[5]  Melvin A. Park,et al.  Ion dynamics in a trapped ion mobility spectrometer. , 2014, The Analyst.

[6]  S. Valentine,et al.  Overtone mobility spectrometry: Part 1. Experimental observations , 2009, Journal of the American Society for Mass Spectrometry.

[7]  Y. Mechref,et al.  Profiling of human serum glycans associated with liver cancer and cirrhosis by IMS-MS. , 2008, Journal of proteome research.

[8]  Karl Fraser,et al.  Computational Analyses of Spectral Trees from Electrospray Multi-Stage Mass Spectrometry to Aid Metabolite Identification , 2013, Metabolites.

[9]  D. Clemmer,et al.  Mobility labeling for parallel CID of ion mixtures. , 2000, Analytical chemistry.

[10]  Marcos Dantus,et al.  Tandem mass spectrometry strategies for phosphoproteome analysis. , 2011, Mass spectrometry reviews.

[11]  G. Reid,et al.  Mechanistic insights into the multistage gas-phase fragmentation behavior of phosphoserine- and phosphothreonine-containing peptides. , 2008, Journal of proteome research.

[12]  R. Bischoff,et al.  LC-MS analysis of phospholipids and lysophospholipids in human bronchoalveolar lavage fluid. , 2005, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[13]  Brian C. Bohrer,et al.  Biomolecule analysis by ion mobility spectrometry. , 2008, Annual review of analytical chemistry.

[14]  B. Ruotolo,et al.  Surface-induced dissociation on a MALDI-ion mobility-orthogonal time-of-flight mass spectrometer: sequencing peptides from an "in-solution" protein digest. , 2001, Analytical chemistry.

[15]  Erin Shammel Baker,et al.  Ion mobility spectrometry—mass spectrometry performance using electrodynamic ion funnels and elevated drift gas pressures , 2007, Journal of the American Society for Mass Spectrometry.

[16]  Hailong Zhang,et al.  High Performance IT-MS Sequencing of Glycans (Spatial Resolution of Ovalbumin Isomers). , 2011, International journal of mass spectrometry.

[17]  H. Hill,et al.  Atmospheric pressure matrix-assisted laser desorption/ionization with analysis by ion mobility time-of-flight mass spectrometry. , 2004, Rapid communications in mass spectrometry : RCM.

[18]  H. Hill,et al.  Metabolic Profiling of Human Blood by High Resolution Ion Mobility Mass Spectrometry (IM-MS). , 2010, International journal of mass spectrometry.

[19]  Jody C. May,et al.  Lipid analysis and lipidomics by structurally selective ion mobility-mass spectrometry. , 2011, Biochimica et biophysica acta.

[20]  S. Valentine,et al.  IMS-IMS and IMS-IMS-IMS/MS for separating peptide and protein fragment ions. , 2006, Analytical chemistry.

[21]  B. Ruotolo,et al.  Peak capacity of ion mobility mass spectrometry: separation of peptides in helium buffer gas. , 2002, Journal of chromatography. B, Analytical technologies in the biomedical and life sciences.

[22]  D. Russell,et al.  Increased ion transmission in IMS: A high resolution, periodic-focusing DC ion guide ion mobility spectrometer , 2011 .

[23]  T. Wyttenbach,et al.  Effect of the long-range potential on ion mobility measurements , 1997 .

[24]  Richard D. Smith,et al.  An IMS-IMS analogue of MS-MS. , 2006, Analytical chemistry.

[25]  L. M. Thomson,et al.  Distinguishing between phosphorylated and nonphosphorylated peptides with ion mobility-mass spectrometry. , 2002, Journal of proteome research.

[26]  E. A. Mason,et al.  Theory of plasma chromatography/gaseous electrophoresis. Review , 1975 .

[27]  H. Hill,et al.  Separation of sodiated isobaric disaccharides and trisaccharides using electrospray ionization-atmospheric pressure ion mobility-time of flight mass spectrometry , 2005, Journal of the American Society for Mass Spectrometry.

[28]  J. Bruce,et al.  Design and performance of an atmospheric pressure ion mobility Fourier transform ion cyclotron resonance mass spectrometer. , 2007, Rapid communications in mass spectrometry : RCM.

[29]  Scott A. Shaffer,et al.  A novel ion funnel for focusing ions at elevated pressure using electrospray ionization mass spectrometry , 1997 .

[30]  David E. Clemmer,et al.  Ion Mobility Measurements and their Applications to Clusters and Biomolecules , 1997 .

[31]  Stephen Naylor,et al.  Mapping the human plasma proteome by SCX-LC-IMS-MS , 2007, Journal of the American Society for Mass Spectrometry.

[32]  Gary A. Eiceman,et al.  Ion Mobility Spectrometry in Analytical Chemistry , 1990 .

[33]  D. Clemmer,et al.  Ion trap/ion mobility/quadrupole/time-of-flight mass spectrometry for peptide mixture analysis. , 2001, Analytical chemistry.

[34]  J. Shabanowitz,et al.  A neutral loss activation method for improved phosphopeptide sequence analysis by quadrupole ion trap mass spectrometry. , 2004, Analytical chemistry.

[35]  Vincent Castranova,et al.  Nanoparticle inhalation augments particle-dependent systemic microvascular dysfunction , 2008, Particle and Fibre Toxicology.

[36]  Florian Rasche,et al.  Computing fragmentation trees from metabolite multiple mass spectrometry data. , 2011, Journal of computational biology : a journal of computational molecular cell biology.

[37]  T. Wyttenbach,et al.  Conformation of Macromolecules in the Gas Phase: Use of Matrix-Assisted Laser Desorption Methods in Ion Chromatography , 1995, Science.

[38]  D. Gang,et al.  Carbohydrate structure characterization by tandem ion mobility mass spectrometry (IMMS)2. , 2013, Analytical chemistry.

[39]  D. Russell,et al.  Development of a Fourier-transform ion cyclotron resonance mass spectrometer-ion mobility spectrometer , 2000 .

[40]  A. E. Counterman,et al.  Formation of peptide aggregates during ESI: Size, charge, composition, and contributions to noise , 2001 .

[41]  David H Russell,et al.  Ion mobility-mass spectrometry (IM-MS) for top-down proteomics: increased dynamic range affords increased sequence coverage. , 2012, Analytical chemistry.

[42]  John A. McLean,et al.  Ion mobility–mass spectrometry: a new paradigm for proteomics , 2005 .

[43]  D. Frazer,et al.  Nanoparticle inhalation alters systemic arteriolar vasoreactivity through sympathetic and cyclooxygenase-mediated pathways , 2012, Nanotoxicology.

[44]  H. Hill,et al.  Mass analysis of mobility-selected ion populations using dual gate, ion mobility, quadrupole ion trap mass spectrometry. , 2005, Analytical chemistry.

[45]  J. McLean.  The mass-mobility correlation redux: The conformational landscape of anhydrous biomolecules , 2009, Journal of the American Society for Mass Spectrometry.

[46]  David S. Wishart,et al.  HMDB 3.0—The Human Metabolome Database in 2013 , 2012, Nucleic Acids Res..

[47]  M. Lee,et al.  Developments in ion mobility spectrometry–mass spectrometry , 2002, Analytical and bioanalytical chemistry.

[48]  J. Shabanowitz,et al.  Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[49]  Herbert H. Hill,et al.  Electrospray ionization ion mobility spectrometry , 1994 .

[50]  D. Clemmer,et al.  High-resolution ion cyclotron mobility spectrometry. , 2009, Analytical chemistry.

[51]  S. Valentine,et al.  Development of a high-throughput IMS-IMS-MS approach for analyzing mixtures of biomolecules. , 2008, Journal of proteomics.

[52]  A. Shvartsburg,et al.  An exact hard-spheres scattering model for the mobilities of polyatomic ions , 1996 .

[53]  S. Valentine,et al.  A split-field drift tube for separation and efficient fragmentation of biomolecular ions. , 2003, Analytical chemistry.

[54]  H. Hill,et al.  Separation of isomeric peptides using electrospray ionization/high-resolution ion mobility spectrometry. , 2000, Analytical chemistry.

[55]  Richard D. Smith,et al.  Toward plasma proteome profiling with ion mobility-mass spectrometry. , 2006, Journal of proteome research.

[56]  H. Hill,et al.  Metabolic profiling by ion mobility mass spectrometry (IMMS) , 2008, Metabolomics.

[57]  Steven P Gygi,et al.  Large-scale characterization of HeLa cell nuclear phosphoproteins. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[58]  Martin F. Jarrold,et al.  Structural Information from Ion Mobility Measurements: Effects of the Long-Range Potential , 1996 .

[59]  F. J. Knorr,et al.  Fourier transform ion mobility spectrometry. , 1985, Analytical chemistry.

[60]  J P Reilly,et al.  Gas-phase separations of protease digests , 1998, Journal of the American Society for Mass Spectrometry.

[61]  J. A. Schultz,et al.  Analysis of phosphorylated peptides by ion mobility-mass spectrometry. , 2004, Analytical chemistry.

[62]  Justin M. Prien,et al.  The high mannose glycans from bovine ribonuclease B isomer characterization by ion trap MS , 2009, Journal of the American Society for Mass Spectrometry.

[63]  J. Reilly,et al.  Extracted Fragment Ion Mobility Distributions: A New Method for Complex Mixture Analysis. , 2012, International journal of mass spectrometry.

[64]  Brian H. Clowers,et al.  Hadamard Transform Ion Mobility Spectrometry , 2006 .

[65]  J. Reilly,et al.  An Ion Mobility/Ion Trap/Photodissociation Instrument for Characterization of Ion Structure , 2011, Journal of the American Society for Mass Spectrometry.

[66]  B. Ruotolo,et al.  Coupling high-pressure MALDI with ion mobility/orthogonal time-of-flight mass spectrometry. , 2000, Analytical chemistry.

[67]  T. Badger,et al.  LC-MS/MS analysis of lysophospholipids associated with soy protein isolate. , 2003, Journal of agricultural and food chemistry.