A tandem quadrupole/time-of-flight mass spectrometer with a matrix-assisted laser desorption/ionization source: design and performance

A matrix-assisted laser desorption/ionization (MALDI) source has been coupled to a tandem quadrupole/time-of-flight (QqTOF) mass spectrometer by means of a collisional damping interface. Mass resolving power of about 10,000 (FWHM) and accuracy in the range of 10 ppm are observed in both single-MS mode and MS/MS mode. Sub-femtomole sensitivity is obtained in single-MS mode, and a few femtomoles in MS/MS mode. Both peptide mass mapping and collision-induced dissociation (CID) analysis of tryptic peptides can be performed from the same MALDI target. Rapid spectral acquisition (a few seconds per spectrum) can be achieved in both modes, so high throughput protein identification is possible. Some information about fragmentation patterns was obtained from a study of the CID spectra of singly charged peptides from a tryptic digest of E. coli citrate synthase. Reasonably successful automatic sequence prediction (>90%) is possible from the CID spectra of singly charged peptides using the SCIEX Predict Sequence routine. Ion production at pressures near 1 Torr (rather than in vacuum) is found to give reduced metastable fragmentation, particularly for higher mass molecular ions. Copyright 2000 John Wiley & Sons, Ltd.

[1]  A. Dell,et al.  High sensitivity collisionally-activated decomposition tandem mass spectrometry on a novel quadrupole/orthogonal-acceleration time-of-flight mass spectrometer. , 1996, Rapid communications in mass spectrometry : RCM.

[2]  Stephen A. Martin,et al.  Delayed extraction matrix‐assisted laser desorption time‐of‐flight mass spectrometry , 1995 .

[3]  R. S. Brown,et al.  Mass resolution improvement by incorporation of pulsed ion extraction in a matrix-assisted laser desorption/ionization linear time-of-flight mass spectrometer. , 1995, Analytical chemistry.

[4]  Peter R. Baker,et al.  Role of accurate mass measurement (+/- 10 ppm) in protein identification strategies employing MS or MS/MS and database searching. , 1999, Analytical chemistry.

[5]  P. Chaurand,et al.  Peptide and protein identification by matrix-assisted laser desorption ionization (MALDI) and MALDI-post-source decay time-of-flight mass spectrometry , 1999, Journal of the American Society for Mass Spectrometry.

[6]  A. Tolmachev,et al.  New Method for Ion Mobility Determination by Stability Threshold Measurement in Gas Filled Radio Frequency Quadrupoles , 1998 .

[7]  A New Delayed Extraction MALDI-TOF MS-MS for Characterization of Protein Digests , 2000 .

[8]  M. Mann,et al.  Electrospray ionization for mass spectrometry of large biomolecules. , 1989, Science.

[9]  I. Chernushevich,et al.  Collisional damping interface for an electrospray ionization time-of-flight mass spectrometer , 1998 .

[10]  A. Shevchenko,et al.  MALDI quadrupole time-of-flight mass spectrometry: a powerful tool for proteomic research. , 2000, Analytical chemistry.

[11]  P. Roepstorff,et al.  Proposal for a common nomenclature for sequence ions in mass spectra of peptides. , 1984, Biomedical mass spectrometry.

[12]  D. Hochstrasser,et al.  Towards an automated approach for protein identification in proteome projects , 1998, Electrophoresis.

[13]  W. Ens,et al.  ORTHOGONAL INJECTION OF MATRIX-ASSISTED LASER DESORPTION/IONIZATION IONS INTO A TIME-OF-FLIGHT SPECTROMETER THROUGH A COLLISIONAL DAMPING INTERFACE , 1998 .

[14]  I. Chernushevich,et al.  Peer Reviewed: Orthogonal-Injection TOFMS for Analyzing Biomolecules. , 1999, Analytical chemistry.

[15]  A. Podtelejnikov,et al.  Linking genome and proteome by mass spectrometry: large-scale identification of yeast proteins from two dimensional gels. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Jennifer M. Campbell,et al.  The characteristics of peptide collision-induced dissociation using a high-performance MALDI-TOF/TOF tandem mass spectrometer. , 2000, Analytical chemistry.

[17]  B. Chait,et al.  Protein indentification using mass spectrometric information , 1998, Electrophoresis.

[18]  A. Podtelejnikov,et al.  Delayed extraction improves specificity in database searches by matrix-assisted laser desorption/ionization peptide maps. , 1996, Rapid communications in mass spectrometry : RCM.

[19]  W. Ens,et al.  Quantitative evaluation of protein-protein and ligand-protein equilibria of a large allosteric enzyme by electrospray ionization time-of-flight mass spectrometry. , 1998, Rapid communications in mass spectrometry : RCM.

[20]  B. Spengler Post-source decay analysis in matrix-assisted laser desorption/ionization mass spectrometry of biomolecules† , 1997 .

[21]  M. Karas,et al.  Laser desorption ionization of proteins with molecular masses exceeding 10,000 daltons. , 1988, Analytical chemistry.

[22]  R Kaufmann,et al.  Peptide sequencing by matrix-assisted laser-desorption mass spectrometry. , 1992, Rapid communications in mass spectrometry : RCM.

[23]  Simon J. Gaskell,et al.  Metastable decomposition of peptide [M + H]+ ions via rearrangement involving loss of the C-terminal amino acid residue , 1990 .

[24]  A. Shevchenko,et al.  Rapid 'de novo' peptide sequencing by a combination of nanoelectrospray, isotopic labeling and a quadrupole/time-of-flight mass spectrometer. , 1997, Rapid communications in mass spectrometry : RCM.

[25]  M. Mann,et al.  Analysis of the Saccharomyces Spindle Pole by Matrix-assisted Laser Desorption/Ionization (MALDI) Mass Spectrometry , 1998, The Journal of cell biology.

[26]  D. J. Douglas,et al.  Collision cross sections for protein ions , 1993, Journal of the American Society for Mass Spectrometry.

[27]  James P. Reilly,et al.  Improving the resolution of matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry by exploiting the correlation between ion position and velocity , 1994 .

[28]  W. Ens,et al.  Reflecting time-of-flight mass spectrometer with an electrospray ion source and orthogonal extraction. , 1994, Analytical chemistry.

[29]  Gérard Hopfgartner,et al.  Exact mass measurement of product ions for the structural elucidation of drug metabolites with a tandem quadrupole orthogonal-acceleration time-of-flight mass spectrometer , 1999 .