Performance Characteristics of a New Hybrid Quadrupole Time-of-Flight Tandem Mass Spectrometer (TripleTOF 5600)

Andrews, Genna; Simons, Brigitte; Young, J. Bryce; Hawkridge, Adam M.; Muddiman, David C.

doi:10.1021/ac200812d

Cited by 264 publications

(207 citation statements)

References 19 publications

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“…The SWATH-MS and the SWATH-like hyperreaction monitoring (HRM) techniques provide S/MRM-like performance in terms of reproducibility and quantitative accuracy and were implemented in a fast-scanning, high-resolution quadrupole time-of-flight and a quadrupole orbitrap mass spectrometer, respectively (Fig. 2, lower panel) (68,117). In SWATH or HRM mode, the instrument cycles repeatedly through fixed or variable adjacent precursor isolation windows (typically 32 windows of 25 m/z covering 400 -1200 m/z) over the course of chromatographic elution, thus fragmenting all coeluting precursor ions in each window recording multiplexed fragment ion spectra of all peptides in a userdefined retention time versus mass to charge window.…”

Section: Identification and Quantification Of Mhc-associated Peptidesmentioning

confidence: 99%

Analysis of Major Histocompatibility Complex (MHC) Immunopeptidomes Using Mass Spectrometry*

Caron

Kowalewski

Koh

et al. 2015

Molecular & Cellular Proteomics

197

118

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The myriad of peptides presented at the cell surface by class I and class II major histocompatibility complex (MHC) molecules are referred to as the immunopeptidome and are of great importance for basic and translational science. For basic science, the immunopeptidome is a critical component for understanding the immune system; for translational science, exact knowledge of the immunopeptidome can directly fuel and guide the development of next-generation vaccines and immunotherapies against autoimmunity, infectious diseases, and cancers. In this mini-review, we summarize established isolation techniques as well as emerging mass spectrometry-based platforms (i.e. SWATH-MS) to identify and quantify MHC-associated peptides. We also highlight selected biological applications and discuss important current technical limitations that need to be solved to accelerate the development of this field. Molecular & Cellular

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Section: Identification and Quantification Of Mhc-associated Peptidesmentioning

confidence: 99%

Analysis of Major Histocompatibility Complex (MHC) Immunopeptidomes Using Mass Spectrometry*

Caron

Kowalewski

Koh

et al. 2015

Molecular & Cellular Proteomics

197

118

View full text Add to dashboard Cite

show abstract

“…Central to this evolution is the increased performance, and availability, of high resolution and accurate mass (HR/AM) instrumentation (44). Namely, developments in time-of-flight (TOF) technology (45), and the advent of the Orbitrap mass analyzer in 2005 (46 -49), have made fast and sensitive MS/MS scanning (50 -53) with Ͻ10 parts-per-million (ppm) mass measurement error routine (54). For discovery experiments, the ability to acquire MS/MS scans with high resolution and low-ppm mass errors offers several advantages, including higher confidence sequence identification (44,55), post-translational modification site localization (56), and improved quantitative accuracy.…”

mentioning

confidence: 99%

“…Driving our inquiry was the newly introduced Q Exactive bench-top quadrupole-Orbitrap MS (QqOrbi) (47), which, along with quadrupole-TOF (QqTOF) instrumentation (45), possesses a geometry essentially equivalent to a QqQ, except that the third quadrupole of the QqQ is replaced by an Orbitrap (or TOF) analyzer (Fig. 1A, 1B).…”

mentioning

confidence: 99%

Parallel Reaction Monitoring for High Resolution and High Mass Accuracy Quantitative, Targeted Proteomics

Peterson

Russell

Bailey

et al. 2012

Molecular & Cellular Proteomics

1,107

953

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Selected reaction monitoring on a triple quadrupole mass spectrometer is currently experiencing a renaissance within the proteomics community for its, as yet, unparalleled ability to characterize and quantify a set of proteins reproducibly, completely, and with high sensitivity. Given the immense benefit that high resolution and accurate mass instruments have brought to the discovery proteomics field, we wondered if highly accurate mass measurement capabilities could be leveraged to provide benefits in the targeted proteomics domain as well. Here, we propose a new targeted proteomics paradigm centered on the use of next generation, quadrupole-equipped high resolution and accurate mass instruments: parallel reaction monitoring (PRM). In PRM, the third quadrupole of a triple quadrupole is substituted with a high resolution and accurate mass mass analyzer to permit the parallel detection of all target product ions in one, concerted high resolution mass analysis. We detail the analytical performance of the PRM method, using a quadrupoleequipped bench-top Orbitrap MS, and draw a performance comparison to selected reaction monitoring in terms of run-to-run reproducibility, dynamic range, and measurement accuracy. In addition to requiring minimal upfront method development and facilitating automated data analysis, PRM yielded quantitative data over a wider dynamic range than selected reaction monitoring in the presence of a yeast background matrix because of PRM's high selectivity in the mass-to-charge domain. With achievable linearity over the quantifiable dynamic range found to be statistically equal between the two methods, our investigation suggests that PRM will be a promising new addition to the quantitative proteomics toolbox. Molecular & Cellular Proteomics 11: 10.1074/ mcp.O112.020131, 1475-1488, 2012.The most widespread protein sequencing technique is the shotgun method. Proteins are digested into peptides, chromatographically separated, and measured by mass spectrometers (1-10). Many types of mass spectrometers are used-quadrupole ion traps, quadrupole ion trap hybrids such as the QLT (quadrupole linear ion trap)-Orbitrap or QLT-FT-ICR, and quadrupole time-of-flight (Q-TOF) hybrids-but, the experiments, from the MS measurement onward, are basically identical: the masses of eluting cationic peptide precursors are measured in a MS scan, and the most abundant precursors are selected in series for successive tandem MS events (MS/MS). This process, called data-dependent acquisition, continues for the duration of a chromatographic separation, and constant MS operation in this manner can generate hundreds of thousands of spectra in days. These spectra are then mapped to peptide or protein sequence databases using highly-evolved database search algorithms (11-13). Successful results can be obtained within just a few days and are nothing short of spectacular: tens of thousands of unique peptide spectral matches mapping to several thousand unique protein isoforms have become the norm. Although this approach certainly ...

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“…DMS experiments were performed on a quadrupole time-of-flight mass spectrometer (specifications similar to reference [27]) equipped with a planar DMS cell that was incorporated between the mass spectrometer's sampling orifice and the electrospray source ( Figure 1) [3]. Various modifier gases including HDX reagents were injected into the transport gas via the 'curtain gas' line (total flow 25 L/min with nitrogen) and/or supplied through the 'throttle gas' line via bubbler.…”

Section: Dms Conditionsmentioning

confidence: 99%

Differential Mobility Spectrometry-Hydrogen Deuterium Exchange (DMS-HDX) as a Probe of Protein Conformation in Solution

Zhu

Campbell²,

Chernushevich³

et al. 2016

J. Am. Soc. Mass Spectrom.

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Abstract. Differential mobility spectrometry (DMS) is an ion mobility technique that has been adopted chiefly as a pre-filter for small-to medium-sized analytes (<1 000 Da). With the exception of a handful of studies that employ an analogue of DMS-field asymmetric waveform ion mobility spectroscopy (FAIMS)-the application of DMS to intact biomacromolecules remains largely unexplored. In this work, we employ DMS combined with gas-phase hydrogen deuterium exchange (DMS-HDX) to probe the gas-phase conformations generated from proteins that were initially folded, partially-folded, and unfolded in solution. Our findings indicate that proteins with distinct structural features in solution exhibit unique deuterium uptake profiles as function of their optimal transmission through the DMS. Ultimately we propose that DMS-HDX can, if properly implemented, provide rapid measurements of liquid-phase protein structural stability that could be of use in biopharmaceuticals development.

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Performance Characteristics of a New Hybrid Quadrupole Time-of-Flight Tandem Mass Spectrometer (TripleTOF 5600)

Cited by 264 publications

References 19 publications

Analysis of Major Histocompatibility Complex (MHC) Immunopeptidomes Using Mass Spectrometry*

Analysis of Major Histocompatibility Complex (MHC) Immunopeptidomes Using Mass Spectrometry*

Parallel Reaction Monitoring for High Resolution and High Mass Accuracy Quantitative, Targeted Proteomics

Differential Mobility Spectrometry-Hydrogen Deuterium Exchange (DMS-HDX) as a Probe of Protein Conformation in Solution

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