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Orbitrap FusionEdit

Orbitrap Fusion is a flagship instrument in the field of modern analytical chemistry, designed to deliver flexible, high-resolution mass analysis for complex biological and chemical samples. Developed by Thermo Fisher Scientific, it combines three distinct mass-analysis technologies into a single platform: a quadrupole for precursor selection, a high-resolution Orbitrap analyzer for accurate mass measurements, and a linear ion trap for rapid MS/MS and MSn experiments. This hybrid arrangement enables researchers to perform comprehensive experiments—from broad discovery proteomics to targeted quantitation and advanced fragmentation strategies—within a single instrument.

Since its introduction, the Orbitrap Fusion has become a workhorse in many laboratories, particularly in proteomics, metabolomics, and related disciplines. By enabling high mass accuracy, fast scan speeds, and a versatile fragmentation toolkit, it supports detailed protein sequencing, identification of post-translational modifications, and reliable quantitation across complex samples. The instrument’s capability to switch seamlessly among different fragmentation modes and analysis paths makes it suitable for both discovery and hypothesis-driven workflows. For example, researchers use it to study signaling networks, characterize proteoforms, and quantify labeled samples with multiplexed tagging technologies.

Overview

  • Architecture: The Orbitrap Fusion integrates a quadrupole mass filter, a linear ion trap, and an Orbitrap mass analyzer. This triad provides precise precursor selection, fast MS/MS, and high-resolution discovery measurements, all in one platform. See also quadrupole mass filter and linear ion trap.
  • High-resolution analysis: The Orbitrap component delivers high mass accuracy and resolving power, which improves confidence in identifying and quantifying ions in complex mixtures. See also Orbitrap.
  • Fragmentation options: Users can employ collision-induced dissociation (CID), higher-energy collisional dissociation (HCD), and electron-based methods such as electron transfer dissociation (ETD) and related technologies (ETciD, EThcD) to suit different analytes. See also CID, HCD, ETD.
  • Quantitation and multiplexing: The instrument supports multiplexed labeling workflows (for example with TMT or iTRAQ tags) and can perform MS3 experiments to improve quantitative accuracy in challenging samples. See also TMT and iTRAQ.
  • Data acquisition modes: It enables data-dependent acquisition (DDA) workflows as well as targeted and multiplexed approaches, providing a broad range of experimental designs. See also data-dependent acquisition.
  • Applications: The system is widely used in proteomics, as well as in metabolomics and lipidomics, for comprehensive structural elucidation and quantitative studies. See also proteomics.

Technology and design

  • Hybrid mass analyzers: The core concept is to place three complementary analyzers in one instrument, allowing researchers to alternate between precise mass measurement and rapid tandem analyses. See also Orbitrap and quadrupole mass filter.
  • Precursor selection: The quadrupole section selects which ions enter the high-resolution analyzer, enabling targeted experiments and isolation of specific m/z ranges before MS/MS. See also quadrupole.
  • High-resolution MS1 and rapid MS2: The Orbitrap provides high-resolution MS1 spectra for accurate mass determinations, while the linear ion trap handles fast MS/MS scans, improving overall throughput. See also mass spectrometry and linear ion trap.
  • Fragmentation toolkit: CID and HCD provide conventional fragmentation, while ETD-based methods expand the range of analytes that can be sequenced, including large peptides and labile modifications. See also HCD, CID, ETD.
  • SPS-MS3 and quantitative accuracy: Synchronous Precursor Selection (SPS) MS3 enables improved quantitation with isobaric labeling by reducing interference in multiplexed experiments. See also SPS-MS3 and TMT.
  • Instrument software and workflows: Control and analysis rely on vendor software and compatible data-processing pipelines, with ongoing improvements to data interpretation and ease of use. See also Xcalibur.

Performance and considerations

  • Sensitivity and dynamic range: The Fusion platform is designed to detect low-abundance species in complex mixtures while maintaining a wide dynamic range, which is crucial for modern proteomics and metabolomics studies.
  • Resolution and mass accuracy: High resolving power and mass accuracy support confident identification of close-lying species and accurate determination of elemental compositions.
  • Flexibility vs. complexity: The instrument’s flexibility comes with a degree of operational complexity and cost. Laboratories typically require trained personnel for method development, maintenance, and data interpretation.
  • Complement to newer systems: While newer models exist, the Orbitrap Fusion remains widely used for established workflows, and its capabilities continue to influence contemporary designs in hybrid mass spectrometry. See also mass spectrometry and thermo fisher scientific.

Applications in research

  • Proteomics: Large-scale protein identification, post-translational modification mapping, and deep proteome coverage are common goals. Techniques such as SPS-MS3 with TMT labeling are frequently employed to improve quantitative accuracy in multiplexed studies. See also proteomics and TMT.
  • Phosphoproteomics and glycoproteomics: High-resolution MS/MS helps localize modification sites and characterize labile glycoforms, supported by ETD-based fragmentation strategies. See also phosphoproteomics and glycoproteomics.
  • Metabolomics and lipidomics: The broad scan capabilities and high mass accuracy support identification and quantitation of small molecules and lipid species in complex biological samples. See also metabolomics and lipidomics.
  • Clinical and translational research: The robustness and multiplexing capabilities make the instrument suitable for translational studies that require reliable quantitation across multiple samples.

History and development

  • Evolution of hybrid approaches: The Orbitrap Fusion represents a synthesis of high-resolution mass analysis with rapid tandem MS capabilities, reflecting broader industry trends toward multi-analyzer platforms.
  • Related models: The Orbitrap Fusion family has evolved into subsequent iterations (notably the Orbitrap Fusion Lumos) that enhance speed, sensitivity, and workflow flexibility, while maintaining core architectural principles. See also Orbitrap Fusion Lumos.
  • Influence on methods and standards: The platform has helped shape best practices in quantitative proteomics, including favored labeling strategies and fragmentation workflows, and has contributed to widespread adoption of high-accuracy mass spectrometry in life sciences. See also proteomics.

See also