Thermo Scientific Exactive Plus Orbitrap LC-MS System

Importance of the Topic

High-resolution accurate-mass (HR/AM) Orbitrap LC-MS technology has become a cornerstone in modern analytical chemistry, enabling rapid, sensitive and reliable screening of complex samples. Its applications span food safety, environmental monitoring, clinical research, forensic toxicology, drug discovery and biopharmaceutical analysis. By delivering exceptional resolution and mass accuracy, this approach reduces false positives, enhances trace-level quantitation and streamlines workflows in high-throughput laboratories.

Study Objectives and Overview

The Thermo Scientific Exactive Plus benchtop Orbitrap LC-MS system is designed to push the boundaries of speed, resolution and dynamic range. This summary reviews its key performance metrics, upgrade options and practical benefits. The system aims to:

• Provide up to 12 high-resolution spectra per second for narrow UHPLC peaks.
• Offer ultrahigh resolving power (up to 140,000 FWHM) to separate near-isobaric compounds.
• Maintain sub-ppm mass accuracy across chromatographic peaks without the need for lock masses.
• Extend the mass range to m/z 6000 for biomolecule and large-molecule analysis.

Methodology and Instrumentation

The Exactive Plus employs Thermo Fisher’s latest Orbitrap technology with image current detection and enhanced automatic gain control (AGC) via a C-Trap charge detector. Key system components include:

• Orbitrap mass analyzer with resolution settings up to 140,000 at m/z 200.
• Scan speeds up to 12 scans per second for full-MS acquisitions.
• Fast polarity switching (positive/negative) within 250 ms at 35,000 resolution.
• Extended mass range to m/z 6000 to accommodate singly charged ions and biomolecules.
• Optional higher-energy collisional dissociation (HCD) cell for all-ion fragmentation (AIF).
• On-site upgrade path to a quadrupole-equipped Q Exactive for targeted MS/MS analyses.

Main Results and Discussion

Performance testing demonstrates:

• Stable baseline resolution of narrow UHPLC peaks (e.g., clofentezine) with 13 scans at 70,000 resolution.
• Effective removal of isobaric interferences across the mass range, maintaining resolving power above 50,000 at high m/z.
• Scan-to-scan mass accuracy of 0.6 ppm RMS across chromatographic peaks, supporting reliable compound identification.
• Dynamic range spanning more than four orders of magnitude in a single scan, enabling simultaneous detection of trace-level and abundant analytes.
• High-quality isotopic resolution of large biomolecules such as insulin (≈5730 Da) using MALDI source coupling.

Benefits and Practical Applications

The Exactive Plus LC-MS system offers significant advantages for routine and research laboratories:

• High throughput screening of environmental pollutants, pesticide residues and pharmaceutical compounds.
• Accurate quantitation in clinical and forensic toxicology without extensive method development.
• Retrospective data analysis through full-scan high-resolution datasets, enabling post-acquisition interrogation of unknowns.
• Reduced maintenance due to the robust, maintenance-free Orbitrap analyzer.

Future Trends and Opportunities

Emerging directions include integration with advanced data processing software for automated workflows, deeper coupling with UHPLC and MALDI sources for omics applications, and further expansion of MS/MS capabilities via seamless Q Exactive upgrades. There is growing interest in high-resolution screening of lipids, metabolites and intact proteins in complex biological matrices.

Conclusion

The Thermo Scientific Exactive Plus Orbitrap LC-MS system delivers unparalleled speed, resolution and mass accuracy for comprehensive screening and quantitation. Its modular design and upgrade path to Q Exactive ensure adaptability to evolving analytical challenges, making it a future-proof investment for diverse applications in analytical chemistry.

Reference

• Thermo Fisher Scientific Inc. Thermo Scientific Exactive Plus Orbitrap LC-MS System Application Note. 2016.