Thermo Scientific Orbitrap Exploris 240 mass spectrometer

Importance of High-Resolution Accurate-Mass Spectrometry

High-resolution accurate-mass (HRAM) mass spectrometry has become a cornerstone technique in modern analytical chemistry. It enables confident identification and quantitation of a broad range of analytes—from small molecules and metabolites to peptides, proteins, and intact biotherapeutics. Sub-ppm mass accuracy, high resolving power, and robust calibration are essential for reliable non-targeted analysis, structural elucidation, and quantitative workflows in research, quality control, and translational applications.

Objectives and Overview of the Article

This article presents the Thermo Scientific Orbitrap Exploris 240 mass spectrometer as a versatile, high-performance platform. It highlights operational simplicity combined with intelligent data acquisition to accelerate discovery and deliver quantitative precision. Key application areas include proteomics, metabolomics, small-molecule screening, and biopharmaceutical characterization.

Methodology and Used Instrumentation

The Orbitrap Exploris 240 system integrates several advanced components and methods:

• EASY-IC internal calibration for consistent sub-ppm mass accuracy across m/z 40–6,000 over multiple days.
• High-resolution settings up to 240k FWHM, enabling baseline separation of matrix interferences and isotopic clusters.
• Polarity switching for simultaneous positive/negative analysis of complex samples.
• Thermo Scientific Vanquish Flex Duo UHPLC for increased throughput and minimal downtime between injections.
• FAIMS Pro interface to enhance proteome coverage through gas-phase fractionation in shotgun and multiplexed TMT workflows.
• AcquireX intelligent data acquisition to generate sample-relevant MS2 spectra by iterative inclusion and exclusion lists.
• BioPharma option extending mass range to m/z 8,000 for native and intact protein analysis.

Main Results and Discussion

• Small molecules: Sub-1-ppm mass accuracy was maintained for veterinary drugs in meat over 15 days, supporting robust non-targeted analysis.
• Quantitation: Full-scan resolution at 60k delivered linear response over five orders of magnitude (0.1–10,000 ng/mL) for plasma-borne drugs, with an LLOQ of 0.1 ng/mL.
• Proteomics: High MS2 identification rates from 10–1,000 ng HeLa digest loads combined with FAIMS improved peptide and protein group detection in 90-minute runs.
• Biopharma: Denaturing and native intact mass measurements of monoclonal antibodies achieved clear glycoform profiles and stable deconvoluted masses (<0.5 ppm drift) over 18 days. Subunit separations revealed low-level oxidation variants.

Benefits and Practical Applications

The Orbitrap Exploris 240 platform offers:

• Operational simplicity with ready-to-run templates and single-click calibration.
• High throughput supported by automated UHPLC coupling and intelligent acquisition workflows.
• Flexible application scope from environmental screening and food safety to clinical translational research and biopharmaceutical QC.
• Integrated software ecosystem (Compound Discoverer, mzCloud, TraceFinder, Chromeleon CDS) for seamless qualitative and quantitative data processing.

Future Trends and Potential Uses

Advances in automation, data-driven acquisition strategies, and AI-enabled data analysis will further increase throughput and reduce manual intervention. Expanded intelligent workflows can streamline large-cohort proteomics and metabolomics studies, while cloud connectivity may enable real-time instrument monitoring and predictive maintenance. Integration of multi-omics data will drive systems biology and precision medicine applications.

Conclusion

The Orbitrap Exploris 240 mass spectrometer combines exceptional mass accuracy, resolving power, and versatile acquisition modes with intuitive operation and comprehensive software support. It delivers high-quality qualitative and quantitative results across diverse analytical challenges, making it a valuable tool for academic, industrial, and clinical laboratories.