Thermo Scientific Orbitrap Exploris Series 4.2 SP1 Instrument Control Software Release Notes

Importance of Topic

Controlling modern high‐resolution mass spectrometers requires robust, reliable instrument control software. The Orbitrap Exploris Series 4.2 SP1 release streamlines installation, improves data quality through firmware updates (notably FAIMS Pro and Pro Duo), and delivers critical defect fixes to enhance day‐to‐day operation in proteomics, small molecule analysis, and gas chromatography–mass spectrometry (GC–MS) applications.

Objectives and Overview

This release note aims to inform users about:

• Installation prerequisites and system requirements
• Supported instrument models and software compatibility
• New features, firmware updates, and defect corrections since version 4.2
• Known issues and workarounds

Methodology and Instrumentation

System Requirements

• PC: 3.0 GHz Quad‐core Intel, 32 GB RAM, 512 GB SSD, 1920×1080 display, two 1 Gbps NICs
• OS: Windows 10 Enterprise 2016 LTSB, 2019 or 2021 LTSC
• Xcalibur 4.6 and compatible Chromeleon versions

Network and Installation

• Dedicated NIC for instrument traffic, static IPv4 (172.16.0.101/16), no Internet route
• Disable firewalls during install; default install path: C:\ProgramData\Thermo\Exploris
• Backup key configuration files and folders before upgrade
• Restore procedure requires stopping the Thermo Exploris Core Service and replacing instrument files

Použitá instrumentace

• Orbitrap Exploris 120, 240, 480, MX
• Orbitrap Exploris GC and GC 240
• FAIMS Pro and FAIMS Pro Duo interfaces (firmware updated)

Main Results and Discussion

Compatibility Matrix

• Version 4.2 SP1 (4.2.362.21) supports all Exploris models (120–MX, GC, GC 240)

New Features & Improvements (4.2 SP1 vs 4.2)

• Fixed collision energy behavior in targeted DDA and SIM (ID 356984)
• Resolved older method import errors (ID 347689)
• Multiple GC method editor fixes and HCD tooltip corrections
• Improved full‐scan signal stability in small molecule mode

Known Issues

• USB divert valve configuration requires separate MX software (ID 153093)
• Standalone Method Editor install blocked if full ICS present (ID 153505)
• MongoDB must be manually uninstalled when downgrading (ID 280624)

Benefits and Practical Applications

• Streamlined installation with clear backup and restore workflows reduces downtime
• Firmware update for FAIMS ensures optimal ion focusing and reproducibility in LC–MS workflows
• Defect fixes enhance method transfer reliability, locking mass calibration accuracy, and method editor stability
• Extended compatibility with Chromeleon drivers simplifies integration into regulated environments

Future Trends and Applications

Emerging directions include cloud‐delivered system template and method updates, tighter integration of AI‐driven calibration diagnostics, expanded AcquireX support for complex small‐molecule workflows, and enhanced automation of FAIMS CV optimization. Continued firmware and software enhancements will further reduce user intervention and maximize instrument uptime.

Conclusion

The Orbitrap Exploris Series 4.2 SP1 Instrument Control Software release represents an important step in refining user experience, improving data integrity, and broadening instrument capability. Clear installation guidance, firmware updates for FAIMS, a robust compatibility matrix, and resolution of critical defects ensure that laboratories can maintain high performance across diverse analytical workflows.

Reference

• Orbitrap Exploris Series Operating Manual
• Orbitrap Exploris GC and Orbitrap Exploris GC 240 Operating Manual