Orbitrap Exploris MX mass detector

Importance of the Topic

High resolution accurate mass spectrometry is a cornerstone in modern biopharmaceutical analysis. It supports late stage development, manufacturing and quality control by delivering precise mass information day after day across multiple sites in a compliant manner.

Objectives and Study Overview

This white paper presents the Orbitrap Exploris MX mass detector as a fit for purpose solution for routine mass monitoring in biopharma laboratories. It demonstrates how the system accelerates method deployment from development through commercialization and routine quality control using a high resolution accurate mass (HRAM) workflow.

Methodology

The study integrates the Orbitrap Exploris MX detector with Thermo Scientific Vanquish UHPLC systems and Chromeleon chromatography data system software. Key workflows include peptide mapping using multi attribute method MAM 2.0, intact protein analysis under native and denaturing conditions, glycan profiling and oligonucleotide mass confirmation. HRAM data acquisition with internal recalibration ensures long term mass stability.

Used Instrumentation

• Thermo Scientific Orbitrap Exploris MX mass detector
• Thermo Scientific Orbitrap Exploris 240 mass spectrometer
• Thermo Scientific Vanquish Flex and Horizon UHPLC systems
• Thermo Scientific Chromeleon CDS software
• Thermo Scientific BioPharma Finder software
• Thermo Scientific HyperBridge software
• Thermo Scientific MAbPac SEC 1 and DNAPac RP HPLC columns

Main Results and Discussion

Long term mass stability studies over six weeks showed deviations below 3 parts per million for multiple peptide analytes, ensuring robust peptide monitoring. Intact mAb profiling under native conditions at m/z up to 8000 yielded baseline resolved glycoform patterns with mass accuracies below 6 ppm. Denaturing analyses provided glycoform resolution below 10 ppm. Oligonucleotide intact mass confirmation of a 38 mer sequence demonstrated clear deconvolution of low level impurities and failed sequences using advanced ReSpect and Xtract algorithms.

The seamless transfer of MAM methods from Orbitrap Exploris 240 in development to Exploris MX in QC was achieved via standardized eWorkflows in Chromeleon CDS and HyperBridge, reducing assay variability between sites.

Benefits and Practical Applications

• High confidence sequence confirmation and PQA monitoring in development and QC
• Reduced assay complexity by consolidating multiple tests into one MAM workflow
• High uptime and automated maintenance alerts decrease downtime and increase throughput
• Compliance ready with data integrity and security features of Chromeleon CDS
• Global support network ensures rapid installation qualification and ongoing training

Future Trends and Opportunities

Integration of AI driven data interpretation and cloud based analytics will further streamline HRAM workflows. Expansion of MAM 2.0 into cell and gene therapy analytics and enhanced real time monitoring in manufacturing are expected. Continued improvements in instrument automation and remote diagnostics will support fully connected smart laboratories.

Conclusion

The Orbitrap Exploris MX mass detector paired with Thermo Scientific UHPLC and software platforms delivers a fit for purpose HRAM solution for biopharma laboratories. It enables robust, compliant and high confidence mass monitoring across peptides proteins and oligonucleotides, accelerating development and QC workflows with streamlined method transfer and high productivity.