A pioneering study led by the National Physical Laboratory (NPL) has reported significant findings regarding the noise structure of Orbitrap mass spectrometers, a critical tool in the analysis of complex biological processes. The study, published in Nature Communications, addresses the challenges posed by noise in mass spectrometry, which can affect the limit of detection and introduce bias in computational methods used to simplify complex spectra.
Mass spectrometers play a vital role in understanding biological processes by separating ionized molecules based on their mass-to-charge ratio. Orbitrap mass spectrometers are particularly valued in industry, academia, and healthcare for their exceptional ability to resolve molecules with nearly identical masses, thanks to their precise mass-to-charge measurements. However, the noise structure inherent in these instruments has not been well understood until now.
In collaboration with Dr. Michael R. Keenan (Independent), Thermo Fisher Scientific, The Francis Crick Institute, AstraZeneca, IONTOF GmbH and Imperial College London, NPL has comprehensively analysed the noise structure of Orbitraps. The study introduces a new fundamentals-based scaling method that effectively separates and orders chemical information from the noise, addressing a long-standing issue in the field. Previously, researchers had to rely on arbitrary scaling methods or no scaling at all, leading to potential biases in data interpretation.
The findings of this study have important implications for the scientific community. By determining how noise affects the limit of detection, the research paves the way for improvements in signal processing and allows for the calibration of the intensity scale. This advancement will enhance the accuracy and reliability of data obtained from Orbitrap mass spectrometers, ultimately benefiting various applications in biological research and healthcare.
As the understanding of noise in Orbitrap mass spectrometers evolves, the potential for improved analytical techniques and more reliable data interpretation continues to grow, marking a significant step forward in the field of mass spectrometry.
Ian Gilmore, Senior NPL Fellow, commented: “This foundational study, is the culmination of many years work, requiring a highly collaborative and multidisciplinary team with experts in statistics, physics and biology. I am very grateful to the team and believe the results will have enduring benefit for the mass spectrometry community.”
Alexander Makarov, Director of Research, Life Science Mass Spectrometry at Thermo Fisher Scientific commented: "This truly multidisciplinary study has equipped us with an advanced toolkit for modelling noise in Orbitrap spectra, which will enable improvements in the quality of mass analysis across a wide range of applications — from mass spectrometry imaging to isotope ratio measurements."
29 Jul 2025