New Study Unveils Noise Structure of Orbitrap Mass Spectrometers

A groundbreaking study led by the National Physical Laboratory (NPL) has recently shed light on the noise structure of Orbitrap mass spectrometers, vital instruments in the analysis of complex biological processes. Published in the renowned journal Nature Communications on July 29, 2025, this research addresses the challenges posed by noise in mass spectrometry, which impacts detection limits and introduces biases in computational methods used to simplify intricate spectra.

Mass spectrometry is crucial for understanding biological processes by separating ionized molecules based on their mass-to-charge ratio. Orbitrap mass spectrometers are particularly esteemed in academic, industrial, and healthcare settings for their exceptional ability to resolve molecules with nearly identical masses due to their precise mass-to-charge measurements. However, the inherent noise structure within these instruments had remained poorly understood until now.

In this comprehensive study, the NPL collaborated with a multidisciplinary team of experts, including Dr. Michael R. Keenan (Independent), representatives from Thermo Fisher Scientific, The Francis Crick Institute, AstraZeneca, IONTOF GmbH, and Imperial College London. Together, they introduced a novel fundamentals-based scaling method that efficiently separates and organizes chemical information from noise. This advancement addresses long-standing issues within the field, as researchers previously relied on arbitrary scaling methods or none at all, which could lead to significant biases in data interpretation.

The implications of the findings are substantial for the scientific community. By elucidating how noise affects detection limits, the research provides a framework for enhancing signal processing and calibrating intensity scales. Such improvements are expected to bolster the accuracy and reliability of data obtained from Orbitrap mass spectrometers, which will ultimately benefit various applications in biological research and healthcare.

Ian Gilmore, a Senior Fellow at NPL, remarked, "This foundational study is the culmination of many years of 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 benefits for the mass spectrometry community."

Alexander Makarov, Director of Research in Life Science Mass Spectrometry at Thermo Fisher Scientific, added, "This truly multidisciplinary study has equipped us with an advanced toolkit for modeling 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."

As the understanding of noise in Orbitrap mass spectrometers continues to evolve, the potential for improved analytical techniques and more reliable data interpretation grows, marking a significant step forward in mass spectrometry. The study by Michael R. Keenan et al., titled 'Orbitrap Noise Structure and Method for Noise Unbiased Multivariate Analysis,' can be accessed in Nature Communications (2025). DOI: 10.1038/s41467-025-61542-2.