Towards the smart lab: A comprehensive approach to mass spectrometry quality control

Introduction

Mass spectrometry (MS) is a powerful analytical technique that can be used to characterize complex biological samples. Its high sensitivity enables the identification of hundreds to thousands of proteins or small molecules in a single MS experiment. Unfortunately, due to this high sensitivity even the smallest changes in conditions of operation can give rise to a considerable variability, leading to a limited repeatability and reproducibility between individual experiments. Therefore, to inspire confidence in the obtained results it is of vital importance that appropriate quality control (QC) measures are taken to monitor and control the existing variability. Here we present how a systematic approach to quality control makes it possible to objectively assess the quality of a mass spectrometry experiment.

Methods

Various QC metrics have been defined to objectively assess the performance of an MS experiment. These metrics are typically derived from the spectral data, potentially augmented by the corresponding identification results. Additionally, low-level mass spectrometer instrument parameters can be used as a complementary source of performance information. Although we have previously shown that both these types of QC metrics can be used to accurately discriminate high-quality MS experiments from low-quality experiments, these approaches still only deal with quality information that is internal to the operation of a mass spectrometer. In contrast, external processes that are completely unrelated to the MS instrumentation, such as environment variables, can have a profound impact on the experimental results as well.

Preliminary Data

We will show how simple networked smart sensors can be employed to systematically monitor laboratory environment variables, such as the ambient temperature. By linking this information to the experimental quality we can obtain vital insights into how shifts in the laboratory environment influence the mass spectrometer operation and have an impact on the experimental results. For example, for a Thermo Scientific Q-Exactive instrument, among other things, we find that the pressure of the vacuum slightly changes according to the ambient temperature. Indeed, it is known that turbo pumps generating the vacuum frequently malfunction, notably when exposed to sustained and excessive heat. Additionally, we observed an inverse correlation between the ambient temperature and the electrospray voltage.

These small fluctuations cannot be measured using traditional QC metrics, but they can nevertheless have a non-negligible effect on the experimental quality. It is only through the complete integration of traditional spectral-derived QC metrics, low-level instrument parameters, and environment variables that a complete view on all factors impacting the experimental results can be obtained. Through such a comprehensive approach to quality control the unique “technological passport” of an MS instrument can be established, which makes it possible to objectively assess the instrument’s functioning and evaluate the reliability of an experiment at a glance. This enables an innate approach to quality control, a mindset that is mandatory to inspire confidence in and to advance the field of biological mass spectrometry.

We have implemented this comprehensive QC functionality into the iMonDB software, a user-friendly tool to track and visualize a range of QC metrics. The iMonDB is available as open source online, and can easily be set up to start monitoring the quality of your mass spectrometry laboratory.

Novel Aspect

A wide range of qualitative information is used to establish the unique "technological passport" of an MS instrument.