Fellgett Revisited: On the Nature of Noise in Two-Dimensional Mass Spectrometry.

Two-dimensional mass spectrometry (2DMS) is a truly data-independent acquisition technique used in the analysis of complex mixtures; however, the nature of the noise within these spectra is not well understood. In this work, 2DMS is tested for conformity with the Fellgett principle: (signal/noise) ∝ √ (no. of data points). Since 2DMS functions through the modulation of ions through a fragmentation region across many scans, the individual scans are considered data points in this experiment. Random noise was shown to be prevalent as the main source of noise in this experiment with minor systematic noise. This means that the minimum size for a 2DMS spectrum that displays a target fragment ion can be determined using a fast-2D equation detailed herein. The effects of existing denoising algorithms were also found to change the relationship between the signal-to-noise ratio and the scan numbers to be of a quasi-linear nature rather than the square root trend observed before denoising.