Single-cell inductively coupled plasma mass spectrometry (SC-ICP-MS) has emerged as a powerful tool for elemental analysis at the single-cell level. However, this approach suffers from two limitations: 1) Cellular debris and aggregates may be misclassified as intact cells, leading to overestimated counts; 2) Conventional data processing algorithms also rely solely on peak intensity for elemental contents quantification, with no cell size information extracted from the same transient signal. Here, we introduce three sequential filtering steps based on peak shape analysis to exclude cellular debris and aggregates. We then present a novel data processing algorithm to simultaneously obtain elemental contents and relative cell size. Crucially, both parameters are derived from the same transient SC-ICP-MS signal, enabling paired mass–size analysis without additional measurements. Notably, our size distributions required no empirical binning adjustments and exhibited good normal or lognormal distribution. Applying our method to model algal species (e.g., Synechocystis sp. PCC 6803 and Chlamydomonas reinhardtii), we found that cells of comparable size exhibited significant heterogeneity in elemental contents (e.g., Mg, P, Fe, Zn), revealing previously hidden physiological diversity behind similar cell sizes. The ability to resolve size-specific heterogeneity thus provides a mechanistic basis for interpreting single-cell elemental profiles in phytoplankton physiology and assessing the impacts of marine metal pollutants on microbial commumities.

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