Quantitative determination of trace metals in single yeast cells by time-resolved ICP-MS using dissolved standards for calibration.

Time-resolved inductively coupled plasma mass spectrometry (ICP-MS) for studying cellular heterogeneity or detecting metals in single cells draws increasing attention in the recent years. Considering the full width of a single-cell event is about 0.5-0.9 ms, dependent on the duration of the ion plume generation in typical ICP condition, dwell time shorter than the transient event was suggested for fully profiling it. Herein we investigated the effect of dwell time (0.1-10.0 ms) on the signal profiles of single-cell events, signal-to-background ratio, duty cycle of detection, the limit of detection, and the ability of cell counting by the time-resolved ICP-MS, using yeast (Saccharomyces cerevisiae) cells as example. Two calibration equations with respect to the length of dwell time (0.1 ms or 5.0 ms), simply using dissolved metal standard solutions, were constructed and successfully applied to the determination of K, Mg, Zn, Mn, and Cu in single yeast cells. The limit of detection (LOD, fg per cell) obtained at dwell time 0.1 ms was 1.68 (K), 0.29 (Mg), 0.17 (Zn), 0.01 (Mn), and 0.02 (Cu) for single-cell analysis of yeast cells; the LOD (fg per cell) at 5.0 ms was 80.0 (K), 10.3 (Mg), 1.6 (Zn), 0. 14 (Mn), and 0.24 (Cu), respectively. The results showed that a short dwell time leading to high signal-to-background ratio and low LOD was a prerequisite for the quantitative analysis of ultra-trace content of metals in single cells.