Time-resolved ICP-MS measurement for single-cell analysis and on-line cytometry

A method of simultaneous cell counting and determination of constituent metals in single cells using time-resolved inductively coupled plasma-mass spectrometry (ICP-MS) is reported. A unicellular alga, Chlorella vulgaris, was used as a model in this study. Algae suspensions of number density of 10 ⁶/mL were converted into fine aerosols using conventional solution nebulization for sample introduction into the ICP. The metals in each cell are converted into a plume of gaseous analyte ions in the ICP. Each metal in the plume produces a current spike at the detector of the mass spectrometer. ICP-MS intensity spikes of major elements, such as Mg of 10⁸ atoms/cell, and trace elements, such as Mn and Cu of 5 × 10⁶ atoms/cell, were detected readily. The number density of the cells in an algae suspension can be determined by counting the number of the ICP-MS intensity spikes of the major element (Mg) over a fixed period of time. The uncertainty in cell counting was approximately 2% RSD, similar to that of hemacytometry. The ICP-MS spike intensity of an element is related to its quantity in the algal cell. Quantitative determination of the metal contents of the algal cells using metal oxide particles for calibration is feasible. Semi-quantitative measurement is also possible using aqueous standards for calibration. Rapid measurement of sorbed analyte ions on the biological cells without separation of the cells from the original suspension is demonstrated in kinetic study of the interactions of metal ions and algae in aqueous standards.