Quantitative elemental analysis of human leukemia K562 single cells by inductively coupled plasma mass spectrometry in combination with a microdroplet generator

Abstract

Single-cell inductively coupled plasma mass spectrometry (scICP-MS) is an emerging technique for the determination of elemental contents in individual cells. No standardized system for the introduction of cultured mammalian cells has been established owing to difficulties in cell transport and detection. The transport efficiency of human chronic myelogenous leukemia K562 cells (hereinafter “K562 cells”) in a conventional sample introduction system comprising a pneumatic nebulizer and a total consumption spray chamber is low owing to cell damage. To improve cell transport efficiency, we installed a piezo-actuator-driven microdroplet generator (μDG) into the sample introduction system of an ICP-MS for fast time-resolved analysis. Cell transport efficiency was drastically improved by using a μDG. For the determination of elemental contents, calibration curves were created by analyzing microdroplets of ionic standard solutions generated by the μDG. The pulsed signals originating from the microdroplets were analyzed and the sensitivity (i.e., signal intensity per elemental mass) was calculated for each element. The quantification protocol was validated using silver nanoparticles, titanium dioxide nanoparticles, and dried yeast cells. Finally, we introduced intact K562 cells and detected signals with high throughput. The average masses of five essential elements in single K562 cells were precisely determined as follows: 270 ± 100 fg for Mg, 23.0 ± 2.0 fg for Zn, 7684 ± 675 fg for P, 2136 ± 165 fg for S, and 14.4 ± 1.2 fg for Fe. These values are consistent with the values obtained by solution nebulization ICP-MS analysis after the acid digestion of K562 cells.