Piezo-Driven Microdroplet Generator Enhances ICP-MS Accuracy

According to a recent study conducted by researchers at Chiba University in Japan, a new advancement in single-cell inductively coupled plasma–mass spectrometry (scICP-MS) could potentially address long-standing challenges preventing the widespread adoption of the technique. These challenges include cell transport and detection efficiency (1). The findings this study produced were published in the Journal of Analytical Atomic Spectrometry (1).

ICP-MS is an atomic spectroscopy technique often used for elemental analysis. scICP-MS improves upon ICP-MS because it measures trace metals at the single-cell level (2). However, scICP-MS comes with several key limitations, which has prevented its widespread adoption (1). One limitation is that there has been the lack of a standardized system for introducing cultured mammalian cells into the sample stream. Conventional systems, such as those employing pneumatic nebulizers and total consumption spray chambers, often damage fragile cells during transport, leading to low transport efficiency and compromised accuracy (1). This is problematic for delicate cell types, such as human chronic myelogenous leukemia K562 cells (1).

Acute lymphoblastic leukemia ALL is a type of blood cancer that occurs when the bone marrow produces too many abnormal lymphocytes, a type of white blood cell. Generated with AI. | Image Credit: © Thipphaphone - stock.adobe.com

Led by Yu-ki Tanaka, the research team explored making improvements to a standard ICP-MS instrument to try and address this limitation. To do so, the researchers experimented with integrating a μDG into the sample introduction system of an ICP-MS instrument (1). The μDG uses piezoelectric actuation to generate microdroplets, enabling the nondestructive transport of cells into the system for analysis (1). By using uDG in the ICP-MS instrument, the researchers observed a noticeable improvement in cell transport efficiency (1).

Calibration curves for elemental analysis were made using the droplets the μDG generated. The calibration curves were all based on ionic standard solutions (1). Using these curves to determine the sensitivity, which is the signal intensity per elemental mass, the researchers figured out how sensitive each element was in the samples under study (1). Validating the quantification protocol was achieved using silver nanoparticles, titanium dioxide nanoparticles, and dried yeast cells, demonstrating the method's versatility and precision (1).

These single-cell measurements were consistent with bulk concentration values obtained through solution nebulization ICP-MS following acid digestion, confirming the reliability of the μDG-ICP-MS approach.

The development of the μDG-ICP-MS system represents a significant step forward in the field of single-cell analysis. Its ability to transport cells nondestructively and with high efficiency opens the door to more accurate studies of cellular elemental composition. This is particularly relevant for research into disease mechanisms, cellular metabolism, and nanotoxicology.

By overcoming the limitations of traditional sample introduction systems, the team demonstrated the potential of μDG-ICP-MS as a powerful tool for single-cell elemental analysis. Their method not only improves transport efficiency but also ensures precision in quantifying elemental content, even in challenging samples like mammalian cells (1).

The implications of this study extend beyond the analysis of cultured mammalian cells. The validated quantification protocol, combined with the μDG's adaptability, suggests that this system could be applied to a variety of cell types and nanoparticles (1). The authors suggest that future studies should investigate how this technology can be used in other application areas, suggesting that environmental monitoring and clinical diagnostics could benefit from using their quantification protocol demonstrated in this study (1).

As Tanaka and colleagues have demonstrated, it is now possible to achieve nondestructive, high-throughput, and highly precise analysis of single cells, paving the way for new insights into cellular processing (1).

References

1. Tanaka, Y.-K.; Katayama, H.; Iida, R.; Ogra, Y. Quantitative Elemental Analysis of Human Leukemia K562 Single Cells by Inductively Coupled Plasma Mass Spectrometry in Combination with a Microdroplet Generator. J. Anal. At. Spectrom. 2025, 40 (1), 216–225. DOI: 10.1039/D4JA00364K
2. Davison, C.; Pascoe, J.; Bailey, M.; et al. Single Cell-Inductively Coupled Plasma-Mass Spectrometry (SC-ICP-MS) Reveals Metallic Heterogeneity in a Macrophage Model of Infectious Diseases. Anal. Bioanal. Chem. 2024, 416 (29), 6945–6955. DOI: 10.1007/s00216-024-05592-3