Trace metals are crucial for the growth of all living organisms. Understanding the role of these trace metals on the metabolism is essential for maintaining a stable state of the organism. Additionally, human beings are also facing constant exposure to various harmful heavy metals due to various types of pollution. Collectively, these aspects have led to research and development in the field of analytical techniques that can help in identifying the level of these trace metals in our cells.
Inductively coupled plasma mass spectrometry (ICP-MS) is an analytical technique used for the analysis of elemental compositions in various samples including biological samples. In recent times, the single-cell ICP-MS (scICP-MS) technique has been widely used in medical and biological fields for the analysis of single-living cells in bacteria, fungi, microorganisms, plants, and mammals. The sample introduction system of scICP-MS consists of a conventional pneumatic nebulizer and a total consumption spray chamber. A pneumatic nebulizer converts the sample (cell suspension) liquid into a mist.
Although the transport efficiency of traditional scICP-MS analysis using a nebulizer reaches 10% for yeast cells, it cannot be used for mammalian cells owing to their fragile nature. Chemical fixation is known to enhance the strength of mammalian cells, but it greatly affects the elemental contents, leading to inaccuracy of the analysis. There is thus a need to develop a sample introduction system that does not cause any damage to the mammalian cells.
Toward this end, a group of researchers from Japan has now demonstrated the potential of a microdroplet generator (µDG) as the sample introduction system for the efficient and quantitative elemental analysis of mammalian cells. The team, comprising Assistant Professor Yu-ki Tanaka along with Ms. Hinano Katayama, Ms. Risako Iida, and Professor Yasumitsu Ogra from the Graduate School of Pharmaceutical Sciences, Chiba University, Japan introduced a µDG into the sample introduction system of an ICP-MS, revealing that the system was capable of accurately conducting the elemental analysis. Their study was published on December 2, 2024, in Volume 40 of the Journal of Analytical Atomic Spectrometry . Elaborating further, Dr. Tanaka says, "Till now, scICP-MS has been applied to bacteria, fungi, plant cells, and red blood cells. We have expanded the potential of scICP-MS technology to mammalian cultured cells, developing a robust analytical technique for measuring elemental content in mammalian cultured cells."
In the study, the researchers used two sample introduction systems for particle and cell sample analysis. The first one was the conventional system comprising a concentric glass nebulizer and a total consumption spray chamber. The other system comprised a µDG inserted into the fabricated T-shape glass plumbing, with one end of the glass plumbing being fit to a total consumption spray chamber and the other end being fit to an ICP torch.
The researchers found that the cell transport efficiency increased drastically with the use of µDG. Moreover, they also estimated magnesium, iron, phosphorus, sulfur, and zinc in the K562 cells (also known as human chronic myelogenous leukemia K562 cells) and found that µDG maintained the cell's original structure in contrast to the conventional system that usually alters the cell's structure. It is thus highly suited for single-cell elemental analysis since it does not affect the cell's structure, resulting in highly efficient detection of the cells. "Our findings demonstrate the potential of μDG as a universal sample introduction system in scICP-MS," explains Asst. Prof. Tanaka.
These findings suggest that the size of cultured K562 cells influenced the shear stress-induced through nebulization, leading to cell damage. An increase in cell size intensifies the shear stress, causing significant damage. The µDG can preserve the structure of K562 cells, resulting in highly efficient detection and quantitative measurement of elemental signals from individual cells.
The ICP-MS technique is widely applicable in environmental monitoring, energy, pharmaceutical, food, and agriculture industries, and clinical research. "One promising social implementation of scICP-MS technology is for the prognosis and diagnosis of diseases. Health conditions can be evaluated by analyzing the elemental composition within the body and even at the level of individual cells. Blood cell samples, which can be easily collected from both patients and healthy individuals, serve as a primary target for diagnostics and prognostics using scICP-MS," concludes Asst. Prof. Tanaka, optimistically.
About Assistant Professor Yu-ki Tanaka
Dr. Yu-ki Tanaka is an Assistant Professor at the Graduate School of Pharmaceutical Sciences at Chiba University, Japan. He received his Doctor of Science degree from Kyoto University in 2017. His research interests include heavy metals, toxicity, single-cell/particle analysis, and isotopic composition analysis. He is currently working on a method to accurately measure the trace of elements within a single nanoparticle or cell. He has over 30 publications, 1,900 reads and more than 300 citations. He is a member of notable academic societies like the Pharmaceutical Society of Japan, the Japanese Society of Toxicology, and the Japan Society for Plasma Spectrochemistry.