Inductively Coupled Plasma Mass Spectrometry (ICP-MS) is a prominent technique for analyzing the elemental composition of single cells. However, the conventional method for sample introduction in ICP-MS can be detrimental to larger mammalian cells. In response to this challenge, researchers have developed a new method using a microdroplet generator that maintains cell integrity while providing accurate elemental analysis. This innovative technique could lead to improved disease diagnosis and prognostic capabilities.
Trace metals are vital for the health of all living organisms. Understanding their influence on metabolism is essential for maintaining balance within these organisms. Moreover, humans are regularly exposed to dangerous heavy metals through various forms of pollution. These issues have prompted a surge in research focused on analytical methods capable of detecting trace metal concentrations in human cells.
Inductively Coupled Plasma Mass Spectrometry (ICP-MS) is a significant analytical tool used to determine the elemental composition of various samples, including biological ones. Recently, single-cell ICP-MS (ScICP-MS) has gained popularity in medical and biological research for examining living cells from diverse sources, including bacteria, fungi, microorganisms, plants, and mammals. Typically, the traditional ScICP-MS sample introduction system involves a pneumatic nebulizer and a total consumption spray chamber that converts liquid cell suspensions into a fine mist for examination.
Although the standard ScICP-MS approach achieves a 10% transport efficiency for yeast cells, it does not perform well for more fragile mammalian cells. While chemical fixation can provide structural support to mammalian cells, it negatively impacts their elemental composition, leading to erroneous results. Consequently, there is an urgent need for a sample introduction technique that safeguards mammalian cells from damage.
In response to this challenge, researchers from Japan have demonstrated the effectiveness of a microdroplet generator (µDG) as a sample introduction system, allowing for precise and accurate elemental analysis of mammalian cells. This research team, including Assistant Professor Yu-ki Tanaka, along with colleagues Hinano Katayama, Risako Iida, and Professor Yasumitsu Ogra from the Graduate School of Pharmaceutical Sciences at Chiba University, Japan, successfully integrated a µDG into an ICP-MS sample introduction system, yielding accurate elemental analyses. Their findings were published on December 2, 2024, in Volume 40 of the Journal of Analytical Atomic Spectrometry. Dr. Tanaka explained, “Previously, ScICP-MS was limited to studies involving bacteria, fungi, plant cells, and red blood cells. We have now expanded its use to mammalian cultured cells, thereby creating a reliable method for quantifying elemental content.”
The research compared two different sample introduction systems to analyze particles and cells. The first system consisted of the traditional setup with a concentric glass nebulizer and a total consumption spray chamber, while the second system utilized the µDG, which was connected to a specially designed T-shaped glass configuration, linking one end to the total consumption spray chamber and the other end to an ICP torch.
Using the µDG, researchers noted a considerable improvement in cell transport efficiency. They measured magnesium, iron, phosphorus, sulfur, and zinc levels in K562 cells (human chronic myelogenous leukemia cells) and discovered that the µDG preserved the cells’ original structure, unlike the conventional method, which often compromised it. This advancement makes the µDG ideal for single-cell elemental analysis, resulting in effective detection of individual cells. “Our findings emphasize the potential of µDG as a versatile sample introduction system in ScICP-MS,” remarked Assistant Professor Tanaka.
The study further revealed that the size of cultured K562 cells influences the shear stress generated during the nebulization process, which can lead to cell damage. Shear stress increases with cell size, causing significant harm. The µDG’s design effectively protects K562 cells, thereby improving the detection and quantification of elemental signals from individual cells.
ICP-MS techniques have diverse applications, spanning environmental monitoring, energy, pharmaceuticals, food safety, agriculture, and clinical research. “A particularly exciting application for ScICP-MS technology lies in disease diagnosis and prognosis. By examining elemental compositions within the body, including at the single-cell level, we can assess health conditions. Blood samples, easily collected from patients or healthy individuals, serve as excellent candidates for diagnostics and prognostics through scICP-MS,” Assistant Professor Tanaka concluded with enthusiasm.
