Launch of Trace Element Analysis Service for Single Cells

Toray Research Center, Inc. (Location: 1-7-2 Nihonbashi-Honcho, Chuo-ku, Tokyo; President: Yoshiki Makabe; hereinafter referred to as "TRC") has established a new cell introduction technology and optimized measurement conditions for its "single cell Inductively Coupled Plasma Mass Spectrometry (scICP-MS)"※1 analysis technique, which measures trace elements in single cells with high sensitivity. As a result, TRC is launching a contract analysis service, the first of its kind among contract analysis companies in Japan, capable of quantifying trace elements in single cells at the fg (femtogram = 1/1,000 trillionth of a gram) level. This service allows for direct measurement of elemental amounts on a per-cell basis, which previously could only be evaluated as an average value from a large number of cells.

Consequently, it enables quantitative understanding of cell-to-cell variability (heterogeneity), with expected applications in the pharmaceutical, biotechnology, food, and environmental fields for evaluating drug effects, cell functions, trace element uptake, and toxicity. Furthermore, by analyzing elemental amounts as a distribution rather than an average, it becomes possible to assess characteristic elemental biases in abnormal cells and cell selectivity in drug uptake.

TRC leverages its advanced inorganic element analysis technologies and know-how cultivated over many years to support the acceleration of customer research and technological development.

【Background】

Trace elements present in cells (such as Mg, P, S, Fe, Zn) play essential roles in life activities, including enzyme activity and intercellular signal transduction. In recent years, attention has focused on how heterogeneity among cells within the same cell population, differing in elemental amounts or pathological states, deeply influences variations in drug efficacy, toxicity expression, and functional differentiation. Capturing these cell-to-cell differences is a critical challenge in the development of novel pharmaceuticals and the elucidation of their mechanisms of action.

Generally, Inductively Coupled Plasma Mass Spectrometry (ICP-MS), which offers the highest sensitivity for elemental measurement, is used to evaluate the elemental amounts of microscopic targets like cells. However, conventional ICP-MS analysis requires cells to be lysed and measured collectively. Therefore, the obtained elemental information is limited to average values, making it difficult to directly evaluate differences between individual cells. Additionally, sample loss during pre-measurement steps such as cell washing and errors in cell counting also affected accuracy.

【Technical Overview】

In contrast, scICP-MS is a technique that introduces dispersed cells one by one into an ICP-MS instrument to directly measure elemental amounts at the single-cell level. To achieve high-precision measurements with minimal damage to cells, TRC has combined a microdroplet generator (μDG)※2 as a cell introduction device, enabling measurements with suppressed cell destruction or damage (Figure 1). Furthermore, by optimizing detection conditions, TRC has achieved high-sensitivity and reproducible single-cell analysis.

Figure 1: Schematic diagram of scICP-MS and comparison with conventional ICP-MS analysis involving digestion (chemical pretreatment).

【Analysis Example】

As a model case, the distribution of magnesium (Mg) content, one of the major minerals, within single yeast cells, the simplest eukaryotic cells※3, was evaluated (Figure 2). Contamination and insufficient instrument sensitivity can cause interference from trace impurities in the solution or background signals from the instrument, burying the cell peaks and making analysis difficult. By cleaning the cells and containers to remove contamination, the separation between the measurement background and cell peaks was achieved, enabling single-cell analysis.

Mg is a representative essential element involved in many cellular functions, and evaluating its distribution serves as one indicator for understanding differences in cellular states. The results of this analysis showed an average Mg content of approximately 2.0 fg/cell, with a confirmed distribution spread among individual cells.

Figure 2: Distribution analysis of Mg content in yeast cells.

Such analysis can yield insights such as:

- Differences in metabolic states between cells

- Evaluation of variability in stress response or nutritional status

- Quantifying quality (homogeneity)

Yeast is one of the most fundamental model organisms for cell research, and these results demonstrate the broad applicability of this technology from basic research to applied fields.

【Future Prospects】

This technology, which makes it possible to evaluate trace elements at the single-cell level, previously a difficult task, is expected to find applications in the following fields:

- Pharmaceutical field: Research on drug distribution and mechanisms of action within cells

- Biotechnology field: Research on cell function and differentiation control

- Food field: Evaluation of elemental absorption and accumulation in cells

- Environmental field: Evaluation of cellular effects and accumulation of toxic elements

Using these fields as examples, analyzing elemental amounts in cells through single-cell analysis is expected to lead to research on elements that are characteristically high or low in abnormal cells, and on the cell selectivity of drug uptake.

TRC will continue to support customer research and technological development and contribute to society through the development and advancement of cutting-edge analytical technologies, including single-cell analysis.

【Glossary】

※1 Single cell Inductively Coupled Plasma Mass Spectrometry (scICP-MS)

A method for directly quantifying extremely small amounts of elements contained in cells by introducing individual dispersed cells into an ICP-MS instrument, which is highly sensitive to inorganic elements.

ICP-MS is a technique that detects elements ionized by high-temperature plasma using a mass spectrometer. Since plasma has high ionization efficiency, it can detect and measure even trace elements with extremely high sensitivity.

※2 Microdroplet Generator (μDG)

A device that generates microdroplets of about tens of micrometers by controlling a nozzle with voltage. It enables introduction with minimal damage to cells.

※3 Eukaryotic cell

A cell possessing a nucleus enclosed by a nuclear membrane and organelles such as mitochondria. These cells constitute organisms like humans, animals, plants, and fungi. Because their basic structure is the same as animal and plant cells, the cell introduction and measurement conditions found using yeast cells are easily applicable to scICP-MS analysis.

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