Single-Cell Analysis Using Inductively Coupled Plasma Mass Spectrometry

Single-cell analysis by inductively coupled plasma mass spectrometry (ICP-MS) has emerged as a transformative approach for quantifying elemental composition and metalloprotein expression at the level of individual cells. By generating a high-temperature plasma to atomise and ionise single cells or ablated material, ICP-MS enables detection of trace metals and metal-tagged biomolecules with femtogram sensitivity. Variants such as single-cell ICP-MS (SC-ICP-MS) analyse cells in suspension to determine total elemental mass per cell, while laser ablation ICP-MS (LA-ICP-MS) and laser ablation-time-of-flight MS (LA-ICP-TOF-MS) provide spatial mapping of metal distributions within tissues or cell clusters. Coupling metal-nanocluster-labelled antibodies with SC-ICP-MS permits multiplexed protein quantitation, and integration with mass cytometry (CyTOF) allows simultaneous phenotyping of cell surface markers and endogenous metal content. These innovations have opened new avenues in metallomics, toxicology, nanoparticle biodistribution, cellular stress response and clinical biomarker discovery.

Research from Nature Portfolio

Mass cytometry by time-of-flight has been applied to quantify inorganic nanoparticle uptake and immune phenotyping at single-cell resolution. In a foundational study, gold nanoparticles (3 nm core) were tracked without additional labels, achieving a detection limit of around ten particles per cell. By combining nanoparticle quantitation with multiplexed metal-tagged antibodies for surface markers, researchers mapped biodistribution of therapeutic nanoparticles in lymphoid tissues and demonstrated targeted delivery to dendritic cell subsets. This work provided critical insights into nanoparticle fate in vivo and laid the groundwork for optimising nanomedicine design and vaccine efficacy studies.

Single-Cell Analysis Using Inductively Coupled Plasma Mass Spectrometry publication trend

The graph below shows the total number of articles in single-cell analysis using inductively coupled plasma mass spectrometry across all publications each year (not limited to Nature Index journals).

Technical terms

Inductively Coupled Plasma Mass Spectrometry (ICP-MS): An analytical technique that ionises samples in a high-temperature plasma and separates ions by mass-to-charge ratio for elemental quantitation.

Single-Cell ICP-MS (SC-ICP-MS): A method that introduces whole cells in suspension into the plasma, enabling quantification of total elemental content per cell event.

Laser Ablation ICP-MS (LA-ICP-MS): A variant that uses a focused laser beam to remove and ionise microscale sample regions, providing spatially resolved elemental maps.

Time-of-Flight Mass Spectrometry (TOF-MS): A mass analyser that measures ion flight times over a fixed distance to achieve simultaneous detection of a wide mass range.

Mass Cytometry (CyTOF): A technique combining metal-tagged antibodies with ICP-TOF-MS to enable simultaneous multiparameter phenotyping of individual cells.

References

1. The stochastic association of nanoparticles with algae at the cellular level: Effects of NOM, particle size and particle shape. Ecotoxicology and Environmental Safety (2021).
2. Expanding the boundaries of atomic spectroscopy at the single-cell level: critical review of SP-ICP-MS, LIBS and LA-ICP-MS advances for the elemental analysis of tissues and single cells. Analytical and Bioanalytical Chemistry (2023).
3. Capabilities of Single Cell ICP-MS for the Analysis of Cell Suspensions from Solid Tissues. Nanomaterials (2022).