Inductively Coupled Plasma Mass Spectrometry (ICP-MS) is a highly sensitive elemental analysis technique capable of detecting and quantifying elements at ultra-low concentrations, ranging from milligrams to nanograms per liter. By integrating an ICP instrumentation for sample atomization with mass spectrometry (MS) for precise detection, ICP-MS offers a comprehensive solution for elemental analysis in various fields of research and industry.
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What Makes Inductively Coupled Plasma Mass Spectrometry (ICP-MS) Ideal for Elemental Analysis?
Inductively coupled plasma mass spectrometry (ICP-MS) is an analytical technique that combines an ion-generating argon plasma source with mass spectrometry detection to determine isotopic and trace elemental concentrations in solid, liquid, or gaseous samples.
ICP spectroscopy enables the detection and quantification of elements in a sample by ionizing them within the sample matrix, which is then separated by the mass spectrometer based on their mass-to-charge ratio. A detector counts the selected ions per second, allowing for the determination of the elemental concentrations.
ICP-MS offers low detection limits, a wide elemental detection range, and simultaneous analysis of multiple elements, making it a valuable tool in elemental analysis across various industries, such as environmental monitoring, food and pharmaceutical safety, life science research, consumer product testing, mining, and metals analysis.
How is Elemental Analysis Performed Using Inductively Coupled Plasma Mass Spectrometry (ICP-MS)?
The elemental analysis process using ICP-MS involves the following steps:
The Sample Introduction
ICP-MS analysis requires liquified sample solutions, and solid and biological samples are usually digested before analysis. The sample solution is transformed into an aerosol mist using argon gas in a nebulizer. After passing through a spray chamber to remove larger droplets, the argon gas carries the fine droplets to the ICP plasma torch.
The sample introduction components are optimized to work effectively with the ICP, ensuring that the aerosol contains small, uniformly sized droplets dispersed across the central channel of the plasma for efficient ion production.
The ICP (plasma) Ion Source
The ion source (ICP) uses a radio frequency (RF) generator at about 1.5 KW to create an ionized argon gas plasma in a quartz tube. The aerosol droplets carrying the sample material are dried and decomposed in the high-temperature plasma, forming individual atoms that are then ionized.
The ionization level of each element in the plasma depends on its ionization energy and the plasma temperature. Typically, natural elements are ionized to a minimum of 75% under normal plasma conditions, contributing to the high sensitivity of ICP-MS.
However, certain elements like Arsenic (As), Cadmium (Cd), and Mercury (Hg) are less ionized, requiring careful plasma optimization to achieve low detection limits and high sensitivity for these elements.
The Vacuum Interface
A vacuum interface separates the plasma ion source from the quadrupole mass spectrometer, facilitating the transfer of ions from the atmospheric pressure plasma to the mass spectrometer's vacuum chamber.
This interface includes metal plates or cones with small holes, where a sampling cone extracts ions from plasma and a skimmer cone directs them to the high vacuum region.
An optimal aperture size of 0.5 to 1.0 mm is essential for efficiently operating the mass filter and detector, balancing ion transmission and background levels. Smaller cone apertures offer advantages in terms of vacuum conditions but require a robust plasma and a high transmission ion lens system for optimal.
Ion Focusing and Separation
Once the ions have traversed the interface cones, they are concentrated into a narrow beam using an ion "lens." The lens consists of adjustable voltage metal plates that attract or repel ions based on their charge.
By adjusting the plate voltages, ions are steered and focused into a narrow beam. Various ion lens designs ensure high ion transmission and reduce interference from uncharged particles.
The collision/reaction cell (CRC) is installed in modern ICP-MS systems to help separate analyte ions from interfering ions, particularly polyatomic ions, through collision or reaction modes.
In collision mode, a nonreactive gas such as helium (He) is used to reduce the kinetic energy of ions through collisions, selectively removing polyatomic ions from the ion beam.
On the other hand, the reaction mode involves pressurizing the CRC with a reactive gas, such as hydrogen (H2) or oxygen (O2), that facilitates quick reactions between interfering ions and gas molecules to eliminate interferences.
The Mass Spectrometer (MS)
The mass spectrometer (MS) in ICP-MS instruments uses a quadrupole to filter ions based on their mass-to-charge ratio (m/z).
The quadrupole consists of pairs of rods with applied RF and DC voltages, creating an electric field that allows only ions at the set mass to pass through the filter. In addition, it rapidly scans across a wide range of masses, enabling the detection and counting of ions at each specific mass.
In the standard elemental analysis, the mass spectrum is constructed by accumulating data from multiple scans across the desired masses. Other measurement modes include time-resolved analysis with recorded ion counts per scan and single mass monitoring for specialized measurements such as single nanoparticle analysis.
The Electron Multiplier Detector
The ICP-MS electron multiplier (EM) detector uses ionized dynodes (high voltage electrodes) to release electrons that cascade down and generate a detectable pulse.
The EM detector offers high sensitivity for detecting ultralow concentrations and a wide dynamic range of approximately 10-11 orders of magnitude. This enables the measurement of trace elements at concentrations below 0.1 ppt while simultaneously measuring major elements at much higher concentrations, all within the same analysis.
Finally, data analysis software processes the detector counts for each mass, calculating element concentrations in unknown samples by comparing them to known concentration reference solutions through calibration plots.
Limitations and Challenges Associated with Elemental Analysis via ICP-MS
The accuracy of ICP-MS depends on user skill and technique, requiring careful standard and sample preparation to avoid calibration curve errors and contamination.
Interferences can occur when plasma-generated substances have the same mass as the analyte species, but these can be addressed by examining low-abundance isotopes or using element correction equations.
ICP-MS is limited in detecting gaseous elements such as carbon, helium, hydrogen, and elements without naturally occurring isotopes.
With the growing need for improved detection capabilities, achieving high sensitivity for analytes while minimizing background noise presents a significant obstacle in instrument development. Consequently, it becomes crucial to maintain an ultra-clean laboratory and ensure a pristine sample preparation environment to detect elements at extremely low levels.
Triple-Quadrupole ICP-MS: Advancing Elemental Analysis in Clinical Applications
The introduction of triple-quadrupole (tandem mass spectrometry) in ICP-MS has significantly improved elemental analysis. These instruments have an additional quadrupole, enabling more controlled and predictable reaction processes in the sample. This advancement is particularly beneficial in clinical applications like measuring titanium in blood.
The triple-quadrupole configuration helps accurately exclude interferences from isobaric elements and polyatomic ions, leading to more quantification and greater clinical interest in detecting elevated titanium concentrations, indicating joint failure in surgical reconstruction applications.
ICP-MS is poised to retain its dominance in elemental analysis due to its unparalleled detection limits and versatility. In addition, ongoing efforts to enhance sensitivity, reduce cost and interferences, and integrate with separation techniques, along with advancements in data handling and automation, will further improve the efficiency and reliability of this technique.
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References and Further Reading
Reddy, D. N., Al-Rajab, A. J., & Reddy, G. R. (2018). Biomedical and Pharmaceutical Applications of Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). InTech. https://doi.org/10.5772/intechopen.74787
Wilschefski, S. C., & Baxter, M. R. (2019). Inductively coupled plasma mass spectrometry: introduction to analytical aspects. The Clinical Biochemist Reviews, 40(3), 115. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6719745/
Agilent. (2023). An Introduction to the Fundamentals of Inductively Coupled Plasma – Mass Spectrometry (ICP-MS). [Online]. https://www.agilent.com/en/product/atomic-spectroscopy/inductively-coupled-plasma-mass-spectrometry-icp-ms/what-is-icp-ms-icp-ms-faqs
Barron, A. R. (2015). ICP-MS for Trace Metal Analysis - Physical methods in chemistry and nano science. Available from: https://chem.libretexts.org/Bookshelves/Analytical_Chemistry/Physical_Methods_in_Chemistry_and_Nano_Science_(Barron)/01%3A_Elemental_Analysis/1.06%3A_ICP-MS_for_Trace_Metal_Analysis
ICP-MS Systems and Technologies- (2023). ICP-MS Systems and Technologies. [Online]. https://www.thermofisher.com/pk/en/home/industrial/spectroscopy-elemental-isotope-analysis/spectroscopy-elemental-isotope-analysis-learning-center/trace-elemental-analysis-tea-information/inductively-coupled-plasma-mass-spectrometry-icp-ms-information/icp-ms-systems-technologies.html
Thomas, R. (2013). Practical guide to ICP-MS: a tutorial for beginners. https://doi.org/10.1201/b1492