Lab Manager | Run Your Lab Like a Business
Gloved hand holds a flask in a lab
iStock, MadamLead

An Overview of Ultrasensitive Trace Metal Analysis

Advanced techniques overcome challenges with ultra-low detection levels

Aimee Cichocki

Aimee Cichocki, BSc, MBA, is the managing editor for Separation Science. She has a decade of experience as a development chemist. She can be reached at

ViewFull Profile.
Learn about ourEditorial Policies.
Register for free to listen to this article
Listen with Speechify

Trace metal analysis is a critical tool in a wide range of scientific fields, from environmental monitoring to biomedical research. The goal is to detect and quantify low levels of trace metals, often providing insight into complex processes and helping to ensure product quality and safety.

Trace metals are those that are present at an average concentration below 100 parts per million. But factors such as advanced research into the potential negative impacts of trace metals and increasingly stringent regulations mean there is demand for increased accuracy (and higher sensitivity) in trace metal analysis data.

Get training in Technical Safety Topics and earn CEUs.An IACET-accredited five-course stream in the Academy.
Technical Safety Topics Stream

Traditional methods for trace metal analysis include atomic spectroscopy and X-ray fluorescence, but these offer relatively low sensitivity. However, the advent of new technologies and techniques makes ultrasensitive

analysis possible, and scientists can now detect and quantify even the smallest levels—part per trillion—of metals and other elements.

Of course, detection at such low levels comes with challenges. And as is the case with many analytical methods, there is continued demand to increase speed while reducing complexity and costs.

Key applications of ultrasensitive analysis

Ultrasensitive trace metal analysis is used for a wide range of applications in which it’s helpful to detect and quantify extremely low levels of metal ions. These often pertain to cases where trace metals might pose health or safety risks. Metal ions play essential roles in various biological processes, for example, helping to facilitate oxygen transportation and acting as catalysts in enzyme systems. But even very small amounts of certain metals can negatively impact human health.

As industry regulations tighten, it's essential to detect and quantify these trace metals to ensure compliance with standards and guidelines.

As such, it’s no surprise that ultrasensitive analysis is considered crucial in the pharmaceutical industry, where it can help ensure the quality and safety of drugs. Potential sources of metal ions in pharmaceuticals include catalysts used in the production process, contaminants present in raw materials or reagents, metal manufacturing equipment, and packaging materials. It’s a similar case for food and beverages, as well as other consumer goods, such as dietary supplements and cannabis products. 

Another key application of ultrasensitive trace metal analysis is in environmental industries, where it is used to monitor levels of heavy metals and other contaminants in water, soil, air, and tissue. These contaminants can negatively impact the environment as well as human, animal, and plant health. As industry regulations tighten, it’s essential to detect and quantify these trace metals to ensure compliance with standards and guidelines. 

Core techniques used for detecting trace metals

A common technique used in trace metal analysis is inductively coupled plasma optical emission spectroscopy (ICP-OES). This relies on emission spectra to identify and quantify elements. However, its sensitivity is limited to parts per billion, so ICP-OES is only suitable if regulatory levels are correspondingly high.

Significant advances in instrumentation and techniques have paved the way for far lower detection levels. The primary technique used in ultrasensitive analysis is inductively coupled plasma mass spectrometry (ICP-MS). In this method, an aerosolized sample is ionized using hot argon plasma, and ions are sorted based on their mass-to-charge ratio.

ICP-MS is highly sensitive and can detect metals and other elements at levels as low as parts per trillion or even quadrillion in some cases, depending on the equipment. This technique can analyze almost any element, including isotopes, and handle solid, liquid, or gaseous samples. It can measure multiple elements in one run, even those present in vastly different quantities (for example, major versus trace elements).

While ICP-MS dominates the field, other technologies are in use or under investigation for application in ultrasensitive analysis. For example, graphite furnace atomic absorption can achieve levels of detection below parts per billion. That said, it has several limitations, including slow processing times and the ability to analyze a small number of elements. Other exploratory techniques in this field include the use of carbon nanotube microelectrodes to detect heavy metals at parts per trillion levels in drinking water and the application of thin film optical coatings to detect ultra-low concentrations of heavy metal ions.

Challenges in the field of ultrasensitive analysis

Dealing with extremely low detection levels comes with inherent challenges. One of the key hurdles is interference, particularly spectral interference, which can compromise the accuracy of results. In ICP-MS, spectral interference occurs when the signal from a specific ion of interest is affected by the presence of other ions with similar mass-to-charge ratios. This can lead to inaccurate measurements or difficulty in detecting certain ions.

To mitigate this, various interference removal systems are used. The system will depend on the application, but the two primary methods of interference removal are collision reaction cell (CRC) technology and high resolution technology. The latter is physical and uses magnetic and electrostatic fields. CRC technology is the most commonly used technique for interference removal and uses either a single quadrupole or triple quadrupole system to remove interference.

Ultrasensitive analysis techniques offer incredibly powerful tools for measuring trace elements at extremely low levels.

Another obstacle comes in the form of noise. Instruments usually show a background signal, even when not being used. The signal can fluctuate, causing what’s referred to as background noise. When analysis is underway, the signal will change in response to the presence of the substance (this change is called the analyte signal). The signal-to-noise ratio compares the strength of the desired signal to the level of background noise. In ICP-MS, it’s important to have an optimal signal-to-noise ratio, particularly when stringent regulatory requirements apply.

Of course, as analytical techniques become more intricate, equipment costs inevitably increase. Added complexity can also mean that a high level of expertise is required to execute analytical protocols, resulting in increased hiring and training costs. In addition, advanced features may lead to longer analysis times, which can be limiting for high-throughput applications. As such, an overarching goal in ultrasensitive analysis method development is to create fast, simple, cost-effective methodologies.

Ultrasensitive trace metal analysis plays a critical role in ensuring the quality and safety of products, monitoring and protecting the environment, and advancing our understanding of the role of trace metal ions in various fields of science. Ultrasensitive analysis techniques offer incredibly powerful tools for measuring trace elements at extremely low levels. While these technologies come with their own sets of challenges, advancements in the field are allowing scientists to uncover new insights and meet increasingly stringent regulatory requirements.