Concerns about PFAS contamination in water, soil, food, packaging, and personal care products are growing as more studies link these compounds with adverse health effects. Though the U.S. Environmental Protection Agency (EPA) has recently enacted guidance for monitoring PFAS compounds in drinking water, laboratory testing is the only way to know whether someone has accumulated high levels of PFAS in their body. While clinical laboratories worldwide have started offering PFAS testing for human samples, one thing is clear: The number of known PFAS compounds and isomers is high and challenging to resolve with traditional chromatography.
PFAS research and toxicological studies
While research is ongoing on the health effects of PFAS, there are more than 9,000 currently known PFAS compounds, and likely many more will be added to that list in the future. Some of these compounds are isomers with linear or branched molecular structures and can impact toxicity or other chemical properties.
From a screening and regulatory perspective, this poses a unique challenge that Fred Strathmann, PhD, Clinical Laboratory Improvement Amendments (CLIA) laboratory director and the senior vice president, US Business, MOBILion Systems, Inc., highlighted: “I think the challenge right now is even in the environmental world, they are still struggling with which specific compounds we should be looking at. Are isomers important? Are the branched forms worth separating? Are they more meaningful? Is it the linear form that we need to think about? Many toxicology and clinical studies still need to be done to understand whether these are causative effects or correlations.”
Techniques like ion mobility may effectively address this challenge. In addition to the advantage ion mobility offers for separating structural isomers, it may shorten run times by reducing reliance on liquid chromatography. Although extensive population studies with thousands of samples will be required to better understand the health effects of PFAS in a human population, per Strathmann, the time needed to run each sample is critical: “In something like PFAS, where if you have a 20-minute run time, that's three samples per hour you can get through.” Strathmann believes that the separation power of ion mobility can help cut down the run time to five minutes or less, depending on the degree of separation of branched isomers required.
Ion mobility as a clinical testing tool
The introduction of ion mobility paired with mass spectrometry in the last decade opened many analytical possibilities to address scientific problems, particularly when standard liquid chromatography/mass spectrometry (LC/MS) couldn’t provide adequate resolution and/or specificity for biological research. Ion mobility works by separating molecules based on their size and shape as they move through an inert gas under the influence of an electric field. The time molecules take to move through is directly or indirectly related to their collision cross-section—a parameter often referred to as a unique molecular identifier. Ion mobility offers a new analytical option for branched PFAS isomers that can’t be chromatographically resolved from their linear counterparts.
However, ion mobility may add to the complexity and cost of testing and take up valuable bench space in smaller clinical labs. While companies like MOBILion have introduced cutting-edge features, the challenge of analytical complexity with LC/MS persists for clinical laboratorians Could ion mobility make mass spectrometry robust and knock out the need for liquid chromatography?
Probably not entirely, according to Strathmann: “There’s too much complexity in biological samples to just send it right into the mass spec because you still have to deal with ionization and suppression.” However, he believes that ion mobility could reduce our reliance on liquid chromatography (LC): The LC could introduce samples and reduce matrix effects and ion mobility can separate analytes of interest according to their collisional cross-section (CCS).
Ion mobility and LC: A powerful duo
Strathmann added that ion mobility can make clinical mass spectrometry easier: “If you ask the average clinical mass spectrometrist whether mass spectrometry is difficult, they’ll usually say it’s a challenging technique but most of the difficulties they discuss are on the LC side.”
By using the LC as a matrix removal tool and relying on ion mobility as a separation technique, we can reduce the complexity of multi-analyte assays—which is one of the reasons to rely on LC—and yet maintain reproducibility. In doing so, we can make clinical mass spectrometry an even more powerful, robust, and user-friendly testing method for clinical laboratories.