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Advancing Chromatography-Free Mass Spectrometry in Clinical Research and Other Non-Clinical Applied Workflows

Discover how chromatography-free approaches like DART mass spectrometry streamline analysis in clinical research and toxicology.
Written byAimee Cichocki and Jeffrey Zonderman
Laboratory technician handling test tubes for chromatography-free approaches
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While Direct Analysis in Real Time (DART) mass spectrometry (MS) has been known for qualitative work in areas such as food authentication and non-clinical forensic drug analysis, recent developments are helping it move into clinical research, toxicology, and environmental monitoring.

We spoke with Jeff Zonderman, Senior Vice President at Bruker Applied MS, to discuss how DART MS is evolving from a specialist tool into a practical option for high-throughput, quantitative analysis without chromatographic separation.

From Niche to Broader Use

Historically, DART was associated with qualitative, high-resolution mass spectrometry in research and government laboratories. Applications included verifying the authenticity of food products and supporting forensic agencies in drug seizure analysis. These early uses demonstrated the value of fast, ambient ionization but did not address the requirements of routine quantitative workflows.

Zonderman notes that IonSense, as a smaller company developing DART, lacked the resources to optimize it for automation, biological sample analysis, and full integration with the mass spectrometer. With the acquisition by Bruker, recent work has focused on addressing those limitations. The technology itself has not changed at its core, but it has been refined for practical deployment—streamlined hardware, fully integrated software, and simplified operation. “The technology is similar, just optimized,” he explains, with engineering improvements producing cleaner spectra and greater reliability.

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Rethinking the Role of Chromatography

In many laboratories, chromatography steps add time, cost, and complexity to analysis. Instruments, solvents, consumables, and method development all contribute to the overall workload. By removing chromatography, DART can simplify sample preparation, reduce solvent use, and lower maintenance needs.

Zonderman emphasizes that in high-throughput settings, it is chromatography, not the mass spectrometer, that causes many of the bottlenecks. “If we remove the HPLC, you remove substantial cost, all that waste, and all the robustness and expertise requirements that DART just doesn’t need,” he advises. This can be particularly valuable for laboratories running non-clinical routine drug screens, where many target compounds are well-suited to direct ionization.

Building Confidence Through Data

Convincing scientists to change established workflows requires clear evidence. Zonderman describes how early conversations about DART often began with skepticism. Analysts wanted to see clear peaks, control for matrix effects, and ensure quantitative reliability. Over the past two years, collaborative studies have provided that evidence, with peer-reviewed publications comparing DART results to established LC-MS/MS methods.

Clinical Research, Toxicology, and Environmental Applications

In clinical research, DART is being applied to small molecule assays that benefit from rapid turnaround. Zonderman notes that many drugs of abuse respond strongly in DART analysis, making the technique well-suited for screening applications in research settings where speed and throughput are critical.

Beyond clinical research, there is growing interest in applying DART to environmental and food testing. Potential targets include persistent contaminants such as per- and polyfluoroalkyl substances (PFAS), microplastics, dioxins, and steroids, as well as pharmaceutical residues in wastewater. In these areas, the combination of rapid screening and minimal sample preparation could help laboratories process more samples while reducing operational costs and solvent waste.

The Role of Education and Collaboration

According to Zonderman, one of the main factors in building adoption has been education, providing scientists with the technical background and real-world examples needed to assess whether chromatography-free approaches fit their needs. This includes tutorials, conference presentations, and partnerships with researchers willing to challenge and validate the technology.

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He stressed that skepticism in the scientific community is valuable, as it drives rigorous testing. “Leaders in the industry are skeptical because they challenge what comes out before they support it,” he explains. Independent data, reproducible results, and credible collaborators have been essential in moving the conversation forward.

From Proof of Concept to Implementation

The discussions around DART are shifting from theoretical potential to practical deployment. Laboratories are asking how to budget for the technology, integrate it into workflows, and train staff. Zonderman described this as an exciting phase, seeing the technology move beyond proving the concept to supporting real-world adoption.

As more laboratories publish validation data and share implementation experiences, chromatography-free approaches such as DART could become a recognized option in certain routine analyses. In settings where speed, reduced resource use, and simpler workflows are priorities, DART’s ability to deliver quantitative results without chromatography may offer a compelling alternative.

Meet the Author(s):

  • Aimee Cichocki is the Associate Editorial Director at Separation Science and Chromatography Forum. Aimee brings a broad range of experience in creating, editing, and formatting scientific content. With a degree in medicinal chemistry, a 10-year background in formulation chemistry, an MBA, and a diverse background in publishing, Aimee guides editorial initiatives at Separation Science and Chromatography Forum. Aimee is dedicated to ensuring the delivery of informative, reliable, and practical content to our audience of analytical scientists.

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  • Jeffrey Zonderman

    Jeffrey Zonderman serves as the Senior Vice President of Bruker Applied Mass Spectrometry, a new division of the company focused on providing mass spectrometry-based solutions for the applied market segments such as forensics, food, environmental, industrial/polymer, and clinical research. Jeffrey graduated from Northeastern University with a bachelor’s in biology and has been involved in mass spectrometry and chromatography for over 30 years. Before joining Bruker, Jeffrey worked in applications, sales/marketing and general management roles.  His previous position was CEO of IonSense Inc, a company that was a key innovator in ambient ionization technology and commercialized DART (Direct Analysis in Real Time) technology.  As Senior VP of Bruker Applied MS, Jeffrey looks to expand the applications of DART technology, amongst others, for chromatography-free mass spectrometry based workflows with improved robustness, ease of use, cost of ownership and sustainability, in routine testing laboratories.

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