Non-target screening (NTS) has evolved into a powerful analytical approach for exploring the unknown across fields ranging from environmental science to metabolomics, food analysis, and industrial process monitoring. Thomas Letzel, founder and executive director of the AFIN-TS as well as associate professor at the Technical University of Munich, has been closely involved in the field’s development and continues to push its analytical and digital frontiers.
Ahead of The Analytical Scientist’s upcoming roundtable symposium, “New Frontiers in Non-Target Screening,” Letzel shares his perspective on the evolution of NTS, the challenges of managing complex analytical data, and the importance of collaboration across disciplines.
Please give a brief introduction to mass spectrometric non-target screening (NTS)?
Most people have probably heard about the topics “non-target screening,” “non-target analysis,” or “unknown analysis.” These are essentially synonyms for the same concept, formerly known as “analytical scanning with mass spectrometry (MS)” without predefined molecular targets. MS scanning is well known in its coupling (via ionization sources) with chromatographic separation systems such as GC, HILIC, RPLC, and SFC. Popular hyphenations include GC-EI-MS and LC-ESI-tandem MS. However, current NTS is much more than just instrumental analysis. Because an incredibly high amount of molecular data is produced with such systems, data handling, data processing, data evaluation, and data interpretation have become increasingly important and are now core disciplines within this analytical strategy. NTS is well established in the metabolomics sector as well as in (environmental) water analysis – both of which began adopting it almost 20 years ago – but today it is finding its way into many other disciplines, including food, pharma, chemical production, and more.
When did you first become interested in NTS, and what drew you to the field at that stage of its development?
My early days in analytical research (almost 30 years ago) involved GC-EI-MS in dioxin analysis, as well as work in a huge European consortium analyzing allergic compounds in cleaning agents (with a sniffing option). This resulted in many compounds that remained unknown – especially when they had a strong smell at the sniffing port but showed no MS signal, and vice versa. Furthermore, many of these signals showed EI spectra but had no match in the large EI databases.
Also in my early days using LC-MS scanning concepts, many signals remained without further identification. During my PhD studies, I searched for reaction products of soot compounds (such as PAHs) after reaction with ozone in cities, and later, during my postdoc, I looked for inhibitors using online enzymatic reaction assays. In both cases there were many unknown compounds.
From the very beginning, this triggered my interest in finding better possibilities to handle these unknowns from a physico-chemical point of view. Today, this is becoming a reality with all the digital options we now have, allowing us to look much deeper below the analytical surface.
What motivated you to launch AFIN-TS and what are its core aims today?
In addition to the prioritization and identification of unknown substances, the main motivation of our start-up company is to support other laboratories with NTS and with the implementation of NTS in their own laboratories. At AFIN-TS itself, we continue to pursue research into new topics in NTS and, above all, aim to answer analytical questions that could not previously be thought of or asked. So far, we have been very successful in opening up new fields and establishing NTS there. In fact, the more complex the customer sample, the more likely we are to be able to help.
At the same time, it is also a major concern for us to provide training through our consulting and further education initiatives, as well as to communicate the associated fundamentals and establish them as a basis in all laboratories. HPLC and GC, as well as MS, are just as important to us as very polar separation techniques such as HILIC and, to some extent, SFC.
Every year we give numerous online courses and, in particular, in-house training sessions (also for laboratories that do not yet work with NTS). Last but not least, I am still a university lecturer.
What do you see as the biggest scientific or practical challenges currently facing the NTS field?
Instrumental analysis such as chromatography hyphenated with HRMS(/MS) is available in many forms today and can be used very reproducibly and robustly. The greatest challenges at present, however, are the sustainable and retrospective use and active storage of analytical data. Evaluation modules based on machine learning tools, neural networks, and other data-driven approaches require machine-readable and unambiguous data (assignments).
For this reason, AFIN-TS has been working for several years on the creation and use of so-called “holistic NTS data management platforms” – such as our “NTS-Hive” – that are machine-readable, actively stored via interfaces, and usable in a FAIR way (not least in combination with LIMS archives). NTS-Hive is based on Open Semantic Lab (and realized with our colleagues from the Fraunhofer ISC), extended by structured metadata, and allows the permanent availability of NTS data and all sample-relevant information. At this level, it becomes possible to evaluate NTS data across datasets using various other evaluation programs and tools.
This enables prioritization, annotation, and identification of NTS data to be carried out more reliably and on a broader basis. It also opens up the possibility of retrospective data viewing and evaluation, and of combining it with data from quantitative analytics – something that was previously only possible with great effort or not at all.
From an analytical perspective, which techniques or workflows are currently at the cutting edge of NTS? Are there any particularly exciting developments on the horizon?
There is currently a great deal of effort going into the development of instrumental analysis, but to be honest, in my opinion it is currently more important to apply non-target screening and its robust systems in different scenarios and to ask novel and different questions. In other words, we need to “rethink analytical questions” while at the same time applying the available instrumental equipment in a robust and well-evaluated way.
This can already be supported with currently available NTS IS-mixes and data-handling platforms. Furthermore, we need to ensure that robust data processing and interpretation are carried forward into the future availability of smart digital pipelines and workflows.
NTS is now applied across many disciplines, from environmental science to food safety and human health. Why is it important to bring researchers from these different domains together, and what can they learn from one another?
There is a short answer: various disciplines with somehow similar questions use more or less identical instrumental analysis and sometimes address similar analytical questions. Thus, they are heavily driven by common digital solutions such as data processing, data evaluation, and data interpretation. In the long run, such data-driven pipelines and workflows in NTS are moving in the same direction.
Currently, we can see these trends in NIAS analysis and pharmaceutical/chemical process monitoring, which originally draw heavily on established NTS environmental analysis and untargeted metabolomics. The same is true for authenticity studies in plastic recycling, which have their basis in food fraud analysis strategies. However, we also see that these later disciplines are further pushed forward by new players entering the field. This has been made possible because different disciplines have come together – for example, at the International Conferences on Non-Target Screening (ICNTS) over the past decade.
Taking a broader view, what could continued advances in NTS mean for society at large?
We have seen a discussion emerging in recent years in the public domain. For example, several weeks ago the international journalistic consortium Correctiv reported on the (unknown) impurities in the River Rhine that are analyzed and detected using NTS. They spoke about the “bad guys” coming from industrial wastewater, but forgot that non-target screening analyzes organic molecules and not some “mysterious chemical cocktail.” These pollutants can indeed originate from industry, but also from us as consumers via wastewater treatment plants, and – at this time of year – from decaying leaves, flowering plants, and other biogenic matter that ultimately end up as molecules in the river.
It is important to approach these new perspectives in a nuanced and well-explained way, because the view should not be “black” or “white,” because it is rather mostly “grey.”
It is our responsibility to ensure that the public is involved in the discussion, so that we do things differently from the “Big Tech” AI drivers, which tend to exploit (and even celebrate) the lack of knowledge among the user community rather than educate them. This is also a major concern for AFIN-TS, as public understanding and acceptance are integral to the broader adoption of NTS. It is not easy, but we are doing our best. For example, we are in regular contact with journalists from interested circles and try to explain and contextualize the approaches being used.
Finally, what can participants expect from the upcoming roundtable webinar – and who should attend?
My hope is that everybody with an analytical interest will attend.
Participants should enjoy the various views across the disciplines and realize how similarly we think within NTS. Hopefully, everyone will feel the power of “looking over the edge” and bring home something new to their own discipline.
The New Frontiers in Non-Target Screening: Roundtable Symposium is organized in collaboration with the International Conference on Non-Target Screening (ICNTS). Interested in the upcoming ICNTS27 conference? Find more information and register for news here: https://afin-ts.de/icnts27/. And for those attending analytica 2026 in Munich, AFIN-TS welcomes visitors at Hall A3, Booth 311, from March 24–27.
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