The Current Challenges in Molecular Measurement Science

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Recently, we spoke to Tom Metz of the Pacific Northwest National Laboratory (PNNL), whose career has focused on molecular measurement science using mass spectrometry (MS).

Spectroscopy can fall under the umbrella of molecular measurement science. This discipline focuses on the precise quantification and analysis of molecules, including proteins, nucleic acids, and metabolites (1). Molecular measurement science involves the use of multiple advanced analytical techniques, such as mass spectrometry (MS), chromatography, and spectroscopy to determine molecular structures, analyte concentration, and interactions of molecules in different matrices. National laboratories and Institutions like the US National Institute of Standards and Technology (NIST) contribute to the analytical sciences by developing measurement standards and technologies to support innovation and reliability in molecular analyses (1).

Recently, we spoke to Tom Metz of the Pacific Northwest National Laboratory (PNNL), whose career has focused on molecular measurement science using mass spectrometry (MS) (2–4). As part of our coverage of the American Academy of Forensic Sciences (AAFS) Conference, he discussed some of the current challenges in molecular measurement science. His response from that conversation is below.

Tom Metz: I would say that my career is focused on molecular measurement science using mass spectrometry, and particularly for trying to use that technology in the study of molecules smaller than proteins. I think the biggest technical challenge is that normally we only confidently identify and quantify a small molecule if we've seen it before, either by purchasing a version of the molecule from a reliable chemical supplier, or by acquiring a pure form of the molecule from another source. Maybe we synthesize it, and we send it through the machine. We see the signatures that the machine produces. And then, if we see similar signatures, like a blood sample, we say, “Oh, we've got this compound in that blood sample,” and we then might be able to quantify it accurately. But again, if you look at a broad chemical space, it's probably less than 1% of that chemical space you can get in a pure form and in a bottle.

And so then the question is how do we confidently identify and quantify the soup of chemicals that's in us every day, either because there are the chemicals that our bodies are producing naturally, or because I had coffee and I've got caffeine in my system, or I'm in a room that has new carpet, and the new carpet is off-gassing, and those compounds are making their way into my body interacting with my cells and receptors, and they're responding in some way. Maybe it's detrimental to my health. I'm not sure. It would be wonderful to be able to just query all these molecular interactions using tools like mass spectrometry (MS). However I feel that the current implementation of MS instrumentation, as good as it is, is delivering interesting and wonderful results out of studies that have been published. But I think we're still just scratching the surface of knowledge of that small molecule compartment in biological samples using the current implementation of MS technology. So I think that it needs to change dramatically, and that's what we've tried to do under the program that we've had here at the PNNL. Now what we need to do, or to show some discoveries using our implementation of it, is to essentially provide the proof points to the community that we need to move in a slightly new direction using MS technology.

You can view all our coverage from the AAFS Conference at the following link: https://www.spectroscopyonline.com/conferences/american-academy-of-forensic-sciences-aafs

References

  1. NIST, Biomolecular Measurement Division. NIST.gov. Available at: https://www.nist.gov/mml/biomolecular-measurement (accessed 2025-04-01).
  2. Wetzel, W. AAFS 2025: Tom Metz Discusses Developments in Field Deployment Devices. Spectroscopy. Available at: https://www.spectroscopyonline.com/view/aafs-2025-tom-metz-discusses-developments-in-field-deployment-devices (accessed 2025-04-01).
  3. Wetzel, W. AAFS 2025: Tom Metz Talks About Current Challenges in Molecular Measurement Science. Spectroscopy. Available at: https://www.spectroscopyonline.com/view/aafs-2025-tom-metz-talks-about-current-challenges-in-molecular-measurement-science (accessed 2025-04-01).
  4. Wetzel, W. AAFS 2025: Tom Metz Discusses Applying Metabolomics and Lipidomics in Studying Disease. Spectroscopy. Available at: https://www.spectroscopyonline.com/view/aafs-2025-tom-metz-discusses-applying-metabolomics-and-lipidomics-in-studying-disease (accessed 2025-04-01).
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