Nuclear Magnetic Resonance (NMR) spectroscopy is an important tool in industry as well as in the scientific community. Flemming Hofmann Larsen has been a part of both worlds and has used NMR spectroscopy in a range of different fields including food and drink, health, dermatology, and metabolomics.
The collaboration between universities and the industry is one of the great strengths of Danish NMR, and Flemming is one of the many important links that secure this collaboration.
NMR spectroscopy is an almost indispensable tool in companies doing organic chemistry. 1H NMR is one of the best methods to determine quickly and effectively which compounds are in your sample. At LEO Pharma they are using walk-up instruments with autosamplers, where the chemists can insert their samples and select the spectra they need. The software then forwards the results to the scientist’s own office, where they can work with the data themselves.
“The use of NMR spectroscopy in the industry does not differ much from how it is used in the academic world. It is one of many analytic tools used to characterize the structure and function of product samples. Regarding NMR, the universities and the industry are deeply intertwined”, explains Flemming Hofmann Larsen, Principal Scientist at LEO Pharma.
Flemming Hofmann Larsen took his masters’ degree in chemistry at the University of Aarhus (AU) with a focus on solid-state NMR and did his PhD at the same university continuing his research within the field of solid-state NMR. After finishing his PhD and a post-doc at AU, he was hired as a materials consultant at Danfoss and then as post-doc at Department of Earth Sciences in Cambridge.
He then spent three years together with Flemming Poulsen at SBiNLab, at the University of Copenhagen (UCPH) where he did 3D structural assessment of proteins and had responsibility for the NMR equipment.
After SBiNLab he went to the Department of Food Science at The Royal Veterinary and Agricultural University (merged with University of Copenhagen in 2007) in the group of Søren Balling Engelsen. Here he used NMR spectroscopy to study both fluids, gels, and solid materials such as juice, wine, coffee, tea, cheese and bread, but also specific food ingredients such as starch, pectin, milk protein and plant extracts.
During his time at UCPH, he was also involved in metabolomics on serum and urine from animals or humans obtained in nutritional trials. The objective of these studies was to investigate changes in the metabolite profile due to a specific diet for the animal or person.
In 2018 Flemming got a job at LEO Pharma. Today he is principal scientist and responsible for NMR spectroscopy in the analytical characterization group at the company. This includes both solid-state and liquid-state NMR. Structural determination is one of his main assignments, as this information is needed for documentation for approval by the authorities.
“Sometimes I characterize the active molecules, other times I investigate how the active molecules interact with other substances (excipients) in the product. From these experiments we produce data supporting eg. the required stability of the product according to the climate zone it is intended for.”
“NMR is a wonderful technique for such tasks, which illustrates the versatility of NMR. All these NMR data and much more other kinds of data are needed to obtain the final approval of the product by the authorities.”
NMR can make better coffee
“Like with proteins and pharmaceuticals, where you want to observe the interactions between, for example ligands and proteins, in food science, you want to observe the relationship between carbohydrates, lipids, peptides, and proteins.”
One example of Flemming’s research fields is coffee, which many would call an utmost important field of research within the scientific world. During his research, he looked at how coffee changed at different temperatures and how the degree of roasting, light, medium or dark, changed the taste and stability. He also made the coffee at different temperatures to find out exactly what temperature was optimal for a specific coffee quality.
At UCPH Flemming taught on a course about beer brewing and wine making, where the students eg. looked at different beer types as Lager, IPA, brown ale and how the types differed in alcohol percent, but also how there was a difference in the small organic acids in the beer, and how this effected the taste. This is a great example of how closely related the food industry and biochemistry are.
“One surprise for us as teachers on this course was how many of the students attended the course without having the proper biochemical background because they thought it would be an easy course. They soon realized that the process of producing fermented beverages required scientific knowledge.”
Collaboration and difference between NMR at universities and in the industry
Back when Flemming was at UCPH, he collaborated with eg. Danisco (now IFF), KMC, CP Kelco, Novozymes and Chr. Hansen. With Danisco for instance, fermentation of milk by lactic acid bacteria were studied by time series of 1H NMR spectra, where yoghurt was produced in the NMR tube while situated in the magnet; a unique way of using NMR spectroscopy providing valuable information for understanding the processes in the industry.
Today, Flemming collaborates with other universities and companies. The Annual DANNMR Meeting, which he and colleagues at LEO Pharma organized in 2023, is a great example of the close collaboration within the Danish NMR community. With around a hundred participants this year, from all the six Danish universities and a dozen different companies, it illustrates how well functioning the collaboration is. As a reoccurring event, with a new organizer every year, it is safe to say that many people invest in making this collaboration work.
Flemming also collaborates with universities by taking in master and PhD students, for them to write their projects in collaboration with his company. A popular way of writing a project.
Right now he has an industrial PhD together with Birthe Kragelund at UCPH, where the student gets the opportunity to be part of both worlds.
Strength of Danish NMR
“There is great collaboration between the universities and the industry in Denmark compared to many other countries, where this cooperation can be quite complicated.” Flemming says. He also believes that despite our small size as a country, Denmark ranges very widely technically in the NMR field; some people are looking at proteins and biological systems with liquid-state NMR, while others are looking at cement and environmental samples by solid state NMR.
“One subject, which could be explored further by NMR in Denmark, would be bioethanol and biomass, but otherwise I feel we are well covered.”
“Denmark has a high percentage of NMR instruments compared to its population”, he emphasizes “In this context the user facilities at UCPH, DTU and AU are a great advantage, as this allows for access to high magnetic fields or special probes that are not available in other Danish NMR laboratories.”