Ron Heeren Ron Heeren Harry Heuts

“Designing a device is like painting a picture”

Written by  Annelotte Huiskes Thursday, 25 September 2014 10:50

Deducing from a single hair what drug a person has taken and when, to within an hour’s accuracy. This is just one of the possibilities offered by mass spectrometry (put simply, the photography of molecules). Ron Heeren is a specialist in this technology. As of 1 September, Heeren is a ‘university professor’ in Maastricht, a special post granted on the basis of his scientific achievements. His research group in Maastricht will focus on medical applications of the mass spectrometer. “It’s a fantastic tool for personalised medicine”, he says. Together with fellow university professor, the nanobiologist Peter Peters, he is joint head of the new Maastricht MultiModal Molecular Imaging Institute (M4I). With the launch of the M4I, Maastricht is now the largest imaging centre in Europe.

Heeren has been fascinated by technology for as long as he can remember. As a boy, he took radios apart and used the parts to build a new one. In fact, this is what he still does – only with mass spectrometers instead of radios. “You have to understand devices. Designing a device is like painting a picture. It’s a whole creative process: to capture the final image, you have to know your tools inside out. You have to know what every brush, cloth or paint does. It’s no different with a device. What does the vacuum do, how do these particles move through that device, what happens when those particles are detected, how do they fall apart? And how can I influence that process? For me, it’s great fun to teach my students and PhD candidates to understand a device and solve complex problems together.”

The best of three worlds

The technology of the mass spectrometer is the common thread running through Heeren’s career. After his PhD on nuclear fusion at the high-tech FOM Institute for Atomic and Molecular Physics (AMOLF) in Amsterdam, he decided to transfer within the institute to biomolecular research. He was keen to see results in his lifetime, he explains, and that was unlikely with nuclear fusion. “To try to understand biomolecules is to try to understand the complexity of life. It’s a puzzle that makes putting a radio together pale in comparison. But the minute you find a piece of the puzzle, you can make a real difference. It’s the best not of two but of three worlds: technology, science and social relevance.”

Anatomy lesson

In 1992, Heeren was among the first in the world to build a mass spectrometer that enables users to examine large, intact proteins. Three years later, he pioneered the use of this technology in the study of molecular processes in painting. “The idea behind the MOLART project, led by Jaap Boon, was to investigate the ageing processes of paintings using mass spectrometry. My students and I developed techniques to prepare samples from paintings for analysis with the imaging mass spectrometer. We were involved in the research for the restoration of Rembrandt’s The Anatomy Lesson of Dr. NicolaesTulp.”
“A microscope only sees colours; the mass spectrometer sees the particles that the colour is made of. Say you’re studying a painting with a blue plant. Why are the leaves blue? With a microscope, you might see transparent particles and blue particles. The transparent ones may once have been yellow, but you can’t see that. With a mass spectrometer, however, I can see which molecules those transparent particles are made up of; for example, that the original yellow particles have become discoloured, turning the green leaves blue. Shedding light on the molecular composition of these particles helps us to understand the ageing process of a painting.”

Living tissue

The next challenge was to apply these molecular imaging techniques to living tissue. In 1997 Heeren set up his own research group at the AMOLF, developing new techniques for the rapid imaging of relatively large surfaces (200 x 200 microns). “On the surface of a cell you can see the molecules that determine how the cell organises itself. In stem cells, molecular signals determine whether a stem cell will develop into, say, cartilage or a lung. The same molecules also regulate processes of health and disease. Understanding these molecular signals enables us to manipulate them, which can be of interest for the pharmaceutical industry. For instance, in collaboration with the Netherlands Cancer Institute, we’ve examined a whole series of tumours. The technology lets us see exactly which cells on a tissue section are healthy, which ones are next to be infected, and which ones are already diseased or dead. And that in turn says something about which treatments will and won’t work. This is becoming a key driver in medical practice: personalised medicine.”


According to Heeren, imaging is an excellent diagnostic and prognostic tool that pathologists could use to analyse biopsies. “Unfortunately, very few pathologists are familiar with these possibilities. This is another reason to make the transition to clinical practice in Maastricht after 25 years of fundamental research at a top institute like AMOLF. Fundamental research is important, but you have to be able to validate new methods. You can only do that if you have access to a bio bank with donated tissue material, and researchers who are enthusiastic about innovative techniques and want to contribute to translational research. Maastricht has a huge bio bank with all sorts of tissues that we can use for our validation studies. I dare to predict that in ten years’ time, this imaging technique will be a standard diagnostic tool and patients will be assessed on their individual molecular status. We’re already well on the way in oncology, neurology and cardiovascular medicine – three fields that feature prominently in Maastricht.”


But the clinical applicability of mass spectrometry is not limited to diagnostics. Heeren is already in discussions with surgeons at the MUMC+ on the iKnife, an application of molecular imaging developed by a colleague. During an operation, the knife analyses the molecular information from the smoke that is released when you cut tissue. It then gives a red light if it detects tumour tissue and a green light if it doesn’t. “This helps the surgeon remove the tumour with extreme precision, which improves the patient’s prognosis and healing process. We aim to further develop this intra-operative mass spectrometry here in Maastricht.”
Another draw card for Heeren was the potential for investment in equipment and people through the Kennis-As programme in Limburg. The new M4I institute, which consists in Heeren’s mass spectrometry lab and Peter Peters’s nanoscopy lab, is already the largest imaging centre in Europe. “Our high-resolution techniques make the processes in cells visible, but understanding them is an entirely different story. We’re only just starting to gain insight into this remarkable process. But what I enjoy about it is precisely this complexity. Or as my hero Richard Feynman [the physicist and Nobel Prize winner] put it: ‘the inconceivable nature of nature’.” 


Ron Heeren (1964) obtained his PhD on plasma-surface interactions at the University of Amsterdam in 1992.After two years of post-doctoral work on FTICR mass spectrometry he joined the MOLART research team at the FOM-Institute for Atomic and Molecular Physics as a project leader, heading the instrumental developments for paint cross-section analysis in early 1995.After working as a postdoctoral researcher on mass spectrometry for two years, in early 1995 he joined the MOLART research team at the FOM Institute AMOLF.In 1999 he started a research group focussing on macromolecular ion physics with high resolution mass spectrometry and the development of imaging mass spectrometry at AMOLF.Four years later, he started a research group focusing on the development of mass spectrometry imaging. He was appointed professor at the Faculty of Chemistry in Utrecht in 2001. As of 1 September, Heeren is university professor at Maastricht University. 
More information about the Maastricht MultiModal Molecular Imaging Institute (M4I).
Also watch the video portret of Ron Heeren.


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