The day started off with a blue sky and a warm sun shining down on almost 50,000 ambitious runners who were ready to embark on a legendary journey of 42 kilometres and 195 meters through the streets of Rotterdam. In the hours before the start, all signs indicated that it would be a warm and dry day, hence a good friend of mine, who I was supporting that day, decided to wear some short shorts and a sleeveless shirt. Still, he did not fully trust the Dutch weather and weather predictions, so he asked me to bring along his running jacket and to remain on standby during the race for the unlikely situation that the weather conditions would change.
Well, the weather did change, and the entire city got covered with rain clouds in a matter of minutes just before the starting signal would be given. For a brief moment, I tried to find my friend to hand over his jacket before his race would start, yet I soon realized that it was quite difficult to locate him standing in a crowd of 50,000 runners. I thus decided to take a firm sprint of roughly 2 kilometres and to subsequently line up alongside the route where the transfer could take place. Because at that point, the crowd would be more spread out over the marathon course due to the varying running paces of the different runners, hence it would be easier for me to spot him there.
The reason for sharing this story is that it features a principle that can readily be translated to the work I do and thus can help me explain my work a bit further. Instead of crowds, however, I work with complex human materials such as blood and urine which contain thousands and thousands of interesting molecules. Instead of a marathon course, I work with a separation technique called ‘liquid chromatography’, or LC, which allows for the separation of these molecules. And instead of my eyes, I use the technique called ‘mass spectrometry’, or MS, to detect the molecules, which can typically be done much more reliably if they reach the detector alone (or in small groups) as compared to when no separation is applied.
With regard to LC separation, the numerous molecules in our blood and urine have different properties, just like you and I may have different heights, weights, hair colors, or running paces. When using LC, we use cylinders packed with tiny particles, and the particles we use determine the nature of separation we will achieve. To illustrate, imagine that we have a diverse group of people standing at the beginning of a long street, and that we wish to use this long street to separate the adults from the children. In such a case, you could fill the street with all kinds of toys which will slow down the children while the adults will likely continue walking and reach the end of the street first. With LC, we play around with different types of particles that can, for example, slow down fat-loving molecules, water-loving molecules, small molecules, large molecules, et cetera, and we often need to select and optimize the separation conditions that best fit the molecules we are interested in.
Thinking back to my time in Groningen, I remember working in a field in which our group had years and years of experience, and the available LC and MS instruments had already been operating under optimal conditions for years. Moreover, instrumental errors did emerge occasionally, yet these errors were typically not resolved by us students, as our group had an excellent team of technicians who could carry out almost any type of maintenance work needed to resolve the issues caused by us. Nonetheless, my PhD provided me with loads of ‘hands-on’ experience in our field of research, yet the experience I gained was limited to preparing samples, operating instruments, and processing analytical data, and I clearly lacked experience with maintaining the instruments.
When joining my current group, I could, again, benefit from enormous amounts of ‘in-house’ experience, and the instruments I intended to use for my project were fully functional within a day, thanks to three of my colleagues. Admittedly, they did the actual work, and I stood behind them with my hands in my pockets trying to remember everything they said and did. But this time, I was truly committed to becoming self-supportive to a certain degree, as practical knowledge of the technologies used in blood and urine testing is key to realizing true developments in the field. The recent COVID-19 pandemic has, for example, taught us that problems occur when we need to rely on commercial ‘black box’ instruments and on a lab full of people like me who know how to start measurements while not fully understanding the technical principles and being amply capable of developing novel tests ourselves.
Where am I today? Well, with joy and some pride I can state that I am really getting the hang of it. In the last year, I did not only become responsible for my own LC system, which I treat as if it was my own child, but I also became responsible for a similar type of instrument. This system is a bit older than ‘mine’ and needed to be checked, cleaned, and revised before it could be used again. I did initially postpone this work to really get to know my own system first, but in the last weeks I successfully revived the other system, while occasionally taking some advice from my colleagues (of course). This system is now continuously being used by our group’s newest PhD student, who happens to be my former Master’s student, I am looking forward to sharing my recently acquired knowledge with her and to do some exciting scientific projects together.
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