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Techniques & Tools Mass Spectrometry

Enlightened, Empowered: The Ion Magician

How did you find your way into analytical science?

I was always good at math and science in high school, but I didn’t really like it initially – I actually wanted to be a politician or historian, but did not have the prerequisites required for these studies in the German system. So I took a year out to travel, mostly hitchhiking, through North America. Upon returning, my advisor at the University of Freiburg told me that I should study what I am good at. He took one look at my record and recommended chemistry... Needless to say, I do like science now... and considering the political situation today, I definitely made the right decision.

You tend to stir up controversy – is that a hint of politics coming through?

It is true that I have been controversial (though less so nowadays), but it’s not because I want to be political; if I could, I would lay low! Somehow, our research accomplishments stirred the pot. At the beginning of my PhD, I educated myself, read the right papers, and applied that knowledge to new problems – a very traditional approach. But my PhD co-advisor – Hans-Joachim Rӓder – at the Max Planck Institute for Polymer Research sent me down a different path; he reminded me that there is a world outside of the literature. It’s a piece of advice that I took to heart. I certainly acknowledge and build on what has been done, but I also realize that there is much more that hasn’t been done – and my approach is freer as a result. We do some crazy experiments that other people don’t do because they think it will result in failure. I think there are great opportunities out there – it’s how we stumble upon cool things. One of my mottos is: “If I can do it, why shouldn’t I?”

“Crazy experiments” and funding models don’t always go hand-in-hand... How do you find a balance?

I was extremely lucky. I did my initial crazy experiments when I became assistant professor at Wayne State; I still had plenty of money in the bank, so to speak. But I didn’t have my own mass spectrometer back then (I was waiting for a second generation instrument) – I made my first discovery because I twisted the arm of a colleague and used his instrument to test a laser-assisted ionization concept that I’d had in mind for two years ... and it worked! I made the discovery in spring 2009, and then my student presented it at the ASMS conference just a couple of months later. I wrote my first grant on the topic in July 2009, and received a National Science Foundation (NSF) Career Award... I was off to a good start! I guess there was a whole bunch of luck that just came together at the right time, but it meant that I was able to create more and more evidence, which led to more discoveries and more funding. To answer your question: I think the funding agencies are interested in the crazy (step change) stuff, but they also want to play it safe – so you need at least some evidence... and a plan.

And did everything go to plan?

We had lots of ideas about what we had discovered, and what the next steps should be – and guess what? We applied our knowledge, and it was plain wrong! Nevertheless, I saw a great opportunity, and others wanted to join me on the journey of discovery. One of my students, Ellen Inutan, performed an experiment that delivered something totally unexpected: we discovered that we didn’t need to use anything for ionization with our matrix – no laser, no voltage, no heat, no desolvation gas. If you simply put the matrix:analyte close to the vacuum of a mass spectrometer, you create ESI-like ions and with exceptional sensitivity – it’s what we now call matrix-assisted ionization (MAI). It went against everything we (and everyone else) knew – I sometimes refer to it as “magic” ionization, poking a little fun at early criticism (1).

How have you dealt with criticism?

In the beginning, it was a tremendous problem – we got one rejection after another. Not even the ‘lower level’ journals wanted to publish our manuscripts. It was particularly concerning because we knew how important it was and how easily this could have been reproduced and published by another group. On one occasion, I was told by an associate editor from a high-end journal, “A reviewer sent me a personal note, stating, ‘the investigator is a woman, she’s only from Wayne State University, she is young... and she’s only out for big hype.” I replied, “Do you honestly think I work this hard just for one big-hype paper?”  Her somewhat understandable reply was “I simply can’t take the chance that this established reviewer is correct” and she stuck with her decision not to publish our work. Several months later the article in question and three more on different aspects of MAI were published in other journals. Including movies with our papers and oral presentations really helped – sometimes people just need to see things with their own eyes. The community now accepts our work – and my students and I have been honored with numerous accolades, despite or because of the previous criticism.

It certainly paid off – you started MSTM to commercialize MAI with Charles McEwen...

Right. Up to now, we’ve been working with MS systems that are optimized for ESI and MALDI. Imagine what we could do if we have a source that is tuned to do this new ionization process. Charles McEwen and I are inventors of several issued patents on ionization, so it was a natural fit. We applied for NSF funding and went through STTR Phase I right away, and we are now in STTR Phase II. NSF has been extremely good to us; they provide  opportunities and I’ve been very happy to be part of bringing fundamental research to commercialization.

I not only try to pass on knowledge – but also the strength to be confident and open-minded.

How do you motivate your students to follow “crazy” ideas rather than staying on the tried and tested path?

I try to take away some of the fear. Ellen Inutan was actually my first graduate student, and I remember how scared she was about “destroying” our first mass spectrometer – she didn’t want to touch it! Sure, it was an extremely expensive instrument, but I told her, “If we break it, we can fix it!” It’s actually mind-boggling how intimidated some students can be – especially women. As a community, we need to invest more in the education of our students; they need to be free enough – financially and emotionally – to do the crazy stuff. Many discoveries have been made by students who didn’t follow the ‘script.’ If we can encourage students (and their mentors) to take chances, we will absolutely make more progress in science. I not only try to pass on knowledge – but also the strength to be confident and open-minded. Good role models are essential. I had very strong women in my family; my mother, my aunts, my grandmothers – they all followed expectations only as much as they needed to... The apple did not fall far from the tree.

Any outstanding research from other groups this year?

Oh yes, there are many groups doing amazing research in mass spectrometry! The cryogenic ion mobility mass spectrometry work by David Russell and the fundamental studies also in collaboration with David Clemmer are extremely interesting to me. I’ve also seen a couple of really cool talks on SLIM (structures for lossless ion manipulation) from Dick Smith’s group at PNNL. I was blown away. The ion mobility spectrometry (IMS) resolution boost gained by the use of long-path SLIM devices is astonishing. The technology is a step change in my eyes – mass spectrometry as we know it could even become obsolete. Just kidding – but it is mightily impressive...

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  1. S Trimpin, “‘Magic’ ionization mass spectrometry”, J Am Soc Mass Spectrom, 27, 4–21 (2016).
About the Author
Rich Whitworth

Rich Whitworth completed his studies in medical biochemistry at the University of Leicester, UK, in 1998. To cut a long story short, he escaped to Tokyo to spend five years working for the largest English language publisher in Japan. "Carving out a career in the megalopolis that is Tokyo changed my outlook forever. When seeing life through such a kaleidoscopic lens, it's hard not to get truly caught up in the moment." On returning to the UK, after a few false starts with grey, corporate publishers, Rich was snapped up by Texere Publishing, where he spearheaded the editorial development of The Analytical Scientist. "I feel honored to be part of the close-knit team that forged The Analytical Scientist – we've created a very fresh and forward-thinking publication." Rich is now also Content Director of Texere Publishing, the company behind The Analytical Scientist.

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