On an IM-MS Crusade

Did you always want to be a scientist?
 

In elementary school I wanted to be an archaeologist – likely because I was obsessed with the Indiana Jones film series, which blended my two favorite school subjects: history and science. Though history became more of a hobby, science remained part of my dream career in some form or another. In middle school, I gravitated towards geology and geochemistry (I got my first taste of lab work in an Earth science class). Once I reached high school, I became interested in chemistry whilst taking some excellent courses and interacting with wonderful science teachers. These experiences really opened my eyes to another area of science – and I’ve never looked back.

What drew you to analytical science?
 

I had an excellent introduction to the concepts of chemical measurement science in middle school and high school, but it was my undergraduate education that solidified my journey toward analytical science. At Saint Louis University, I conducted research with Dana Spence and engaged in problem-solving aspects of different forms of spectroscopy – from NMR to IR analysis. Mass spectrometry didn’t click for me until I attended a talk by J. Throck Watson, who visited the university to talk about his research. He opened up a new world for me and I’ve been infatuated with mass spec ever since.

You regularly work with Ion mobility-mass spectrometry (IM-MS) – where do you expect this technique to go in the future?
 

IM-MS has been on a strong growth trajectory for the past three decades. This growth has dramatically accelerated through the plethora of instrument companies now offering IM-MS equipment. Fundamentally, the excitement in IM-MS has been driven by its ability to provide additional capabilities and information content across several important application areas. These include (but are not limited to) those endeavors associated with complex mixture analyses, mass spectrometry imaging (MSI), and structural biology. I would expect the impact of IM-MS within these areas to intensify in the future as new IM-MS technologies and data sets are developed.

Additionally, as next-generation IM-MS technologies, such as SLIM and cyclic IMS, emerge, it is evident that there is a need for a renewed community effort to establish collision cross-section (CCS) standards. After all, many CCS measurements from these systems rely on outdated data (over 15 years old) generated using less sensitive equipment with 10-100 times lower ion mobility resolution.

In the immediate future, I’m particularly excited about conducting high-dimensional ion mobility experiments alongside mass spectrometry; for example, IM-IM-MS. I believe this approach will significantly enhance the impact of IM-MS in quantifying molecules within complex mixtures – an area usually dominated by conventional liquid chromatography (LC)-MS/MS methods. Moreover, despite the current large size of most IM-MS instruments, I anticipate that we’ll see a trend towards smaller, bench-top versions in the future – especially as the technology begins to touch a wider array of measurement science areas.

What trends are you seeing in protein and biopharma analysis?
 

There are several developments currently taking place in biopharma that offer an interesting set of challenges for those of us in the mass spec technology space. Overcoming challenges like throughput and automation in data collection and analysis has been a long-standing issue for MS-based assays. However, there are many developments, including those supported by AI, that are poised to make various MS-related assays and information accessible to biopharma researchers at a pace that aligns with their throughput requirements. 

In biophysics, ongoing structural MS developments hold the potential to significantly reshape protein and nucleic acid engineering challenges. I anticipate continued progress and investment in these areas over the years; as we explore the potential of MS-related techniques in conjunction with established biophysical assays and computational approaches, we’ll see enhanced development and improved biotherapeutics.

You were awarded the Biemann Medal at ASMS 2023. What do awards like this mean to you?
 

The Biemann Medal was a wonderful surprise – I probably incoherently babbled to Julia Laskin, the current ASMS President, for a while when she told me last year! Recognition through awards like this is always extremely gratifying, but I really feel like a spokesperson for the researchers in my lab and the broader mass spec community, who, in my view, are the real reason our work gets any recognition at all. It’s been an absolute pleasure to see how this dynamic and exciting field has developed over the past 20 years, and I can’t wait to see what the future holds!

What is the biggest challenge facing the field? And how can we overcome it?
 

There are so many big challenges to choose from, it’s hard to select just one as the biggest! One notable challenge is the ever-present dynamic range problem associated with complex mixture analysis. This was highlighted at the inception of MS-based proteomics and remains a difficult problem, despite progress. 

Closer to my own area of work, validating gas-phase measurements of biomolecular structure for structural biology and, by extension, biopharmaceuticals is still a formidable challenge. However, in the broader realm of mass spectrometry, the current primary hurdle is the increasingly prohibitive cost of MS equipment and related information. Speaking specifically about proteomics, upcoming disruptive protein sequencing technologies may challenge the dominance of MS in that area. The response of the MS community to these emerging technologies remains to be seen…

How can mass spectrometrists continue to make a substantial contribution to science and society?
 

One of the strengths of the mass spec community is our active and vocal communication. ASMS has been an outstanding conference and vehicle to showcase what our field is all about, giving us a place to engage with the broader scientific landscape. In the future, I would look to ASMS to lead in this area, alongside a smaller group of growing meetings, including the Advancing Mass Spectrometry for Structural Biology and Biophysics (AMS) meeting. These groups should take on an important role in showcasing MS-related science and provide additional venues for active community growth and outreach. Despite progress in the past, there’s much more work to be done regarding diversity and inclusivity in these spaces, and these efforts should be accelerated to maximize the impact of MS-related science.

What advice can you offer to the next generation of analytical scientists?
 

Everyone has their own career journey, so looking through the prism of one experience can give young people a skewed view of how to be successful. That being said, it’s important for young scientists to work hard and cultivate their career options through every avenue open to them. In short, I’d say: “Be fearless in selecting your options and take advantage of all opportunities available to you!”

What are your hopes for the future?
 

My hopes for the future are quite personal. When I look at my children, I suppose I do what all parents do and hope we can make the world a better place. As scientists, we hold even more responsibility to shape the future and use our discipline to leave the world better than we found it.

If you hadn’t pursued a career in analytical science, what would you be doing?
 

I’d hope I’d have converted one of my other passions into a career – maybe history or cooking. Neither of these would have provided me with the career I have today, so I’m very happy that things worked out the way they did!