Winner: Dwight Stoll

Most widely recognized for his world leading research in the development of 2D-LC the ChromSoc is proud to award Dwight Stoll the Jubilee medal for his achievements so far and look forward to his future accomplishments. Daniel Meston had the opportunity to get an insight into how Prof. Stoll views his work and professional career up until this point.

What do you feel are the most important advances in 2D-LC over the last decade?

As you know, a lot has happened over the last decade, and we could make a long list, but I’ll just name two here:

  • I think the single most important development to really move the field forward has been the dramatic improvement in the capabilities of commercially available hardware and software for 2D-LC. We still have a long way to go in terms of software for data analysis. But, it is critically important that industrial labs can now do high quality 2D-LC separations. This is very different from where we were in the early 2000s when most groups were building their own instruments using pieces designed for other purposes. The increased interest in 2D-LC from industrial laboratories is currently driving much of the investment in continued research in multi-dimensional separations.
  • I think the development of Active Solvent Modulation (ASM) has been very important, because it has provided a relatively easy-to-use means for users to solve what we refer to as the mobile phase mismatch problem that we face in many 2D-LC separations. ASM is not a perfect solution for all of these challenges, but again it provides a relatively easy-to-use means of dramatically reducing the seriousness of the challenge, for some of the most attractive pairings of separations. For example, we and others have demonstrated the benefits of ASM for coupling RP with RP and HILIC with RP in a variety of applications.

Speaking of active solvent modulation (ASM) do you see this as your most impactful result? Was it serendipity or after a period of research that you thought of the idea?

I would say that my interest the solution we now call ASM started with a notebook sketch in 2012, which I still have hanging on my office wall. So, this development has taken a long time to mature, as many new technologies do. We had known for many years that the solvent mismatch problem that ASM addresses is very serious, but things had progressed to the point where it was clear this was one of the big challenges we should really focus on next. I don’t think I’d necessarily pick this particular development as our most impactful one. I’m very happy about several things we’ve done along the way, starting with the realization in the mid-2000s that gradient elution LC can be done reproducibly following only seconds of column re-equilibration after completing one gradient and starting the next one.

You have collaborated widely with both academia and industry. In your experience what makes a good partnership and what advice would you provide to get the most out of these collaborations?

I think the most important element in these collaborations is to identify an area of research where there is clear mutual interest from both partners. This can be tricky because academics need to publish their work, and industrial partners don’t want their secrets published. Also, academics tend to work on projects with long (3 to 10 year) timelines, whereas industrial partners typically prefer shorter projects. But, my experience has been that talking through these issues eventually leads to an identification of a research topic that is mutually agreeable to everyone involved.

More recently you have made significant progress in defining approaches to model separations in 2D-LC. What are your broad findings on this and are there particular phase types you would recommend for method development?

Well, I am most pleased and optimistic about the potential to model what I would call the physical aspects of these separations (e.g., pressure drops, injections into the second dimension, dispersion in loops). If you are talking about choosing columns, then frankly I am pretty pessimistic about that, because we don’t really know how to do that very well, even for 1D chromatography. Yes, we can make broad suggestions, such as – use RP, or SEC, or IEX for this or that set of molecules. But, the challenge is that there are literally thousands of phases to choose from, and we cannot make more precise recommendations with enough accuracy to be useful. We are working on things in that direction, but I think it is going to take years to make real progress on that front.

Following on from this – where do you feel 2D-LC is best utilised?

In the 2000s a lot of research was focused on comprehensive 2D-LC methods, which are essential for deep characterization of complex samples, such as protein digests and natural product extracts. In the 2010s, though, it was exciting to watch the explosive growth in the adoption of non-comprehensive methods – multiple heartcutting and selective comprehensive methods  in particular – for more targeted analysis.

You have given a number of online seminars recently, what are the major benefits you see to the use of webinar style lectures and do you think they will still have a place post-COVID?

This is a great question, and one that a lot of us are thinking and talking about now. To me, right now, the biggest benefit of the online seminar format is the reach/cost ratio. Over Zoom (or whatever platform you prefer), I can reach hundreds of people interested in our work without leaving my office! I’ll also say, however that it is nearly impossible to build relationships in this type of format, so these interactions absolutely do not replace social interactions at conferences where long-term scientific relationships are built and maintained. I think the likely scenario is that in the future we will have a mix of formats – many conferences will return to something close to their pre-COVID formats, we will have more online seminars than we did in the past, and I think conferences and organizations will experiment with hybrid formats, where some attendees are in person, and some attend virtually.

You have mentioned previously about the importance of setting long term goals for yourself. Has your career up until this point went to plan and what do you foresee in the future?

I joke with my students that I don’t think too hard about specific plans beyond about a month, because by the time a month goes by things change a lot, and we must adjust our plans anyway. A large majority of the specific research projects I am working on today I did not anticipate at all even three years ago. But you are right that I do think it is important to have some long term goals. One of the reasons I think this is important is that these goals can help guide decision making. For example, should I apply for this research grant, or get involved in that collaboration? If these opportunities are not aligned with my long-term goals, then I have to say no, because they will distract me from making progress toward the long-term goals.

In what direction do you see the next advances in specifically 2D-LC and in broader separation science?

I’ll be really interested to see if large-scale use of “printed” separation media can be realized during my working career. There are several groups and some start-up companies dabbling with 3D printing as a means of preparing separation media, as an alternative to the packed particle columns that dominate the industry today. If we really do see a shift from slurry packed particles to printed columns, that would be a genuinely revolutionary shift in my view.

I am obviously biased, but I really do think multi-dimensional chromatography will continue playing a bigger and bigger role in separation science in general. The instrument hardware and software available from major vendors continue to improve, and the development of data analysis tools for these separations is a very active research area.

Finally, there is a lot of effort being invested by both academic and industrial labs into development of 2D-LC for biopharmaceutical analysis, and it is exciting to see the kinds of really innovative things groups are doing in this space. I’d say about 75% of the work of my group is focused on this area right now, and there is no end in sight. Biopharmaceutical analysis is already complicated, and the samples we are seeing are getting more complicated by the day, not simpler.