The 2020 Emerging Leader in Atomic Spectroscopy: Advancing Ambient Desorption Ionization Mass Spectrometry

By pursuing research focusing on a fundamental understanding of the physics and chemistry underlying ambient desorption ionization mass spectrometry (ADI-MS), Jake Shelley, the 2020 winner of the Emerging Leader in Atomic Spectroscopy award, has delved into the underlying science behind desorption and ionization phenomena, as well as the issues associated with sample matrix effects inherent for plasma-based mass spectrometry.

Jerome Workman, Jr.

When he was a student of Professor Gary M. Hieftje at the Indiana University, Jake Shelley completed research requiring detailed understanding in the fundamental physics of ADI-MS and the associated matrix effects. His initial research explored the nature of three plasma-based ADI-MS sources: the low-temperature plasma (LTP) probe, the flowing atmospheric-pressure afterglow (FAPA) source, and the direct analysis in real time (DART) source. The main area of study involved ion-suppression events, which typically result in a decrease in analyte signal. Shelley’s research demonstrated that the fundamental issues of matrix effects are essential to applying ADI-MS for both quantitative and qualitative analysis. In his current position as the Alan Paul Schulz Professor of Chemistry at Rensselaer Polytechnic Institute (RPI), in Troy, New York, he has continued to explore improved understanding of ambient ionization source–mass spectrometry.

In recognition of his work, Shelley is the winner of the 2020 Emerging Leader in Atomic Spectroscopy Award, which will be presented by Spectroscopy at the Winter Conference on Plasma Spectrochemistry, which will be held in Tucson, Arizona, January 12−18, 2020. This interview examines Shelley’s work on ambient ionization sources for mass spectrometry.

Please tell us about some of your earliest research interests. How did you get started in science? What has kept you motivated? What is the most exciting part of your work day?

While in high school, I became fascinated with criminal law as well as chemistry (thanks to an excellent Advanced Placement Chemistry teacher, Meg Cox!), and I thought my destiny was in forensic science. I had always enjoyed tinkering with electronics and computers, but it wasn’t until an internship in the Chemistry Division at Los Alamos National Laboratory that I realized building new instrumentation was an active area of chemical research. After that exposure, my biggest research interest quickly became designing, creating, and testing new analytical methodologies to solve problems that could not be addressed with commercial equipment.

I stay motivated in this research area by filling the gaps that currently exist in analytical capabilities and through the pursuit of ubiquitous, extremely selective tools; something similar to a tricorder, or how crime shows portray analytical science. It is exciting to work with my group to produce instruments that are, at first glance, indistinguishable from magic, then dig into the fundamentals to explain the basis of the observed phenomenon. As a result, watching my students progress and grow on a daily basis and to see them formulate their own research ideas is extremely rewarding.

You have continued to explore improved understanding of ambient ionization for mass spectrometry (1). What is the potential for this approach, and for what applications do you think it will be most beneficial?

It is hard to believe that ambient desorption/ionization (ADI) has been around for 15 years already. While this approach to mass spectrometry analyses has already had a major impact in a number of areas (for example, forensics and medical diagnostics), these methods have not been as widely adapted as many people believed. Part of the issue lies in the limited (or even lack of) quantitative capabilities of most of the ADI-MS methods when directly analyzing amorphous samples with complex matrices. In addition, the analyte range for ADI methods is limited to mainly small molecules. Expanding the range of detectable analytes to include elemental species and larger (bio)polymers would be a major boost for the field. These advances would take ADI-MS beyond a rapid screening tool, and make it a more viable analytical resource. Fortunately, there are a few research groups working on addressing these issues.

Would you explain for the readers of Spectroscopy the significance of the role of the helium dimer ion (He2⁺) in the formation of the afterglow of a helium-based dielectric-barrier discharge (2)?

This work, performed along with a previous Emerging Leader awardee George Chan, showed that the helium dimer (He2⁺) serves as an energy carrier from the dielectric-barrier discharge (DBD) to the plasma jet in the open air. Helium-based plasmas, including the low-temperature plasma (LTP) probe, direct analysis in real time (DART), and flowing atmospheric-pressure afterglow (FAPA), have been major players in ADI-MS from early on, but surprisingly little research was done to explore the plasma chemistry and reagent-ion formation from the plasmas. In fact, most people in the field would point to Chip Cody’s original DART publication that theorized that only helium metastable atoms (He^m) were involved in reagent-ion formation and treat that theory as absolute fact. What we realize now is that plasma chemistry is much more complex than that, and reagent ions come from multiple, unique species including He^m, He2⁺, He2^*, He⁺, and so forth.

In your work, you have developed a handheld, wireless low-temperature plasma (LTP) source for mass spectrometry (3), multiple applications and design changes to these LTPs, and the design and fabrication of a tunable flowing atmospheric-pressure afterglow (FAPA) plasma ionization source for mass spectrometry (4). You have even worked to create nanoparticle encapsulation of anticancer agents (5). What research was the most exciting to you, and why?

The development of portable ionization sources and other instrumentation (for example, the backpack mass spectrometer [6]) always holds a special place in my heart. Taking these tools out in the environment for the first time, like when we directly analyzed fruits and vegetables in the supermarket, is always exciting. Being able to make unique measurements for the first time with devices designed and crafted in the lab, while amazing and inspiring the general public with these technological capabilities, is a special experience.

Of all your research so far, what are your most meaningful papers that you would like to highlight for our readers?

We recently published an article in the Journal of the American Society for Mass Spectrometry (September issue) that discussed the use of cross correlation as a data treatment and analysis approach for ADI-MS data (7). Essentially, the method allows one to automatically flag and remove background ions from a direct-analysis mass spectrum, greatly reducing the complexity of the resulting spectra. Additionally, we can group ions in a mass spectrum based the chemical species from which they originated, and extract single-component mass spectra from complex mixtures. Most importantly, cross correlation is a post-processing tool that is performed within seconds, and that can be applied to old datasets. Such powerful, automated data processing is another step towards seeing wide-spread utility of ADI-MS.

What is the most difficult or challenging aspect of your current research activities? How do you manage a research group, while at the same time mentoring and directing students?

The most difficult aspect of my career is juggling the many administrative duties and obstacles professors face nowadays while trying to build and sustain a strong research program, as well as foster and support student growth. Because of that, I have not been able to work in the laboratory myself as much as I would prefer. Fortunately, I have an amazing and talented group of undergraduate and graduate students that are churning out great results and new ideas.

How were you able to direct your research toward discovery of solutions to important problems? What made you choose the path of research you are engaged in now?

From my standpoint, many of the discoveries we have made over the years have come through serendipity… perhaps informed or educated serendipity, though. For instance, I knew that the solution-cathode glow discharge (SCGD) would be a pretty good ionization source for elemental and small-molecule mass spectrometry, based my previous experience with AP glow discharges as ionization sources (8). When Andy Schwartz and I first combined SCGD and MS, we both had an inkling that ionization of biomolecules would also be possible, due to the appearance of Taylor cone structures at the plasma-solution interface. It was serendipitous that not only could we form intact gaseous ions from peptides, but that we could tunably fragment them at atmospheric pressure to get sequence information (9).

What areas would you like to see this research expand into when looking toward the future? Do you plan to stay in mass spectrometry work or are there another analytical techniques (or other research) that looks promising to you?

Moving forward, my group is pursuing the development of combined (or so-called multimodal) analytical instruments to gain more comprehensive information from samples quickly. While mass spectrometry is a great tool, it is not the only one nor is it capable of providing every answer, especially to very complex problems. By combining orthogonal spectroscopic methodologies, the benefits of each are multiplicative. For instance, right now we are developing a chemical-imaging platform that will simultaneously provide elemental and molecular images through the combination of mass spectrometry and laser-induced breakdown spectroscopy (LIBS). In another instance, we are working with Prof. Igor Lednev’s lab to combine mass spectrometry and Raman spectroscopy for the analysis and categorization of organic gunshot residues. As part of our recently established Rensselaer Astrobiology Research and Education (RARE) Center, we will be applying every analytical tool possible to analyze complex reaction mixtures from realistic early-Earth environments in search for the chemical origins of life.

What would you tell those young people interested in science about how to best prepare for a career in research?

Work hard, stay focused, and (most importantly) have fun.

References

• J.T. Shelley and G.M. Hieftje, J. Anal. At. Spectrom. 25(1), 345–350 (2010).

• G.C.Y. Chan, J.T. Shelley, J.S. Wiley, A.U. Jackson, C. Engelhard, R.G. Cooks, and G.M. Hieftje, Anal. Chem.83(10), 3675–3686 (2011).

• J.S. Wiley, J.T. Shelley, and R.G. Cooks, Anal. Chem.85(14), 6545–6552 (2013).

• S.P. Badal, S.D. Michalak, G.C-Y Chan, and J.T. Shelley, Anal. Chem.88(7), 3494–3503 (2016).

• Z. Yue, H. Wang, D.J. Bowers, M. Gao, M. Stilgenbauer, F. Nielsen, J.T. Shelley, and Y.R. Zheng, Dalton Trans. 47(3), 670–674 (2018).

• P.I. Hendricks, J.K. Dalgleish, J.T. Shelley, M.A. Kirleis, M.T. McNicholas, L.F. Li, T.C. Chen, C.H. Chen, J.S. Duncan, F. Boudreau, R.J.  Noll, J.P. Denton, Anal. Chem. 86(6), 2900–2908 (2014).

• Y. You, S.P. Badal, and J.T. Shelley, J. Am. Soc. Mass Spectrom.30(9), 1720–1732 (2019).

•  A.J. Schwartz, K.L.  Williams, G.M.  Hieftje, and J.T. Shelley, Anal. Chim. Acta950, 119–128 (2017).

• A.J. Schwartz, J.T. Shelley, C.L. Walton, K.L.  Williams, and G.M. Hieftje, Chem. Sci. 7(10), 6440–6449 (2016).

Jake Shelley is the Alan Paul Schulz Career Development Professor Of Chemistry, at the Rensselaer Polytechnic Institute, in Troy, New York. His current research interests lie in the development of new hardware and software tools for mass spectrometry, which enable rapid and sensitive detection and identification of analytes in complex matrices. Specifically, his group approaches these tasks through development, fundamental characterization, and application of instrumentation. Currently, Prof. Shelley’s group is aiming to expand the capabilities of ambient mass spectrometry through added dimensionality of analysis without compromising the speed of the analysis. The goal is to develop an ionization source, which operates at atmospheric pressure that can provide molecular, structural, and atomic information of species present on a sample surface. Overall, this research addresses a major focus of modern analytical chemistry–rapid, in situ detection of relevant compounds without the need for sample modification or a priori information of sample constituents. Such methods of analysis are needed in a wide range of areas including homeland security, drug development and production, chemical synthesis, and environmental analyses.