Focus on Ion Mobility Spectrometry, Honoring Gert von Helden, Martin F. Jarrold, and David E. Clemmer, Recipients of the 2018 John B. Fenn Award for a Distinguished Contribution in Mass Spectrometry
The 2018 John B. Fenn Award for a Distinguished Contribution in Mass Spectrometry was presented on June 4, 2018 to Prof. Gert von Helden, Prof. Martin F. Jarrold, and Prof. David E. Clemmer for their pioneering contributions to the development of ion mobility spectrometry (IMS). This Special Focus Issue of JASMS celebrates this occasion with a collection of research papers by the awardees, colleagues, and friends.
Martin Jarrold, David Clemmer, and Gert von Helden receiving the 2018 Fenn Award from ASMS President Vicki Wysocki.
The editors of JASMS are pleased to begin this issue with a personal perspective of the awardees and their achievements by Prof. Michael T. Bowers; Mike has been a mentor and close colleague of these three young scientists over the years, and he has been a pivotal figure in the development of IMS.
Forward by Prof. Michael T. Bowers
In the winter of 1979/1980, a letter arrived at the University of California, Santa Barbara (UCSB) addressed to me. In it was a query on whether I would be interested in having a Ph.D. student at Warwick University work as a postdoc in my laboratory. I had been on sabbatical at Warwick for two 6-month visits in the 1970s and hence was interested. I also noticed the letter had taken several months to arrive and that the applicant was hoping to get a NATO postdoctoral fellowship and needed a sponsor. I rushed off an affirmative answer to the young man making the inquiry, Martin Jarrold. It turns out I was in the nick of time as Martin, assuming my indifference, was about to accept an offer from Paul Kebarle at the University of Alberta, but fortunately he decided to come to UCSB. Just before Martin arrived in Santa Barbara (in 1980), we had obtained a VG ZAB-2F reverse geometry sector mass spectrometer. Perhaps the hottest topic at the time was the mechanism of collision-induced dissociation. Fred McLafferty had suggested CID (or CAD as he called it) distributions were independent of internal energy and hence structurally reliable regardless of parent ion history. That suggestion did not sit well with my chemical physics instincts and so I had postdoc Andreas Illies do some proton transfer experiments and report them at the 1980 ASMS meeting at the Waldorf Astoria in New York. Well there was a major hullabaloo at the session and Burnaby Munson (President) and Catherine Fenselau (VP Programs) decided to have a workshop on the topic chaired by Keith Jennings the following year in Minneapolis. I put Martin and Andreas on the project and Martin was asked to present the results at the workshop. I think I can say without any doubt that essentially the entire conference showed up at the workshop! After an introduction by Jennings, Martin was asked to present his results (later published as “Internal Energy and Angular Momentum Effects on Collision Induced Dissociation Fragmentation Patterns,” Org. Mass Spec. 1983, 18, 388–395) that carried the day in spite of rather major and persistent objections from Fred. All ended well, however, with the workshop concluding with Fred’s daughter arriving with a very large, candled cake and we all sang happy birthday to Fred. Martin had just arrived in the field (he used crossed molecular beams for his Ph.D. studies) and he found himself on center stage, a place he has been reluctant to exit ever since! All good things come to an end and so did Martin’s postdoc years at UCSB, however, not before he published 36 papers and started several major new projects in the group that flourished for years. He departed for Bell Labs in 1985 to begin his independent career and soon became a world leader in determining the physical and chemical properties of clusters, particularly silicon clusters. Our paths would soon cross again, but more on that in a bit.
Martin Jarrold speaking during the Award Lecture.
I was asked to give a plenary lecture at the British Mass Spectrometry Society meeting in York, UK, in summer 1988. After the lecture, a young German student came up to me at lunch and asked to have a chat. He said he was currently a summer intern for VG in the UK, a company his father worked for, and that he was considering doing a foreign Ph.D. He had his sights set on John Beynon, one of the world’s leading mass spectrometrists and the designer of the VG ZAB instrument, but he liked my lecture. We talked for a while and then he asked me where Santa Barbara was. I remember drawing a map of the USA on a napkin and placing an “X” at Santa Barbara’s location and told him to keep it for future reference! I returned to UCSB and did not think about it again until a letter arrived saying he wanted to come to UCSB, and how could he go about making that happen? We did not really have a procedure for vetting German undergraduates at UCSB in those days, but somehow we managed, and Gert von Helden arrived on campus in Fall 1989. One of our major interests when Gert arrived was the chemistry of transition metal ions and the assembly of transition metal clusters. We had just built a reverse geometry sector mass spectrometer, patterned after the VG ZAB, and were in the process of designing and adding a drift/reaction cell, and a quadrupole mass analyzer, to study mass selected/mass detected transition metal ion chemistry. In the process, we needed to determine the ion’s residence time in the drift cell so we could do kinetics. Consequently, we put in an electronic gate that could be pulsed open at the entrance to the cell to obtain arrival time distributions. When we saw two peaks in the arrival time distribution for our test atomic cobalt ions, we were more than a little confused but eventually recognized it was due to two separate Co+ electronic state configurations (d8+ and d7s1+), and modern ion mobility spectrometry was born! Well at least sort of. It was Gert who decided that what we really should be studying was not electronic states of transition metals but the structural evolution of carbon clusters, the hot topic of the day (Smalley, Curl, and Kroto received the Nobel Prize for the discovery of fullerenes in 1996), so he took that project on. The inaugural meeting of the new Gordon Research Conference (GRC) on “The Structures, Energetics and Dynamics of Gaseous Ions” was being held in the Spring of 1991 in Ventura. I remember coming back to UCSB one afternoon and Gert was super excited because he had just observed that C7+ had two peaks in the arrival time distribution, one due to a linear structure (like C6+ and smaller clusters) and one due to a monocyclic ring. I took him back to Ventura with me for the evening session so he could tell everyone about his discovery, but in those days, the GRC was very strict and they would not let him in! Hence, I carried the ball and used my clout as a founder of the conference and showed his data.
Gert von Helden speaking during the Award Lecture.
Results simply poured out after that and we finally published a Communication that Fall on his results (“Structures of Carbon Cluster Ions from 3 to 60 Atoms: Linears to Rings to Fullerenes,” J. Chem. Phys. 1991, 95, 3835–3837). Modern IMS was launched in earnest with this iconic paper. Gert set about getting a better handle on the structures of these species, using theory to generate model structures and an upgraded version of the projection approximation to generate cross sections from the model structures to compare to experimental cross sections. We were also curious about the mechanism of fullerene formation since the first fullerene mysteriously appeared at C30+ at a size where planar ring systems were dominant. Gert experimentally determined that fullerenes came from dissociation of energized large planar ring systems by elimination of a small carbon fragment (C1, C2, or C3) and rearrangement of the remaining atoms to fullerene. We submitted the work to Nature, where it was eventually published. Gert continued to work on carbon but realized that a more general ion source than laser desorption was needed if synthetic polymers and biologically interesting molecules were to be investigated. Hence, he designed and built a MALDI source for our sector machine and turned his attention to biological molecules near the end of his stay in the group. He collaborated with Thomas Wyttenbach on what was to become a second iconic paper on the structure of the nonapeptide bradykinin (“Gas Phase Conformations of Biological Molecules: Bradykinin,” J. Am. Chem. Soc. 1996, 118, 8355–8364). Our cross-section measurements for bradykinin became the standard for testing new instruments as IMS progressed and bradykinin soon became what I term the “hydrogen atom of peptides,” as it was used in seemingly every conceivable type of measurement on peptide ions. Gert left the group in 1995 to accept a postdoc with Gerhard Meier at the University of Nijmegen in the Netherlands, and turned his interest to spectroscopy and the development of free electron lasers for the spectroscopy of ions. Like Martin Jarrold before him, he was prolific, publishing 28 papers during his UCSB years, and he changed the face of what we did as a research group for many years after he left.
Back to crossing paths with Martin Jarrold. Martin had left Bell Labs for a faculty job at Northwestern, arriving there in Fall 1992. He was aware of Gert’s IMS work and had decided to get involved in ion mobility with his initial emphasis on silicon and aluminum clusters. However, one of his students, J.M. Hunter, became interested in carbon including the evolution of fullerenes from carbon rings and they submitted a paper to Science, appearing about the same time as Gert’s Nature paper. Hence for a period of a few years, Martin’s group and my group competed doing IMS of carbon with some healthy overlap but mainly complementary work. The important point was that Martin had established an independent and highly successful program using IMS to interrogate initially clusters and eventually biological molecules. He saw the importance of both developing the experimental method and understanding how cross sections were determined from model structures. He designed the first “high resolution” instrument and most importantly, along with his student Alex Shvartsburg, developed the trajectory method and the related hard sphere scattering model for calculating cross sections (“Structural Information from Ion Mobility Measurements: Effects of the Long Range Potential,” J. Phys. Chem. 1996, 100, 16,082–16,086). His energy and insight contributed greatly to putting IMS on a sound scientific foundation. And, looking over the shoulder with 20/20 hindsight, he developed a program that attracted David Clemmer to his lab as a postdoc for two years beginning in 1993. David brought his expertise in metal ion chemistry to the lab and combined it with Martin’s expertise in clusters and generated a series of very nice papers on metal/carbon mixed systems. And perhaps most importantly, they ushered in the idea of studying protein conformations using IMS, something that would ultimately dominate the field a decade later. That first protein was cytochrome c, a molecule that has come to compete with ubiquitin as the “hydrogen atom of proteins” in mass spectrometry (“Naked Protein Conformations: Cytochrome c in the Gas Phase,” J. Am. Chem. Soc. 1995, 117, 10,141–10,142). But let us not get ahead of ourselves with David.
David Clemmer grew up in rural Colorado and attended Adams State College in Alamosa, CO (about midway between Denver and Albuquerque, NM) before heading to the University of Utah for a Ph.D. He chose to work with Peter Armentrout, whose main interest at the time was metal ion chemistry. This was a fortuitous choice since the Armentrout group members were regular attendees at the annual Lake Arrowhead Conference held in January at the UCLA Conference Center. This Conference has a near 50-year history with the last 40 meetings held at its current site at Lake Arrowhead. Most of the talks are given by graduate students and the focus is on “Ion Chemistry and Mass Spectrometry.” My group was one of the foundational groups and attended every year, and by the time David attended, my research group’s talks included ion mobility. This is a conference where graduate students “grow up,” giving their talks before a sophisticated and rigorous group of faculty mentors. It gave David a chance to see friendly but at times intense interplay between research groups and an understanding that you had better be able to defend what was on a slide if you chose to show it. I say this because I do not remember in-depth “discussion” of any of David’s talks at the conferences he attended, which must mean he knew how to defend what he put on his slides! The Arrowhead conferences also introduced him to ion mobility, which grew in interest as he matured. I found out later that he and Peter Armentrout talked about building an IMS cell for the front of their guided ion beam machine but it did not get done before he left Peter’s group for a postdoc, first in Japan and then a second postdoc with Martin as mentioned above. And, what is hard to conceive of now, there was only my group and Martin’s doing mass detected IMS anywhere in the world at that time, and we had only been doing it for a few years. It was a narrow window that opened and David chose to dive through.
David Clemmer speaking during the Award Lecture.
After two fruitful years as a postdoc in the Jarrold group, David accepted a position in the Chemistry Department at the University of Indiana. And he hit the ground running. Though trained as a Physical Chemist, he was appointed into both the Physical and Analytical divisions at IU and he took the opportunity to expand the fledgling IMS technology in analytical directions. He made many contributions in those early years, and he recognized the important fact that a significant increase in duty cycle was needed if drift tube IMS were to have an analytical future. This improvement would allow for the measurement of mixtures, and coupling IMS with other separation devices currently used in mass spectrometry, on time scales that were analytically useful. The key insight was the difference in timescales between an IMS measurement (milliseconds) and a time of flight (TOF) measurement (microseconds), allowing the total mass spectrum to be determined for each IMS pulse. David termed this process “nesting” and he and his group were able to analyze the results of a complete tryptic digest of cytochrome c and other systems in minutes, speeding up the analysis time by orders of magnitude (“ESI/Ion Trap/Ion Mobility/Time of Flight Mass Spectrometry for Rapid and Sensitive Analysis of Biomolecular Mixtures,” Anal. Chem. 1999, 71, 291–301). Once this door was opened, the Clemmer group proceeded to develop methods to parallelize CID measurement, analyze proteomics samples, and carry out IMS-IMS-MS measurements, all of which were firsts in the field.
Before finishing, I want to emphasize several points. The first is that breakthroughs in science most often result from a combination of serendipity, talent, and the interest and courage to do new things. I have outlined how all three of these factors were at play in the discovery and emergence of modern ion mobility in the persons of Martin Jarrold, Gert von Helden, and David Clemmer. These three extraordinary scientists had the insight to take a sliver of data and understanding and expand it into not only a scientifically important result but also into a whole new field of science. They did not have instrument manufacturers to provide state-of-the-art machines that they could use and exploit. The framework of IMS simply did not exist in the beginning either instrumentally or theoretically, and these are the people that brought those essential elements into existence. And as a first-hand observer at the nexus of IMS evolution, I can assure you it was an exciting, intense, competitive, and rewarding experience for all involved. It is the kind of time all of us that have given ourselves to a life of scientific discovery live for. All involved knew something big was taking place in those early days but only years later, in reflection, could it be put into perspective. A simple look at the current ASMS program (2019) tells some of the story. There are four sessions on IMS, and the technique will play a central role in many other talks and in the poster sessions. IMS is no longer novel of itself but is being rediscovered and reconfigured in new instruments and applications each year. It is now a central part of what many of us do and most of us take for granted. Thanks Martin and Gert and David! You are most deserving of the ASMS John Fenn Award for a Distinguished Contribution to Mass Spectrometry.
As a final point, I note that these early seminal discoveries were not a singular bright spot with the players burning out in the heat of the furnace. All three have gone on to be scientific leaders today. Martin and David are named professors at Indiana University and Gert is a W2-level research group leader at the Fritz Haber Institute of the Max Planck Society in Berlin and an Honorary Professor at Raboud University in Nijmegen, Netherlands. David continues to push back the frontiers of IMS instrumentation and resolution, Martin has turned to developing Charge Detection Mass Spectrometry and applying it to a range of very large and previously inaccessible entities, and Gert continues to do spectroscopy on clusters and other interesting species, and recently coupled an IMS source to a free electron laser for mass and shaped selected spectroscopy of ions. You will be hearing much more from all three of them in the future. And finally, I am delighted and honored to have all three of them as part of my “Academic Family,” but most importantly to be able to count them not only as colleagues but as friends.
Martin Jarrold, David Clemmer, Jack Beauchamp, Peter Armentrout, Mike Bowers, and Gert von Helden following the Award Lecture.
This Special Focus honoring the 2018 Fenn awardees contains 22 research papers, beginning with a contribution from Martin Jarrold (and Benjamin Draper) on Charge Detection Mass Spectrometry; in the following three papers, David Clemmer and co-workers focus on structural insights from ion mobility spectrometry. The remaining 18 papers from colleagues and friends discuss a variety of applications and developments in IMS, as well as in other areas of mass spectrometry.
1. “Real time analysis and signal optimization for charge detection mass spectrometry” by Benjamin E. Draper and Martin F. Jarrold.
2. “Determination of gas phase ion structures of locally polar homopolymers through high resolution ion mobility spectrometry-mass spectrometry” by Xi Chen, Shannon A. Raab, Timothy Poe, David E. Clemmer, and Carlos Larriba-Andaluz.
3. “Substance P in solution: trans-to-cis configurational changes of penultimate prolines initiate non-enzymatic peptide bond cleavages” by Christopher R. Conant, Daniel R. Fuller, Tarick J. El-Baba, Zhichao Zhang, David H. Russell, and David E. Clemmer.
4. “Substance P in the gas phase: conformational changes and dissociations induced by collisional activation in a drift tube” by Christopher R. Conant, Daniel R. Fuller, Zhichao Zhang, Daniel W. Woodall, David H. Russell, and David E. Clemmer.
5. “Effects of individual ion energies on charge measurements in Fourier transform charge detection mass spectrometry (FT-CDMS)” by Andrew G. Elliott, Conner C. Harper, Haw-Wei Lin, and Evan R. Williams.
6. “A Semi-empirical framework for interpreting traveling wave ion mobility arrival time distributions” by Sugyan M. Dixit and Brandon T. Ruotolo.
7. “Dual polarity ion confinement and mobility separations” by Isaac K. Attah, Sandilya V.B. Garimella, Ian K. Webb, Gabe Nagy, Randolph V. Norheim, Colby E. Schimelfenig, Yehia M. Ibrahim, and Richard D. Smith.
8. “Determination of gas-phase ion mobility coefficients using voltage sweep multiplexing” by Tobias Reinecke, Austen L. Davis, and Brian H. Clowers.
9. “Simultaneous quantification of nucleosides and nucleotides from biological samples” by Liqing He, Xiaoli Wei, Xipeng Ma, Xinmin Yin, Ming Song, Howard Donninger, Kavitha Yaddanapudi, Craig J. McClain, and Xiang Zhang.
10. “Proteomic analysis of FNR-regulated anaerobiosis in Salmonella Typhimurium” by Zhen Wang, Jingjing Sun, Mengdan Tian, Zeling Xu, Yanhua Liu, Jiaqi Fu, Aixin Yan, and Xiaoyun Liu.
11. “Thermodynamics and reaction mechanisms for decomposition of a simple protonated tripeptide, H+GAG: a guided ion beam and computational study” by A. Mookherjee and Peter B. Armentrout.
12. “Cyclic ion mobility mass spectrometry distinguishes anomers and open-ring forms of pentasaccharides” by Jakub Ujma, David Ropartz, Kevin Giles, Keith Richardson, David Langridge, Jason Wildgoose, Martin Green, and Steven Pringle.
13. “Evidence of cis/trans-isomerization at Pro7/Pro16 in the lasso peptide microcin J25” by Kevin Jeanne Dit Fouque, Julian D. Hegemann, Séverine Zirah, Sylvie Rebuffat, Ewen Lescop, and Francisco Fernandez-Lima.
14. “Structural analysis of polyurethane monomers by pyrolysis GC TOFMS via dopant-assisted atmospheric pressure chemical ionization” by Evan A. Larson, Junghyun Lee, Andrew Paulson, and Young Jin Lee.
15. “Evaluating separation selectivity and collision cross section measurement reproducibility in helium, nitrogen, argon, and carbon dioxide drift gases for drift tube ion mobility-mass spectrometry” by Caleb B. Morris, Jody C. May, Katrina L. Leaptrot, and John A. McLean.
16. “Native ion mobility mass spectrometry: when gas phase ion structures depend on the electrospray charging process” by Nina Khristenko, Jussara Amato, Sandrine Livet, Bruno Pagano, Antonio Randazzo, and Valérie Gabelica.
17. “Space charge effects in ion mobility spectrometry” by Juan Fernandez de la Mora.
18. “Selective gas-phase mass tagging via ion/molecule reactions combined with single analyzer neutral loss scans to probe pharmaceutical mixtures” by Dalton T. Snyder, Lucas J. Szalwinski, Alice L. Pilo, Nina K. Jarrah, and R. Graham Cooks.
19. “Rapid solution-phase hydrogen/deuterium exchange for metabolite compound identification” by Sandra N. Majuta, Chong Li, Kinkini Jayasundara, Ahmad Kiani Karanji, Kushani Attanayake, Nandhini Ranganathan, Peng Li, and Stephen J. Valentine.
20. “Principles of ion selection, alignment, and focusing in tandem ion mobility implemented using structures for lossless ion manipulations (SLIM)” by Rachel M. Eaton, Samuel J. Allen, and Matthew F. Bush.
21. “Increasing the upper mass/charge limit of a quadrupole ion trap for ion/ion reaction product analysis via waveform switching” by Kenneth W. Lee, Gregory S. Eakins, Mark S. Carlsen, and Scott A. McLuckey.
22. “Fundamental studies of new ionization technologies and insights from IMS-MS” by Sarah Trimpin, Ellen D. Inutan, Santosh Karki, Efstathios A. Elia, Wen-Jing Zhang, Steffen M. Weidner, Darrell D. Marshall, Khoa Hoang, Chuping Lee, Eric T.J. Davis, Veronica Smith, Anil K. Meher, Mario A. Cornejo, Gregory W. Auner, and Charles N. McEwen.
On behalf of the JASMS Editors and the entire ASMS community, we extend our warm congratulations to Gert von Helden, Martin Jarrold, and David Clemmer, as recipients of the 2018 Fenn Award. We look forward to many more years of exciting developments in ion mobility spectrometry.
Michael T. Bowers
University of California at Santa Barbara Santa Barbara, CA, USA
David H. Russell
Associate Editor, JASMS
Texas A&M University College Station, TX, USA
Veronica M. Bierbaum
Associate Editor, JASMS
University of Colorado Boulder, CO, USA