This special focus issue of the Journal of the American Society for Mass Spectrometry celebrates the accomplishments of Dr. Richard D. Smith, the recipient of the 2013 ASMS Award for a Distinguished Contribution in Mass Spectrometry, and who serves as a Battelle Fellow, Chief Scientist in the Biological Sciences Division, and Director of Proteomics Research at Pacific Northwest National Laboratory (PNNL) in Richland, WA. The award is for his development of the electrodynamic ion funnel.
Dick has made internationally recognized contributions to the advancement of analytical chemistry, and especially mass spectrometry (MS), over an extended period of time. A recurring theme for Dick’s distinguished research is instrumental innovations that couple extremely sophisticated analytical separation methods with increasingly intricate mass spectrometers, enabling quantitative identification and characterization of complex mixtures. He has used ground-breaking applications characterizing biological systems (e.g., proteomics, metabolomics) to showcase the technologies he develops, and is internationally recognized for these areas. Dick is a visionary and clearly recognizes that the development and application of innovative technologies is a never-ending game. He also understands that technology is essential for the characterization of biological systems. However, initial demonstrations of any technology are often met with significant skepticism, and Dick has definitely had his share. Many of the contributions from Dick’s laboratory started out as immature strategies with major barriers to overcome for meaningful qualitative and quantitative biological measurements. Although many of these creative and innovative technologies have not been easy and required a decade or more of investment, Dick has proved through significant persistence and effort that many become useful to the biological community, removing much of the doubt that preceded their introduction. Dick’s unwavering energy, intellect, and passion have taken many of his ideas from concept to commercialization.
When Dick began his career at PNNL in 1976, only GC/MS successfully combined separations with mass analysis. The MS community was strongly motivated to enlarge their “molecular universe” to include nonvolatile compounds, particularly in biological research. Most efforts focused on developing an effective LC/MS interface, including Dick’s initial efforts involving fast ion bombardment of the LC effluent spray deposited on a moving ribbon MS interface. However, he soon broke with tradition by developing the “direct fluid injection” interface, coupling high-resolution capillary supercritical fluid chromatography with MS. He continued this work into the 1980s, developing increasingly effective, robust interfaces, with later versions of this technology still being used today. Because important classes of biological compounds have limited solubility in supercritical fluids, Dick developed a “sheath flow” interface for coupling capillary zone electrophoresis (CZE) to MS using the electrospray ionization (ESI) approach introduced by John Fenn in 1984. This crucial development instantly increased the sensitivity of MS-based analyses by orders of magnitude and inspired Dick to explore ESI-based methods in more detail.
While Dick has been instrumental in many technological developments in MS such as Fourier-transform ion cyclotron resonance (FTICR) MS and on-line separations, the focus of this award is specifically for his development of the ion funnel used in many high performance mass spectrometers. The genesis of the ion funnel to enhance ESI-MS sensitivity was born during the early 1990s. During this time period, ESI-MS was determined to be one of the methods-of-choice for analyzing biomolecules. However, ESI had great challenges because less than 1% of the total ion current generated at the source was measurable by the mass spectrometer, and most ions were lost in the higher pressure transfer regions of the instrument. To increase measurable ion current, it was necessary to focus ions generated in atmospheric pressure and deliver them to the high vacuum region of the detector. Although this idea seemed simple, it proved to be very challenging and required years of design changes and alterations to reduce capacitance and develop appropriate power supplies.
The oldest working form of the ion funnel was originally created in 1997 to replace ion transmission-limited skimmers and to efficiently capture ions in the expanding gas jet while radially focusing them. It has been adapted for a variety of uses and proven to be a broadly applicable tool for ion focusing and manipulation at elevated pressures that challenged conventional approaches. Although the funnel has undergone several iterations in the last 15 years, the defining features have not changed: closely spaced ring electrodes of gradually decreasing inner diameter, out-of-phase rf potentials applied to adjacent electrodes, and a longitudinally-applied DC gradient. The ion funnel concept continues to be adapted in a growing number of applications including ion trapping, ion cooling, low pressure electrospray, and ion mobility spectrometry; however, its original use, decreasing ion losses in the interface of high pressure sources, has remained its most prevalent. Currently, forms of the funnel are employed in present-day Bruker Daltonics, Agilent Technologies, and Thermo Scientific MS instrumentation.
The increasing role of MS in the physical and biological sciences can be attributed in large part to the versatility afforded by the growing number of ionization methods and its increasing sensitivity. The development of the electrodynamic ion funnel in Dick’s laboratory has been an important factor in this increasing role. The sensitivity provided by the ion funnel has greatly improved mass spectrometers today, allowing routine detection of low concentration species that would have been undetectable 15 years ago. The amount of sample required for each measurement has been greatly reduced, allowing analysis of sample-limited systems. These improvements have allowed scientists to address biological problems where sensitivity is fundamentally required (e.g., at the single-cell level) or would be otherwise impractical (e.g., sampling from small tumors or from a substantial number of biological systems). The ion funnel is one key instrumental development that allowed these experiments to be common-place today, rather than extraordinary.
Dick’s more recent developments in ion mobility for an additional dimension of separation further enhances MS sensitivity. His group has applied ion funnels at both the source and exit of the ion mobility drift cell to make the fast separation a lossless addition prior to MS analysis. Further gains in sensitivity have also been realized by developing a highly effective approach for multiplexing ion mobility separations. His next phase for improving separations was hinted in Dick’s ASMS award lecture, where he described a revolutionary new concept using “Structures for Lossless Ion Manipulations” to enable more effective separations and ion manipulations in conjunction with MS.
Another of Dick’s significant contributions to science is the people he has inspired, energized, and mentored. To date, Dick has mentored over 30 high school students, 60 graduate students, 200 post-doctoral fellows, and 160 staff scientists. These once-budding scientists are now deeply woven into the international landscape of science as leaders in industry, government laboratories, and academia. Dick was also recognized by PNNL for his outstanding mentoring in 2000, further proving the impact he has made on the scientists he has guided.
This special focus issue contains papers devoted to advancing high performance mass spectrometry and reflects Dick’s interests and accomplishments. The contributing authors were selected by current PNNL staff member Erin Baker (source of the photograph of Dick and his wife, Elaine) and past PNNL members David Muddiman and JASMS Associate Editor Joseph Loo. Many of the authors were suggested by Dick himself.
“Solution Dependence of the Collisional Activation of Ubiquitin [M + 7H]7+ Ions” by Huilin Shi, Natalya Atlasevich, Samuel I. Merenbloom, and David E. Clemmer
“Large-Scale Collision Cross-Section Profiling on a Traveling Wave Ion Mobility Mass Spectrometer” by Christopher B. Lietz, Qing Yu, and Lingjun Li
“Detecting and Removing Data Artifacts in Hadamard Transform Ion Mobility-Mass Spectrometry Measurements” by Spencer A. Prost, Kevin L. Crowell, Erin S. Baker, Yehia M. Ibrahim, Brian H. Clowers, Matthew E. Monroe, Gordon A. Anderson, Richard D. Smith, and Samuel H. Payne
“Improving the Sensitivity of Mass Spectrometry by Using a New Sheath Flow Electrospray Emitter Array at Subambient Pressures” by Jonathan T. Cox, Ioan Marginean, Ryan T. Kelly, Richard D. Smith, and Keqi Tang
“Mapping Antiretroviral Drugs in Tissue by IR-MALDESI MSI Coupled to the Q Exactive and Comparison with LC-MS/MS SRM Assay” by Jeremy A. Barry, Guillaume Robichaud, Mark T. Bokhart, Corbin Thompson, Craig Sykes, Angela D. M. Kashuba, David C. Muddiman
“Comparison of Data Acquisition Strategies on Quadrupole Ion Trap Instrumentation for Shotgun Proteomics” by Jesse D. Canterbury, Gennifer E. Merrihew, Michael J. MacCoss, David R. Goodlett, and Scott A. Shaffer
“Revealing Ligand Binding Sites and Quantifying Subunit Variants of Noncovalent Protein Complexes in a Single Native Top-Down FTICR MS Experiment” by Huilin Li, Piriya Wongkongkathep, Steve L. Van Orden, Rachel R. Ogorzalek Loo, and Joseph A. Loo
“Application of Printed Circuit Board Technology to FT-ICR MS Analyzer Cell Construction and Prototyping” by Franklin E. Leach III, Randolph Norheim, Gordon Anderson, and Ljiljana Pasa-Tolic
The original announcement of the Award for a Distinguished Contribution contained the following passage: “Dr. Smith’s obsession with sensitivity has provided a basis to greatly improve mass spectrometers.” During his award presentation, Dick attempted to give reasons for the inaccuracies of the word “obsession.” Although the Oxford English Dictionary (www.oed.com) defines obsession as “a recurrent, intrusive, inappropriate thought, impulse, or image causing significant distress or disturbance to social or occupational functioning,” it also defines it as “an idea, image, or influence that continually fills or troubles the mind.” Those of us who have worked closely with Dick might argue that “obsession” accurately describes his persona. We only see the positive aspects of this word in Dick. The mass spectrometry community has benefited greatly from this obsession. On behalf of the editors at JASMS and Dick’s friends and former and present colleagues, we congratulate Dick for his much-deserved award.
Dick and his wife, Elaine.
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Baker, E.S., Muddiman, D.C. & Loo, J.A. Focus on Advancing High Performance Mass Spectrometry, Honoring Dr. Richard D. Smith, Recipient of the 2013 Award for a Distinguished Contribution in Mass Spectrometry. J. Am. Soc. Mass Spectrom. 25, 1997–1999 (2014). https://doi.org/10.1007/s13361-014-1007-8