MSACL 2018 US Abstract

Topic:

The Triple Quadrupole: Innovation, Serendipity and Persistence

Richard Yost (Presenter)
University of Florida

Bio: Dr. Yost is the Colonel Allen R. and Margaret G. Crow Professor and Head of Analytical Chemistry at the University of Florida. He is recognized internationally as a leader in the field of analytical chemistry, particularly tandem mass spectrometry (MS/MS). He may be best known for inventing as a graduate student with Chris Enke the triple quadrupole mass spectrometer, which 40 years later represents over $1B in sales each year. Dr. Yost received his BS degree in Chemistry in 1974 from the University of Arizona, having performed undergraduate research in chromatography with Professor Mike Burke. He received his PhD degree in Analytical Chemistry in 1979 from Michigan State University, having performed graduate research with Professor Chris Enke. He then joined the faculty of the University of Florida.

Dr. Yost's professional activities have focused on research and teaching in analytical mass spectrometry, particularly tandem mass spectrometry (MS/MS). His group’s research has reflected a unique balance between instrumentation development, fundamental studies, and applications in analytical chemistry. His group has led in the application of novel mass spectrometric methods and techniques to areas such as metabolomics, clinical, biomedical, pharmaceutical, environmental, petrochemical, and forensic chemistry. Dr. Yost has supervised the research of well over 100 graduate students during the past 37 years, graduating over 85 PhDs from his group. He has served as PI or Co-PI on grants and contracts totaling over $50M of funding. Research in the group has led to over 180 publications and 16 patents. He still loves teaching undergraduates and graduates in the classroom each semester. Dr. Yost recently completed terms on the Florida Board of Governors (Regents) and the University of Florida Board of Trustees. He is director of the NIH-funded Southeast Center for Integrated Metabolomics. He is also a Professor of Pathology at both the University of Florida and the University of Utah/ARUP. His research has been recognized with the highest award in his discipline, the 1993 ASMS Award for Distinguished Contribution in Mass Spectrometry. He currently serves as the Vice President for Programs of the American Society for Mass Spectrometry, and will become President in July 2018.

Short Abstract

In this presentation I will provide a personal perspective on the conceptualization, development and demonstration of the analytical capabilities of the triple quadrupole mass spectrometer. And in that perspective, I will try to illustrate the roles of innovation, serendipity and persistence that are fundamental to scientific research. The triple quadrupole mass spectrometer has become the most common mass spectrometer in the world today, with sales of over $1 billion per year. It is today the gold standard for quantitative analysis in metabolomics, clinical analysis, drug discovery and development, environmental analysis, and a wide variety of other application areas. That invention and related research have helped propel mass spectrometry into the most commonly used analytical method in the world.

Long Abstract

In this presentation I will provide a personal perspective on the conceptualization, development and demonstration of the analytical capabilities of the triple quadrupole mass spectrometer. And in that perspective, I will try to illustrate the roles of innovation, serendipity and persistence that are fundamental to scientific research. The triple quadrupole mass spectrometer has become the most common mass spectrometer in the world today, with sales of over $1 billion per year. It is today the gold standard for quantitative analysis in metabolomics, clinical analysis, drug discovery and development, environmental analysis, and a wide variety of other application areas. That invention and related research have helped propel mass spectrometry into the most commonly used analytical method in the world.

When I arrived at Michigan State University as a new PhD student in 1975, I was interested in building the “ultimate computerized analytical instrument”. I chose to work with Professor Chris Enke, widely respected for his insight into the role of electronics and computers in chemical instrumentation. But Dr. Enke's research was in electrochemistry, which was of no interest to me. However, I had learned about a new mass analyzer, the quadrupole, during my undergraduate courses at the University of Arizona, and I decided that I wanted to incorporate the quadrupole into that ultimate analytical instrument. Together, Dr. Enke and I conceived of putting three of these quadrupoles together in series, selecting a parent ion in the first quadrupole, fragmenting it by collision with gas molecules in the second, and analyzing the daughter ions in the third quadrupole. Dr. Enke told me that, if I wanted to pursue that research, I would have to write a grant proposal. So I wrote a grant proposal to NSF and ONR to develop a computer-controlled triple quadrupole instrument. Unfortunately, the idea was so different from what the world’s mass spectrometrists were doing and what they understood that the reviews were uniformly negative, and the NSF proposal was not funded.

The ONR saw value in the proposal, however, (all nuclear subs already had a mass spectrometer on board), and so they funded the proposal. I ordered 1000 pounds of stainless steel and boxes of electronic and mechanical components, and built that first triple quadrupole mass spectrometer over the next two years. A chance meeting with Professor Jim Morrison from LaTrobe University in Australia was critical to that development, since he had built, but never published, a triple quadrupole instrument for obtaining the optical spectra of ions. Two months in his lab was instrumental in refining the design of the system. Back at MSU, my fellow students and I demonstrated the capabilities of this novel instrument for fundamental studies, for structure elucidation of compounds, and for analysis of mixtures, and it was patented by MSU. I completed my PhD in 1979, and moved to the University of Florida as an Assistant Professor. Within a year, the first triple quadrupole instruments were commercially available, based on that patent.

My research at UF over the 38 years since, building on the invention of the triple quadrupole mass spectrometer, has helped transform tandem mass spectrometry (MS/MS) from a niche research area, largely for fundamental chemistry studies, into a practical, widely available analytical technique. The conceptualization of computer-controlled tandem (or "hyphenated") analytical instruments such as MS/MS has been central to the development of a wide range of important analytical instruments, including "tandem-in-time" instruments that can provide MS/MS/MS... or MSn capabilities, laser microprobe MS/MS to image compounds in biological tissue, and ion mobility/mass spectrometry (IMS/MS) for analysis of complex biological samples. The invention of the triple quadrupole mass spectrometer and subsequent research not only led directly to the development and commercialization of a powerful and widely-used instrument, but also stimulated the development of a variety of tandem mass spectrometer systems that are deployed in almost every conceivable chemical and biological enterprise.

There are a number of areas in which the triple quadrupole mass spectrometer and my UF group's research have had dramatic impact, including clinical analysis and neonatal testing (recognized by the presentation of the first MSACL Distinguished Contribution Award to David Millington in 2015), drug discovery and development, and environmental analysis. More broadly, the research and developments outlined above serve as a model of the contributions of analytical chemistry and instrumentation development to great scientific discoveries. One can hardly name a significant advancement in science that was not made possible by the inventions and development of a tool to see something or measure something, and that includes everything from litmus paper to giant telescopes on mountain tops. And common to these inventions and developments have been innovation, serendipity and persistence.


References & Acknowledgements:


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