Advancing Separation Science Throughout a Lifetime of Achievements: Daniel W. Armstrong, the Winner of the 2020 Lifetime Achievement in Chromatography Award

February 27, 2020
Jerome Workman, Jr.

Daniel W. Armstrong, of the University of Texas at Arlington, is the winner of the 2020 LCGC Lifetime Achievement in Chromatography Award, which honors an outstanding and seasoned professional for a lifetime of contributions to the advancement of chromatographic techniques and applications. He recently spoke to us about his work and his career.

Daniel W. Armstrong, of the University of Texas at Arlington, has a lifetime of achievements in separation science, including his most widely recognized contributions in the field of enantiomeric separations. His contributions are known in the fields of molecular recognition (chiral and isomeric), ionic liquids (synthesis, characterization and use), ordered media (including micelles and macrocyclic compounds), enantiomeric separations, mass spectrometry (MS), and applied work in drug development, environmental, and food analysis. He is the winner of the 2020 LCGC Lifetime Achievement in Chromatography Award, which honors an outstanding and seasoned professional for a lifetime of contributions to the advancement of chromatographic techniques and applications. He recently spoke to us about his work and his career.

Many consider you to be the “father” of micelle and cyclodextrin-based separations, because your work elucidated the first chiral recognition mechanism by cyclodextrins (1–4). You have many publications related to this subject. What papers represent the most seminal work in this area? What prompted you to investigate this separations approach? What was your most surprising discovery from this work?  

While it was not our first publication on cyclodextrin isomeric liquid phase separations and chiral recognition, our 1986 Science paper (Science, 232, 1132–1135) probably received the most attention for a number of reasons. We easily separated underivatized drug enantiomers. It was the first paper of its type on associative small-molecule molecular modeling with energy minimization calculations. At that time there were only two computer systems in the world that could do this. We compared two cases where there was chromatographic retention, but only one was enantioselective. We then definitively showed why this occurred. The knowledge gained from this study led to the successful development of a number of new chiral selectors. We were told that this paper, in part, provided impetus for the FDA to pass their 1992 guidelines for stereoisomeric drugs.

The 1992 Analytical Chemistry paper (Anal. Chem.64, 873–879, 1992) was a mechanistic study involving gas chromatography (GC). We showed that there were multiple enantioselective retention mechanisms and that inclusion complexation was not necessary in many cases. Subsequently, this was shown to be true for liquid chromatographic (LC) separations as well. This work was preceded by an important theoretical study (Anal. Chem.60, 522–528, 1988) that doesn’t often get its due credit because it was well beyond the simple practical applications focus of the time. In late 1983, cyclodextrin-based LC stationary phases became the first reversed phase “chiral columns” to be commercialized (by Advanced Separation Technologies).

You and your research group were the first to develop macrocyclic antibiotics as chiral selectors, and you are recognized as one of the world’s leading authorities on the theory, mechanism, and use of enantioselective molecular interactions (5). This work has been cited numerous times by other researchers. How was your specific research approach different from your contemporaries at that time?

Early on, it was never our goal to develop columns for practical use or for commercial purposes. We were interested in understanding molecular recognition. That remains a prime focus of much of our work. Of course, there is a correlation between enhanced molecular recognition and chromatographic selectivity. Also, chromatography provides a simple way to study the effects of different solvents, salts, temperatures, and so forth on chiral recognition. It also provides a means to obtain relevant physico-chemical information. The macrocyclic glycopeptides (antibiotics) are a case in point. They probably provide a greater variety of functionality than any other chiral selector and in a relatively compact “package”. Consequently, they may be the most broadly selective class of chiral selectors, however, their chiral selectivity differs considerably in different chromatographic modes and conditions. How and why this occurs can provide numerous avenues for research. Such studies have led us to synthetically modify essentially all chiral selectors that we have worked with. Indeed, modified chiral selectors often provide the more interesting results. Proper synthetic changes can enhance beneficial properties and often, just as importantly, diminish unwanted properties of a chiral selector. This entire process leads to a better understanding of chiral recognition and enantiomeric separations. Of course, it would be short-sighted to ignore the obvious practical consequences of this work.

What do you consider the most important research publications you have produced relative to chiral separations over the last two- and one-half decades of your research in this field?

So, this is research that was published after the initial exciting and transformative decade of “chiral separations.” Certainly, the first paper on macrocyclic antibiotics as chiral selectors appeared just after that time period (Anal. Chem., 66, 1473–1484, 1994). The first cyclofructan based stationary phase represents the most recent major class of chiral selectors published (Anal. Chem. 81, 10215–10226, 2009). Perhaps the most important, relatively recent, advance in chiral separations has not been in new chiral selectors or chiral recognition theory, but rather the advent of new “high efficiency” supports, such as superficially porous particles. This moved enantiomeric separations into the realm of ultrafast and even sub-second separations as we demonstrated in 2015 (Anal. Chem. 87, 9137–9148, 2015) and 2018 (Anal. Chem. 90, 3349–3356, 2018).

There is one area which much of this research impacts that I have been convinced for years is important, but has been relatively ignored. It is D-amino acids in biological systems. The importance of D-amino acids is slowly being recognized in many different fields. Our 2017 paper on this topic (“D-Amino Acid Levels in Perfused Mouse Brain Tissue and Blood: A Comparative Study,” ACS Chem. Neuro. 8, 1251–1261,(2017) is a case in point. Such biological studies are becoming more prevalent over the last several years and will continue to escalate in number and importance.

Your work to characterize the solvent properties of room-temperature ionic liquids (ILs) has become essential to multiple fields in chemistry (6–8). What do you feel are the most important applications of room-temperature ILs for the analytical sciences?

Research involving ionic liquids (ILs) is pervasive and has impacted most areas of science and technology. Certainly, ILs in synthesis and process chemistry have received a lot of attention, but important advances in the analytical sciences also have been reported over the last two decades. There are several reviews on the topic. The intrinsic properties of ILs have made them useful in electrochemistry and battery research. All types of sensors have used ILs to broaden and improve their utility. Applications in areas of spectroscopy have been reported. Of course, ILs have become very important in separation science, no more so than in extractions, headspace solvents and as stationary phases for GC. We have been involved in the later areas of this research. We have probably synthesized and tested a greater variety of ILs than any other laboratory. Our goals were to knowledgeably enhance certain desired properties of ILs. These properties included thermal stability, fluidity, viscosity, site specific interactions, and so forth. As a practical consequence of our work, the first new class of commercial GC stationary phases in several decades was produced. This includes the most polar stationary phases known. IL stationary phases are often preferred in comprehensive GCXGC. Their nonvolatile nature makes them exceptional headspace solvents. Also, they are preferred for the GC analysis of water.

You and your research team have developed the new enhanced mass spectrometry (MS) technique of (paired ion electrospray ionization (PIESI) as one of the most sensitive methods for ultratrace anion analyses and speciation (9,10). What are some of the greatest insights or advances that the development and application of the PIESI technique has allowed you to discover?

Our PIESI work evolved from our synthetic work on dicationic and polycationic ionic liquids. My good friend and colleague Sandy Dasgupta thought that very dilute solutions of such molecules could be useful for electrospray ionization (ESI)-MS detection of perchlorate in the positive mode. Indeed, it worked beautifully and easily provided sub parts per trillion detection limits. We went on to test our di- and trications (as fluoride ion salts) on a large variety of anions and their utility was quite broad. However, the structure of the PIESI reagents made a significant difference as to their efficacy. This led to our studies on the “PIESI mechanism.” By understanding the mechanism, we were able to synthesize the next generation of PIESI reagents, which became available commercially. This technique has been applied to all manner of anionic species from simple inorganic ions to pesticides (and their degradants), phospholipids, nucleotides, anionic drugs, and chelated metal ions.


You have developed the first high efficiency capillary electrophoresis (CE) separation approach for microorganisms, such as bacteria, viruses, and fungi (11,12). How has this breakthrough extended the use of separation science into the mainstream of biology and colloid science?

Doing CE on intact microorganisms was very different than analyzing molecules in that molecules tended to behave much more predictably and reproducibly. Such is the difference between chemistry and biology. However, the results were so interesting and potentially important that we had to push on and see where it would lead. In this technique the term high efficiency must be qualified as under many conditions, focusing of the microorganism occurs and so a true capillary column efficiency cannot be obtained. Regardless, this work provided a new, nontraditional (for biology) approach for the analysis and quantification of microbes. It also can be used to determine whether the analyzed microorganisms are alive or dead and can give the percentages of each. Since laser-induced fluorescence (LIF) detectors can detect a single cell, this approach can be used as a test for sterility of samples. It has even been used on sperm cells as a fertility test. Today, we more often see such microbial studies done in a microfluidic or chip-based format.

What do you consider to be the most important new areas of research in the chromatography field? What do you see as your greatest contribution to the field?

I sincerely hope one area will be molecular rotational resonance spectroscopy-based detectors for GC and LC, since we just did the first paper on it (Angew. Chemie Int. Ed, DOI: 10.1002/ange.201910507). This technique can have greater specificity than high-resolution MS and nuclear magnetic resonance (NMR). High-speed separations and multidimensional separations will continue to grow. Separations-based sensors could be very important. Separations-based diagnostic devices may be the wave of the future if they are simple, sensitive, selective, and effective.

I’ve worked in many areas and will continue to. It is for posterity to decide the value of any research contributions I’ve made. That said, perhaps my greatest contribution is the over 100 analytical PhDs I’ve mentored and nearly an equal number of postdocs and visiting scholars and collaborators. The majority of my graduate students were the first person in their family to go to college at any level. They have all done well and that makes me quite happy. 

What words of advice do you have for young researchers just getting started, or even undergraduates considering a future career in science?

I love doing research and working with graduate and undergraduate students. It has been fun and very rewarding. I think it is a great career choice. However, you should know that this is not the only rewarding career for chemistry or other science majors. Approximately 60% of my graduate students work in the pharmaceutical industry and many of those are doing fundamental work in drug discovery and development. Some work for instrument manufacturers, column companies, or consumer product companies. Often, they are “troubleshooters” or problem solvers, a role that involves scientific detective work. I have done a lot of work with brilliant scientists that also have law degrees. They work in patent law and are at the forefront of commercially important science and technology-and they are well rewarded. In all cases, the common factors for success or advancement are working hard, working smart, and constructive imagination.

How do you organize your work schedule to enable you to teach, mentor, guide research, invent, and start new companies? What skill set is needed to accomplish all this?

Basically, you have to be willing to work many weekends, holidays, and nights. Also, it is beneficial to have good people working with you. You have to be able to minimize nonproductive, time-wasting activities such as meetings, most non-research related paperwork, social media, most administrative activities, administrators, and so forth.


(1) W.L. Hinze and D.W. Armstrong, Thin layer chromatographic separation of ortho, meta, and para substituted benzoic acids and phenols with aqueous solutions of α-cyclodextrin. Anal. Lett.13(12), 1093–1104 (1980).

(2) D.W. Armstrong and G.Y. Stine, Evaluation of partition coefficients to micelles and cyclodextrins via planar chromatography. J. Am. Chem. Soc. 105(10), 2962–2964 (1983).

(3) D.W. Armstrong and W. DeMond, Cyclodextrin bonded phases for the liquid chromatographic separation of optical, geometrical, and structural isomers. J. Chromatogr. Sci.22(9), 411–415 (1984).

(4) D.W. Armstrong, W. DeMond, A. Alak, W.L. Hinze, T.E. Riehl, and K.H. Bui, Liquid chromatographic separation of diastereomers and structural isomers on cyclodextrin-bonded phases. Anal. Chem.57(1), 234–237 (1985).

(5) D.W. Armstrong, W. Li, and J. Pitha, Reversing enantioselectivity in capillary gas chromatography with polar and nonpolar cyclodextrin derivative phases. Anal. Chem.62(2), 214–217 (1990).

(6) A. Berthod, L. He, and D.W. Armstrong, Ionic liquids as stationary phase solvents for methylated cyclodextrins in gas chromatography. Chromatographia53(1–2), 63–68 (2001).

(7) J.L. Anderson, J. Ding, T. Welton, and D.W. Armstrong, Characterizing ionic liquids on the basis of multiple solvation interactions. J. Am. Chem. Soc. 124(47), 14247–14254 (2002).

(8) J.L. Anderson, R. Ding, A. Ellern, and D.W. Armstrong, Structure and Properties of High Stability Geminal Dicationic Ionic Liquids.  J. Am. Chem. Soc.127(2), 593-604 (2005).

(9) C. Xu, and D.W. Armstrong, High-performance liquid chromatography with paired ion electrospray ionization (PIESI) tandem mass spectrometry for the highly sensitive determination of acidic pesticides in water. Anal. Chim. Acta792, 1–9 (2013).

(10) C. Xu, E.C. Pinto, and D.W. Armstrong, Separation and sensitive determination of sphingolipids at low femtomole level by using HPLC-PIESI-MS/MS. Analyst, 139(17), 4169–4175 (2014).

(11) D.W. Armstrong and J.M. Schneiderheinze, Rapid identification of the bacterial pathogens responsible for urinary tract infections using direct injection CE. Anal. Chem.72(18), 4474–4476 (2000).

(12) D.W. Armstrong, J.M. Schneiderheinze, J.P. Kullman, and L. He, Rapid CE microbial assays for consumer products that contain active bacteria. FEMS Microbiol. Lett.194(1), 33–37 (2001).

Daniel W. Armstrong, the 2020 winner Lifetime Achievement in Chromatography Award winner, received his B.A. degree from Washington & Lee University, Lexington city, Virginia; and his M.S. degree in Oceanography, and a Ph.D. in Chemistry from Texas A&M University. He is the R.A. Welch Distinguished Professor of Chemistry and Biochemistry at the University of Texas at Arlington. He has worked on an extremely broad range of separation techniques including high performance liquid chromatography (HPLC), gas chromatography (GC), supercritical fluid chromatography (SFC); micellar liquid chromatography, thin-layer chromatography; countercurrent chromatography; capillary electrophoresis (CE); and field flow fractionation, among others. He developed the theory and mechanistic background behind many of the practical advances in these techniques. Further, he advanced the use of separations techniques as a means to obtain important physico-chemical data. His most recent work in ultrafast separations and signal processing is driving fundamental changes in the field. Armstrong has over 700 publications, including 33 book chapters, and 35 patents. He has been named by the Scientific Citation Index as one of the world’s most highly cited scientists; his work has been cited over 43,000 times, having a Hirsch (h-) index of 105 (G.S.).