Pioneers in GasChromatography T
he development of any new analytical technique requires collaboration between groups of scientists who may have quite different backgrounds and talents, such as chemists, physicists, biologists, and engineers. To stimulate awareness of how new instruments—and through them, new fields—are created, a new type of symposium recognizing the collaborative work of those involved in the invention, development, and implementation of analytical instrumentation was initiated at the 1990 Pittsburgh Conference and Exposition in New York City. The First James L. Waters Annual Symposium Recognizing Pioneers in the Development of Analytical Instrumentation featured four presentations on the development of gas chromatography. Leslie S. Ettre of the Perkin-Elmer
Corporation spoke on the early evolution of GC, concentrating on the period between 1955 and 1960. GC was one of the first real instrumental techniques, beginning as gas adsorption chromatography, said Ettre. In 1946 Erika Cremer at the University of Innsbruck, Austria, developed a "gas chromato-
FOCUS graph" that contained all of the essential elements: a carrier gas source, a separation column, a thermal conductivity detector, and a galvanometer as a recording device. The system appeared to be so primitive, however, that few people expressed any interest in it. About the same time, said Ettre, Jaroslav Janak developed a gas adsorption
chromatographic system with which separated gas fractions could be collected. Again, this "instrument," mounted on the wall and connected with glass and tygon tubes, was too primitive to elicit much interest. The first gas-liquid partition chromatographic system was described by A.J.P. Martin and A. T. James in their landmark 1952 paper, which also introduced the theory of GC. If not for scientists such as D. H. Desty of British Petroleum and N. H. Ray of ICI England, who recognized the potential of GC and "translated" the work of James and Martin into practical, easy-to-use systems by adding syringe injection and a thermal conductivity detector, GC may have remained a laboratory tool using self-made gadgets, said Ettre. He stressed that the role of instrument developers—the engineers who translat-
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FOCUS ed the scientific ideas into reliable commercial products—must not be forgotten. The first commercial gas chromatographs were introduced in 1955 by BurrellCorp. (Pittsburgh, PA), the PerkinElmer Corp. (Norwalk, CT), and the Podbielniak Co. (Chicago, IL). Burrell had been involved since the early 1940s in the development of separation units based on gas adsorption. One of the first American papers on GC was pre sented at the September 1954 ACS na tional meeting, and within six months the company introduced its first com mercial instrument, the Kromo-Tog. The Podbielniak Co. produced lowtemperature distillation systems for analyzing liquefied petroleum gases. In December 1955, realizing the potential of GC to replace such distillation sys tems, Podbielniak introduced its first GC unit—the Chromacon—at a chemi cal exposition in New York City, Ettre continued. The first Perkin-Elmer instrument, the Model 154 Vapor Fractometer, was introduced in May 1955 and was imme diately successful. It featured a sensi tive thermistor detector, both adsorp tion- and partition-type packings, sy ringe injection, and a temperaturecontrolled column. Typical examples of applications were also made avail able to prospective users. In 1956 five more commercial gas chromatographs were introduced from Fisher Scientific; Beckman; Consoli dated Electronics Corporation; Hallaikainen Instruments Company; and Wilkens Instrument and Research, Inc., founded by Keene Dimick and his brother-in-law Ken Wilkens. By 1957, said Ettre, the stage was set. GC was well established, its theory was understood, and a number of commer cial instruments were available. In 1958-59, several new developments spurred further refinement of GC to more of what we know today, related Ettre. Ionization detectors—in partic ular the argon ionization detector and the flame ionization detector—were in troduced in 1958 and significantly im proved the sensitivity of the instru ments. The argon ionization detector (AID) was developed by James Lovelock and was incorporated into an instrument from W. G. Pye & Co. called the argon chromatograph. Within a year, the AID was also incorporated into Barber-Colman Co. instruments. The flame ion ization detector (FID) was described almost simultaneously by two groups, McWilliam and Dewar of ICI Australia and Pretorius and co-workers at the University of Pretoria (South Africa). Both the FID and the new capillary 1016 A
Μη 1958-59, several new developments spurred further refinement of GC to more of what we know today." columns invented by Marcel Golay were almost immediately picked up by the instrument companies, and at the 1959 Pittsburgh Conference PerkinElmer demonstrated practical applica tions of the Model 154 using the FID and capillary columns. Temperature-programming capabil ity was also introduced in 1958, with the first instrument by Burrell Corpo ration. At Du Pont, Dal Nogare devel oped linear temperature programming; and in 1959, his co-workers C. E. Ben nett, A. J. Martin, and Frank Martinez left Du Pont to form F&M Scientific Corporation. Their first instrument, the Model 202 GC, was also introduced at the 1959 Pittsburgh Conference. (In 1965 F&M was sold to Hewlett-Pack ard, which continued its Avondale, PA, operation as a separate division.) The final development of the late 1950s, concluded Ettre, was the intro duction of the fixed-needle microsyringe by Clark Hamilton. This was a tre mendous improvement over the largevolume hypodermic syringes available before 1958, and it contributed greatly to the development of GC.
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Keene Dimick, developer of the Aero graph gas chromatograph, was sched uled to speak next on the emergence of GC but was unable to attend the sym posium because of grave illness. (Sadly, Dimick died of cancer shortly after ward.) Harold McNair, one of Dimick's long-time co-workers, read Dimick's prepared remarks, sometimes diverg ing from his notes to relate personal experiences about his times with Di mick. GC, noted Dimick, was born in 1952, when Martin and James pub lished their paper on the analysis of fatty acids and amines by gas-liquid partition chromatography. Although the tremendous potential power of this technique was unknown even to its originators, within a year it allowed Di mick to deal with his immediate ana lytical problems and eventually he launched a successful and interesting business. Dimick's first exposure to GC was in 1953 in the Department of Agriculture laboratory in California, where he used a laboratory-built gas separator to iso late the organic components of straw berry flavors. After spending 6 years isolating the essence of strawberry from 30 tons of strawberries, related Dimick, he was reluctant to give up the project for lack of a way to separate the components of the oil. In 1956, when Dimick visited many of the flavor, perfume, and essential oil companies in New York, he discovered that the researchers at these companies were almost completely ignorant of GC. He decided on the trip home that there must be a way to capitalize on this made-to-order opportunity sparked by the big eyes of the chemists he had visited. Dimick and his brother-in-law, Ken Wilkens, spent the summer of 1956 building gas chromatographs in Dimick's garage in Walnut Creek, CA. By fall, they had built and sold five instruments and were receiving about five orders per month. Wilkens bought a bicycle shop in Napa to manufacture the instruments, and Dimick set up a testing and research laboratory in a small bedroom in his house. They in corporated in December 1956 under the name Wilkens Instrument and Re search, naming their product the Aero graph. Throughout 1957 sales declined, and by the end of the year, said Dimick, they were selling only one instrument per month. After realizing that they needed more exposure and advertising, they began to mail application litera ture and in April 1958 published their first catalog and exhibited the Aero graph at the ACS Instrument Show in San Francisco. From that point on, mail order played an ever increasing
role in marketing the Aerograph. During the next 9 years, the company grew from 3 employees (Dimick, his wife Adele, and Wilkens) to more than 400. No enterprise can succeed without talented people who are highly motivated toward success, noted Dimick, and Wilkens Instrument and Research was no exception. Early employees who made names for themselves in the following years include T. Z. Chu, now head of Finnigan MAT; Harold McNair, now a faculty member at Virginia Tech; and Jack Gill, who created a major instrument division of SpectraPhysics and today heads his own venture capital company. Over the next few years, Dimick's group of scientists developed many new products, including the Hy-FI hydrogen FID, an electron capture detector, a temperature-programmed instrument, and the Auto Prep chromatograph. By 1960 sales had climbed to $3 million, and in 1961 Aerograph International, a European subsidiary, was established. The company that originated in the Dimick home was to stay in this unusual site for the first four years—nearly half its lifetime as an independent company. Chemists tested equipment in the living room and operated from nine desks throughout the house. The accounting department was in the kitchen, and the shipping department used the garage. The original bedroom laboratory became the sales office. Finally, in 1960, the company moved to a nearby rented warehouse, where sales reached nearly $7 million. In 1964 the company moved to its present Walnut Creek facilities, and in 1965, it was sold to Varian Associates. The company that had started with the purchase of a $420 Varian recorder was sold back to Varian for $12 million. James Lovelock described the development of the electron capture detector and its role in "green politics." In the early 1950s, said Lovelock, he was working in the experimental biology division of the National Institute for Medical Research in London, developing methods for preserving living cells in the frozen state. His job was to discover the nature of damage caused by freezing, and he found that sensitivity to freezing damage seemed to be connected to the fatty acid composition of the cell membrane lipids. Martin and James had developed their gas chromatograph in a lab one floor above him, continued Lovelock, and he asked them about the potential of using the new instrument to analyze the fatty acid content of the cell lipids. At first Martin was enthusiastic, but when he learned of the small size of Lovelock's
samples (only a few hundred micrograms), he suggested either the use of larger samples or the invention of a detector more sensitive than the gas density balance they were using. Lovelock decided that inventing a new detector would be more fun than obtaining more sample, so he set out to modify an ionization anemometer he had made in 1949. He tried a detector made from a simple cylindrical ion chamber with a volume of about 2 cc and with a 20-mC 90 Sr source behind it. The chamber was connected to a source of direct current and the central electrode to a homemade electrometer. The detector responded to hydrocarbons but lacked the necessary sensitivity, and when chloroform was present in the hydrocarbon mixture it caused a negative peak that paralyzed the detector for hours. Thus it appeared to Lovelock as if he had found a detector with all the sensitivity that could be wished, but for only one substance: chloroform. Because he was so interested in detecting fatty acids, he temporarily abandoned work on the ECD in favor of a last try at developing a better ionization cross-section detector. For the next few years, Lovelock concentrated on this work. He aimed to improve the argon detector which, until the more reliable FID was invented in 1959, was the detector of choice for most gas chromatographers. Then in 1958 he was invited to spend a year at Yale working with Sandy Lipsky in applying GC to biomedical problems. There the ECD was reduced to practice by replacing the 90 Sr source with a safer tritium source and developing the pulse method of operation. By the end of 1959, said Lovelock, the ECD had been developed to a point where it was not much different from those used today—the only developments yet to come were the use of a 63 Ni source and the pulse feedback method of constant current operation. The extreme sensitivity of the ECD, noted Lovelock, made possible the discovery of the ubiquitous distribution of usually trivial quantities of pesticides and other chemicals, opening a niche for what is now the environmental industry. A common sense approach must be taken, he said, in that with sensitive instruments, it is all too easy to find carcinogens everywhere—even when the danger from them is insignificant. For example, prior to the invention of the ECD, it would have been permissible to set the acceptable limit of pesticide residue in foodstuffs at zero, because in practice anything below the limit of detection is zero. After development of the ECD, however, the detection limit became so low that to
apply it as the lower acceptable level of pesticide residues would have caused the rejection of nearly everything edible, even organically grown vegetables. Lovelock concluded by stating that the ECD has led to a new awareness of the Earth and the dangers that loom ahead. As citizens and scientists, we must keep society on course for a reasonable future and sustain the tangible benefits to ourselves from our work in environmental science. We need to speak out against the greedy use of public funds and support for big science. We need to turn our hearts and minds toward what should be our prime environmental concern: the care and protection of the Earth itself and especially the forests of the humid tropics. He concluded by pointing out that we must be moderate and aim for a world that is healthy and beautiful for our children. Finally, Albert Zlatkis discussed the role of international symposia in the progress of GC. Between 1960 and 1962, two series of symposia on GC were held: one organized by the British Petroleum Institute and the other by the Instrument Society of America. Although both were successful, it was decided that an international forum on chromatography was needed. The First International Symposium on Advances in Chromatography was held in Houston in January 1963 and featured presentations by such renowned chromatographers as James Lovelock, Ernst Bayer, Istvan Halasz, Evan Horning, and Sandy Lipsky. The meeting grew over the next 25 years, and LC eventually took a prominent place next to GC. Since 1975 symposia have been held abroad and in the United States in alternate years in cities such as New York, Oslo, Houston, Tokyo, Berlin, and Minneapolis. Zlatkis concluded by pointing out that the evolution of chromatography can be seen in the programs of these symposia. He remarked, "When we started our symposia, most of the applications were still in the petrochemical and chemical industries. Since then, GC has become an indispensable technique in biochemical and clinical science and in protecting the environment." This evolution would not have been possible without both the dedicated work of researchers in the field and the continuous improvement in instrumentation. Clearly, these sentiments were shared by all who attended the First Annual Waters Symposium to honor the pioneers of GC. The full text of the presentations made at the symposium will be published in upcoming issues of LC/GC. Mary Warner
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