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Joseph Jack Kirkland, considered by many to be one of fathers of high performance liquid chromatography (HPLC), is the winner of LCGC’s 2015 Lifetime Achievement Award.
Joseph Jack Kirkland, considered by many to be one of fathers of high performance liquid chromatography (HPLC), is the winner of LCGC’s 2015 Lifetime Achievement Award. Kirkland's vast contributions to the field include the development of the first spherical packing designed specifically for modern HPLC, the development of siloxane bonded phases, and establishing processes for manufacturing spherical, small-particle (5-μm) totally porous packings that introduced a major leap forward in the performance of HPLC columns. Kirkland recently spoke to LCGC about his career and work.
Kirkland will be honored at the Pittcon 2015 conference in New Orleans, Louisiana, in a symposium on Monday, March 9, (session 590, room 244), along with LCGC’s 2015 Emerging Leader in Chromatography, Caroline West. This will mark the first time that the LCGC awards are included in the Pittcon technical program.
Were you always interested in a scientific career?
Kirkland: Having been gifted a Gilbert chemistry set at the age of 10, I quickly developed a strong interest in science and chemistry in particular. My subsequent A.B., M.S., and PhD degrees focused on chemistry in general and analytical chemistry in particular. I was always interested in the quantitative aspects of chemistry and the techniques of solving problems.
How did you get started in chromatography?
Kirkland: My dissertation studies required that I conduct some simple classical chromatographic separations, but my real interest in chromatography occurred in 1955 at DuPont. I had a problem in analyzing mixtures of methylamines, but after several weeks of using classical methods and infrared spectroscopy my work was largely unsuccessful. Then I learned that there was a chemist in another DuPont department, Dr. Steven Dal Nogare, who was conducting research on a new separations method called gas chromatography (GC). When I contacted him, it was suggested that I give him some samples of interest, which I did. The next day he called and said that my problem was solved. That result obviously got my attention, so I immediately arranged to get a duplicate simple, DuPont-constructed GC instrument, through Steve’s help. My career with GC then began.
Who was the biggest influence on your career when you were just getting started?
Kirkland: My analytical chemistry professor and subsequent close friend at Emory University, R.A. Day, was strongly influential in my approaching a career in analytical chemistry. To this day, I remember his first lecture, which was focused on measurement precision and accuracy, with an emphasis on significant figures. At DuPont I was fortunate to be hired by the department manager, Dr. Ralph K. Iler, an internationally renowned silica and colloid chemist. It was even more fortunate that our laboratories were adjacent, as Ralph was still conducting research in addition to managing. As a result, some of his incredible knowledge rubbed off on me strictly by association. Dr. Iler was largely the catalyst for my interest in silica chemistry and its utility in gas and liquid chromatography.
Why did you decide on a career as an industrial scientist rather than an academic?
Kirkland: I have always thought of myself as a problem solver, which is more suited for industry needs. I really never seriously even considered teaching until Dr. Lloyd R. Snyder and I agreed to work on an educational program in HPLC for the Continuing Education Department of the American Chemical Society (ACS) in 1971. That teaching project lasted for 21 years and drew in more than 5000 attendees who were interested in learning about HPLC.
Despite being an industrial scientist, you still contributed to the education of a lot of scientists through your many books, scientific publications, lectures, and short courses. How did you get involved in those projects, and why did you think it was important to participate?
Kirkland: The ACS courses that Dr. Snyder and I taught were extremely important in the development of our skills in HPLC. Attendees not only asked questions for which we had to find answers, but we also learned what was important to those using HPLC to solve real problems. The input that came from these courses really gave us the background for books on HPLC that we coauthored over many years. My scientific publications partially resulted in my interest in “spreading the word” about HPLC, but some of the publications contained technical information about new products or techniques that were designed to increase the knowledge and utility of the HPLC method. I suspect that all of this indicates that the science relating to chromatography was not only important for my career, but that it is also a strong and rewarding hobby.
You are hailed as a pioneer of modern liquid chromatography. What was the first major breakthrough you had with LC? How did that impact the rest of your career?
Kirkland: My first major breakthrough in HPLC was the development of the 30-µm silica superficially porous particle (SPP) in about 1967 (which DuPont commercialized and called Zipax). Before commercialization, we were effectively using this material in the Agricultural Chemicals Department for analyzing pesticides by HPLC. The commercial and technical success of Zipax enhanced my interest in SPP, and I continued to research SPP technology throughout my career. My development of small (6-µm) totally porous silica microspheres occurred in about 1972 (DuPont called the commercial particles Zorbax totally porous microspheres). The availability of these small particles ended the commercial aspects of SPP like Zipax. Subsequently, I developed high-purity porous silica microspheres, called Zorbax Rx, that reinforced the utility and value of this approach. It was more than 20 years before SPP technology reemerged commercially when I developed the 5-µm Poroshell particles for peptide and protein separations. However, the real boost in SPP came in 2006. While I was directing research at Advanced Materials Technology (AMT), we introduced small (2.7-µm) SPPs for the very fast separation of small molecules. This technology was strongly embraced by HPLC users. Other manufacturers quickly cloned and extended this technology so that it now is widely used globally. Since that time, AMT has developed and commercialized very small wide-pore SPPs optimized for separating peptides and proteins.
What did you first think about HPLC when it was introduced in the 1960s? What do you think of HPLC and ultrahigh-pressure liquid chromatography (UHPLC) today?
Kirkland: I first learned about what we now call HPLC when visiting Eindhoven Technical University in 1964. There I found Dr. J.F.K. Huber doing some of the first experiments in what we now call HPLC. This demonstration galvanized me to return home and gain the support of my manager to conduct research on this new technique. The reason was that my department had many difficult analysis problems with nonvolatile compounds that could not be solved by GC, so liquid chromatography seemed to be the answer. This certainly proved to be the case for us, and HPLC and the higher pressure UHPLC now are widely used as major analysis tools throughout the scientific community.
Can you tell us about the development of the first spherical packing designed specifically for HPLC (Zipax)?
Kirkland: When I began research on HPLC in 1965, I recognized that two problems that existed at that time needed some help to make the method sufficiently powerful and practical: a sensitive and reliable detector and better column packing materials. The former problem was relatively easy to resolve, as I adapted a recently developed, highly sensitive, and stable DuPont UV process monitor with a low-volume flow cell to produce a very useful UV detector. The second problem was more difficult. At that time, 100–125 µm irregular silica particles normally used for GC were used in HPLC columns. Papers by Professor Calvin Giddings and others had predicted that smaller particles would be required to produce better separations, so I focused on smaller particles. I had previously used Ralph Iler’s particle multilayering method to prepare some GC packing materials, so it occurred to me that this method might be used to develop spherical particles for HPLC. I decided to use sized silica glass beads as a core starting material. Silica has a negative charge, so a positively charged polymer was selected as the layering agent to be held by ionic forces. After layering this polymer, the coated beads were then positively charged, so that a single layer of 200-nm negatively charged silica sol particles could then be added to the beads held by ionic forces. The polymer-silica sol treatment was continued four more times, so that a 1-µm-thick layer was produced. The organic polymer was removed by heating and the resultant beads sintered at high temperature to produce the required strength. Considerable effort was needed for the sintering step to gain the desired strength without collapsing the porous shell. The final particles were about 30 µm overall with a 1-µm-thick porous shell composed of 1000-Å pores. Development of these particles required about three months (part-time, as I was also working on other analytical problems). These SPPs were used for liquid–liquid chromatography by filling the pores with stationary phase liquid. DuPont commercialized these patented particles as Zipax column packing. Zipax later was bonded with a nonsoluble silicone, which eliminated some of the disadvantages of the liquid–liquid method, and allowed reversed-phase technology to be developed with gradient separations. DuPont called this Zipax-modified commercial material Permaphase column packing.
Can you tell us about the development of the spherical small-particle totally porous packings (Zorbax)?
Kirkland: The development of the previously mentioned totally porous silica microsphere particles for HPLC, Zorbax, again occurred as an extension of one of Ralph Iler’s projects. Dr. Iler found that by coacervating various inorganic sols with a urea–formaldehyde polymer, small spherical particles resulted. The polymer was removed by heating, leaving porous microspheres. I used this technology as a basis and found that by varying the size of silica sols, porous silica microspheres with definable pores and narrow pore size distributions could be made. By altering synthesis conditions, silica particles of a particular size also could be made, so I concentrated on 5–6 µm particles, which I believed would be useful for performing fast HPLC separations. A main problem in this project was how to load these small particles into efficient columns for separations. It was found that the then-used dry method of packing larger Zipax particles produced poor results. A wet particle slurry method previously reported for preparing columns of large polymeric ion-exchange particles was studied and adapted to produce efficient columns of the porous silica microspheres. In my 1972 ACS Chromatography Award address, I described the utility of these particles, which at that time were used for liquid–liquid and liquid–solid (adsorption) chromatography. The use of these particles for reversed-phase HPLC was quickly developed largely by chemists in DuPont’s HPLC Application Laboratory. Later, it was found that silanes could be bonded to the surface of these silica particles to create appropriate stable and useful stationary phases. Studies continued so that porous silica microspheres with different pore sizes were synthesized for columns to perform high-performance size-exclusion chromatographic separations for synthetic polymers of DuPont’s interest. These studies on synthetic polymers were conducted with my coworker and friend, Dr. Wallace W. Yau. The research on the porous microspheres came over a two-year period that was interrupted by my transfer from the Agricultural Chemicals Department to DuPont’s Central Research Department in 1972.
Of the 32 U.S. patents you hold, which ones do you think have had the greatest impact in your field?
Kirkland: Patent-wise, my work on Zorbax and Zorbax Rx particles probably have had the most total impact on HPLC utility, as these materials continue to be widely used globally.
What led you to cofound Rockland Technologies? What did you learn from that experience and what advice would you offer a scientist trying to start a new company?
Kirkland: I was still working in Central Research in the late 1980s when DuPont decided to abandon the HPLC column business. DuPont contacted my friend and ex-coworker, Dr. Joseph DeStefano, (now in Central Research), who previously managed of this technology to see if there was interest in a leveraged takeover. There was strong interest by DuPont in continuing to supply customers that were using DuPont HPLC columns. Dr. DeStefano contacted me and three other ex-DuPonters with HPLC technical and business experience. As a result, an agreement was made with DuPont to take over the column business. Dr. DeStefano then retired from DuPont, but I continued my DuPont position. However, DuPont allowed me to conduct research activities for the new company, Rockland Technologies, on my own time as a consultant. I retired from DuPont in 1992 and then participated full-time as research director for Rockland Technologies. My involvement with Rockland exposed me to the business community, of which I had limited previous experience. Decisions for research were then often based on commercial possibilities, and activities were more focused on user needs and desires. Starting a new company like Rockland Technologies requires a strong technical background in product focus, a decent business and marketing experience, a willingness to take a chance for an opportunity, and hard work.
Your have an impressive body of publications. How important is it to you to share your work with the scientific community? Has anything you published led to unexpected collaborations?
Kirkland: Sharing my work with the scientific community has been a two-way street. This effort has led to many important discussions and sharing of ideas, and in the process has resulted in my getting acquainted with some top-flight scientists and some very nice people. An unexpected collaboration resulted in interactions with DuPont biochemists in a project on arthritis (one of my personal problems). We studied the progressive ageing-deterioration of proteoglycans in bovine joints using sedimentation field flow fractionation equipment that I had developed for characterizing microparticles and very high molecular weight components. Another unexpected highly successful collaboration was developed with Dr. Henk Claessens at Eindhoven Technical University in developing technology and insights regarding the use of silica-based column packing for high-pH HPLC separations. High-pH operation with silica-based columns was not popular at that time because of the dissolution of silica support during use. We were able to develop a stationary phase and operating conditions that allowed useful and practical separations at high pH.
What chromatography problem would you most like to see solved in the next 5–10 years? Do you have any plans to solve it yourself?
Kirkland: The next 5–10 years for HPLC technology will be focused on high-performance separations in the biosciences. Rapid, efficient, and effective separations will be required for a wide variety of biomaterials for which there is now a lack of experience. I am currently working in this area, but my years are limited as the calendar moves on. It is likely that field flow fractionation methods will be required to solve some of the difficult problems involving very large biomolecular components and particulates, as HPLC is much less effective for separations of these materials.
What advice would you offer a scientist just starting out?
Kirkland: Effective research needs a good formal educational background to get started. However, to continue to perform effective research through the years, real interest in science must be continuously stimulated. To maintain skills, literature must be assimilated, technical meetings attended, and networks with other scientists developed. In fact, science must also be sort of a hobby, where new technology is always promoted.