Pat Sandra: LCGC’s 2017 Lifetime Achievement Award Winner

Pat Sandra is known for his expansive knowledge across a wide spectrum of analytical techniques, blending the world of academia and private enterprise, and bringing separation science into the mainstream consciousness. He has combined analytical excellence, innovation, and a unique gift for problem solving into a career which has lasted almost 50 years. Sandra recently spoke to LCGC about his career and work.

Were you always interested in a scientific career?

Not really. At the start of my high school studies, I chose the specialization Latin and Greek. Only after three years and influenced by the great classes given by the biology-chemistry teacher, I changed to Latin and sciences. Initially, I was planning to study medicine but one week before registration at the university, I changed to chemistry. This decision was most probably driven by the fact that my brother studied medicine and didn’t pass at the first summer examination period. Too difficult for me?

How did you get started working with chromatography?

The head of the Department of Organic Chemistry at Ghent University in Belgium, Prof. Maurits Verzele, invited me, after I obtained my Master’s degree, to join his research team in natural product research. The subject he proposed for my PhD studies was “The contribution of hops to the flavour of beer.” From the start it was clear to me that to unravel the complexity of a beer extract, high-performance analytical techniques were needed. A lot of research was going on in capillary gas chromatography (GC) and Verzele’s group was pioneering in this respect through the development of the static coating technique. As part of the subject of my thesis I started to prepare glass capillary columns. The first results motivated me so much that I immediately planned to perform further research, after my PhD, in chromatography.

Who was the biggest influence on your career when you were just getting started?

Definitely Maurits Verzele, who was not only the promotor of my PhD work but also the person who believed in me by offering me an assistant professor position in his group. This allowed me to continue my research in capillary GC in the period 1975–1986. During that period, I had the opportunity to meet a lot of important scientists in the field, including Martin and Synge (the Nobel prize winners), Huber, Horvath, Zlatkis, Lipsky, Grob, Jennings, Desty, Kaiser, Schomburg, Cramers, McNair, Novotny, and Pretorius, to name a few.  

Why did you choose an academic career path?

I didn’t choose-I became obsessed by chromatography! And an academic career was the only possibility to pursue my hobby. The good salary also did not hurt.

What has been the most challenging research project you have undertaken?

Preparing highly inert capillary columns (glass and fused silica) with immobilized apolar and polar­-often home-made-stationary phases was by far the most challenging. This was only possible through the efforts, in a short period of time, of many colleagues. As an example, immobilization of the stationary phase was published almost at the same time by Grob, Jennings, our group, Schomburg, and Lee.

What has been the most rewarding?

I consider our present research at the Research Institute for Chromatography (RIC) on biopharmaceuticals and biosimilars the most rewarding. This subject started when my son Koen, a biochemist, joined the company and the milestones we reached in this very challenging analytical work were amazing! We were used to analyzing and characterizing molecules of up to 1000 Da and we suddenly faced molecules exceeding 150,000 Da. The complete portfolio of liquid chromatography (LC) modes, in unidimensional or multidimensional format, in combination with high resolution mass spectrometry, must be applied. Moreover, I personally, as an analytical organic chemist, had to study a lot to keep up with Koen and his biochemical staff.

Over the years, you have mentored many PhD students and worked with numerous postdoctoral researchers. How have your students impacted your career?

My PhD students and postdocs have been very important for me. They not only did the practical work but also pushed me to go deeper in specific subjects, to broaden my fundamental knowledge, to replan and reorganize experiments, and more. I had several brilliant students in all fields of separation sciences giving me insights into the pros and cons of the different separation techniques for given applications. Some of them joined the RIC, and others selected an academic career, though the majority are now working in industry.

You have done pioneering work in all main forms of chromatography-LC, GC, and supercritical fluid chromatography (SFC)-as well as capillary electrophoresis (CE). How did you end up working with such a broad range of techniques? Have you found one of these areas to be of strongest interest to you?

Interest and a need to solve problems. I was always of the opinion that a teacher in separation techniques and mass spectrometry-indeed in all fields-should have practical knowhow and fundamental knowledge. This is only possible when you are actively involved in the development and optimization of the different techniques.

Although I was working in the different fields continuously, during some periods research was more intense in specific techniques. For example, from 1970 to 1985 capillary GC was the highlight of my research; from 1985–1995 SFC and CE were central; and from 2003 to 2011 LC was the topic of choice because this was the period of the Pfizer Analytical Research Centre.

Early on in your career you conducted a lot of pioneering research into capillary GC. What memories stand out from that period and what do you feel is the lasting impact of that research?

Research was conducted in the different parts of the capillary GC system: injection, column, and detection. Most pioneering and still applied in column manufacturing are crosslinking of the stationary phase, application of autocrosslinkable silanol-terminated silicone phases, and selectively tuning in one column. Other important developments are multidimensional systems including multiple and organoleptic detection, automated on-column injection, and a fair few more.

One thing you have championed is the drive for good sample preparation. What advances have you seen in this area recently that have impressed you? And do you feel the gauntlet you laid down to the chromatography community has been picked up?

Sampling and sample preparation are indeed the most important steps in an analytical protocol. Errors made at the beginning cannot be corrected. We are making progress in sample preparation and automated systems are becoming more and more common. Still, many intensively applied methods like Soxhlet extraction (invented in 1879) are old-fashioned and should be replaced by modern alternatives like accelerated solvent extraction (ASE) or pressurized liquid extraction (PLE). An Italian colleague recently described the application of a slightly modified espresso machine for very fast quantitative extraction of polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyl (PCBs) from solid matrices like sediment. Such innovative ideas can eventually lead to simple automated systems for routine analysis. Important to note, however, is that in the recent literature a great number of papers related to new sample preparation methods are presenting unrealistic approaches because state-of-the-art instrumentation is not applied in checking their real performance. An example is describing a new technique to enrich contaminants at the high ppb level using LC with UV detection while LC coupled to tandem mass spectrometry (MS/MS) allows ppt level detection. Performance at concentrations a thousand times lower are not at all documented and thus useless.

Your research has led to a number of patents. Stir-bar sorptive extraction was particularly innovative. What was the inspiration for that technique?

Stir-bar sorptive extraction (SBSE) was invented through a simple experiment performed to prove that what we claimed in a publication on sorptive extraction, namely that the mechanism was partitioning and not adsorption, was correct (1). The partitioning of PCBs between water and the polydimethylsiloxane (PDMS) layer of a solid-phase microextraction (SPME) experiment was disturbed by adsorption of the compounds on the used Teflon stir bar. This immediately led to the idea to coat a glass stir bar with a very thick layer of PDMS, providing sensitivities in the ppt level when combined with thermal desorption-GC–MS. Gerstel commercialized the product under the name of Twister and the technique is now intensively applied in different countries for environmental, food, and forensic analyses.

Aside from SBSE, what other patents are you particularly proud of?

The development of the PyroVial was very exciting and will most probably be very rewarding once the commercial version is finished and introduced. With the Pyrovial, pyrolysis takes place in a closed vial. The pyrolysate can then be solubilized in a solvent or derivatized with a reagent and analyzed by GC, LC, SFC, and even CE. This broadens the applicability of pyrolysis because now involatile or thermally labile products can be analyzed and identified. Until now only on-line GC combined with pyrolysis limits the technique to volatile pyrolysis fragments.

Could you elaborate on some of the developments that have arisen from this work?

Present experiments with the PyroVial include studies on mutagen formation in Maillard reactions and structure elucidation in polar synthetic polymers.

Seventeen years ago, you played a role in solving the Belgian PCB–dioxin crisis. Could you talk a little about the role you played in that crisis and your thoughts about its wider implications for chromatography’s role in public life?

My most important contribution was that I made the link between the dioxins and the PCBs present in the food samples. By concentrating on the PCB precursors, which were present in the food at much higher concentration, the analysis of our food samples became much simpler, faster, and cheaper. This was indeed needed as tens of thousands of samples had to be analyzed before our food was released. This also led to a national and European initiative of PCB monitoring that is still performed today, and also contributes to the European food safety program.

Another moment when your work crossed into the mainstream was your involvement in the 1994–1995 Formula One cheating controversy. Could you talk about that scandal, the role you played in its conclusion, and how the experience impacted your career?

ELF, a French petroleum company, was producing dedicated fuels for Formula One racing that, after production, were approved by the sport’s governing body, the FIA. The 1995 Grand Prix race in Brazil was won by Michael Schumacher for the Benetton team but several hours after the conclusion of the race, Schumacher was disqualified because the chemical "fingerprint" of the used fuel sample (from ELF) did not match the approved sample. The RIC was consulted by ELF and asked to reanalyze the approved sample and the sample taken from the car immediately after the race. Based on the results obtained with state-of-the-art instrumentation (including electronic pressure control), we could prove that both petrol samples were qualitatively the same and that subtle quantitative differences could never have had an influence on the result. I defended ELF at a FIA appeal hearing in Paris and was able to convince the judges (in French) to overturn the exclusion.

Your work also stands out for the broad range of application areas it is applicable to, such as petrochemistry, environmental analysis, flavor and fragrance analysis, cosmetics, food analysis, pharmaceutical analysis, and life sciences. Did you intend to target those application areas or did the research lead you there naturally?

The fundamental research in chromatography, capillary electrophoresis, and mass spectrometry was an important aspect of the broad application range because use of the techniques in the different fields is based on the same technologies. However, at RIC we were targeting all applications fields from the very start in 1986. Not only our research at the RIC but also the courses we organized, in-house and at the customers’ sites, were tailored to the different application fields. Important in all of this is my basic education in organic chemistry.

Among many other notable chromatography meetings, your organization of the International Symposium on Capillary Chromatography (ISCC) stands out. The 2016 ISCC was the 40th. How did that symposium first come about and what are your thoughts on its tremendous success and growth over the years?

In the 1970s, interest in capillary GC was growing and Rudolf Kaiser organized the first International Symposium on Capillary Gas Chromatography in Hindelang, Germany, in May 1975. One of my first papers, entitled “Routine steroid analysis by gas chromatography on open tubular columns,” was presented at the meeting by M. Verzele, the head of the department. For the 1977 meeting in Hindelang, I was invited by Rudolf to present my work and I was impressed by his knowledge, enthusiasm, and entrepreneurial skills. Apparently I also made a good impression on him because he invited me to join the scientific committee of the meeting. It was a great honor as I was only 31 years old!

After the closing address of the 4th meeting in 1981 in Hindelang, Rudolf invited me to have a walk in the beautiful mountains of the Alps and asked me, to my great surprise, to take over the chairmanship of the meeting. After some hesitation, I decided to accept. The meeting outgrew Hindelang and because I was consultant for Carlo Erba in Italy, we visited several places in the surroundings of Milan and selected Riva del Garda, a town located on a lake at the southern edge of the Italian Alps, near the Dolomites. This selection was a winner; even today changing the location in Europe would be impossible because the participants love Riva. With Sorin Trestianu as local organizer and Jack Rijks as co-chairman, the 5th meeting was organized and was very successful with more than 400 participants. Until 2012, I was the chairman of the meeting that is now known as the ISCC & GC×GC meeting. At the end of the 2012 meeting I asked Luigi Mondello, of the University of Messina in Italy, to take over the chairmanship-time for the younger generation! In 1989, we decided to organize the meeting in the other continents of the world, with symposia taking place in the US with Stuart Cram, Karen Hyver, Milton Lee, Frank Svec, and Dan Armstrong as chairman or co-chairman, in Japan with Kiyokatsu Jinno, and in China with Guowang Xu. Organizing this symposium series has probably been my most important contribution to the development of chromatography.

In 1986 you founded the Research Institute for Chromatography (RIC). What was the inspiration for its start up?

The answer is twofold. First, the entrepreneurship of Rudolf Kaiser having his own institute inspired me to do the same, and second, I had a very hard time at the university realizing my research ideas and decided to quit. Two years later I was invited by the dean of the faculty to return part-time to the department and to lead the group of separation sciences. Since 1988, I combined the two jobs. A similar situation arose later with my extra-ordinary professorship in Eindhoven, The Netherlands, and professorship in Stellenbosch, South Africa.

Starting up a chromatography company is an enormous challenge. What are some of the biggest challenges you faced in those early years? And what advice would you give to those thinking of branching out of academia into business?

I was relatively lucky that I could start RIC in a period in which interest in chromatography and mass spectrometry was exploding. For example, all of the courses that we organized in the beginning were fully booked. Moreover, from the start I surrounded myself with my best ex-students, starting with Frank David. This created an academic atmosphere within an enterprise. The biggest challenge is, of course, finding the funding for all your ideas and research dreams! This is especially hard in the beginning!

You 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?

Sharing our work with the scientific and industrial community has been of the utmost importance to us and is by far, together with presentations at international symposia and seminars, the best marketing and PR. Scientific publications and application notes have led to collaborations with “big” players who we initially thought were unreachable.

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?

Developments that allow us to analyze macromolecules (biopolymers and synthetic polymers) with the same performance as we now analyze small molecules. Solving? We can only hope that we can contribute to realize this.

What advice would you offer a scientist just starting out?

Don’t forget to study the fundamentals and to learn from the history, preferably at the beginning of your career. I estimate that today, only 10% of the chromatography users know the resolution equation–the master equation of chromatography.

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Reference

E. Baltussen , P. Sandra , F. David , H. Janssen , and C. Cramers, Anal. Chem.,71 (22), 5213-5216 (1999).