Celebrating Innovation – and 25 Years of SPME and GC×GC

Solid phase micro-extraction (SPME) was a revolutionary sampling technique invented by Janusz Pawliszyn in 1990, followed by the introduction of comprehensive two-dimensional gas chromatography (GC×GC) by the late John Phillips in 1991. And there is a link between them; these two prolific analytical scientists crossed paths in the early 1980s when Pawliszyn obtained his PhD under the guidance of Phillips at Southern Illinois University. A lesser-known link is that I have been fortunate enough to get hands-on experience of both techniques – and I’d like to share my opinions by comparing apples with oranges!

SPME is an extremely simple method for collecting and concentrating compounds prior to chromatographic analysis. You expose a small fiber to your sample for a specified period of time then directly desorb the fiber in a carrier stream leading to the separation column. The brilliance of the design is that it matches the size scale of the sampling material (the fiber) to the small radial scale of a modern chromatography column. I find myself looking at the tiny fiber hanging out of the assembly and appreciating the ingenuity of the inventors. The development of such a simple yet effective device deserves a standing ovation – especially when the route to needless complexity seems to be more than common these days. Indeed, it is the very simplicity of the technique that allows a user to become proficient in the implementation of SPME sampling in a single afternoon. I know I did. But...

The small size of the fiber does lead to one major drawback that I experienced with SPME. Essentially, compounds with low partition coefficients can quickly reach an equilibrium state with the fiber sorbent material, which means that sample collection could be biased. For example, in the case of a complex VOC mixture, the larger molecular weight VOCs with bigger partition coefficients are collected more efficiently than the smaller molecular weight VOCs with smaller partition coefficients. Why? Because highly volatile, smaller compounds saturate quickly on the small SPME fibers, whereas less volatile and bigger compounds keep accumulating for a longer time. The result is a chromatogram where peak size is heavily influenced by both the concentration of the components but also by their partition coefficients. Fortunately, new sorbent materials have been (and continue to be) introduced to address this issue. For instance, SPME fibers based on ionic liquids, carbon nanotubes (Guibin Jiang), polymeric ionic liquids (Jared Anderson) and so on, are being tested for their efficiency.

From an “ease of adoption” point of view, GC×GC is the polar opposite of SPME. GC×GC adds a second stage of gas chromatographic separation to an otherwise conventional GC analysis.  And when done correctly, GC×GC generates beautiful two-dimensional chromatograms that greatly increase the information content and peak capacity of the analysis. The early days of GC×GC research were largely devoted to developing the modulation hardware and data analysis strategies for generating high-resolution separations. The second (and current stage) of GC×GC research has focused on demonstrating the utility of this analytical technique for tackling a wide range of analytical applications. And though both phases of development have been highly successful, GC×GC has not benefitted from the broad adoption that we have seen for SPME.

Perhaps one reason for the delay is relatively lukewarm support from major instrument manufacturers. A few years back, my former PhD advisor (John Seeley, Oakland University), was invited to give a talk to a major analytical instrumentation company in USA. Right after Seeley’s talk, a prominent person in the organization told him, “GC×GC is just a solution in search of a problem”.  Clearly, pictures of beautiful separations by themselves are not enough to sway the skeptics. And though the criticism may have been semi-valid 15 years ago, the literature is now full of examples of tough problems being solved by GC×GC.

So what is really holding GC×GC back? In my opinion, there is a level of complexity that is inherent and unavoidable in GC×GC.  Unlike SPME, where the process can be separated into discrete steps, GC×GC involves multiple simultaneously occurring processes (separation in the primary column, modulation, separation in the secondary column, detection). It results in a highly complex system where small changes to individual experimental parameters can significantly alter the appearance of the resulting 2-D chromatogram. Indeed, becoming proficient at optimizing a GC×GC separation involves understanding the confounding influence of multiple experimental settings. The high sensitivity to multiple conditions has been nicely outlined by Tadeusz Gorecki (University of Waterloo) in a series of articles appearing in academic journal and trade publications. Certainly, GC×GC involves a “steep learning curve”, but many of us have found it to be well worth the effort. To make GC×GC more acceptable, experts and commercial vendors should continue to search for more user friendly designs. I also believe we should also develop “cookbook” methods that allow new adopters to experience success in a shorter period of time. Finally, we need to continue to develop theoretical methods that allow users to “pre-optimize” experimental conditions. I remember being horrified when I heard at a GC×GC workshop that the best column selection strategy was “trial and error”.  Clearly, we can do better than that.

Experienced users of GC×GC also have to guard against over-selling or over-mystifying the technique. The enhanced peak capacity of GC×GC is not always a complete solution. There remain critical pairs that are still hard to resolve. For example, even with its extremely high peak capacity, GC×GC can barely separate m and p-xylenes (I hope Jack Cochran, who had done such analysis, would agree). “Orthogonality” is a nebulous concept that I feel has been given too much importance in the early development of GC×GC.

Orthogonality in GC×GC means different things to different people, but it was most often used to describe the difference in the retention mechanisms between the primary and secondary stationary phases. The old rule of thumb was that the primary column should be non-polar and the secondary column should be as polar as possible, the belief being that it maximized “orthogonality”.  We now know that unique and highly effective column combinations that go beyond the maximum orthogonality dogma can be found with the aid of simple GC×GC retention models. For example, we found that siloxanes can be best separated from complex hydrocarbon mixtures by using two non-polar columns, DB-1 and SPB-Octyl.

In my view, both SPME and GC×GC have consolidated their positions as effective analytical techniques. But they are obviously (and fortunately) very different. SPME is constantly in search of new, selective and more efficient sorbents, whereas GC×GC is striving to become more user friendly and cost effective.