The LCGC Blog: Reunifying Separation Science
This blog – and my introduction to you – stems from reflections on my recent transition from graduate trainee to postdoctoral fellow. With this new step in my academic journey, my research focus has shifted from using comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GC×GC-TOFMS) for discovery-based analyses to exploring new possibilities with liquid chromatography–tandem mass spectrometry (LC–MS/MS). Shifting research directions is always a big undertaking – diving into foundational studies and catching up on the latest breakthroughs – but I was energized by the challenge and eager to dive in. After all, I am a chromatographer. Sure, the separation mechanisms are different, but the chromatograms are all the same.
However, I did not anticipate that some may see this transition from GC to LC research as stepping into uncharted territory. At the most recent American Chemical Society (ACS) Fall Meeting, after presenting some highlights from both my PhD and postdoctoral work, I was asked, “What has the switch from GC to LC been like?” I struggled to find an answer to such an easy question, because I honestly did not see it as such a big deal. Now, I cannot help but find myself stuck between these two camps: “Team GC” versus “Team LC.” As a community, it seems that we have created these unnecessary divisions in the field of separation science. Maybe it is because we all love separations so much that we must resolve ourselves into two peaks?
Let us take a step back and consider what makes chromatography so powerful: its ability to continuously adapt and evolve to meet new and diverse analytical challenges. Whether it is the robustness of GC or the versatility of LC, each technique brings its own resolving strengths to the sample matrix. That is why chromatography is still a key tool in the analytical chemistry toolbox. Yet, this unspoken rivalry of LC versus GC has done a disservice to the broader goals of separation science. For instance, before finishing my PhD, a GC colleague joked about my postdoctoral switch, saying that LC stands for “lousy chromatography.” Now, as a mentor to graduate students, I hear similar sentiments, like one student quipping that GC must be easier. While these comments may be lighthearted or out of frustration, they represent a divide in our field. We are all chromatographers; we should not be championing one technique over another. Instead, we should be learning from developments in both fields and applying them holistically to our research problems. Many of science’s most exciting breakthroughs come from the intersection of ideas.
This mindset is one that I have carried throughout my journey as a chromatographer. My initial introduction to separation science was as an undergraduate researcher, staring at ChemStation with butterflies in my stomach, hoping that the peaks will show that my LC column fabrication worked. Changing fields for my graduate research and tackling data analysis methods for GC×GC-TOFMS felt normal to me. My undergraduate research was focused on improving resolution via LC column selectivity. Naturally, my PhD research was also going to focus on improving resolution, this time with the help of a modulator, a second column, and some fancy mathematics. Now, I draw on lessons from both experiences as I pursue my postdoctoral research, where I am optimizing both LC–MS/MS and data analysis methods to monitor changes to the brain metabolome in vivo. To me, GC and LC are complementary, and not opposing, techniques.
However, not everyone sees it this way. The division between GC and LC practitioners is evident in how we present chromatography. Looking at recently published articles often makes me realize that very few GC and LC papers cite one another despite working on similar broader topics. Some of the largest chromatography-based conferences tend to be focused on solely one technique or silo presentations into sessions designated to focus on a particular method. There are very few opportunities to see GC and LC talks in the same conference or session and have meaningful discussions stem from the presented work. While we may have achieved baseline resolution (Rs > 1.5) between chromatography “camps,” we are fundamentally limiting opportunities to solve complex research problems and generate new ideas.
Fortunately, I am not the only one who recognizes that there is something to be gained by having experts learn from one another. Multidimensional GC and LC researchers have been joining forces since the 2000s to improve their techniques and move the field forward. For example, Stoll et al dedicated significant portions of the introduction and future prospectus of their review on comprehensive two-dimensional LC (LC×LC) to discussing the cross-disciplinary insights gained from GC×GC (1). Further, modern review articles continue to discuss multidimensional GC and LC research in tandem (2–5). Similarly, conferences like the Multidimensional Chromatography Workshop aim to bridge the knowledge gap for multidimensional chromatographers (6). This workshop is excellent at organizing presentations by research topic, not technique, and hosting combined focus groups to ensure both “Team GC” and “Team LC” are learning from one another. I am optimistic that this subgroup of researchers can serve as a model for reunifying separation science.
I do not want this blog post to just be an abstract plea for unity. Despite these divisions, we remain united by our shared passion for separation science. For instance, one of the foundational textbooks from my graduate separations class was J. Calvin Giddings’ Unified Separation Science (7). If you take a minute and flip through Giddings’ book, you will realize that all chromatographers speak the same language and follow the same universal principles. We all have the same end-goal for our research: to improve the separation, identification, and quantitation of analytes in a matrix. Instead, I want you to take this post as a call to action to step outside your comfort zone. If you are an LC researcher, attend a GC session at your next conference, and vice versa. Read papers outside your immediate area of expertise. Ask how developments in the other technique could inform your work. Collaboration across these “camps” has the potential to unlock new solutions and expand the impact of separation science. At the end of the day, they are all just peaks!
References
(1) Stoll, D. R.; Li, X.; Wang, X.; Carr, P. W.; Porter, S. E. G.; Rutan, S. C. Fast, Comprehensive Two-Dimensional Liquid Chromatography. J. Chromatogr. A 2007, 1168 (1–2), 3–43. DOI: https://doi.org/10.1016/j.chroma.2007.08.054
(2) Bos, T. S.; Knol, W. C.; Molenaar, S. R. A.; Niezen, L. E.; Schoenmakers, P. J.; Somsen, G. W.; Pirok, B. W. J. Recent applications of chemometrics in one- and two-dimensional Chromatography. J. Sep. Sci. 2023, 43 (9–10), 1678–1727. DOI: 10.1002/jssc.202000011
(3) Abdulhussain, N.; Nawada, S.; Schoenmakers, P. Latest Trends on the Future of Three-Dimensional Separations in Chromatography. Chem. Rev. 2021, 121 (19), 12016–12034. DOI: 10.1021/acs.chemrev.0c01244
(4) Cain, C. N.; Trinklein, T. J.; Schöneich, S.; Ochoa, G. S.; Rutan, S. C.; Synovec, R. E. Advances in Chromatography, 1st Ed.; Vol. 59; CRC Press, Boca Raton, Florida, 2022; pp. 145-191.
(5) Duarte, R. M. B. O.; Brandão, P. F.; Duarte, A. C. Multidimensional Chromatography in Environmental Analysis: Comprehensive Two-Dimensional Liquid Versus Gas Chromatography. J. Chromatogr. A 2023, 1706, 464288. DOI: 10.1016/j.chroma.2023.464288
(6) The Multidimensional Chromatography Workshop. MDCW 2024. https://www.multidimensionalchromatography.com/ (accessed 2024-12-13)
(7) Giddings, J. C. Unified Separation Science, 1st Ed.; John Wiley & Sons, New York, New York, 1991.
About the Author
Caitlin N. Cain is a postdoctoral research fellow at the University of Michigan. She is supported by the National Institutes of Health – National Research Service Award for Individual Postdoctoral Fellows. Her research specializes in the development of chemometric techniques to improve chromatographic non-targeted analyses. Previously, she earned her Ph.D. in Chemistry from the University of Washington in 2024 and B.S. degrees in Chemistry and Forensic Science from Virginia Commonwealth University in 2019. Her research efforts have been recognized by numerous accolades, including the inaugural LCGC Rising Stars of Separation Science Award. She proudly serves as an executive committee member for the ACS SCSC (Subdivision on Chromatography and Separations Chemistry).
