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Techniques & Tools Preparative/Process Chromatography, Gas Chromatography, Liquid Chromatography, Thin Layer Chromatography

Unifying Chromatography on All Fronts

While reading the January 2019 issue of The Analytical Scientist, the use of the term “unified chromatography” by Caroline West to discuss the combination of supercritical fluid chromatography (SFC) and high performance liquid chromatography (HPLC) jumped out at me (1). I have myself used “unified chromatography” to describe linking experimental single molecule observations with statistical modeling of ion-exchange chromatography (2). And West and I are not the first – this “unified” terminology can be traced through generations of separation scientists back to the 1965 seminal work “Dynamics of Chromatography” by J. Calvin Giddings (3), which was followed by “Unified Separation Science” by the same author (4).

Unification brings together specialties that might seem disparate, but ultimately have a common goal.

What does it really mean to “unify”? To me, unification brings together specialties that might seem disparate, but ultimately have a common goal. In the medical field, the “bench-to-bedside” approach connects basic research to disease treatment in the clinic. In physics, linking electromagnetic, weak, and strong forces is pursued in the Grand Unified Theory. Can we similarly take a “Peak to Production” or “Grand Unified Separation” approach?

There are several ways in which we can unify. First, we can link different forms of chromatography. Typically, the physical state of the mobile phase is used to classify instrumentation: gas (GC), liquid (LC), and supercritical fluid chromatography (SFC). As West highlights, these chromatographic methods can be combined (1) – creative instrumentation compatible with all three mobile phase conditions have been demonstrated and are even commercially available. Multimodal and gradient columns unify stationary phases by combining different physical and chemical mechanisms that cause separation, yielding improved selectivity and capacity, along with a reduction in equipment and materials.

Unification can also connect experimental, computational, and theoretical approaches across the molecular, analytical, and industrial scales at which chromatography is studied. Starting from the molecular level, computational molecular dynamics, statistical mechanical modeling, and single molecule experiments seek to understand the fundamental energetics and kinetics that lead to separations. Moving up a level, we observe the average of many molecules eluting in analytical-scale separations. Experimentally, novel stationary phases with new chemistries and nanomaterials are developed, while
ensemble contributions of flow and kinetics are quantified with modeling fluid mechanics and the van Deemter equation. Finally, large amounts of material must be separated robustly and reproducibly in industry. Iterative screening for method development is commonly required, but data scientists can help make informed choices using library-based computational approaches (5).

How can we promote and accelerate unification? I think an easy first step is to stop isolating ourselves in strict classifications, whether that be experimentalist/theorist, academic/industry, physicist/chemist/engineer, or GC/LC/SFC-user. Collaboration, reading the literature, and attending new conferences with a broader perspective can lead to exciting research directions. For example, during my PhD, despite writing my entire thesis on chromatography, I never actually ran a column! I instead relied on my collaborators to do the “real” separations while I hung out with my microscope. My lack of instrumental knowledge became apparent within the first few weeks of my postdoc, when I struggled to use a fast protein liquid chromatography (FPLC) setup. If only I had shadowed my former collaborators, I would have understood some of the challenges and been able to pursue more informed research directions.

Inspired by this idea of unification, I’m looking into equipping my new lab for HPLC in addition to my microscope so I can study chromatography on multiple scales, and I’m expanding my research from ion-exchange chromatography to chiral separations. These are small steps, but I believe if our field as a whole takes a more interdisciplinary approach, we will be in a better position to tackle the grand challenges – predicting separations and developing routine instrumentation that can handle any separation. I hope others will join me in my quest for unification.


By Lydia Kisley, Department of Physics, Case Western Reserve University, Cleveland, Ohio, USA.

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  1. C West, “Breaking Barriers.” In: Landmark Literature 2018: Part 1. The Analytical Scientist, 72, 27 (2019).
  2. L Kisley et al, “Unified super-resolution experiments and stochastic theory provide mechanistic insight into protein ion-exchange adsorptive separations”, Proc Natl Acad Sci USA, 111, 2075–2080 (2014).
  3. JC Giddings “Dynamics of Chromatography”; Marcel Dekker, Inc., New York, 1965; Vol. 1.
  4. JC Giddings, “Unified Separation Science”; Wiley: New York, 1991.
  5. P Haddad, “(Practically) Perfect Predictions”, The Analytical Scientist, 72, 37–41 (2019).
About the Author
Lydia Kisley

Department of Physics, Case Western Reserve University, Cleveland, Ohio, USA.

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