HPLC 2025 Preview: Columns, Capillaries, and Chaos

High performance liquid chromatography (HPLC) faces challenges due to column disorder, leading to band broadening and reduced separation performance. Recent advances using computational fluid dynamics and Brenner’s macro-transport theory have revealed insights into multi-capillary and spatially periodic columns, identifying the role of capillary arrangement and disorder in band broadening and suggesting optimization strategies. LCGC International’s Rising Star of Separation Science Winner for the LC Category, Bram Huygens from the Vrije Universiteit Brussel in Brussels, Belgium, recaps the work he presented for his award and his current research focus.

Q. Congratulations on being awarded the LCGC International Rising Star Award for the liquid chromatography category at the end of 2024. Your presentation at the award ceremony focused on research into multicapillary columns. Can you tell us why researching multicapillary columns is important? What benefits could they potentially offer the analyst?

Researching various column designs has long been a focus of our group. The unique selling point of these multicapillary columns is that they offer the optimal trade-off between pressure drop and separation performance. Unfortunately, there are quite a few complications between this theoretical principle and the practical reality in the laboratory, which we seek to overcome through our recent research (1,2).

Q. Your talk at HPLC 2025 is called “Columns, Capillaries, and Chaos: On the Relation Between Disorder and Band Broadening.” This research continues from the work you described at ISC 2025. How does the application of macro-transport theory enhance our understanding of the dominant mechanisms of band broadening in multicapillary columns, particularly in comparison to traditional packed bed models?

Indeed, with this research, we are improving upon the models we have developed before, and macro-transport theory is the best tool for that job. I have had the pleasure of learning about this mathematical framework in the group of Alessandra Adrover and Stefano Cerbelli, and was amazed by just how powerful it is. Computations I used to struggle with for months were suddenly completed within hours! This allows us to perform many more simulations than we would otherwise, varying the parameters of the column designs to evaluate their effect on band broadening.

Apart from being able to generate vast data sets of plate heights predictions, macro-transport theory also allows us to isolate different mechanisms of band broadening by performing simulations of hypothetical scenarios that would not be possible in practice. What if the diffusion coefficient of an analyte approaches zero? What if the retention factor of an analyte approaches infinity? And so on. These hypothetical scenarios, however absurd they may appear, tell us a lot about the underlying mechanisms of band broadening.

Q. In the context of multicapillary columns, what specific metrics or computational strategies were used to quantify the impact of capillary arrangement disorder on band broadening?

To evaluate the effect of the inevitable disorder within a multicapillary column, both from the differences in diameter and the scattered arrangement of the capillaries, we found that Fourier analysis was a valuable method. Through Fourier analysis of the cross-section of a multicapillary column, we can distinguish between the short-range disorder, that is, the differences between neighbouring capillaries and the long-range disorder, that is, the differences between sections of the column. It is through the summation of all these effects, which is actually a Fourier series, that the overall band broadening can be modelled.

Q. What are the critical design parameters identified for mitigating disorder-induced band broadening in multicapillary columns, and how do these parameters interact with each other?

One of the best strategies to reduce the disorder happens to be quite straightforward: increasing the number of capillaries within the column. By “jamming” as many capillaries within the column as possible, they are naturally forced into a more regular arrangement.

Apart from that, there must be sufficient “diffusional bridging” between the capillaries, that is, analytes must move freely through the mesoporous monolith that surrounds the capillaries. Fine tuning the internal structure of the mesoporous material could therefore also offer a way forward to improve the column design.

Q. In the context of packed bed columns, when introducing chaotic dynamics by breaking the symmetry of unit cells in spatially periodic geometries, what are the implications for scaling up these models to predict real-world behavior?

There is much to discover here. By breaking the symmetry of our simulations, we seek to bridge the gap between macro-transport theory, which assumes the geometry is spatially periodic, and the structure of a packed bed column, which is naturally disordered. In doing so, we hope to make our models more relevant to the real world, but perhaps we will have to introduce some further complications for our models to scale up.

Q. Considering the limitations of reducing complex column geometries to a unit cell in macro-transport models, how do you validate the simulations against experimental data, particularly when modeling flow-induced dispersion in disordered systems?

In the end, the proof of the pudding is in the eating: Do the equations fit van Deemter curves as measured on packed bed columns? Here, we feel encouraged by the fact that our logarithmic equation for the eddy dispersion, derived from a relatively simple geometric model, agrees quite well with some experimental data sets (3). But more data sets will be needed for further validation.

Q. Are you planning to explore this research further?

I am not done with band broadening just yet! Our recent research on the chaotic dynamics, in collaboration with Joris Heyman and Tanguy Le Borgne, offers perspectives for further discovery. To be continued!

Columns, Capillaries, and Chaos: On the Relation Between Disorder and Band Broadening (OR12)

MO-04 – Fundamentals

Monday, June 16, 10:45 am–12:30 pm

References

(1) Huygens, B.; Parmentier, F.; Desmet, G. Exact Analytical Expressions for the Band Broadening in Polydisperse 2-D Multi-capillary Columns with Diffusional Bridging. J. Chromatogr. A 2021, 1659, 462632. DOI: 10.1016/j.chroma.2021.462632

(2) Huygens, B.; Parmentier, F.; Desmet, G. Transient Taylor-Aris Dispersion in N-capillary Systems: Convergence Properties of the Band Broadening in Polydisperse Multi-capillary Columns with Diffusional Bridging. J. Chromatograph. A 2022,1678, 463346. DOI: 10.1016/j.chroma.2022.463346

(3) Huygens, B.; Desmet, G. A Logarithmic Law for the Velocity- and Retention-dependency of the Eddy Dispersion in Chromatographic Columns. J. Chromatogr. A 2024, 1730, 465088. DOI: 10.1016/j.chroma.2024.465088

Bram Huygens © Image courtesy of interviewee

Bram Huygens is a postdoctoral researcher at the Vrije Universiteit Brussel, and a member of the group of Gert Desmet. Through the modeling of band broadening, he sheds new light on the separation performance of chromatographic systems, from the conventional packed bed columns to the upcoming multicapillary columns. In doing so, he seeks to contribute to the fundamentals of separation science and demonstrate the potential of applied mathematics within the field.