Study Explores How Minimal Surface Geometry Enables Micromixers to Function as LC Separation Columns

To enhance the performance of micro- and nano-liquid chromatography (LC), researchers from Sapienza Università di Roma (Rome, Italy) and ETH Zürich (Zürich, Switzerland) investigated the performance of a capillary LC system. Their findings were published in the Journal of Chromatography A (1).

Liquid chromatography (LC) column performance is mainly limited by the contribution to axial dispersion of the mobile phase. To mitigate this, different strategies have been proposed, all based around enhancing transversal transport to reduce analyte bandwidths’ rates of growth. These approaches include triggering secondary flows exploiting inertia-driven cross-sectional flows in coiled capillaries, leveraging turbulent transport, and using supercritical fluids, among other potential options. Microfluidic channels hosting spatially periodic supports for the stationary phase have been a large part of this research in the past two decades of research, despite currently representing approximately 5% of the LC market. Specifically, micro-pillar array columns (µPACs), composed of a shallow rectangular channel enclosing a staggered lattice of cylindrical posts supporting a porous adsorbing layer, have been singled out for strong separation performance, comparatively low pressure drops, and relative ease of manufacturing.

In this study, the scientists investigated and numerically predicted the separation performance of a capillary LC column hosting a periodic alternate sequence of helicoidal baffles arranged in a Kenics mixer (KM) configuration. The KM-LC column’s performance was compared to those of packed, random-monolithic, and µPAC columns, carried out by matching the capillary diameter of the KM to the size of the flow-through pores of the other geometries.

Potential further enhancement of LC efficiency was displayed, with a with a minimal plate height reduced by a factor 3 for an unretained solute, and by a factor 2 for a solute with retention factor k = 2 with respect to the best performing columns reported. This improvement in performance was achieved without compromising in terms of pressure losses, as shown by a significant reduction in separation impedance observed across all practically relevant flow velocities when compared to other LC technologies.

Overall, the scientists proposed that the performance enhancement of KM geometry can stem from a combination of factors: namely, the minimal nature of the helicoidal surface, which influences the rate of viscous dissipation, and the chaotic advection mechanism in the mobile phase, which mitigates the increase in plate height as eluent velocity increases. The proposed geometry not only entails significantly lower values of the minimal plate and of the separation impedance with respect to existing technologies exploiting periodically structured supports but also determines a different scaling of the plate height with the eluent velocity when the latter is increased beyond its optimum value.

The results obtained in this study suggest that KM geometry might be ideally suited for SFC applications, where the low viscosity of carrier fluids make it possible to reach relatively large values of the reduced velocity. In turn, this unfolds the performance enhancement of chaotic advection at affordable pressure drop values. However, the researchers do emphasize that tailored investigations are in place to assess this possibility, as larger values involved through SFC can potentially alter a flow’s fluid dynamics and kinematic features.

Reference

(1) Biagioni, V.; Procopio, G.; Agosta, L.; et al. Turning a Micromixer into a Separation Column: The Role of Minimal Surfaces and Transversal Transport in Enhancing the Performance of Micro/Nano Liquid Chromatography. J. Chromatogr. A 2025, 1758, 466161. DOI: 10.1016/j.chroma.2025.466161