Harnessing an elastic flow instability to improve the kinetic performance of chromatographic columns

TL;DR

This study demonstrates that adding a small amount of a flexible polymer to the mobile phase induces elastic flow instabilities in HPLC columns, which can enhance efficiency by reducing flow heterogeneity and peak asymmetry.

Contribution

It introduces a novel method of improving chromatographic column performance by harnessing elastic flow instabilities through polymer addition during operation.

Findings

Flow instability occurs above a threshold flow rate.

Elastic flow instability reduces peak asymmetry.

Column efficiency is significantly improved.

Abstract

Despite decades of research and development, the optimal efficiency of slurry-packed HPLC columns is still hindered by inherent long-range flow heterogeneity from the wall to the central bulk region of these columns. Here, we show an example of how this issue can be addressed through the straightforward addition of a semidilute amount (500~ppm) of a large, flexible, synthetic polymer (18~MDa partially hydrolyzed polyacrylamide, HPAM) to the mobile phase (1\% NaCl aqueous solution) during operation of a 4.6 mm $\times$ 300 mm column packed with 10~$\mu$m BEH$^{\mathrm{TM}}$ 125~\AA \ Particles. Addition of the polymer imparts elasticity to the mobile phase, causing the flow in the interparticle pore space to become unstable above a threshold flow rate. We verify the development of this elastic flow instability using pressure drop measurements of the friction factor versus Reynolds number. In prior work, we showed that this flow instability is characterized by large spatiotemporal fluctuations in the pore-scale flow velocities that may promote analyte dispersion across the column. Axial dispersion measurements of the quasi non-retained tracer thiourea confirm this possibility: they unequivocally reveal that operating above the onset of the instability improves column efficiency by significantly reducing peak asymmetry. These experiments thereby provide a proof-of-concept demonstration that elastic flow instabilities can be harnessed to mitigate the negative impact of trans-column flow heterogeneities on the efficiency of slurry-packed HPLC columns. While this approach has its own inherent limitations and constraints, our work lays the groundwork for future targeted development of polymers that can impart elasticity when dissolved in commonly used liquid chromatography mobile phases, and can thereby generate elastic flow instabilities to help improve the resolution of HPLC columns.