ACO-LC · Applying ACOustic streaming to enhance mass transfer in Liquid Chromatography of large molecules

Liquid chromatography (LC) is a prominent analytical technique serving life-sciences, chemical and pharmaceutical sciences, which plays a key role in virtually all research and development concerned with liquid phase (bio)chemistry. The performance of pressure-driven LC has continuously increased during the past century, with improvements realized by ordering the packing and reducing the particle size. Now that the point is reached where sub-micron ordered packings can be reliably produced, the performance limitation of LC lies in the principle itself, more precisely in the slow mass transport of analytes between the field lines with varying cross-sectional Poiseuille velocity vectors. Distribution of analytes in the sample bands over different local velocities results in Taylor-Aris dispersion, an effect that becomes increasingly important at high velocities, or at low diffusion coefficients. ACO-LC addresses this lateral diffusion limitation by inducing acoustically generated lateral flows obtained in resonance mode. The resulting vortices in this so-called acoustic streaming regime carry the analytes much faster than purely diffusive processes, therewith reducing the dispersion dependency on size and mobile phase velocity. While the efficacy of this acoustic vortex LC methodology has been recently shown in microfluidic channels in the host group, the channel dimensions need to be scaled to the micron-scale range, with the resonance condition maintained. In ACO-LC, innovative geometrical approaches will be pursued to overcome frequency limitations of commercial piezoceramic actuators. Improved separations of glycosylated hemoglobin variants are aimed for in glass substrates, which are compatible with integrated UV-VIS absorption. This improved separation application is of interest to millions of diabetes patients for routine separations and tackles an additional separation challenge encountered in multi-ethnic groups.