Stereosynthesis of stationary phase with precision defined separation selectivity

Chemical separation is based on molecules' differential interactions with a stationary phase and a mobile phase. To enable efficient thermodynamics and molecular kinetics, micrometer-size spheres with bonded chemistry have become the general choice for stationary phase materials. For half a century, the application of stationary-phase chemistry to microspheres has been a random, unordered and bulk process in the manufacture of chromatographic materials. Such a non-stereoresolving synthetic strategy results in the co-location of multiple functional groups, which share the same space, including those that are designed to function with different or opposite selectivities, such as hydrophobic and hydrophilic, cation exchange and anion exchange, and so on. The co-location of these functional ligands can cause severe interference with each other, leading to deviation from, or even having a detrimental effect on, the designed separation selectivity. This non-spatially resolved stationary-phase chemistry diminishes the effectiveness of mixed-mode separation and constrains the feasibility and freedom of multi-functionality assemblies when pursuing high separation performance. In this study, through microfluidic precision manufacturing, microspherical stationary phases were stereosynthesized with well-defined functional domains and the realization of quantitatively tunable chemical selectivity. With a classical mixed-mode stationary phase as a benchmark, it was found that the originally existing, but seriously constrained, chromatographic retentivity can now be unleashed by the spatially resolved arrangement of chemical functionality. The current study suggests that, as an unexplored structural parameter, the spatial distribution of stationary phase chemistry is an independent characteristic, which can enable the precision design and free tuning of thermodynamics, providing a new approach towards high-performance chromatography.