Microfluidic Precision Manufacture of High Performance Liquid Chromatographic Microspheres

Abstract A key bottleneck in developing chromatographic material is the chemically entangled control of morphology, pore structure, and material chemistry, which holds back precision material manufacture in order to pursue advanced separation performance. In this work, a precision manufacture strategy based on droplet microfluidics was developed, for production of highly efficient chromatographic microspheres with independent control over particle morphology, pore structure and material chemistry. The droplet‐synthesized microspheres display extremely narrow particle size distribution (CV<3 %), enabling a 100 % production yield due to complete elimination of sieving steps. More importantly, the size of the droplet‐synthesized microspheres is freely adjustable without the need for re‐optimizing chemical recipes or reaction conditions. The resulting materials exhibit excellent separation efficiencies, achieving a reduced plate height of h min =1.67. This precision manufacture strategy also allows for flexible pore design and continuous pore size adjustment across three orders of magnitudes, providing a novel vehicle for resolution fine‐tuning targeting protein separation. Besides traditional silica, organic–inorganic hybrid silica, zirconia, and titania microspheres can also be precisely synthesized on the same platform, supporting various separation applications and operating conditions. Powered by precision manufacture, super‐throughput production, and versatile chemistry, the high‐performance droplet‐synthesized separation material will pave the way towards green and precision chromatographic industry.