Voxel-Resolved Bottom-up Engineering of High-Performance Chromatographic Material Based on Stereolithography 3D Printing

Manufacturing of high-performance chromatographic column material has long been esteemed as an art rather than science, this raised a great challenge in securing separation precision, method transferability and process scaling-up in purification of biomolecules, as demanded in biological and pharmaceutical industries. Herein, we report a bottom-up engineering strategy for high-performance chromatographic material fabrication based on stereolithography 3D printing. With voxel-resolved manufacturing capability, this engineering strategy enables manufacturing of highly reproducible chromatographic materials in diverse scale, shape and volume. Extremely consistent micro-structures of printed chromatographic materials were demonstrated by the superb column-to-column and batch-to-batch repeatability of separation performance (with retention time coefficient of variation CV=2.04%) between 1,000 columns. The ultra-fast and high-resolution separation capability of the resultant columns was demonstrated by hydrophobic interaction chromatography and reversed-phase LC separations of proteins and monoclonal antibodies. Resolution > 1.5 was achieved for critical pairs within only one minute. The present stationary-phase manufacturing strategy offered high-fidelity chemistry and morphology preservation in various dimensions, which facilities the transition from analytical column formats (4.6 mm i.d.) to industrial preparative column format with i.d. in the range of 10-80 mm.