Digital design of chromatographic resins to improve mass transfer for large biomolecules: An exploration of concept

Abstract Chromatography offers a powerful platform for the purification of cell and gene therapy (CGT) products. However, commercial chromatographic resins suffer from limited capacities due to poor mass transfer, and the ideal resin structure for improving capacity remains unclear. Here, a concept of digital resin design is proposed to accelerate the structure design of high‐capacity resins for CGT products. The digital design procedure was performed by generating virtual resin structures, analyzing the key structure characteristics, and simulating the dynamic diffusion of biomolecules in turn. The results revealed that nanofiber‐based structures have a superior mass transfer ability for 100 nm‐size model molecules compared to nanoparticle‐based structures, as evidenced by 7.7 and two times improvement in the molecule breakthrough amount from structures and molecule diffusion displacement, respectively. The superiority of nanofiber‐based resin was further demonstrated by mRNA adsorption experiments. These results indicate that digital resin design is a useful tool for resin development.