Synthesis and optimization of wide pore superficially porous particles by a one-step coating process for separation of proteins and monoclonal antibodies

摘要

Superficially porous particles (SPPs) with pore size ranging from 90A to 120A have been a great success for the fast separation of small molecules over totally porous particles in recent years. However, for the separation of large biomolecules such as proteins, particles with large pore size (e.g. >= 300 angstrom) are needed to allow unrestricted diffusion inside the pores. One early example is the commercial wide pore (300 angstrom) SPPs in 5 mu m size introduced in 2001. More recently, wide pore SPPs (200 angstrom and 400 angstrom) in smaller particle sizes (3.5-3.6 mu m) have been developed to meet the need of increasing interest in doing faster analysis of larger therapeutic molecules by biopharmaceutical companies. Those SSPs in the market are mostly synthesized by the laborious layer-by-layer (LBL) method. A one step coating approach would be highly advantageous, offering potential benefits on process time, easier quality control, materials cost, and process simplicity for facile scale-up. A unique one-step coating process for the synthesis of SPPs called the "coacervation method" was developed by Chen and Wei as an improved and optimized process, and has been successfully applied to synthesis of a commercial product, Poroshell 120 particles, for small molecule separation.