Surface modification of regenerated cellulose membrane based on thiolactone chemistry - A novel platform for mixed mode membrane adsorbers

Mixed-mode membrane chromatography (MMC) is an effcient separation technology for protein purification. However, tedious preparation methods and difficulty on ligand density control for its stationary phase limit the application of MMC. Herein we explored a one-pot multistep reaction based on the thiolactone chemistry as a platform for membrane surface modification design toward mixed mode membrane adsorbers. The regenerated cellulose (RC) membrane was modified by the atom transfer radical polymerization (ATRP) of styrene-thiolactone (St-Tla), followed by the amine-thiol-ene conjugation. N-butylamine/methacrylic acid and octylamine/methacrylic acid were selected as the modifier to prepare two different mixed mode membrane adsorbers, RC-HIC/IEC (hydrophobic/ion-exchange) and RC-RPC/IEC (reversed phase/ion-exchange). SEM, FT-IR and XPS results showed that the membrane adsorbers were successfully prepared. The RC-HIC/IEC membrane had a statistic adsorption capacity of 73.5 mu g/cm(2) for human immunoglobulin G (IgG) under the conditions of pH = 8 and 0.5 mol/L NaCl in PB buffer. The RC-RPC/IEC membrane showed a capacity of 70 mu g/cm(2) for alpha-chymotrypsin (alpha-CTP) under the conditions of pH = 6.5 in PB buffer. The feasibility of tethering multi functions onto membrane surface via the thiolactone chemistry was demonstrated in this work.