Optimization of ultrafiltration/diafiltration processes for partially bound impurities.
Ultrafiltration and diafiltration processes are used extensively for removal of a variety of small impurities from biological products. There has, however, been no experimental or theoretical analysis of the effects of impurity- product binding on the rate of impurity removal during these processes. Model calculations were performed to account for the effects of equilibrium binding between a small impurity and a large (retained) product on impurity clearance. Experiments were performed using D-tryptophan and bovine serum albumin as a model system. The results clearly demonstrate that binding interactions can dramatically reduce the rate of small impurity removal, leading to large increases in the required number of diavolumes. The optimal product concentration for performing the diafiltration shifts to lower product concentrations in the presence of strong binding interactions. Approximate analytical expressions for the impurity removal were developed which can provide a guide for the design and optimization of industrial ultrafiltration/diafiltration processes.
Department of Chemical Engineering, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
Jiahui
J
Shao
Andrew L
AL
Zydney
D045424:Complex Mixtures / Q000302:isolation & purification*; D003198:Computer Simulation; D017551:Microdialysis / Q000379:methods*; D044085:Microfluidics / Q000379:methods*; D008956:Models, Chemical; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000302:isolation & purification*; D012995:Solubility; D014364:Tryptophan / Q000302:isolation & purification*; D014462:Ultrafiltration / Q000379:methods*
D045424:Complex Mixtures; D012710:Serum Albumin, Bovine; D014364:Tryptophan