Separation of hyaluronic acid from fermentation broth by tangential flow microfiltration and ultrafiltration

This work examined the use of a two-stage tangential flow filtration process for the separation of hyaluronic acid from fermentation broth. Micro-filtration (MF) membranes (0.45, 0.20 mu m in pore diameter) and ultrafiltration (UF) membranes (MWCO 300, 100 kDa), made from polyvinylidene fluoride, were used to achieve the separation in series. Operating conditions of each stage were firstly optimized to give the best separation. Then, the two-stage membrane process was undertaken with two separating schemes: the first using MF followed by UF with pure water as diafiltrate, the second similar to the first except permeate from previous UF stage as diafiltrate for MF stage. The optimal conditions were transmembrane pressure 0.1 MPa, crossflow velocity 1.25 m/s, solution pH 4.0 and enhanced ionic strength 0.25 mol/l NaCl for MF membranes, and 0.15 MPa, 1.25 m/s, pH 7.0 and 0.1-0.25 mol/l NaCl for UF membranes, respectively. The two schemes could effectively separate and purify HA with above 77% overall yield and about 1000 purification factor. The second scheme seemed to be more effective for its higher overall yield (89%) and saving water. (c) 2006 Elsevier B.V. All rights reserved.