Free-solvent model shows osmotic pressure is the dominant factor in limiting flux during protein ultrafiltration

In protein ultrafiltration (UF), the limiting flux phenomenon has been generally considered a consequence of the presence of membrane fouling or the perceived formation of a cake/gel layer that develops at high operating pressures. Subsequently, numerous theoretical models on gel/cake physics have been made to address how these factors can result in limiting flux. In a paradigm shift, the present article reestablishes the significance of osmotic pressure by examining its contribution to limiting flux in the framework of the recently developed free solvent osmotic pressure model. The resulting free-solvent-based flux model (FSB) uses the Kedem–Katchalsky model, film theory and the free solvent representation for osmotic pressure in its development. Single protein tangential-flow diafiltration experiments (30 kDa MWCO CRC membranes) were also conducted using ovalbumin (OVA, 45 kDa), bovine serum albumin (BSA, 69 kDa), and immuno-gamma globulin (IgG, 155 kDa) in moderate NaCl buffered solutions at pH 4.5, 5.4, 7 and 7.4. The membrane was preconditioned to minimize membrane fouling development during the experimental procedure. The pressure was randomly selected and flux and sieving were determined. The experimental results clearly demonstrated that the limiting flux phenomenon is not dominated by membrane fouling and the FSB model theoretically illustrates that osmotic pressure is the primary factor in limiting flux during UF. The FSB model provides excellent agreement with the experimental results while producing realistic protein wall concentrations. In addition, the pH dependence of the limiting flux is shown to correlate to the pH dependency of the specific protein diffusion coefficient.