Optimization of the operating parameters for membrane separation of proteins is usually performed in industry by varying one factor at a time. While this procedure cannot ensure that an optimum is found, it is generally too time consuming and costly to determine optimal operating conditions by simultaneously varying all factors. This paper presents a procedure that can be generically used by, e.g., the biotechnology industry, for determining close to optimal operating conditions for cases where relatively little data are available. The procedure fits a polynomial regression model to the operating parameters and performs a multidimensional optimization of the empirical model with regard to some important operating parameter, e.g., a combination of selectivity and purity. The technique is illustrated with a membrane ultrafiltration (UF) process for the separation of hen egg lysozyme (Lys) from ribo nuclease A (RNase A) and in a second case study for separating hemoglobin (Hb) from bovine serum albumin (BSA).
Industrial & Engineering Chemistry Research 53, No. 13, pp. 5103-5109 (2014)