Ultrafiltration processes offer some choices in control strategies, depending on the type of process control and the level of automation desired. One of the simplest strategies involving the least amount of automation is to operate at a constant retentate pressure or constant transmembrane pressure. Constant retentate pressure processes maintain selected feed flow rate and retentate pressures throughout the process while the filtrate rate and filtrate pressures are uncontrolled. Similarly, constant transmembrane pressure processes keep the feed and retentate pressures at a set value throughout the operation. Successful operation depends on the optimization of the feed rate or pressure, and the retentate pressure to avoid membrane fouling. A key drawback of this
ULTRAFILTRATION CONTROL STRATEGIES
method is the risk that run-to-run variability in starting concentrations or volumes may lead to inconsistent processing times and significant flux decay.
Although more commonly used for microfiltration applications, another control option that may be used for some protein ultrafiltration processes is to control the filtrate flux by using a pump on the filtrate outlet or a control valve on the retentate outlet. For controlled filtrate flow operation, ideally the feed and retentate pressures remain constant and process development efforts focus on optimizing the feed and filtrate flow rates to achieve high product yields without fouling the membrane. This strategy is more often employed for MF operations since membrane fouling would occur quickly due to the high permeability unless the filtrate flux is reduced via a pump or valve (van Reis et al. 1991; Maiorella et al. 1991). In UF processes, controlling the filtrate flux is not as desirable because selecting too low a value for the flux leads to longer process times or greater membrane areas, and selecting too high a value leads to osmotic pressure limitations as protein concentration increases (van Reis et al. 1997).
A third control strategy, in which the solute concentration at the membrane wall is held constant throughout ultrafiltration and diafiltration, has also been proposed (Meireles et al. 1991a; van Reis et al. 1997). Van Reis and coworkers used the osmotic pressure model, the osmotic virial expansion and the stagnant film model to develop three control equations for maintaining a constant Cw throughout UF and DF:
where AP is transmembrane pressure, J is filtrate flux, Lfm is the fouled membrane resistance, a and b are the first and second coefficients, Cw is the wall concentration, C0 is the initial concentration, V is volume, V0 is initial volume, and k is the mass transfer coefficient.
van Reis and coworkers concluded that controlling the filtrate flux (8) rather than the transmembrane pressure to maintain a constant Cw was the preferred control strategy. Implementation of this control method requires careful optimization of the selected wall concentration. Too low a wall concentration leads to low filtrate fluxes, longer processing times and/or very large system sizes. Selection of a high wall concentration yields higher filtrate fluxes, but can also lead to solubility losses and filtrate losses. Solubility losses refer to lost product that has aggregated or denatured during the filtration process. Filtrate losses refer to product that has not been retained by the membrane during filtration. In addition to optimizing the wall concentration, since the mass transfer coefficient, k, may have different values depending on the specific buffering components, it may be beneficial to utilize two or more sets of parameters during the protein concentration and diafiltration processes. Implementation of this control strategy requires the use of an automated system both for development and production-scale operations.
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