Continuous diafiltration

Constant-volume batch diafiltration is the most efficient process mode. Sequential batch diafiltration is a series of dilution-concentration steps. Continuous diafiltration practiced in one or more stages of a cascade system has the same volume turnover relationship for overall recoveries as sequential batch diafiltration. The residence time however is dramatically reduced. If recovery of permeable solids is of primary importance, the permeate from the last stage may be used as diafiltration fluid for the previous stage. This countercurrent diafiltration arrangement results in higher permeate solids at the expense of increased membrane area. 

Batch, feed bleed, continuous, diafiltration, multistage Figure 1. Schematic of cross-flow filtration. 

Figure 9. Batch and continuous diafiltration process modes.

Continuous diafiltration is generally more efficient and preferred. In this approach, a batch of the solution to be desalted is maintained at constant volume by adding pure water (dialysate) at the same rate permeate is removed. In this way, the proteins (or other macromolecules retained by the membrane) remain at their initial concentration while the salt concentration decreases continuously. This has been called "constant volume molecular washing" because the salts are washed out of solution. Continuous diafiltration reduces the processing time required in the discontinuous process. 

Since continuous diafiltration involves the processing of a fixed volume (V0), it is convenient to speak of the number of volume turnovers, Vt/V0 required to... 

Consider a time interval dt over which a differential volume dV(, of the buffer is added to the well-stirred feed vessel containing a solution volume Vfo to start with, this solution has a solute concentration Cg, (the lower molecular weight impurity or the macrosolute of interest). Continuous diafiltration is carried out such that the solution volume in the feed vessel remains constant at V/q. Therefore the volume of ultrafiltrate produced in time dt is dVb- it has a species i concentration of Cip at time t. A molar balance on species i leads to... 

The purpose of continuous diafiltration in purification of a protein solution from a small molecular weight impurity (e.g. NaCl) can become clear from this result. Suppose the value of DF is 6, i.e. the volume of buffer solution added (= the volume of permeate) is six times that of the feed (here also the retentate) solution. Let / , for salt (NaCl) = 0.0 and Ri for protein = 0.995. Then, for salt,... 

Therefore the impurity (salt) concentration is reduced to 0.2% of the original level at the cost of a loss of 3% of the protein. An ultrafiltration membrane that has a value of Rt= 1 for the protein will be better however, the filtration flux levels would be lower, prompting more membrane area or a higher time for the continuous diafiltration process. 

Example 6.4.10 Compare the purification achieved for a protein (species i) in relation to a low molecular weight impurity (species j) for the following two processes one-stage discontinuous diafiltration vs. continuous diafiltration. The initial volume of solution is 10 liter the amount of ultrafiltrate produced is 9.5 liter. The UF vessel is well-stirred. The values of i ,- and Rj for the membrane used are flj = 1, Rj = 0. Employ a separation factor, a,j, to compare. 

There are two other aspects of importance in practical ultrafiltration processing time and the membrane area. A brief treatment of processing time with a view to minimizing it will be considered now. The processing time depends on a variety of factors the total volume to be processed the concentration of retained solids, especially if it leads to gel polarized operation (equation (6.3.143)) the mode of operation (continuous, batch, etc.) (Cherytm, 1986). One approach suggested by Ng et al. (1976) employs the gel-polarized condition and perfect rejection of the protein i for continuous diafiltration operation ... 

If and ku remain unchanged during the continuous diafiltration process, one can determine the optimum processing time, top by determining Cut, which satisfies (dt/dCffl) = 0 ... 

Continuous diafiltration where the buffer volume added is 500 liter. 

We have observed earlier (in Section 6.4.2.1) that, for continuous diafiltration (result (6.4.107)),... 

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