Ultrafiltration continuous diafiltration

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... 

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 ... 

The simplest ultrafiltration is the stirred cell, a batch operation. The most compex is a continuous stages-in-series operation incorporating diafiltration. Industrial practice incorporates the full gamut of complexity. 

Diafiltration is a process whereby an ultrafiltration system is utilized to reduce or eliminate low molecular mass molecules from a solution and is sometimes employed as part of biopharmaceuti-cal downstream processing. In practice, this normally entails the removal of, for example, salts, ethanol and other solvents, buffer components, amino acids, peptides, added protein stabilizers or other molecules from a protein solution. Diafiltration is generally preceded by an ultrafiltration step to reduce process volumes initially. The actual diafiltration process is identical to that of ultrafiltration, except for the fact that the level of reservoir is maintained at a constant volume. This is achieved by the continual addition of solvent lacking the low molecular mass molecules that are to be removed. By recycling the concentrated material and adding sufficient fresh solvent to the system such that five times the original volume has emerged from the system as permeate, over 99... 

Then, water is added continuously while the filtration continues at nearly constant flux. This latter filtration stage, when water is added to maintain a constant flux, is referred to as diafiltration. Proper choice of the diafiltration starting time can minimize the required membrane area, which is often the major part of the capital cost in an ultrafiltration process. 

Figure 6.4.9. Ultrafiltratton in a well-stirred vessel (a) batch ultrafiltration (b) continuous diajUtration/ultrafiltration (c) discontinuous diafiltration using three stages.

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