Laboratory scaledown of protein purification processes involving fractional precipitation and centrifugal recovery

The ability to predict the performance of large-scale processes is central to the rapid development of successful operations at the pilot and industri al scale. In this article, we examine the operation, at laboratory scale, o f precipitation reactors and centrifuges for protein precipitate recovery a nd dewatering and how they might best mimic large-scale reactors and centri fuges, in this case, a pilot-scale batch stirred-tank reactor and a multich amber-bowl centrifuge. Novel approaches to bench-top centrifuge operation a re provided, in particular with a view to delivery of material for subseque nt high-resolution purification, which would be obtained at full pilot scal e. Results are presented in terms of properties of the protein precipitates , the fraction of solids recovered, and the extent of dewatering achieved. Good agreement was obtained at bench scale (a 1000-fold scale down factor) for all of these parameters for pilot-scale, batch-feed operation. In addit ion, the methodology developed allows identification of the extent of break -up that occurs in continuous-feed centrifuges when processing shear-sensit ive materials such as the protein precipitates studied here. (C) 2000 John Wiley & Sons, Inc.