Strategy for selection of methods for separation of bioparticles from particle mixtures

The desired product of bioprocesses is often produced in particulate form, either as an inclusion body (IB) or as a crystal. Particle harvesting is then a crucial and attractive form of product recovery. Because the liquid phase often contains other bioparticles, such as cell debris, whole cells, particulate biocatalysts or parti- culate by-products, the recovery of product particles is a complex process. In most cases, the particulate product is purified using selective solubilization or extraction. However, if selective particle recovery is possible, the already high purity of the particles makes this down- stream process more favorable. This work gives an overview of typical bioparticle mixtures that are encoun- tered in industrial biotechnology and the various driving forces that may be used for particle-particle separation, such as the centrifugal force, the magnetic force, the electric force,andforcesrelatedto interfaces.By coupling these driving forces to the resisting forces, the limitations of using these driving forces with respect to particle size arecalculated.Itshowsthatcentrifugationisnotageneral solution for particle-particle separation in biotechnology because the particle sizes of product and contaminating particles are often very small, thus, causing their settling velocities to be too low for efficient separation by centrifugation. Examples of such separation problems are the recovery of IBs or virus-like particles (VLPs) from (microbial) cell debris. In these cases, separation pro- cesses that use electrical forces or fluid-fluid interfaces show to have a large potential for particle-particle separation. These methodsare not yetcommonly applied for large-scale particle-particle separation in biotechnol- ogy and more research is required on the separation techniques and on particle characterization to facilitate successful application of these methods in industry. 2006 Wiley Periodicals, Inc.