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Figure 1. Relation between starting product concentration in completed broth or medium, and final selling price of the prepared product (Dwyer JL, 1984).

Figure 2. Primary factors affecting separation vs Figure 2. Primary factors affecting separation vs. particle size (Atkinson B and Mavituna F, 1983)

Separation Process Design mimic/similar process new concept process yield and purity cost of production scalability

Separation process design - primary separation (filtration) - separation (extraction) - purification (chromatography) - polishing (crystalization)

Separation Process Synthesis Penicillin Production Figure 3. Penicillin production. After fermentation the biomass is separated by filtration. The antibiotic, which is in the filtrate, is isolated and purified by extraction. It is then polished by crystallization and dried.

Separation Process Synthesis Increasing amount of washing water increases recovery but thus the amount of wastewater generated Vacuum Filter Temperature: material degradation and yield Solvent: type of solvent, solvent to water ratio Mode of Operation: Single or multiple stage Extraction Optimization of operating condition is essential!! Are there other novel concepts of separation???

Multiple Input Multiple Output (MIMO) problem Novel Separation Process Microfiltration Ultrafiltration Reverse Osmosis Product (Penicillin G) Broth Biomass Solvent Figure 4. Possible alternative scheme for Penicillin purification. Ex) spray drying Air: flowrate, temperature, moisture content Slurry: physical properties, feed rate, moisture content Drying Efficiency: moisture content, powder in vent air Multiple Input Multiple Output (MIMO) problem with interaction Spray Dryer

Criteria for Process Synthesis Used in evaluating and designing a bioseparation process product purity cost of production as related to yield scalability reproducibility and ease of implementation robustness with respect to process stream variables

Stages of Bioseparation: An idealized process removal of solids (or recovery), isolation of product, purification, and polishing constitute a sequence of events applied to nearly every product preparation Table 1. Objectives and Typical Unit Operations of the Four Stages in Bioseparation (Harrison et al., 2003) Stage Objective(s) Typical Unit Operations Separation of insolubles Remove or collect cells, cell debris, or other particulates Reduce volume (depends on unit operation) Filtration, sedimentation, extraction, adsorption Isolation of product Remove materials having properties widely different from those desired in product Extraction, adsorption, ultrafiltration, precipitation Purification Remove remaining impurities, which typically are similar to the desired product in chemical functionality and physical properties Chromatography, affinity methods, crystallization, fractional precipitation Polishing Remove liquids Convert the product to crystalline form (not always possible) Drying, crystallization