1. Bioseparation Engineering Introduction

2. Biotechnology built on the genetic manipulation of organisms to produce commercial products or processes Biochemical Engineering responsible for the implementation of the products and processes Two Disciplines of Biochemical Engineering Upstream Engineering (Fermentation) Downstream Engineering (Bioseparation or Purification)

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

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

5. Separation Process Design mimic/similar process/case new concept process yield and purity cost of production scalability (scale-up, scale-down) Easy maintenance Separation Process Synthesis Approaches must be made if future scale-up is in mind *design software *information from equipment vendor

6. Separation Process Synthesis Ex : 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.

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

8. Separation Process Synthesis MicrofiltrationUltrafiltration Reverse Osmosis Broth Product (Penicillin G) Biomass Solvent Figure 4. Possible alternative scheme for penicillin purification. Ex : Spray drying Spray Dryer 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

9. Criteria for Process Synthesis product value, purity, impurities acceptable cost of production as related to yield scalability robustness with respect to process stream variables Alternative process/technology Used in evaluating and designing a bioseparation process

10. Stages of Bioseparation: An idealized process (1)removal of solids (or recovery), (2)isolation of product, (3)purification, and (4)polishing constitute a sequence of events applied to nearly every product preparation StageObjective(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 Reduce volume (depends on unit operation) 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 PolishingRemove liquids Convert the product to crystalline form (not always possible) Drying, crystallization Table 1. Objectives and Typical Unit Operations of the Four Stages in Bioseparation (Harrison et al., 2003)

11. Intracellular, extracellular product Fermentation – broth components In situ separation with fermentation (Ex : ethanol, antibiotics, taxol) Separation for next step (Ex : lactic acid for polymer)