1. 분리정제기술

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

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

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

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

6. 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.

7. 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???

8. 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

9. 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

10. 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