2. Biochemical engineering is no longer an academic
challenge
•US: most new professorships are biomolecularly oriented
•Europe: moving in same direction
–Long searches to find new professors of biochemical
engineering
–Most comes from industry (Patents, few publications)
–Solution: move towards biomolecular focus
•
Metabolic engineering
•
Complex control systems to re-engineer eucaryotic cells
•
Tissue engineering
3. Biotechnology –
major sectors
New pharma compounds
and materials, devices,
Agro-efficiency
Control systems, gene
therapy
Food quality
Agrochemicals
Biodegradation
End-of-pipe solution
Integrated processes
Biomass
Biofuels
Bioelectricity
•
Pharma
•
Agriculture
•
Environment
•
Chemistry
•
Energy
New materials
New compounds
New processes
Green Chemistry
6. Industrial Microbiology and
Fermentation Technology
•Industrial Microbiology is the discipline
that uses microorganisms, usually grown on
a large scale, to produce valuable
commercial products or carry out
important chemical transformations.
•Fermentation Technology is the technology
to grow cells in a large scale with high
efficiency, it also includes product recovery
processes.
16. Flowsheet for developing an industrial
microbial fermentation process
•Strain selection
•Laboratory process development
•Pilot Scale up
•Industrial Scale up
•Downstream process development
•Product packaging techniques
•Other commercial consideration
•Examples
21. Genetic
Engineering
Incorporation into
artificial plasmids of
genes from a wide
variety of sources has
made possible the
transfer of genetic
material across
virtually any species
barrier
Various high value
added products have
been produced from
Genetic engineering
methods
23. Cell Biology Techniques
•
Protoplast fusion (promote high frequencies
of genetic recombinants)
–removing the cell wall with lytic enzymes in the
presence of osmotic stabilizers.
–In the presence of fusogenic agent such as
polyethylene glycol (PEG), protoplasts are
induced to fuse and form transient hybrids or
diploids.
–Regeneration of viable cells from the fused
protoplasts.
24. Laboratory Process Development
Shake Flask Experiments
Optimization of conditions
for cell growth and product
formation using shake flask
experiments:
1. pH
2. Temperature
3. Dissolved oxygen (DO)
4. Substrate choice
5. Maximal and optimal
substrate concentration
6. Others
26. Laboratory Process Development
Lab scale fermentor experiments
•
Batch process
•
Fed-batch process
•
Continuous process
•
Semi-continuous
process
27. Process control and monitoring
•Process parameters to be monitors
Agitation
pH
Cell Dry Weight
Product
Sugar consumption
Temperature
Fermentation time (h)
Computer softwares have been developed to monitor and change the process on line
28. Pilot Scale Up
•Scale up: The transfer of a process from smallscale laboratory equipment to large-scale
commercial equipment
•
Pilot experiment
– test the feasibility of the lab scale
To
fermentation process in a semi-industrial
scale
–
Pilot fermentors normally have a size ranging
from 100 L to 10,000 L, depending on the
products to be mass produced later.
29. Problems emerging during the scale up
•As the size of the equipment is increased, the surfacevolume ratio changes
•Large fermentor has much more volume for a given
surface area, it is obviously more difficult to mix the big
tank than the small flask
•In scale up studies on aerobic fermentations, oxygen
rate in the fermentor is best kept constant as the size of
the fermentor is increased.
–How to keep DO constant?
•
Increase stirring rate
•
Increase air pressure
•
Use pure oxygen
•
Increase air inlet
36. Product Recovery
•What purity is necessary?
–acetic acid or alcohol little purification
–industrial enzymes: moderate purity
–food additives have high purity
–pharmaceuticals super purity
•What is the concentration of the product?
37. Product Recovery
•Is the product in the cell or secreted?
–enzymes and other proteins in cell require cell
harvest and extraction
–secreted products allow for continuous
fermentation
–secreted products reduce costs of purification.
Why?
•Can we improve secretion?
44. Product Packaging
Techniques
•Steril Packaging Techniques for Medical
Applications and Food Preservation
•Pyrogen Free and Steril Packaging for Injection
Purpose
•Freeze Dry Packaging for Foods or Medicines
•Dewatered Packaging (such as Dry Yeast)
•Normal Food Packaging (such as Na-glutamate)
•Salty Packaging
•Preservation Chemicals
•Ordinary Packaging
45. Other Commercial Consideration
Strengths and weaknesses of biotechnological processes
•Strengths
– Reliance on renewable
feedstocks
– Versatility with different
feedstocks
– Food, feed and drug
applications
– Fine chemicals to bulk
chemical applications
– Low temperature
– Operation in aqueous media
– Several reactions achieved in
a single fermentation step
– High level of automation
– Stereospecificity
– Complex molecules
converted and/or produced
–“
Benign”
effluents produced
•Weaknesses
– Feedstocks are oxidized and
unsuitable for many applications
– Feedstock costs fluctuate
– Sterilization is a major cost
– Product often in dilute aqueous
solutions
– Product recovery costly
– Equipment costs high
– Reactions slow leading to poor
volumetric productivity
– Complicated reaction conditions
– Mainly batch operation
– High cell (catalyst) regeneration
costs
– High BOD wastes
46. Other Commercial Consideration
Cost Evaluation
•Outline of total capital investment
•Fixed capital
–Direct costs (Land, site development, buildings,
processing, services)
–Indirect costs (Engineering, construction,
Contingency, Fees)
–Start-up costs
•Working capital
–Inventory, accounts receivable, account payable