Iran University of Science and Technology

School of Chemical Engineering

Membrane Applications in
Biotechnology
Student: Razie Kebriaee
Supervisor: Dr. Mohamadi

May 2009

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Contents
Introduction
Membrane Bioreactors(MBR)
Bubble Free Aeration
Food Biotechnology
Cheese Industry
Enzyme Immobilization
Hemodialysis
Artificial Lung
Pharmacy
Drug delivery systems
Tissue Engineering
Summary
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Introduction
What is biotechnology?
Biotechnology is technology based on biology
• agriculture
• food science
• medicine

Any technological application

• that uses biological systems
• living organisms
• or derivatives thereof
• to make or modify products or processes

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Introduction
Bioinformatics
Blue biotechnology
Green biotechnology

White biotechnology
• Application of nature in industrial production
Red biotechnology
• Applications starting from diagnostics
• Ending in therapy
• Biotechnological production of pharmaceuticals

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Membranes

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 White
Biotechnology

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 MBR

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MBR
Membrane Bio Reactor
Combination of
 a membrane process like microfiltration or ultra filtration
 a suspended growth bioreactor

widely used for

 municipal
 industrial

waste water treatment

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Mechanism
High number of microorganism in MBRs
• The pollutants uptake rate can be increased
• Better degradation
In comparison to the conventional activated sludge
process
• 95%, COD removal
• can be increased to 96-99% in MBRs
• COD and BOD5 removal increase with MLSS concentration

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MBR
 Anaerobic processes
• when a low cost treatment is required
• enables energy recovery
 If maximal energy recovery is desired
• a single anaerobic process will be superior
• to a combination with a membrane process
Fouling
 Intermittent permeation
• the filtration is stopped at regular time interval for a couple of minutes before
being resumed
 Membrane backwashing
• permeate water is pumped back to the membrane
 Air backwashing
• pressurized air in the permeate side of the membrane build up
 Proprietary anti-fouling products
• Nalco's Membrane Performance Enhancer Technology
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Process
A 3L-lab-scale MBR with a hollow fibre UF-membrane
• Continuously operated for 137 days
• The submerged membrane module had a membrane area of 400cm
• The MBR was operated in a cycle of 45 minutes of permeation phase and 15
minutes of relaxation phase
• permeation with a peristaltic pump
• The reactor was fed quasi-continuously by a membrane pump
• constant volume of 3 liters

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Schematic

René et al,2004

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Aeration
Bubble free aeration in bioreactors
• Better mass transfer
• Inhibition of cell damage
• Reducing shear stress

Adsorption of microorganisms

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Food Biotechnology
Applications include
• Removal of suspended solids (haze) from juices and wines
• Concentration of milk proteins
• Recovery of dairy proteins from whey waste streams

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Serum recovery from cheese production
Cheese production is a biochemical process
Precipitation (of the solid cheese)
The remaining solution contains
Water
 the most of the initial lactose, proteins, vitamins and minerals

In the UF process

• Fat and protein in whole milk are concentrated about 2.5
times

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Enzyme Immobilization
Hydrolysis of oils
• Enzyme Immobilization on ceramic membranes
• Lipase is immobilized on a ceramic fome

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 Red
Biotechnology

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 Hemodialysis

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Dialysis in Biochemistry
In biochemistry
• Dialysis process of separating molecules in solution
Water, salts and other small molecules
• tend to move into or out of the dialysis bag
• Proteins, DNA, Polysaccharides
Dialysis liquid similar to plasma composition

Mass transfer N=KA(ΔC)

Clearance coefficient
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Schematic of Hemodialysis

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Dialysis Membranes
Modified Cellulosic Membranes
Increasing biocompatibility
• Cellulose acetates (CA)
• DEAE, modified cellulose, hemophan
• PEG, grafted cellulose
• Vitamin E, modified cellulosic membranes

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Characteristics
Biocompatibility

Size of removed particles

Possibility of sterilization

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Dialysis Membranes
Two classes
• Cellulose
 Thin wall

 Uniform composition

 High diffusive solute transport

• Synthetic
 Membrane wall thickness (20 µm)
 Symmetric or asymmetric
Regenerated cellulose
Purified cellulose Solved in ammonia solution of cupric
oxide
 Poor compatibility
 Resistance to sterilization modes
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Synthetic membranes
Hydrophobic Hydrophilic
Main purpose!
• Higher porosity
• Mimic natural kidney filtration process

Material
 Polyacrylonitrile (PAN)
 Polymethylmethacrylate (PMMA)
 Polysulfone (Psu)
 Polyamide (PA)

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Recently

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Fluid Regime

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Sieving Coefficient

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 Artificial lung

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Respiratory System

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Membrane Oxygenators
 Why engineer lungs?
• Open hearth surgery
 1.2 million since 2005
 3 million km oxygenation membranes

• The lungs have failed

 How lungs work?

• Bring fresh oxygen into body
• Remove unwanted gasses from body

 Membrane Oxygenators
• Basic idea
 is to copy the way O2/CO2 exchange

 across a barrier which allows gases to pass

 not red blood cells

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 Plasma
Mechanism Air Plasma

Oxygen
Capacity

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Contacting Process
ΔPCO2
ΔPO2 =720 =45
mmHg mmHg

Gas Blood Gas

Blood 0
mmHg 760 45
mmHg 40 mmHg
mmHg

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Artificial Lung

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Micro-porous-membrane
Most common
Various materials
• Polypropylene (PP)
• Poly-4-methylpentene (PMP)
• Polyethylene (PE)
• Polyvinyliden fluoride (PVDF)
• Silicon rubber
Direct blood/gas contact
Pore sizes under 0.03 microns
Red Blood Cell: 7 microns

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Compatibility
PROBLEM!
Coagulation and other Immune Responses
Blood thinners are problematic long term.
Solution:
 hemocompatible coatings
• Heparin
 Most commonly used to avoid compatibility issues

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Heparin Coating

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Membrane Production
Two different processes
• Temperature induced phase separation process (70%)
 A suitable polymer
 solvent such as natural seed oils (soybean)
 heated together in an extruder
 pumped to spinneret
 hollow fiber

• Melt spin stretch process

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 Biopharmaceutical

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Membranes in Biopharmaceutical Industry
Relatively low concentrations
Expensive products

Membranes
Micro porous
Ultra filtration (UF)
Virus removal membranes

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 Shaded boxes: UF membranes
Shaded circles: virus removal
All other filtrations : micro porous membranes
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Manufacturing line

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Drug delivery systems
Polysaccharides, alginates, pullulan, waxes,….

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Delivery through the skin
Transdermal patch
 150 µl drug reservoir
 Semi permeable polymer membrane
 PEG,PU

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 Tissue Engineering

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Description

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Membranes
 polyurethane and cellulose acetate

Dr Mehdizadeh et al., 2000

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References
 Blanco, R.M., Terreros, p., Pérez, M.F., Otero, C., González,G.D., (2004) "Functionalization of mesoporous silica for lipase
immobilization Characterization of the support and the catalysts", Journal of Molecular Catalysis B: Enzymatic 3083–93.

 Benson, H.A.E ( 2005), "Transdermal Drug Delivery: Penetration Enhancement Techniques", Current Drug Delivery, 2, 23-33

 Daugirdas, John T and Ing, Todd S.; (1994) Handbook of Dialysis, 2nd Edition, Little, Brown & Co.

 Encapsulation & Immunoprotective, Strategies of Islet Cells, Workshop Proceedings Report, December 6-7, 2001 • Washington, DC,
Organized by RTI – Center for Technology Applications Research Triangle Park, NC

 Gutch,L., Stoner, S. and Corea;H., (1993) 'Review of Hemodialysis for Nurses and Dialysis
 Personnel", 5th Edition, Mosby.

 Huang, L., Cheng, Z.M., (2008) "Immobilization of lipase on chemically modified bimodal ceramic foams for olive oil hydrolysis',
Chemical Engineering Journal 144 103–109

 Huang, L., Cheng, Z.M., (2008)"Immobilization of lipase on chemically modified bimodal ceramic foams for olive oil hydrolysis"
Chemical Engineering Journal 144 103–109.

 Merz, C., Gildemeister, R., El H., (2007) "Membrane bioreactor technology for the treatment of greywater from a sports and leisure club"
Water and urban wastewater management in the Mediterranean area.

 Pal, K.1., Banthia, and D. K. Majumdar, (2007) "Preparation and Characterization of Polyvinyl Alcohol–Gelatin Hydrogel Membranes for
Biomedical Applications", AAPS PharmSciTech.

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 Thanks For Your
Attention and Time

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