Inhoudsopgave
1 Fermentor design and process control......................................................5
1.1 Stirred tank fermentor........................................................................5
1.1.1 Mixing...........................................................................................6
1.1.2 Aeration........................................................................................7
1.1.3 Instrumentation............................................................................8
2 alternatives types of bioreactors.............................................................10
2.1 bubble columns and airlift reactors..................................................10
2.2 fixed cell bed reactor........................................................................11
2.3 fluidized bed reactors.......................................................................11
2.4 Solid state fermentations..................................................................12
3 Down Stream Processing.........................................................................13
3.1 4 major phases of DSP......................................................................13
3.2 Cell harvesting..................................................................................14
3.2.1 Centrifugation.............................................................................14
3.2.2 Filtration......................................................................................17
3.2.3 Filtration aids..............................................................................18
3.3 Cell disruption...................................................................................19
3.3.1 Mechanical cell disruption..........................................................19
3.4 Removal of cell debris.......................................................................21
3.4.1 Membrane Filtration....................................................................21
3.4.2 Packed bed filtration...................................................................21
3.5 Product extraction and concentration...............................................22
3.5.1 Inclusion bodies..........................................................................22
3.5.2 Liquid-liquid extraction...............................................................22
3.5.3 Precipitation................................................................................22
3.5.4 Ultra filtration.............................................................................22
3.5.5 Nanofiltration and reverse osmosis............................................23
3.5.6 Ion exchange chromatography...................................................23
3.5.7 Gel filtration chromatography.....................................................23
3.5.8 Affinity chromatography.............................................................23
4 Sterilizing................................................................................................24
,4.1 Filtration............................................................................................24
4.2 Inactivation kinetics..........................................................................24
4.2.1 K.................................................................................................24
4.2.2 Decimal reduction time (D).........................................................24
4.2.3 Sterilization time (F)...................................................................24
4.2.4 Heat resistance value (Z)............................................................24
4.3 Designing a sterilization protocol......................................................24
4.3.1 Lethality F0..................................................................................25
4.3.2 Media sterilization.......................................................................25
4.3.3 Reactor sterilization....................................................................25
4.3.4 Air sterilization............................................................................26
4.4 Cleaning in place..............................................................................27
4.5 The Sinner circle...............................................................................27
4.6 Detergents........................................................................................28
4.6.1 surfactants..................................................................................28
4.6.2 inorganic components of detergents, or builders.......................28
4.6.3 Acids...........................................................................................29
4.6.4 Base............................................................................................29
4.7 Disinfectants.....................................................................................29
4.7.1 NaCl............................................................................................29
4.7.2 H2O2............................................................................................29
4.7.3 Quaternary ammonium compounds...........................................29
4.8 Applying of products........................................................................29
4.8.1 Manual cleaning..........................................................................29
4.8.2 Soak cleaning.............................................................................29
4.8.3 Spray-washing............................................................................29
4.8.4 Long contact vertical surface cleaning using foams or gels.......29
4.8.5 Spray heads................................................................................30
4.9 CIP cycle...........................................................................................30
4.9.1 Removal of product.....................................................................30
4.9.2 Pre rinse with water....................................................................30
4.9.3 Detergent....................................................................................30
4.9.4 Intermediate rinse with fresh water............................................30
, 4.9.5 Second cycle...............................................................................30
4.9.6 Disinfection.................................................................................30
4.9.7 Final rinse...................................................................................30
5 Mammalian cell culturing........................................................................32
5.1 Culture types....................................................................................32
5.2 Cell isolation.....................................................................................33
5.3 Media composition............................................................................33
5.4 Aseptic techniques............................................................................34
5.5 Specific requirements for bioreactors...............................................34
5.5.1 High surface/volume ratio...........................................................34
5.5.2 Low sheer forces.........................................................................34
5.5.3 Removal of waste metabolites....................................................34
5.6 Static bioreactors..............................................................................35
5.7 Dynamic bioreactors.........................................................................36
5.7.1 Types of Dynamic Bioreactors.....................................................36
6 Biobased economy..................................................................................38
7 Value chains............................................................................................39
7.1 Crop residues....................................................................................39
7.2 Food residues....................................................................................39
7.3 Wood processing residues.................................................................39
7.4 Renewables (CO2).............................................................................39
8 Sugar platforms.......................................................................................41
8.1 Sources for C5 and C6 sugars...........................................................41
8.1.1 Extraction of sucrose from sugar beets......................................41
8.1.2 Glucose and maltose syrup from starch.....................................41
8.1.3 Production of glucose/fructose syrup..........................................41
8.1.4 Production of glucose from lignocellulose...................................41
8.2 Food vs fuel.......................................................................................42
8.3 Bio-ethanol production (C2, biofuel).................................................42
8.3.1 Bio-ethanol in industry................................................................42
8.3.2 Biowanze....................................................................................42
8.3.3 Alcobiofuel..................................................................................44
8.4 Lactic acid production (C3 and PLA).................................................44
, 8.4.1 Companies..................................................................................44
9 Lignin and lignocellulose.........................................................................45
9.1 Lignocellulose...................................................................................45
9.2 Lignin................................................................................................45
9.2.1 Chemical pulping in the paper industry......................................45
9.3 Processing lignin and lignocellulose to chemicals and materials......46
9.3.1 Lignin to bioplastic......................................................................46
9.3.2 Lignin as fuel..............................................................................46
9.3.3 Lignin as material.......................................................................46
9.3.4 Lignin as source of aromatic monomers.....................................46
10 C1 platform: biogas, syngas and gas fermentations............................48
10.1 Biogas.............................................................................................48
10.2 Syngas............................................................................................49
10.3 Valorising C1 molecules through biobased processes.....................49
10.3.1 Important drivers......................................................................49
10.3.2 Problems and conditions...........................................................49
10.3.3 Fermentative processes for C1 gasses.....................................49
11 Oil and fats platform............................................................................51
11.1 Chemical biodiesel production........................................................51
11.2 Enzymatic biodiesel production......................................................52
11.3 Biological surfactantia....................................................................52
12 The proteinn club..................................................................................53
12.1 Companies......................................................................................53
12.1.1 Technology companies..............................................................53
12.1.2 Feedstock providers..................................................................53
12.1.3 Endproduct producers...............................................................53
12.2 Biomass fermentation.....................................................................54
12.2.1 Fungi.........................................................................................54
12.2.2 Yeast.........................................................................................54
12.2.3 Bacteria....................................................................................54
12.3 Precision fermentation....................................................................54
12.3.1 E. coli........................................................................................54
12.3.2 Bacillus subtilis.........................................................................54
1 Fermentor design and process control......................................................5
1.1 Stirred tank fermentor........................................................................5
1.1.1 Mixing...........................................................................................6
1.1.2 Aeration........................................................................................7
1.1.3 Instrumentation............................................................................8
2 alternatives types of bioreactors.............................................................10
2.1 bubble columns and airlift reactors..................................................10
2.2 fixed cell bed reactor........................................................................11
2.3 fluidized bed reactors.......................................................................11
2.4 Solid state fermentations..................................................................12
3 Down Stream Processing.........................................................................13
3.1 4 major phases of DSP......................................................................13
3.2 Cell harvesting..................................................................................14
3.2.1 Centrifugation.............................................................................14
3.2.2 Filtration......................................................................................17
3.2.3 Filtration aids..............................................................................18
3.3 Cell disruption...................................................................................19
3.3.1 Mechanical cell disruption..........................................................19
3.4 Removal of cell debris.......................................................................21
3.4.1 Membrane Filtration....................................................................21
3.4.2 Packed bed filtration...................................................................21
3.5 Product extraction and concentration...............................................22
3.5.1 Inclusion bodies..........................................................................22
3.5.2 Liquid-liquid extraction...............................................................22
3.5.3 Precipitation................................................................................22
3.5.4 Ultra filtration.............................................................................22
3.5.5 Nanofiltration and reverse osmosis............................................23
3.5.6 Ion exchange chromatography...................................................23
3.5.7 Gel filtration chromatography.....................................................23
3.5.8 Affinity chromatography.............................................................23
4 Sterilizing................................................................................................24
,4.1 Filtration............................................................................................24
4.2 Inactivation kinetics..........................................................................24
4.2.1 K.................................................................................................24
4.2.2 Decimal reduction time (D).........................................................24
4.2.3 Sterilization time (F)...................................................................24
4.2.4 Heat resistance value (Z)............................................................24
4.3 Designing a sterilization protocol......................................................24
4.3.1 Lethality F0..................................................................................25
4.3.2 Media sterilization.......................................................................25
4.3.3 Reactor sterilization....................................................................25
4.3.4 Air sterilization............................................................................26
4.4 Cleaning in place..............................................................................27
4.5 The Sinner circle...............................................................................27
4.6 Detergents........................................................................................28
4.6.1 surfactants..................................................................................28
4.6.2 inorganic components of detergents, or builders.......................28
4.6.3 Acids...........................................................................................29
4.6.4 Base............................................................................................29
4.7 Disinfectants.....................................................................................29
4.7.1 NaCl............................................................................................29
4.7.2 H2O2............................................................................................29
4.7.3 Quaternary ammonium compounds...........................................29
4.8 Applying of products........................................................................29
4.8.1 Manual cleaning..........................................................................29
4.8.2 Soak cleaning.............................................................................29
4.8.3 Spray-washing............................................................................29
4.8.4 Long contact vertical surface cleaning using foams or gels.......29
4.8.5 Spray heads................................................................................30
4.9 CIP cycle...........................................................................................30
4.9.1 Removal of product.....................................................................30
4.9.2 Pre rinse with water....................................................................30
4.9.3 Detergent....................................................................................30
4.9.4 Intermediate rinse with fresh water............................................30
, 4.9.5 Second cycle...............................................................................30
4.9.6 Disinfection.................................................................................30
4.9.7 Final rinse...................................................................................30
5 Mammalian cell culturing........................................................................32
5.1 Culture types....................................................................................32
5.2 Cell isolation.....................................................................................33
5.3 Media composition............................................................................33
5.4 Aseptic techniques............................................................................34
5.5 Specific requirements for bioreactors...............................................34
5.5.1 High surface/volume ratio...........................................................34
5.5.2 Low sheer forces.........................................................................34
5.5.3 Removal of waste metabolites....................................................34
5.6 Static bioreactors..............................................................................35
5.7 Dynamic bioreactors.........................................................................36
5.7.1 Types of Dynamic Bioreactors.....................................................36
6 Biobased economy..................................................................................38
7 Value chains............................................................................................39
7.1 Crop residues....................................................................................39
7.2 Food residues....................................................................................39
7.3 Wood processing residues.................................................................39
7.4 Renewables (CO2).............................................................................39
8 Sugar platforms.......................................................................................41
8.1 Sources for C5 and C6 sugars...........................................................41
8.1.1 Extraction of sucrose from sugar beets......................................41
8.1.2 Glucose and maltose syrup from starch.....................................41
8.1.3 Production of glucose/fructose syrup..........................................41
8.1.4 Production of glucose from lignocellulose...................................41
8.2 Food vs fuel.......................................................................................42
8.3 Bio-ethanol production (C2, biofuel).................................................42
8.3.1 Bio-ethanol in industry................................................................42
8.3.2 Biowanze....................................................................................42
8.3.3 Alcobiofuel..................................................................................44
8.4 Lactic acid production (C3 and PLA).................................................44
, 8.4.1 Companies..................................................................................44
9 Lignin and lignocellulose.........................................................................45
9.1 Lignocellulose...................................................................................45
9.2 Lignin................................................................................................45
9.2.1 Chemical pulping in the paper industry......................................45
9.3 Processing lignin and lignocellulose to chemicals and materials......46
9.3.1 Lignin to bioplastic......................................................................46
9.3.2 Lignin as fuel..............................................................................46
9.3.3 Lignin as material.......................................................................46
9.3.4 Lignin as source of aromatic monomers.....................................46
10 C1 platform: biogas, syngas and gas fermentations............................48
10.1 Biogas.............................................................................................48
10.2 Syngas............................................................................................49
10.3 Valorising C1 molecules through biobased processes.....................49
10.3.1 Important drivers......................................................................49
10.3.2 Problems and conditions...........................................................49
10.3.3 Fermentative processes for C1 gasses.....................................49
11 Oil and fats platform............................................................................51
11.1 Chemical biodiesel production........................................................51
11.2 Enzymatic biodiesel production......................................................52
11.3 Biological surfactantia....................................................................52
12 The proteinn club..................................................................................53
12.1 Companies......................................................................................53
12.1.1 Technology companies..............................................................53
12.1.2 Feedstock providers..................................................................53
12.1.3 Endproduct producers...............................................................53
12.2 Biomass fermentation.....................................................................54
12.2.1 Fungi.........................................................................................54
12.2.2 Yeast.........................................................................................54
12.2.3 Bacteria....................................................................................54
12.3 Precision fermentation....................................................................54
12.3.1 E. coli........................................................................................54
12.3.2 Bacillus subtilis.........................................................................54
