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Development of a generic bioprocess flowsheet model for Life Cycle studies KG Harding, JS Dennis, STL Harrison Introduction To assess economic or environmental performance of a process, we need to know: The raw material requirements per unit


  1. Development of a generic bioprocess flowsheet model for Life Cycle studies KG Harding, JS Dennis, STL Harrison

  2. Introduction To assess economic or environmental performance of a process, we need to know: The raw material requirements per unit product (material balance) Equipment size The energy requirements (energy balance) This requires a process flowsheet Engineering flowsheeting packages are often: Complex Data intensive Time consuming to set up Expensive, and Need validation A simplified first estimate allows input for early decision making University of Cape Town Bioprocess Engineering Research Unit 2

  3. Introduction A simplified first estimate allows input for early decision making We report on a generic bioprocess flowsheet model to provide such a first estimate To demonstrate, we use two case studies Pencillin Cellulase University of Cape Town Bioprocess Engineering Research Unit 3

  4. Bioprocess flowsheet Product DSP formation University of Cape Town Bioprocess Engineering Research Unit 4

  5. Inputs & Outputs – Product formation Decisions How much product do you want? How much biocatalyst (micro-organism or enzyme) do you need? Micro-organism as product, intra- or extracellular product? Aerobic or anaerobic process? Continuous, batch or fed-batch process? Product formation Raw materials: C- (x2), N- (x2), O- (aerobic), P- & S- sources (excess?) Product spectrum: Biomass, 1 ° metabolite, 2 ° metabolite University of Cape Town Bioprocess Engineering Research Unit 5

  6. Key parameters – Product formation Gas compression (aerobic) 1 or 2 stage compression, pressure, Cooling water temp, efficiency Yield coefficients Y X/S, Y P/S, Y X/O Metabolic parameters Maintenance coefficients, cell concentrations, growth rate Sterilisation Temp. (steam, sterilisation, reactor, cooling water,…), Efficiency, Pressure Agitation Number of tanks, power per unit volume, tank & impeller geometry Reactor control Antifoam, reactor cooling, water used (distilled, deionised, municipal) University of Cape Town Bioprocess Engineering Research Unit 6

  7. Bioprocess flowsheet DSP University of Cape Town Bioprocess Engineering Research Unit 7

  8. Key parameters –Liberation & S/L separation Centrifugation / washing Energy per unit volume, No of centrifuge/wash cycles, Efficiency Filtration Pressure gradient, Efficiency, Filter area, Flocculent, Filter media (type, height, voidage, density…) Sedimentation Flocculent (Percentage added, density, composition) High pressure homogeniser, Ball mill, Cavitation Extent of cell disruption, Energy efficiency, University of Cape Town Bioprocess Engineering Research Unit 8

  9. Key Parameters – Concentration & Purification Adsorption (efficiency, pressure gradient, cross sectional area) Centrifugation (as before) Evaporation (temperatures, efficiency) Decanter (efficiency, pressure gradients, cross sectional area) Filtration (as before) Precipitation (temperature, precipitation agents, power input, efficiency) Solvent extraction (efficiency, pressure gradient, cross sectional area, solvent, phase splits) Splitter (split fraction) University of Cape Town Bioprocess Engineering Research Unit 9

  10. Key Parameters – Formulation Oven drying Temperatures, Efficiencies Freeze drying Temperatures, Reduced pressure, Vacuum inlet area, Efficiencies Spray Drying Temperatures, Humidities University of Cape Town Bioprocess Engineering Research Unit 10

  11. MS-EXCEL Screenshot University of Cape Town Bioprocess Engineering Research Unit 11

  12. Example Flowsheet: Cellulase University of Cape Town Bioprocess Engineering Research Unit 12

  13. Input assumptions: Cellulase Assumptions Scenario Units Assumptions Scenario H1 Units H1 Extracellular, aerobic product produced in a batch Steam Sterilisation (Cooling agent: Cooling water) reactor Preheated temperature 110 °C Cooling water temperature 25 °C Sterilisation temperature 140 °C Chilled water temperature 5 °C Steam temperature 152 °C Max temperature difference between exiting cooling 10 °C water and hot inlet streams Outlet temperature/Reactor temperature 35 °C Microbial growth conditions (batch production from Trichoderma reesei ) Sterilisation time 8 H Product: Biomass ratio 0.89 - Agitation Carbon 1 source (excess): Cellulose 10 % h Residence time 121.25 Carbon 2 source (excess): Corn liqor 33.3 % Height /Daimeter (fermenter) 3 - Mass percentage Carbon 2 as total carbon 14.38 - kW/m 3 Power per unit volume 0.5 Nitrogen source 1: Ammonia 0 % Rotary vacuum filter Nitrogren source 2: Nutrients 33.3 % Solids removed 100 % Mass percentage Nitrogen 2 as total carbon 80.2 - Liquid retained 100 % Excess Air 2500 % M 2 Cross sectional area 39.95 Maintain rector temperature (Cooling agent: Chilled water) Ultrafiltration Initial cell concentration (into fermenter) 0.76 g/l Solids (product) retained 98 % Initial cell concentration (whole process) 0 g/l Liquid (waste) removed 81 % Final cell concentration 15 g/l Aeration Compressed pressure 608 kPa Compressor efficiency 0.7 - University of Cape Town Bioprocess Engineering Research Unit 13

  14. Mass balance results: Cellulase Component In (kg) Out (kg) In (kg) Out (kg) Heinzle et al. (2006b) Scenario H1 Ammonia 0.082 0.00 0.096 0.00 Trichoderma Reesei 0 1.17 0.06 1.15 Carbon Dioxide 0 1.48 0 3.63 Cellulase 0 0.041 0 0.020 Cellulose 3.62 0.32 3.57 0.26 Corn liquor 0.61 0.12 0.73 0.15 Enzyme 0 14.9 0 15.6 Nutrients 0.33 0.065 0.52 0.10 Oxygen (reacting O 2 only) - - 2.94 0 Water 73.3 59.9 74.9 61.8 TOTAL 77.9 77.9 82.8 82.8 Product recovery (% kg cel) 96.1 98.0 Energy requirements Heinzle et al. (2006b) Scenario H1 Units Electricity 38.6 42.2 kWh/kg cel. (MJ/kg cel) Steam (152 °C, 3 bar) 4.74 4.62 kg/kg cel. (MJ/kg pen) m 3 /kg cellulase Chilled water 0.84 0.56 m 3 /kg cellulase Cooling water 2.62 5.23 University of Cape Town Bioprocess Engineering Research Unit 14

  15. LCA Comparison: Cellulase University of Cape Town Bioprocess Engineering Research Unit 15

  16. Example Flowsheet: Penicillin University of Cape Town Bioprocess Engineering Research Unit 16

  17. 3 sets of input assumptions: Penicillin Assumptions Scenario 1 Scenario 2 Scenario 3 Units Extra cellular, aerobic product produced in a batch reactor Cooling water temperature 5 - - ° C Max temperature difference between exiting cooling water and hot inlet streams 20 - - ° C Stream Sterilisation Reactor temperature 32 - - ° C Microbial growth conditions (batch production of Penicillin from Penicillium chrysogenum ) Product: Biomass ratio 1.2 1.2 1.2 - Carbon 1 source (excess): Glucose 2 - - % Carbon 2 source (excess): Phenoxyacetic acid 1.7 - - % Mass percentage of carbon source 2 as total carbon 10.6 10.6 10.6 % Nitrogen source (excess): Pharmamedia (C 55.7 H 6.7 O 18.9 N 16 S 2.7 (Phyllis 2006)) 14.6 - - % Sulphur source excess 0 - - Oxygen source (excess): Air 1450 - - % Compression: Single stage reciprocating compressor, 601.03 kPa compressed press.. Maintenance coefficient 0.022 0.022 - h Time for over which maintenance is considered 106 106 - h Final cell concentration 45 45 - g/l Yield coefficients: Y x/s 0.45 - - g/g Y p/s 0.81 - - g/g Y x/o 1.56 - - g/g Agitation (11 tanks) Residence time 156.3 - - h Power per unit volume 2.5 2.5 - kW/m 3 Efficiency 1 - - University of Cape Town Bioprocess Engineering Research Unit 17

  18. 3 sets of input assumptions: Penicillin Assumptions Scenario 1 Scenario 2 Scenario 3 Units Post fermentation cooling Outlet temperature 28 - - ° C Filtration Solid fraction removed 100 - - % Liquid fraction removed 91 91 - % Additive: Sulphuric acid 0.028 0.028 0.028 %v/v Centrifugation Solid fraction removed 98 - - % Liquid fraction removed 91.8 91.8 - % Energy per unit volume 3060 - - kJ/m 3 Additive: Butyl acetate (assumed no recycle) 9.2 9.2 9.2 %v/v Additive: Sodium hydroxide 0.25 0.25 0.25 %v/ Reaction: Sodium hydroxide + Sulphuric acid � Sodium sulphate + Water (conversion: 97 % limiting reagent) Precipitation/Crystallisation Outlet temperature 6 - - ° C Residence time 12 - - H Power per unit volume 0.6 - - kW/m 3 Additive: Acetone 12.3 12.3 12.3 %v/v Additive: Sodium acetate 7.8 7.8 7.8 %v/v Reaction: Sodium acetate + Penicillin � Acetic acid + Penicillin V sodium crystals (conversion: 97 % limiting reagent) Centrifugation Solid fraction removed 99 - - % Liquid fraction removed 97.9 - - % Fluid bed drying (Electricity: 72.2 MJ/m 3 ) Product fraction removed 99 - - % Liquid fraction removed 90 - - % University of Cape Town Bioprocess Engineering Research Unit 18

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