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Bioprocess Simulation-
commercially available tools
Bioprocessing…
• Technique that produces a biological material,
such as a genetically engineered microbial strain,
for commercial use.
• In other words, a bioprocess consists of a cell
culture in a bioreactor, which is a process able to
create an optimal growth environment. The
central object of a bioprocess is the cell. A living
cell is a highly complex system which is often
defined as the smallest autonomous biological
unit.
Types of design estimates
Types of design estimates during the lifecycle of
a product.
Bioprocess modeling
• In order to improve process understanding or
performance, different automatic tools can be
developed: simulators able to reproduce system
behaviors, software sensors which allow obtaining
an judgment of an unmeasured signal to maintain
optimal conditions.
• All these tools rely on a representation of the
considered system, a mathematical model. Such a
model may come in various shapes and be express
with varying degrees of mathematical formalism.
Bioprocess modeling
• The engineer prepare a block diagram of all unit
operations, feed streams and waste streams.
• Specify the process’s chemical and biological component,
the feed stream, the method of calculating physical
properties and the data used in the simulation.
• Specify specific design requirements and
operating condition of each unit-operation block.
Empirical Approach
• Measure productivity for
all combinations of plant
operating conditions, and
make correlations.
Advantage: Little thought
is necessary.
Disadvantage: Many
experiments are required.
Modeling Approach
• Establish a model and design experiments to
determine the model parameters. Compare the
model behavior with the experimental
measurements. Use the model for coherent design,
control and optimization.
 Advantage: Fewer experiments are required and
greater understanding is obtained.
Disadvantage: Time is required for developing
models.
1. Unit operation model- to compare the performance and capital
and operating cost of each equipment item.
2. Physical property model- to compute the property of materials
in a bioprocess.
3. Economic evaluation system- to calculate total plant cost,
manufacturing cost, and profitability.
4. Flowsheet system- to cover the integrated flaw sheet with design
constraints and perform sensitivity calculations.
5. Optimization system- to automatically maximize performance.
6. User-friendly computing environment- to allow engineers to
access the system through a continent, interactive work station.
Stages in the modeling procedure
• proper definition of the problem
• formulated in mathematical terms.
• Numerical methods of solution with digital simulation
• The validity of the solution depends on the correct choice of
theory(physical and mathematical model), the ability to
identify model parameters correctly and accuracy in the
numerical solution method.
• Care and judgment must be taken such that the model does
not become over complex
Spreadsheet
• A spreadsheet is an electronic piece of paper with
empty boxes, known as cells. The user can enter
data in those cells, perform calculations, and
generate results. Results from spreadsheets can
be easily plotted in a variety of graphs.
• Spreadsheet applications, such as Microsoft
Excel, Lotus 1-2-3, and Corel Quattro Pro have
become as easy to use as word processors and
graphics packages. In its simplest form,.
Special unit operations…
Pumps and Compressors
•Liquid/slurry pumps
•Single stage compressor
BioReactors
•Continuous fermentation
•Batch and fed batch fermentation
•Immobilized enzyme reactor model
Reactors
•Yield-based reactor
•stochiometric reactor
•Plug flow reactor
•Batch reactor
Heater and heat exchangers
•General process heaters
•Plant heat exchangers
•Air cooler
Sterilization
•Continuous sterilization
•Batch sterilization
•Depth sterilization
•Absolute filtration
Phased separators
•Two phased flash
•Thin-film centrifugal evaporator
•Crystallization
•Spray drying
Primary solid-liquid separation
•Rotatory vacuum filter
•Solid washer
•Counter-current decanter
Process Simulators
• Process simulators are software tools that
enable the user to readily represent and
analyze integrated processes.
• They have been in use in the petrochemical
industries since the early 1960’s.
BioProcess Simulator (BPS)
• The minimum requirements for a biochemical process
simulator are the ability to handle batch as well as
continuous processes and the ability to model the unit
operations that are specific to bioprocessing.
• Aspen Plus (from Aspen Technology): was the first tool of
this type. For a given Flowsheet, BPS used to carry out
material and energy balances, estimate the size and cost of
equipment, and perform economic evaluation. BPS has had
limited commercial success because it was designed that
normally operate only in batch mode.
• BATCHES (from Batch Process Technologies): it having
applications in pharmaceuticals, biochemical's, and food
processing. It is especially useful for fitting a new process
into an existing facility and analyzing resource demand as a
function of time.
• BioPro Designer(superPRO) (from Biotechnology Process
Engineering Center (BPEC): BioPro handles material and
energy balances, equipment sizing and costing, economic
evaluation, environmental impact assessment, process
scheduling, and debottlenecking of batch and continuous
processes.
SuperPro Designer
• It is used to illustrate the role of such tools in bioprocess
design.
• Start by developing a flowsheet that represents the overall
process. Displays the flowsheet of a hypothetical process on
the main window of SuperPro Designer.
• The flowsheet is developed by putting together the required
unit operations and joining them with material flow streams.
• The user initializes the flowsheet by registering (selecting
from the component database)the various materials that are
used in the process and specifying operating conditions and
performance parameters for the various operations.
• Example: A typical chromatography cycle includes
equilibration, loading, washing, elution, and regeneration.
The set of operations that comprise a processing step is called
a “unit procedure operation”. Each unit procedure contains
individual tasks e.g. equilibration, loading, etc. A unit
procedure is represented on the screen with a single
equipment icon.
• In real meaning, a unit procedure is the recipe of a
processing step that describes the sequence of
actions required to complete that step. The recipe of
a chromatography unit procedure is specified. On the
left-hand side of that dialog, the program displays
the operations that are available in a
chromatography procedure; on the right-hand side, it
displays the registered operations.
• The significance of the unit procedure is that it
enables the user to describe and model the various
activities of batch processing steps in detail.
• The initialization dialog of a chromatography elution
operation. Through this dialog, the user specifies the
elution strategy (isocratic or gradient), selects the
buffer streams (two different solutions are required
for gradient elution) identifies the component
(Sodium Chloride in this case) whose concentration
varies during elution, specifies its initial and final
concentration, etc. Through the Labor, etc. tab of the
same dialog window, the user provides information
about labor requirement during this operation.
Advantages of combined modeling and
simulation approach
 Modeling improves understanding.
 Models help in experimental design.
 Models may be used predicatively for design and
control.
 Models can be used in training and education.
 Models may be used for process optimization.
Thanks…

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Bioprocess simulation

  • 2. Bioprocessing… • Technique that produces a biological material, such as a genetically engineered microbial strain, for commercial use. • In other words, a bioprocess consists of a cell culture in a bioreactor, which is a process able to create an optimal growth environment. The central object of a bioprocess is the cell. A living cell is a highly complex system which is often defined as the smallest autonomous biological unit.
  • 3. Types of design estimates
  • 4. Types of design estimates during the lifecycle of a product.
  • 5. Bioprocess modeling • In order to improve process understanding or performance, different automatic tools can be developed: simulators able to reproduce system behaviors, software sensors which allow obtaining an judgment of an unmeasured signal to maintain optimal conditions. • All these tools rely on a representation of the considered system, a mathematical model. Such a model may come in various shapes and be express with varying degrees of mathematical formalism.
  • 6. Bioprocess modeling • The engineer prepare a block diagram of all unit operations, feed streams and waste streams. • Specify the process’s chemical and biological component, the feed stream, the method of calculating physical properties and the data used in the simulation. • Specify specific design requirements and operating condition of each unit-operation block.
  • 7. Empirical Approach • Measure productivity for all combinations of plant operating conditions, and make correlations. Advantage: Little thought is necessary. Disadvantage: Many experiments are required.
  • 8. Modeling Approach • Establish a model and design experiments to determine the model parameters. Compare the model behavior with the experimental measurements. Use the model for coherent design, control and optimization.  Advantage: Fewer experiments are required and greater understanding is obtained. Disadvantage: Time is required for developing models.
  • 9. 1. Unit operation model- to compare the performance and capital and operating cost of each equipment item. 2. Physical property model- to compute the property of materials in a bioprocess. 3. Economic evaluation system- to calculate total plant cost, manufacturing cost, and profitability. 4. Flowsheet system- to cover the integrated flaw sheet with design constraints and perform sensitivity calculations. 5. Optimization system- to automatically maximize performance. 6. User-friendly computing environment- to allow engineers to access the system through a continent, interactive work station.
  • 10. Stages in the modeling procedure • proper definition of the problem • formulated in mathematical terms. • Numerical methods of solution with digital simulation • The validity of the solution depends on the correct choice of theory(physical and mathematical model), the ability to identify model parameters correctly and accuracy in the numerical solution method. • Care and judgment must be taken such that the model does not become over complex
  • 11. Spreadsheet • A spreadsheet is an electronic piece of paper with empty boxes, known as cells. The user can enter data in those cells, perform calculations, and generate results. Results from spreadsheets can be easily plotted in a variety of graphs. • Spreadsheet applications, such as Microsoft Excel, Lotus 1-2-3, and Corel Quattro Pro have become as easy to use as word processors and graphics packages. In its simplest form,.
  • 12. Special unit operations… Pumps and Compressors •Liquid/slurry pumps •Single stage compressor BioReactors •Continuous fermentation •Batch and fed batch fermentation •Immobilized enzyme reactor model Reactors •Yield-based reactor •stochiometric reactor •Plug flow reactor •Batch reactor Heater and heat exchangers •General process heaters •Plant heat exchangers •Air cooler Sterilization •Continuous sterilization •Batch sterilization •Depth sterilization •Absolute filtration Phased separators •Two phased flash •Thin-film centrifugal evaporator •Crystallization •Spray drying Primary solid-liquid separation •Rotatory vacuum filter •Solid washer •Counter-current decanter
  • 13. Process Simulators • Process simulators are software tools that enable the user to readily represent and analyze integrated processes. • They have been in use in the petrochemical industries since the early 1960’s.
  • 14. BioProcess Simulator (BPS) • The minimum requirements for a biochemical process simulator are the ability to handle batch as well as continuous processes and the ability to model the unit operations that are specific to bioprocessing. • Aspen Plus (from Aspen Technology): was the first tool of this type. For a given Flowsheet, BPS used to carry out material and energy balances, estimate the size and cost of equipment, and perform economic evaluation. BPS has had limited commercial success because it was designed that normally operate only in batch mode.
  • 15. • BATCHES (from Batch Process Technologies): it having applications in pharmaceuticals, biochemical's, and food processing. It is especially useful for fitting a new process into an existing facility and analyzing resource demand as a function of time. • BioPro Designer(superPRO) (from Biotechnology Process Engineering Center (BPEC): BioPro handles material and energy balances, equipment sizing and costing, economic evaluation, environmental impact assessment, process scheduling, and debottlenecking of batch and continuous processes.
  • 16. SuperPro Designer • It is used to illustrate the role of such tools in bioprocess design. • Start by developing a flowsheet that represents the overall process. Displays the flowsheet of a hypothetical process on the main window of SuperPro Designer. • The flowsheet is developed by putting together the required unit operations and joining them with material flow streams.
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  • 18. • The user initializes the flowsheet by registering (selecting from the component database)the various materials that are used in the process and specifying operating conditions and performance parameters for the various operations. • Example: A typical chromatography cycle includes equilibration, loading, washing, elution, and regeneration. The set of operations that comprise a processing step is called a “unit procedure operation”. Each unit procedure contains individual tasks e.g. equilibration, loading, etc. A unit procedure is represented on the screen with a single equipment icon.
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  • 20. • In real meaning, a unit procedure is the recipe of a processing step that describes the sequence of actions required to complete that step. The recipe of a chromatography unit procedure is specified. On the left-hand side of that dialog, the program displays the operations that are available in a chromatography procedure; on the right-hand side, it displays the registered operations. • The significance of the unit procedure is that it enables the user to describe and model the various activities of batch processing steps in detail.
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  • 22. • The initialization dialog of a chromatography elution operation. Through this dialog, the user specifies the elution strategy (isocratic or gradient), selects the buffer streams (two different solutions are required for gradient elution) identifies the component (Sodium Chloride in this case) whose concentration varies during elution, specifies its initial and final concentration, etc. Through the Labor, etc. tab of the same dialog window, the user provides information about labor requirement during this operation.
  • 23. Advantages of combined modeling and simulation approach  Modeling improves understanding.  Models help in experimental design.  Models may be used predicatively for design and control.  Models can be used in training and education.  Models may be used for process optimization.

Editor's Notes

  1. Simulator- bioreactors,
  2. BioProcess Simulator (BPS)