Batch-Bioprocess Modeling 20140315

8/10/2019 Batch-Bioprocess Modeling 20140315

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BATCH/BIOPROCESSMODELLING15 & 16 March 2014

Rozaimi bin Abu SamahFKKSA, UMP

Objectives

Construct a process flow via SuperPro Designer

Initialize the process units

Simulate the whole process

Analyze results following the simulation


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Contents

Overview of process simulation

Flowsheet development

Unit procedure initialization

Process scheduling

Resources & inventory tracking

Equipment rating Economic evaluation

What is simulation?

SuperPro Designer?

Tools available in SuperPro designer

Overview of Process Simulation


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Process simulation?

Building a process model

Predicting how a process would actually behave

Performing an experiment (on computer, of course)

Incentives

Highly cost effective

Reasonably accurate Proactive approach

Commercial process simulators

Aspen Plus

HYSYS

Provision

Design II

SuperPro


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SuperPro Designer

SuperproDesigner

BioPro DesignerBiotecnology

Food Processing

BatchProDesigner

Synthetic pharmaceuticals

Specialty chemicals

Agrochemicals

EnviroProDesigner

Water purification

Wastewater treatment

Air pollution control

ScheduleProScheduling and debottlenecking

of multi-product facilities

Available tools

Intuitive user interface

Wide variety of unit operation models

Databases for component and mixtures

M&E balances of integrated processes

Equipment sizing and costing Project economic evaluation

Process scheduling

Throughput analysis & debottlenecking

Waste stream characterization


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Intuitive user interface

Double

click

Operations Gantt Chart


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Scheduling

How can I schedule production during the next 6-18 months?

How can I schedule operations in an R&D facility?

How to adjust scheduling if priorities change?

Can I fit a new product into the facility?

Resource demand chart


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Labor demand chart

Cost breakdown


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Economic evaluation

Getting started

Interface

Example case study Component registration

Flowsheet drawing & editing

Unit procedure initialization

Simulation execution & result checking

Flowsheet Development


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Getting started

Process operation mode

Batch

vs

Continuous

Default annual

operating time


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Interface

Horizontal drawing size:

2 pages

Common icons

Select mode Connect mode stream

connectionSolve run the

simulation


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Unit procedures in SPD to name a few

Vessel procedure Reactor

Seed reactor

Fermentor

Continuous reaction(stoichiometric,kinetic, equilibrium) CSTR

PFR

Fermentor

Filtration Microfiltration Ultrafiltration

Dead end

Distillation Flash

Batch Continuous

Extraction

Mixer-settler

Differential

Centrifugal

Homogenisation

High pressure Bead milling

A batch reactor is utilized to produce component Cfrom reactant A and B (A + BC)

C is later separated by a batch plate & frame filter

Solvent used heptane (soluble for A and B butinsoluble for C)

Task to be performed Mass & energy balances

Process scheduling

Economic evaluation

Example case study


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Component registration

Component Database

Nitrogen, N2 Default

Oxygen, O2 Default

Water, H2O Default

Heptane, C7H16 Designer

A New (user define)

B New (user define)

C New (user define)


Default

component

Databanks in

SuperPro


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Adding new component

Reference

component Newly

added

Editing component properties


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Editing component properties

Please do the changes accordingly

Save your work as Tutorial 1

Component MW Price Value ($/kg)

A 150 Purchase 10

B 25 Purchase 15

C 175 Selling 200

Locating the unit procedures

Stream connection

Flowsheet editing

Flowsheet drawing & editing


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Unit procedure - vessel

Unit procedure plate & frame filter


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Adding a process stream

Single click

Tip: ESCbutton will terminate the stream drawing

Deleting a process stream

Cursor in Select Mode single click until turns red press DEL


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Completing the flowsheetDouble

click toterminatethe stream

Editing a stream elbow

Stream elbow To adjust the

length of thestream to savespace


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Editing tag name of a stream

Changing all the stream ID

Stream ID Change to Stream ID Change to

S-101 Heptane S-106 Wash in

S-102 A S-107 C

S-103 B S-108 B + Heptane

S-104 Emission S-109 Wash out

S-105 Rxt out


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Editing style of a stream/unit procedure

What is a unit procedure?

Initializing an operation

Initializing of a unit procedure


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What is a unit procedure?

In the batchmodelling mode, a unit proceduremay consists of various operations

Reactor procedure: feed charge, reaction, productwithdraw, etc.

Filtration procedure: filtration, cake wash, CIP, etc.

In continuousmode, a unit operation is a unitoperation

Hierarchy in batch modelling

Entire plant

Procedure(s) level

Operation(s)level

Unit procedure in

continuous process


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Function of each unit procedure

Vessel procedure (P-1) Acts as a batch reactorto carry out reaction A + BC Heptaneis used to dissolve components A & B, to aid

separation in P-2

Plate & Frame Filtration procedure (P-2) C is not dissolved in heptane, hence is filtered out by the

filter cloth Heptane is used to wash out trapped heptane and

dissolved A & B from the filter cake

Stream specification

Heptane flow

= 800 kg/batch

Ingredient flow

T, P = defaultSelectcomponent

and clickto insert thecomponent to theright-hand area


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Set spec for stream A & B

Stream ID Component Amount

(kg/batch)

Heptane Heptane 800

A A 50

B B 40

Adding operations to P-1

Three (3) Charge operations:to charge A, B and heptane)

One (1) React(Stoichiometric)operation:

to carry out the reaction One (1) Transfer Out

operation: to deliver productto next unit


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Initializing operations in P-1


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Initializing CHARGE-1

Emission calculation

Click to

perform

emissioncalculation


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Initializing CHARGE operations

Operation Operating condition Emission

CHARGE-1 Charge 800 kg/batch of heptane using stream Heptane Setup time = 5 min Process time: 100 L/min

Performheptane

emission onthis stream

CHARGE-2 Charge 50 kg/batch of A (limiting component) using streamA

Setup time = 5 min

Process time = calculated based on 20 kg/min

Nil

CHARGE-3 Charge 40 kg/batch of B using stream B (B is in excess)Setup time = 5 minProcess time = calculated based on 20 kg/min

Nil

Initializing REACT-1& TRANSFER-OUT-1 operations

Operation Operating condition Volumes Reaction

REACT-1 Final temperature = 50C Heat transfer agent = steam Process time = 6 hours Leave other values as default

Max allowableworking/vessel

volume = 80%

Extent of rxn = 95%

Reaction stoich.: A + BC

TRANSFER-OUT-1

Using stream Rxt out Duration: same as Cloth

Filtration in P-2 (using

Master-Slave Relationship)

Nil Nil


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Initializing REACT-1 in P-1

Final temp = 50C

Process time = 6 h

Heat transferagent = steam


Max allowable

volume = 80 %


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Edit reaction

stoichiometry

Extent of reaction


Add

component

Molar

coefficient

Molar

stoichiometry


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Master-Slaverelationship

Master

Slave

Initializing operations for P-2

Cloth Filtrationoperation:

by default, to filter C

Cake washoperation: to

wash out left over trappedA & B in filter cake

Transfer Outoperation: todeliver product


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Initializing FILTER-1

Operation Operating condition Scheduling

FILTER-1 Particulate component removal = 95 %C (assuming that A & B are completelysoluble in Heptane & C is virtually

insolubleLoss on drying (LOD) = 35 % (this value

cause a portion of heptane & any

soluble component to be held in the wet

cake)65 % is insoluble CFiltrate stream B + Heptane

By default, firstoperation of any batchunit procedure is

scheduled to start at thebeginning of the batch

Start time: relative to

START of TRANSFEROUT-1 operation in P-1procedure


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95 % removal of C

35 % LOD

filtrate


By default

Filtration will only

start when productis transferred out

from P-1


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Initializing CAKE-WASH-1& TRANSFER-OUT-1

Operation Operating condition

CAKE-

WASH-1

Wash In stream: Wash in

Wash Out stream: Wash outWash solvent: heptane (click on Composition, select Auto-

adjust, the program will estimate a value automatically

Wash time: 30 minutesWash type: slurry (a slurry wash will essentially dilute the soluble

component trapped in the cake and remove most of them in the

wash stream, whereas a displacement wash will remove thesoluble components from the cake in a plug-flow fashion)

TRANSFER-

OUT-1

Transfer out using Stream C

Duration: calculated based on 10 kg/min

Execute the simulation

Viewing the results

Simulating a flowsheet


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Simulating the process

Simulating a process

Menu bar: Tasks>Solve M&E BalancesPress Ctrl 3Press F9

Solve icon

Viewing the results

Calculated output variables for each operation can be viewed byrevisiting the corresponding Operation Datadialog windows

To see the calculated equipment sizes, right-click on a unitprocedure & choose Equipment Data

The contents of a piece of equipment as a function of time can beviewed by selecting Equipment Contentsor Operation Sequence

The calculated flow rates & compositions of intermediate & outputstreams can be viewed in the Simulation Data dialog windows ofeach stream


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Viewing the results

List of reports available Stream Report (SR)

Economic Evaluation Report (EER)

Itemized Cost Report (ICR)

Cash Flow Report (CFR)

Throughput Analysis Report (THR)

Environmental Impact Assessment report (EIR)

Emissions Report (EMS) Input Data Report (IDR)

Equipment Report (EQR)

Equipment operation data

Calculated heptaneemission = 0.028 %


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Equipment data

Calculated

vesselvolume =

1628 L

Equipment content


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Stream simulation data

Generating streams report


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Check your results

Reaction A + B C

MW 150 25 175

Initial content, mi0(kg) 50 40 -

Initial mol, ni0(kg-mol) 0.333 1.6 -

X = 95 % (based on A)

Final mol, n (kg-mol) nA0nA0X nB0nA0X nA0X

0.0167 1.283 0.3167

Final content (kg) 2.5 32.083 55.417

Compare with stream result of Rxt out

Operation Gantt chart

Equipment occupancy chart

Recipe scheduling information

Process Scheduling


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Purposes of scheduling

Based on the scheduling information & annual operatingtime (AOT) specified for the plant, the system will

Make sure there is no conflict between start time & end timeof processing steps

Make sure there is no conflict between the specification ofAOT, number of batches, plant cycle time

Calculate the plants batch time, maximum batches possible

and longest procedure & scheduling bottlenecking equipment

Scheduling function in SPD

For each operation

Process time

Setup &

turnaround time Starting time

#of cycles (at

procedure level)

For entire plant

AOT

# of cycles per yearand either

# of batches peryear

Batch cycle time

Batch time slack


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Important scheduling definitions

Setup time (ST)

Duration spent for preparation before the actual executionof an operation

May involve cleaning, vacuuming, setting up equipment

Process time (PT)

Duration that an equipment is in use to carry out anoperation


Turnaround time (TT)

Duration that an equipment is being prepared for the

next cycle

Operation cycle time (OCT) Amount of time for an operations cycle to be

OCT = ST + PT + TT


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Procedure cycle time (PCT)

Duration spent to complete an entire procedure,

including all operations in the procedure

Batch time (BT)

Duration from the first operation till the end of the

last operation in a single batch

Operation Gantt chart

BT

PCT

OCT for

FILTER-1 in P-2

Tasks>Gantt Charts>Operation GC (Ctrl 2)


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Equipment occupancy chartView>Equipment Occupancy Chart>Multiple Batches

Batch time Turnaround time Procedure cycle time

Recipe scheduling informationTasks>Recipe Scheduling Information

Set number of batches to 20, recipe cycle time to 12 h

Update and note the differences


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Resources: ingredient, heat transfer agent,power, labor

Inventory: ingredient, heat transfer agent

Resources & Inventory Tracking

Resources tracking (operator)View>Resource Consumption Tracking Chart>Labor>Multiple Batches operator

Two (2) operators are

needed in total


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Inventory tracking

SPD can analyses & displays inventory information formaterial resources

Given these information, determine how often shouldshipments of B be scheduled?

40 kg of B are used in each batch

There is a 200-kg storage capacity for B with an opening

inventory of 100 kg Loading rate of B into storage is 200 kg/h

10 % for On-Trigger, 90 % for Off-Trigger

Inventory tracking

View>Resource Inventory Chart>Ingredient Multiple Batches

On-Trigger/Off-Trigger B should be replenishedwhen inventory falls to 10 & and halted whenreached 90 % of storage capacity

Click OK & chart will be displayed for two (2)batches

Right-click and set the # of batches to 12


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Inventory tracking

1

2

3

4

5

6

7

8

9

10

11

12

Inventory tracking

Do the same for ingredient A (with the same

information for B)

Suggest solution(s) for the problem occurs


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Design/Sizing Mode vs Rating Mode

Equipment rating

Equipment sizing vs rating

Sizing calculate the dimensions of an equipment forfixed operating condition

Rating calculate the percentage of use of anequipment with fixed dimensions

Default setting in SPD Design mode (sizing)when equipment dimensions are

not specified (eg. Reactor volume, filter area, etc.) Maximum available sizeis specified. If calculated size >

max allowable size, SPD will employ multiple pieces ofequipment with each size < max allowable size


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Filter (PFF-101) sizing

Check oncalculated filterarea fromEquipment Data

Data needed Flux & time

Feed volumefrom P-1

SPD calculatesthe filter area

Calculated

filter area

Maxavailable size

Rating mode for PFF-101

If Rating Modeis selected, the size & number of theunitscan be specified

Task switch the PFF-101 sizing to Rating Mode& do the

following changes Filter size = 2 m2(1 unit) from 1.5 m2

Filtrate flux = 150 L/m2h from 200 L/m2h

Save your file as Tutorial 1 rating mode PFF Determine the filtration time


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Stream classification

Engineering economic review

Cost factors

Economic evaluation Strategies for increasing profits

Economic evaluation

Stream classification

Classify all input and output streams as rawmaterials, revenuesor wastes(solid, liquid orgaseous)

Supply cost data, then only can perform throughput

analysis, plant economic evaluation & environmentalimpact assessment

By default, SPD estimates a purchase or selling pricefor a stream based on the price of each componentand the composition of the stream


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Stream classification Output streams

Classification C revenue

Emission emission

B + Heptane, Wash out aqueous waste

Cost Emission and aq waste disposal cost =

$0.10/kg

Revenue stream (automatically calculated)

Main product rate

Stream C

Reported based on single component C

Engineering economic review

Costs broken downinto

Capital cost Equipment cost

Building cost Operating cost Utilities

Labor

Raw material

Index of economic performance Return on Investment (ROI) Annual Income/Capital Costs * 100 %

Usually aim for 30 %

Internal Rate of Return (IRR) Discounted Cash Flow

Payback Period Time to repay investment

Usually aim < 7 years

Net Present Value (NPV) Value of project in current year currency


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Cost factors (operation level)

For each unitprocedure,you can setcost data foreachoperation

under Labor,etctab

Cost factors (equipment level)

Right click an equipmentprocedure>EquipmentData>(any operation>

Purchase cost Automatically calculated

Set by user Adjustments

Change material ofconstruction

Change operating andmaintenance costs


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Cost factors (section level)

Operating cost

adjustments(labor, facilities,

QA)

Capital cost

adjustments

(piping,

instrumentation)

Cost factors (flowsheet level)

Edit>FlowsheetOptions>Economic EvaluationParameters

Right click onFlowsheet>EconomicEvaluation Parameters

Cater for Overall financing

Time valuation

Income taxes


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Economic evaluation

Pre-simulation check

All streams are classified, especially the main

revenue stream

Filter setting

Rating mode, area = 2 m2, flux = 150 L/m2h

Recipe scheduling information Number of batches = 20, cycle time = 12 h

Economic evaluation steps

Solve M&E Balances

Task>Perform Economic Calculations

Results

View>Executive Summary Reports>Economic Evaluation

Reports>Cash Flow Analysis

Reports>Itemized Cost Report


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Economic evaluation - Results

Strategies to increase profits

Increase # of batches Try larger batches Let SPD calculate max batches

Debottleneck

Size debottleneck equipment capacity Time debottleneck higher equipment use

Capital costs rise with equipment sizes

Operating costs can be optimized with better laborand facility usage


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Biochemical Case Study

Process description

Water, microorganisms, nutrients (glucose) and air are fedinto a bioreactor where at 37C a fermentation takes placeyielding an enzyme and impurities. Biomass is separated ina disk-stack centrifuge and the liquid is stored in a tank. Itis then processed in a diafilter where the remainingbiomass is removed (with a small loss of product). It isstored again and then loaded onto a PBA chromatographycolumn where the enzyme binds and is eluted usingWFI/NaCl mixture.


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Fermentation section

Mode of operation: batch mode


Glucose

Biomass

CO2 Water for injection (WFI)

Enzyme

Impurities

Process flowsheeting

Fermentation process

Equipment: vessel procedure>in a fermentor

Description: transformation of raw material intoenzyme & impurities

Centrifugation Equipment: centrifugation>disk-stack

Description: separation of biomass


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Process flowsheeting

Product storage 1

Equipment: storage>bulk>batch>in a blendingtank

Rename as Storage 1 (right-click, Edit labels)

Description: temporary product storage

Initialization of Fermentation

CHARGE-1: 10000 L of water @ 100 L/min

CHARGE-2: 1000 kg of glucose @ 40 kg/min

HEAT-1 Final T: 37C Heat transfer agent: steam Efficiency: 90 % Duration: calculated based on constant heating rate

0.5C/min


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FERMENT-1 (Stoichiometric) Final T: 37C

Heat transfer agent: cooling water

Process time: 36 h

Fermentor aeration: select airfrom stock mixture(auto adjust)

Reaction (mass stoichiometry) 100 glucose + 80 O255 H2O + 2 enzyme + 3 impurities + 80 CO2+ 40

biomass

Reaction extent: 98 % based on limiting component Enthalpy: -3700 kcal/kg, ref. component: O2, ref. T: 37C


TRANSFER-OUT-1: duration same as

Centrifugation (master-slave relationship)


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Initialization of Centrifugation

Only one (1) operation: CENTRIFUGE-1 (default)

Operating condition

Equipment based on: Solid removal

Duration: 3 h (centrifugation time)

Initialization of Centrifugation

Material balance Component removal %: set by user

Solid component removal %: 98 % for biomass, 0 % for others

Solids concentration in solid streams: 500 g/L

Utilities: Exit T: 15C (set by user)

Agent: chilled water

Scheduling: start when TRANSFER-OUT-1 ofFermentation (P-1) starts


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Initialization of Storage 1

TRANSFER-IN-1

Operating conditions Transfer using: outlet stream from centrifuge

Duration: same as centrifuge (master-slave relationship)

Scheduling: start when Centrifugation (P-2) starts

STORAGE

Duration: to be determined Scheduling: start when TRANSFER-IN-1 starts

Simulate..

Simulate the flowsheet

Solve the error message scheduling problem


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Purification Section 1

Diafiltration (DF) Equipment: filtration>diafiltration Description: removal of all leftover biomass from Storage

1

Product storage Equipment: storage>bulk>batch>in a blending tank

Rename as Storage 2 Description: temporary product storage

Initialization of Diafiltration

Rejection coefficient (RC): 100 % biomass, 20 %impurities, 5 % enzyme

Max solid concentration in retentate: 600 g/L

Product denaturation 4 %

Active product: enzyme

Denatured product: impurities


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Duration: 4 h (filtration time)

Diluant: water (auto-adjust)

Diafiltration data: 5 (volume permeated)

Concentration data:

Prefiltration: Yes, # of conc. Stages: 1, conc. Factor: 5 Postfiltration: No


Utility (select by user)

Exit T: 15C

Agent: glycerol

Specific power: 0.2 kW/m2

Scheduling: start when TRANSFER-OUT-1 of Storage 1starts

Set TRANSFER-OUT-1 of Storage 1 to follow the durationof Filtration in Diafilter using master-slave relationship


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TRANSFER-IN-1

Transfer in using: outlet stream from DF

Start (scheduling) and duration same as DF (master-slave relationship)

STORAGE-1

Duration: to be determined Scheduling: start when TRANSFER-IN-1 starts

Simulate..

Simulate the flowsheet

Solve the error message scheduling problem


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Purification Section 2

PBA Chromatography Equipment: chromatogrphy>adsorption>PBA

chromatography Description: binds and elutes enzyme using a WFI/NaCl

mixture (new mixture to be registered)

Product storage 3 Equipment: storage>bulk>batch>in a blending tank Rename as Storage 3 Description: temporary product storage

New mixture registration

We need a mixture of Nacl/WFI (2M), but it is not

found in the component database

Two (2) ways of registering this mixture

Register as NaCl (2M) & replace the water compoundin this mixture with WFI

Register it from scratch & fill in the physical propertiesthat you have


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PBA chromatography

PBA column loading (Load): estimate the time forloading a column, track recovery yield & estimate

the number and size of columns required

Column washing (Wash): wash away the undesired

impurities that trapped in the column

PBA Chromatography

Column elution (Elute)

A column may be used to bind either product or impurities

For a component that binds to the resin, its amount in theproduct stream = (amount in the feed stream) x (bindingfraction) x (elution yield)

Column regeneration (Regenerate): regenerate the

resin using a solution


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Initialization of PBA chromatography

LOAD-1

Loading flowrate: 200 cm/h (linear velocity)

Resins primary funtion: retain product

Comp. binding & yield

Enzyme: 100 % & 90 %, respectively

Impurity: 20 % & 30 %, respectively

Scheduling: start with TRANSFER-OUT of Storage 2


WASH-1

Volume per cycle: 2 bed volumes (BV)

Wash stream: Wash stream which contains WFI (auto-adjust)

ELUTE-1 Eluant volume Total volume: 8 BV

Volume in product stream: 2 BV (cont..)


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ELUTE-1 (cont..)

Flowrate options: 200 cm/h (linear velocity)

Elution strategy: Gradient

Key comp. data

Name: NaCl

Initial concentration: 0 mol/L Final concentration: 100 mol/L (cont..)


ELUTE-1 (cont..) Eluant A: NaCl/WFI (2M) in stock mixture Eluant B: WFI (auto-adjust)

REGENERATE-1

Linear velocity: 300 cm/h (linear velocity) Volume per cycle: 2 BV Wash stream: Regen stream with WFI (auto-adjust)

Delete EQUILIBRIATE operation


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TRANSFER-IN-1 Transfer from PBA chromatography, using outlet stream

from PBA chromatography Start (scheduling) and duration (operating condition:

master-slave) same as ELUTE-1 in PBA chromatography(Q: why not the last operation?)

TRANSFER-OUT-1 Transfer to: none, using outlet stream from Storage 3 Scheduling: start when TRANSFER-IN-1 completed

Simulate..

Solve the M&E Balances

Manual calculation

Amount of enzyme = 18.071 kg x 1.0 x 0.9 = 16.264 kg

Amount of impurities = 28.897 kg x 0.2 x 0.3 = 1.733 kg

Check with simulation result

Documents

Batch-Bioprocess Modeling 20140315