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    Comparative Analysis of Controller

    Technologies for a CHO320 Fed BatchFermentation

    Stephen Craven

    19th September 2011

    APC9 2011

    York

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    Presentation Overview

    -Bioprocess Control

    - Overview of apPAT Project

    - Controller Strategy Simulations

    - PID Control

    - MPC Control

    - Experimental Verification

    - Conclusions

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    Bioprocess Modelling and Control

    Challenges

    -Their dynamic behaviour is inherentlynonlinear

    -Accurate process models are rarely

    available due to the complexity of theunderlying biochemical processes

    - Reliable biosensors to measureintercellular activities are rarely

    available, making the process statesvery difficult to characterise

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    apPAT Project

    Industry led research prog ram funded by Enterpr ise

    Ireland which aims to develop a PAT enabled mammalian

    cel l b iopro cess

    Modelling and

    Prediction

    Process

    Control

    Online

    Sampling

    Analytics,

    Sensors

    Real time

    monitoring

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    PAT Enabled Fed-batch Bioprocess

    G

    L

    Q

    A

    Sin

    F

    ProcessController

    Raman Probe

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    Process Control

    Process

    Objective:

    Maximize

    Biomass/Productivity

    Control

    Objective:

    Maintain a low

    Glucose/Glutamine level

    in order to avoid a buildup of Lactate/Ammonia

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    Control Strategy Development, Simulation & Application

    Control strategy development

    - PID Control

    - Non-linear MPC (Model Predictive Control)

    Configure

    & Tune

    Simulate

    Real

    Time

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    Control Strategy Development

    Based on the ISA control law consisting of three controlparameters (K, Td, Ti)

    Control parameters tuned via Ziegler Nichols (Closedloop) relay based tuning

    Class ical Contro l

    PID Con tro l ler

    t

    d

    i dt

    tdeTdeT

    teKtu

    0

    )()(1)()(

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    Control Strategy Development

    Setpoint OutputProcess

    P

    I

    D

    )(tKe

    t

    i

    de

    T

    K

    0

    )(

    dt

    tdeKT

    d

    )(

    +

    -

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    Control Strategy Development

    Class ical Contr ol

    PID Contro l ler Tuning

    Ziegler Nicho ls clos ed loop w ith relay ident i f icat ion techn ique.

    7.1UK

    PID: K =

    Ti=

    Td=

    2

    UP

    8

    UP

    = 0.010558

    = 0.4

    = 0.1

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    Control Strategy Development

    Output

    Setpoint

    Process

    ModelObjective

    Function

    Optimisation

    Feed

    Advanced Contro l

    MPC Con trol ler

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    Control Strategy Development

    Indus tr ial MPC Formulat ion

    M

    i

    ikik

    P

    i

    ik

    tutu

    tutRtyMkk 1

    2

    1

    2

    1)(),......,(

    )()((min1

    Subject to,

    maxmin

    maxmin

    uuu

    yyy

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    Bioprocess Model

    Unstructured, non-segregated bioprocess model

    - System of coupled ODEs, mass balance and rate equations

    - Contains approximately 16 model parameters

    - Used a differential evolution parameter optimisationalgorithm to fit the parameter values with the possible rangesconstrained based on published values

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    Control Strategy Development

    Advanced Contro l

    MPC Tun ing

    4 Tuning parameters:

    P =Prediction horizon

    M =Control horizon

    = Output weight matrix

    = Input weight matrix

    Off l ine Tuning Rules

    P =Increase until no further effect

    M =1 (>1, leads to more aggressive control)

    = scale on control variables = 1

    = Increase to avoid aggressive CO

    Tuning results

    P= 10

    M= 1

    = 1

    = 0

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    Control Strategy Development, Simulation & Application

    Control strategy simulation

    - PID Control

    - Non-linear MPC (Model Predictive Control)

    Configure

    & Tune

    Simulate

    Real

    Time

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    Controller Performance Simulation Results

    Stepped Set-point Tracking

    Disturbance Compensation

    Propagation of Measurement Noise

    Perform ance Off-Lin e Testing Criteria:

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    PID Set-point Step Tracking

    0

    5

    10

    15

    20

    25

    30

    0 50 100 150 200 250 300Time (h)

    Concentratio

    n(mM) Cglc

    Set-point

    0

    0.01

    0.02

    0.03

    0.04

    0.05

    0.06

    0 50 100 150 200 250 300Time (h)

    Feed-rate(L/h)

    Controller Output

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    MPC Set-point Step Tracking

    0

    5

    10

    1520

    25

    30

    0 50 100 150 200 250 300Time (h)

    Concentration(mM)

    Cglc

    Set-point

    0

    0.01

    0.02

    0.03

    0.04

    0.05

    0.06

    0 50 100 150 200 250 300Time (h)

    Feedrate

    (L/h)

    Controller Output

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    Controller Performance Simulation Results

    Stepped Set-point Tracking

    Disturbance Compensation

    Propagation of Measurement Noise

    Perform ance Off-Lin e Testing Criteria:

    PID Di b C i

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    PID Disturbance Compensation

    0

    5

    10

    15

    20

    25

    30

    0 50 100 150 200 250 300Time (h)

    Concentratio

    n(mM) Cglc

    Set-point

    0

    0.02

    0.04

    0.06

    0.08

    0.1

    0.12

    0 50 100 150 200 250 300Time (h)

    Feed-rate

    (L/h)

    Controller Output

    Disturbance

    applied

    MPC Di t b C ti

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    MPC Disturbance Compensation

    0

    5

    10

    15

    20

    25

    30

    0 50 100 150 200 250 300Time (h)

    Concentratio

    n(mM) Cglc

    Set-point

    0

    0.02

    0.04

    0.06

    0.08

    0.1

    0.12

    0 50 100 150 200 250 300Time (h)

    Feedrate

    (L/h)

    Controller Output

    Disturbance

    applied

    C ll P f Si l i R l

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    Controller Performance Simulation Results

    Stepped Set-point Tracking

    Disturbance Compensation

    Propagation of Measurement Noise

    Perform ance Off-Lin e Testing Criteria:

    PID P i f M N i

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    PID Propagation of Measurement Noise

    0

    5

    10

    15

    20

    25

    30

    0 50 100 150 200 250 300Time (h)

    Concentratio

    n(mM) Cglc

    Set-point

    0

    0.01

    0.02

    0.030.04

    0.05

    0.06

    0.07

    0 50 100 150 200 250 300Time (h)

    Feed-rate(L/h)

    Controller Output

    Fast on-off

    Control

    PI P ti f M t N i

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    PI Propagation of Measurement Noise

    0

    5

    10

    15

    20

    25

    30

    0 50 100 150 200 250 300Time (h)

    Concentration

    (mM) Cglc

    Set-point

    0

    0.01

    0.02

    0.03

    0.04

    0.05

    0.06

    0.07

    0 50 100 150 200 250 300Time (h)

    Feed-rate

    (L/h)

    Controller Output

    Removal of

    D term leads

    to less abrupt

    control

    Better set-point

    tracking

    MPC P ti f M t N i

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    MPC Propagation of Measurement Noise

    0

    5

    10

    15

    20

    25

    30

    0 50 100 150 200 250 300Time (h)

    Concentratio

    n(mM) Cglc

    Set-point

    0

    0.01

    0.02

    0.03

    0.04

    0.05

    0.06

    0.07

    0 50 100 150 200 250 300Time (h)

    Feed-rate

    (L/h)

    Controller Output

    P = 10

    M = 1

    = 1

    = 0

    MPC P ti f M t N i

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    MPC Propagation of Measurement Noise

    0

    5

    10

    15

    20

    25

    30

    0 50 100 150 200 250 300Time (h)

    Concentration(mM)

    Cglc

    Set-point

    00.010.020.030.040.050.060.07

    0 50 100 150 200 250 300

    Time (h)

    Feed-ra

    te

    (L/h)

    Controller Output

    P = 40

    M = 1

    = 1

    = 0

    MPC P ti f M t N i

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    MPC Propagation of Measurement Noise

    0

    5

    10

    1520

    25

    30

    0 50 100 150 200 250 300Time (h)

    Concentration(mM) Cglc

    Set-point

    0

    0.01

    0.02

    0.03

    0.04

    0.05

    0.06

    0.07

    0 50 100 150 200 250 300Time (h)

    Feed-rate

    (L/h)

    Controller Output

    P = 40

    M = 1

    = 1

    = 10000

    Si l ti St d R lt

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    Simulation Study Results

    Reference tracking:MPC starts adjusting the control signal

    ahead of reference changes, while PID cannot start before.

    MPC gives less control error.

    Disturbance compensation:MPC better than PID. MPC

    can deal with plant-model mismatch.

    Measurement noise:Less propagation through tuned MPCthan tuned PID. By increasing the penalty weight on the input,

    the control action in the presence of measurement noise can

    be dampened to a more smooth control signal.

    SISO/MIMO: PID can only handle one input and one output.

    MPC is a multivariable control strategy.

    Control Strategy Development Simulation & Application

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    Control Strategy Development, Simulation & Application

    Control strategy real time application

    - PID Control

    - Non-linear MPC (Model Predictive Control)

    Configure

    & Tune

    Simulate

    Real

    Time

    3 L Bioreactor Experimental Set up

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    3 L Bioreactor Experimental Set-up

    Real Time Controller Application

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    Real Time Controller Application

    Raman

    Probe

    Spectral

    acquisition

    software

    Spectral

    file

    Calibration

    model &

    real-time engine

    Control

    model &

    real-time

    engine

    Feed Pump

    USBText file

    read/write

    File Directory

    Text file

    read/write

    Text file

    read/write

    Serial

    15 L Bioreactor Experimental Set up

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    15 L Bioreactor Experimental Set-up

    Real Time Controller Application

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    Real Time Controller Application

    Raman

    Probe

    Spectral

    acquisition

    software

    Spectral

    file

    Calibration

    model &

    real-time engine

    Control

    model &

    real-time

    engine

    ABB

    800xa

    control

    system

    USB TCP/IP

    ABB xPAT Data

    Manager

    OPCOPC

    OPC

    Experimental Results

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    Experimental Results

    Communication and controller configuration for real time

    application complete.

    Plan to run MPC and PID control on both the 3 L and 15 L

    bioreactor setups with the Raman probe for real time monitoring of

    glucose concentration.

    Over the next few months, preliminary experimental data for the

    closed loop feedback control fed-batch runs will be gathered.

    3 L Bioreactor Experimental Results

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    3 L Bioreactor Experimental Results

    0

    5

    10

    15

    20

    25

    30

    0 20 40 60 80 100 120 140Time (h)

    Concentration

    (mM)

    Glucose

    Set-point

    0

    0.001

    0.002

    0.003

    0.004

    0.005

    0.006

    0 20 40 60 80 100 120 140Time (h)

    Feed-rate

    (L/h)

    Controller Output

    =50000 =0=20000 =0

    Conclusions and Future Work

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    Conclusions and Future Work

    Fed-batch model has been incorporated into the simulation of

    PID and MPC controller technologies.

    MPC performed best for set-point tracking both in thepresence of noise and disturbances from the simulation study.

    Configured and simulated control strategies are to be appliedin real time with online and at-line PAT on two differentbioreactor scales.

    Apply MIMO MPC for glucose and glutamine control.

    Real time results are to be compared to the results gatheredon a simulation basis.

    Acknowledgements

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    Acknowledgements

    Prof. Brian Glennon

    Dr. Jessica Whelan

    apPAT Research Team

    Enterprise Ireland