Mon 10.00 Comparison of Controller Technologies For Fed Batch Fermentation S Craven

Comparative Analysis of Controller
Technologies for a CHO320 Fed Batch

Fermentation
APC9 2011
York
Stephen Craven
19th September 2011
1
Presentation Overview
- Overview of PAT-Bio Project
- Controller Simulations
- PID Control
- MPC Control
- Experimental Verification
- Conclusions
PAT-Bio Project
Industry led research program funded by Enterprise
Ireland which aims to develop a PAT enabled mammalian
cell bioprocess
Modelling and
Prediction
Real time
monitoring
Analytics,
Sensors
Process
Control
Online
Sampling
Bioprocess Modelling and Control

Challenges of bioreactor control
- Their dynamic behaviour is inherently
nonlinear
- Accurate process models are rarely
available due to the complexity of the
underlying biochemical processes
- Model parameters vary in an
unpredictable manner
- Reliable biosensors to measure
intercellular activities are rarely
available, making the process states
very difficult to characterise
PAT Enabled Fed-batch Bioprocess

F
Sin
X: Biomass
G: Glucose
L: Lactate
V: Volume
Process
Controller
Raman Probe
F: Feed Rate
Sin: Inlet Substrate
Concentration
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 optimisation
algorithm to fit the parameter values with the possible ranges
constrained based on published values
Process Control
Process
Objective:
Maximize
Biomass/Productivity
Control
Objective:
Maintain a low
Glucose/Glutamine level
in order to avoid a build
up of Lactate/Ammonia
Control Strategy Development, Simulation & Application

Control strategy development
- PID Control
- Non-linear MPC (Model Predictive Control)
Real
Time
Simulate
Configure
& Tune
8
Control Strategy Development

Classical Control
PID Controller
Based on the ISA control law consisting of three control
parameters (K, Td, Ti)
1
de(t)
u(t) = K e(t ) + e( )d + Td
Ti 0
dt
Control parameters tuned via Ziegler Nichols (Closed

loop) relay based tuning
9
Ke(t )
Setpoint
+
K
Ti
t
0
e ( ) d
Process
Output
KT d
de ( t )
dt
10

Classical Control
PID Controller Tuning
Ziegler Nichols closed loop with relay identification technique.
PID:
K=
Ti =
Td =
KU
1 .7
= 0.010558
PU
2
= 0.4
PU
8
= 0.1
11

Advanced Control
MPC Controller
Feed
Process
Output
Optimisation
Objective
Function
Model
Setpoint
12

Industrial MPC Formulation
P
min
( y (t
k +i
) R (t k + i )
u ( t k ),......, u ( t k + M 1 ) i =1
+ u (t k + i 1)
i =1
Subject to,
y min y y max
u min u u max
13

Advanced Control
MPC Tuning
4 Tuning parameters:
Offline Tuning Rules
P = Prediction horizon
P = Increase until no further effect
M = Control horizon
M = 1 (>1, leads to more aggressive control)
= Output weight matrix
= scale on control variables = 1
= Input weight matrix
= Increase to avoid aggressive CO
Tuning results
P = 10
M=1
=1
=0
14

Control strategy simulation
- PID Control
Real
Time
Simulate
Configure
& Tune
15
Controller Performance Simulation Results

Performance Off-Line Testing Criteria:
Set-point Tracking
Disturbance Compensation
Propagation of Measurement Noise
16
PID Set-point Step Tracking

Concentration (mM)
30
Cglc
Set-point
25
20
15
10
5
0
0
50
100
150
Time (h)
200
250
300
0.06
Controller Output
Feed-rate (L/h)
0.05
0.04
0.03
0.02
0.01
0
0
50
100
150
Time (h)
200
250
300
17
PID Set-point Step Tracking

Concentration (mM)
30
Cglc
Set-point
25
20
15
10
5
0
0
50
100
150
Time (h)
200
250
300
0.06
Controller Output
Feed-rate (L/h)
0.05
0.04
0.03
0.02
0.01
0
0
50
100
150
Time (h)
200
250
300
18
MPC Set-point Step Tracking

Concentration (mM)
30
Cglc
Set-point
25
20
15
10
5
0
0
50
100
150
Time (h)
200
250
300
Feed rate (L/h)
0.06
Controller Output
0.05
0.04
0.03
0.02
0.01
0
0
50
100
150
Time (h)
200
250
300
19
MPC Set-point Step Tracking

Concentration (mM)
30
Cglc
Set-point
25
20
15
10
5
0
0
50
100
150
Time (h)
200
250
300
Feed rate (L/h)
0.06
Controller Output
0.05
0.04
0.03
0.02
0.01
0
0
50
100
150
Time (h)
200
250
300
20
PID Disturbance Compensation

Concentration (mM)
30
Cglc
Set-point
25
20
15
10
5
Disturbance
applied
0
0
50
100
Feed-rate (L/h)
0.12
150
Time (h)
200
250
300
Controller Output
0.1
0.08
0.06
0.04
0.02
0
0
50
100
150
Time (h)
200
250
300
21
MPC Disturbance Compensation

Concentration (mM)
30
Cglc
Set-point
25
20
15
10
5
Disturbance
applied
0
0
50
100
150
Time (h)
200
250
300
Feed rate (L/h)
0.12
Controller Output
0.1
0.08
0.06
0.04
0.02
0
0
50
100
150
Time (h)
200
250
300
22
PID Propagation of Measurement Noise

Concentration (mM)
30
Cglc
Set-point
25
20
15
10
5
0
0
50
100
150
Time (h)
200
250
300
0.07
Controller Output
Feed-rate (L/h)
0.06
0.05
Fast on-off
Control
0.04
0.03
0.02
0.01
0
0
50
100
150
Time (h)
200
250
300
23
PI Propagation of Measurement Noise

Concentration (mM)
30
Better setpoint tracking
Cglc
Set-point
25
20
15
10
5
0
0
50
100
0.07
150
Time (h)
250
300
Controller Output
0.06
Feed-rate (L/h)
200
0.05
0.04
Removal of
D term leads
to less abrupt
control
0.03
0.02
0.01
0
0
50
100
150
Time (h)
200
250
300
24
MPC Propagation of Measurement Noise

Concentration (m M)
30
Cglc
Set-point
25
20
15
10
5
0
0
50
100
150
Time (h)
200
250
300
0.07
Controller Output
Feed-rate (L/h)
0.06
0.05
0.04
0.03
0.02
0.01
0
0
50
100
150
Time (h)
200
250
300
25

Concentration (m M)
30
Cglc
Set-point
25
20
P = 10
15
M=1
10
=1
=0
0
0
50
100
150
Time (h)
200
250
300
0.07
Controller Output
Feed-rate (L/h)
0.06
0.05
0.04
0.03
0.02
0.01
0
0
50
100
150
Time (h)
200
250
300
26
Concentration (mM)

30
Cglc
Set-point
25
20
15
10
5
0
0
50
100
150
200
250
300
F eed -rate (L /h )
Time (h)
0.07
0.06
0.05
0.04
0.03
0.02
0.01
0
Controller Output
50
100
150
Time (h)
200
250
300
27
Concentration (mM)

30
Cglc
Set-point
25
20
P = 40
15
M=1
10
5
=1
=0
50
100
150
200
250
300
F eed -rate (L /h )
Time (h)
0.07
0.06
0.05
0.04
0.03
0.02
0.01
0
Controller Output
50
100
150
Time (h)
200
250
300
28
Concentration (mM)

30
Cglc
Set-point
25
20
15
10
5
0
0
50
100
0.07
200
250
300
Controller Output
0.06
Feed-rate(L/h)
150
Time (h)
0.05
0.04
0.03
0.02
0.01
0
0
50
100
150
200
Time (h)
250
300
29
Concentration (mM)

30
Cglc
Set-point
25
20
P = 40
15
M=1
10
=1
= 10000
0
0
50
100
0.07
200
250
300
Controller Output
0.06
Feed-rate(L/h)
150
Time (h)
0.05
0.04
0.03
0.02
0.01
0
0
50
100
150
200
Time (h)
250
300
30
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 MPC
than 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.
31

Control strategy real time application
- PID Control
Real
Time
Simulate
Configure
& Tune
32
3 L Bioreactor Experimental Set-up
33
Real Time Controller Application

Raman
Probe
USB
Spectral
acquisition
software
Text file
read/write
Calibration
model &
real-time engine
Spectral
file
Text file
read/write
File Directory
Text file
read/write
Control
model &
real-time
engine
Serial
Feed Pump
34
15 L Bioreactor Experimental Set-up
35
Real Time Controller Application

Raman
Probe
USB
Spectral
acquisition
software
TCP/IP
Calibration
model &
real-time engine
Spectral
file
OPC
ABB xPAT Data

Manager
OPC
Control
model &
real-time
engine
OPC
ABB
800xa
control
system
36
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.
In the next few weeks, preliminary experimental data for the closed
loop feedback control fed-batch runs will be gathered.
37
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 the
presence of noise and disturbances from the simulation study.
Configured and simulated control strategies are to be applied
in real time with online and at-line PAT on two different
bioreactor scales.
Real time results are to be compared to the results gathered
on a simulation basis.
38
Acknowledgements
Prof. Brian Glennon

Dr. Jessica Whelan
PAT-Bio Research Team
Enterprise Ireland
39

Mon 10.00 Comparison of Controller Technologies For Fed Batch Fermentation S Craven

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Comparative Analysis of Controller

Technologies for a CHO320 Fed Batch

Bioprocess Modelling and Control

PAT Enabled Fed-batch Bioprocess

Control Strategy Development, Simulation & Application

- Non-linear MPC (Model Predictive Control)

Control Strategy Development

Control parameters tuned via Ziegler Nichols (Closed

Control Strategy Development

Control Strategy Development

Control Strategy Development

Control Strategy Development

Control Strategy Development

Offline Tuning Rules

P = Increase until no further effect

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

= Output weight matrix

= scale on control variables = 1

= Input weight matrix

= Increase to avoid aggressive CO

Control Strategy Development, Simulation & Application

- Non-linear MPC (Model Predictive Control)

Controller Performance Simulation Results

Propagation of Measurement Noise

PID Set-point Step Tracking

PID Set-point Step Tracking

MPC Set-point Step Tracking

Feed rate (L/h)

MPC Set-point Step Tracking

Feed rate (L/h)

PID Disturbance Compensation

MPC Disturbance Compensation

Feed rate (L/h)

PID Propagation of Measurement Noise

PI Propagation of Measurement Noise

Better setpoint tracking

MPC Propagation of Measurement Noise

MPC Propagation of Measurement Noise

MPC Propagation of Measurement Noise

MPC Propagation of Measurement Noise

MPC Propagation of Measurement Noise

MPC Propagation of Measurement Noise

Simulation Study Results

tracking: MPC starts adjusting the control signal

Control Strategy Development, Simulation & Application

- Non-linear MPC (Model Predictive Control)

3 L Bioreactor Experimental Set-up

Real Time Controller Application

15 L Bioreactor Experimental Set-up

Real Time Controller Application

ABB xPAT Data

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

Conclusions and Future Work

Prof. Brian Glennon

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