Biosystems Control Design
Chapter 23
Chapter 23 addresses a variety of synthesis problems in the field
of biosystems:
• Pharmaceutical Operations
• Bioreactors
• Crystallizers
• Granulation
• Drug Delivery
• Type 1 Diabetes
• Blood Pressure Control
• Cancer Treatment
• Controlled Treatment for HIV/AIDS
• Cardiac Assist Devices
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15
Chapter23
Chapter
Figure 23.1 Schematic of a typical industrial fermentor.
2
7
Biomass (g/L)
15
Chapter23
Chapter
6.5
6
Dilution +10%
Dilution -10%
5.5
5
4.5
4
0
20
40
60
80
100
Time (h)
Figure 23.2 Step response of fermentor model to symmetric
changes in dilution of magnitude 10% from the nominal
value of D=0.202 h-1.
3
6.5
6.4
6.3
Biomass (g/L)
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Chapter23
Chapter
6.2
6.1
Dilution +10%
Dilution -10%
6
5.9
5.8
5.7
5.6
5.5
0
20
40
60
80
100
Time (h)
Figure 23.3 Step response of fermentor model to symmetric
changes in dilution of magnitude 10% from the
nominal value of D=0.0389 h-1.
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15
Chapter23
Chapter
Concentration
Controller
Solvent Addition
Steam Flowrate
Cooling
Jacket
Secondary
Temperature
Controller
Concentration
Crystallizer
Jacket
Temperature
Jacket Temperature
Setpoint
Temperature
Primary
Temperature
Controller
Figure 23.4 Flowsheet of a typical industrial crystallizer showing
concentration and temperature controllers,
including cascade control for temperature.
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Chapter23
Chapter
Hierarchy of Process Information
Plant
operating
variable
trajectories
and
parameters
Controllable,
adjustable
parameters
Intrinsic
process
properties
(MWD, CSD,
PSD)
Measurable,
trackable,
properties
Product
performance
properties
(optical,
flowability,
dustiness)
Customer
requirements
Need relationships between levels to deliver product which
consistently meets the customers needs
6
Specific Challenges in Agglomeration Control
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Chapter23
Chapter
Various process operations
– granulation
– polymerization
– spray drying
Common characteristics
– real-time analysis required for distribution
– complex heat/mass/momentum transfer problems
– multiple attributes of interest (size, shape,
concentration, etc.)
– high dimension, stiff models
– underactuated
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Chapter23
Chapter
Granulation Control – Challenges
Multivariable interactions (5th and 90th percentiles)
No target (setpoint) for 5th and 90th percentiles
– One-sided limits
Data acquisition is difficult
Suggested Operating Objectives:
– Track bulk density to reference
– Minimize control effort if PSD within limits
– Strong action if PSD out of limits
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Chapter23
Chapter
Fresh Feed
Recycle
Granules
Conveyer
Binder
Granulation
Drum
Hot Air In
Wet Granules
Dryer
Dry Granules
Screens
Product
Undersize Particles
Crusher
Oversize Particles
Figure 23.5 Process flowsheet for
granulation circuit with recycle.
9
Case Study
[Pottman, Ogunnaike, Adetayo, and Ennis, Powder Tech., 1999]
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Chapter23
Chapter
Oversized particles
Spray nozzles
Product
Feed
Granulator
Dryer
Classifier
Bulk density
measurement
Undersized particles
Correlated Process Variables
– particle size distribution (5th, 90th percentiles)
– bulk density
Manipulated Variables
– 3 spray nozzles (flow rate) [bounded]
10
Crushed Oversize Particles
y1
Binder Spray Nozzles
u1
u2
y2
u3
15
Chapter23
Chapter
y3
Fresh
Feed
Granulation
Drum
Dryer
Screens
Product
Undersize Particles
Figure 23.6 Simplified process flowsheet for granulator
example. Here u1, u2, u3 are, respectively, nozzles 1,2, and
3, and y1, y2, y3 are, respectively, bulk density, d5 and d90.
11
12
100
10
80
8
60
Input
Output
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Chapter23
Chapter
6
4
40
20
2
0
0
-20
-2
-4
0
50
100
Time
150
-40
0
50
100
150
Time
Figure 23.7 Closed-loop response of granulator to +10 step
change in set point for y1 – left plot is outputs, right plot is
inputs (dashed line, y1 and u1; dotted line, y2 and u2; dashdot line, y3 and u3).
12
60
200
50
150
40
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Chapter23
Chapter
30
Input
Output
100
20
50
0
10
-50
0
-10
0
50
100
Time
150
-100
0
50
100
150
Time
Figure 23.8 Closed-loop response of granulator to +50 step
change in set point for y1 with constraints enforced on the
inputs. The left plot is outputs, right plot is inputs (dashed line,
y1 and u1; dotted line, y2 and u2; dash-dot line, y3 and u3).
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Diabetes Mellitus
World’s most common and costly disease
15
Chapter23
Chapter
About one in every 400 to 600 children and adolescents has
type 1 diabetes mellitus (T1DM)
National Diabetes Fact Sheet, 2005, Centers for Disease Control and Prevention
Complications of T1DM reduce life expectancy by ~15 years
through micro- and macro-vascular disease
–
–
–
–
Heart disease and stroke
Blindness
Kidney disease
Nervous system disease
Evidence that intensive insulin therapy (IIT) reduces
complications
Diabetes Control and Complications Trial Research Group, 1993
Increased hypoglycemic events with IIT
Diabetes Control and Complications Trial Research Group, 1993
14
Model-Based Control Approach for Diabetes
15
Chapter23
Chapter
[Parker, Peppas, Doyle III, IEEE Trans Biomed. Eng. 1999]
Desired
Glucose Level
Model-based
Algorithm
Insulin
Controller
Glucose
Patient
-
Model
Kalman Filter
Update
Filter
-
Compartmental Model
15
Meal Disturbance
15
Chapter23
Chapter
Glucose
Setpoint
Gsp
Insulin
Pump
Controller
Gm
Patient
Insulin
G
Blood
Sugar
Glucose
Sensor
Figure 23.9 Block diagram for artificial b-cell, illustrating the
meal as the most common disturbance. G denotes the blood
sugar of the patient, Gm is the output of the glucose sensor, and
Gsp is the glucose setpoint.
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700
Glucose (mg/dL)
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Chapter23
Chapter
600
500
400
300
200
100
0
0
50
100
150
200
250
300
350
400
Time (min)
Figure 23.10 Open-loop response of patient’s blood glucose
when the insulin pump is turned off.
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180
170
Glucose (mg/dL)
15
Chapter23
Chapter
160
150
140
130
120
110
100
90
80
0
50
100
150
200
250
300
350
400
Time (min)
Figure 23.11 Open-loop response of the patient’s blood glucose
to a constant infusion rate of 15 mU/min from her insulin
pump.
18
180
Glucose (mg/dL)
15
Chapter23
Chapter
160
140
120
100
80
60
40
0
50
100
150
200
250
300
350
400
Time (min)
Figure 23.12 Open-loop response of patient’s blood glucose to
a constant infusion rate of 25 mU/min from her insulin pump.
19
25
Mean Arterial Pressure
Cardiac Output
20
15
15
Chapter23
Chapter
10
5
0
-5
-10
-15
0
10
20
30
40
50
Time (min)
Figure 23.13 Closed-loop response of patient’s mean arterial
blood pressure and cardiac output to a -10 mmHg change in the
MAP set point.
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