Control of Glucose

Concentration by
Insulin in the Liver
52:185 Process Dynamics and Control
Design Challenge II
ICE-COLD Inc.

Aiman M. Alam
Valerie A. Perrin
December 16th, 2004
 Outline
• Glucose Regulation
• Model
• Process Variables
• Block Diagrams
• Stability Analysis
– Routh
– Root-locus
– Bode
– Nyquist
– Simulink
• Controller Tuning
– Cohen & Coon
– Internal Model Control
– Tyreus-Luyben
– Ziegler-Nichols
• Fine Tuning
• Conclusions
 What is Glucose?

• Monosaccharide commonly found in the human body

• Hexose (six carbon molecule)
• Exists as a pyranose ring
• Molecular formula: C6H12O6

C6H12O6 + 6O2 → 6CO2 + 6H2O + Energy

• Blood glucose concentrations in a

healthy adult range from 70-110 mg/dL

Sources:
http://www.psrc.usm.edu/macrog/images/glucose.gif, Retrieved October 5th, 2004
Nelson, D., Cox, M. (2004). Lehninger Principles of Biochemistry (4th Ed.). W. H.Publishers.
 How is Glucose Regulated?

When blood glucose levels are high:

• Insulin produced by beta cells in the pancreas
• As blood glucose concentration rises, insulin concentration
rises to allow for increased glucose uptake by the organs
• High blood glucose levels cause the liver to convert glucose
Insulin
to glycogen
When blood glucose levels are low:
• Glucagon produced by alpha cells of the pancreas
• As blood glucose concentration drops, glucagon concentration increases
• Low blood glucose levels cause the liver to convert glycogen to glucose

Glucagon

Sources:
http://www.bodybuilding.com/fun/glycogen.jpg, Retrieved October 5th, 2004
http://www.cryst.bbk.ac.uk/PPS95/course/8_folds/1gcn.gif, Retrieved October 5th, 2004
http://www.sickkids.on.ca/HowellLab/images/structures/insulin-t6_tmb.gif, Retrieved October 5th, 2004
Nelson, D., Cox, M. (2004). Lehninger Principles of Biochemistry (4th Ed.). W. H.Publishers.
 Overview of Blood Glucose Regulation

Sources:
http://www.fda.gov/cber/genetherapy/pancislet-img1.gif, Retrieved October 6th, 2004
 Model
F1, Ci0, Cg0
Assumptions:
• F1 = F2 = F = 1 L/min
• Perfectly mixed CSTR
• Constant density
• Constant volume = 1 L
V, ρ
F2, Ci, Cg • k1 = 0.0005 L/mg·min
Liver
• k2 = 0.05 min-1
AT
AC Cg = f(Ci0, Cg0)

Component Balances:

d  VCg  d  Cg 
 F1Cg 0  F2 Cg  k1 VCgCi V  FCg 0  FCg  k1VCgCi
dt dt

d  VCi  d  Ci 
 F1Ci 0  F2 Ci  k 2 VCi V  FCi 0  FCi  k 2VCi
dt dt
Process Variables
• Controlled variable: Cg
• Manipulated variable: Ci0
• Disturbance variable: Cg0

Variable Steady state value

Ci0 10 mg/L
Ci 9.5 mg/L
Cg0 1000 mg/L
Cg 995 mg/L
 Open Loop System

Cg0’(s) CgCg0’(s)
Gd
mg/ L mg/ L

Ci0’(s) CgCi0’(s) + Cg’(s)

Gp +
mg/ L mg/ L mg/ L
 Closed Loop System

Cg0’(s) CgCg0’(s)
mg/ L
Gd
mg/ L

Cgsp’(s) ~
Cgsp’(s) E’(s) P’(s) Ci0’(s) CgCi0’(s) +
Gm + Gc Gv Gp + Cg’(s)
mg/ L mA mA mA mg/ L
- mg/ L mg/ L

Cgm’(s) Cg’(s)
Gm
mA mg/ L

Gc K m Gv G p Gd
Cg ' ( s )  Cg sp ' Cg 0 '
1  Gc Gv G p Gm 1  Gc Gv G p Gm
Closed Loop Transfer Functions

Gd

Gv Kv

Gp

Gm Kme-θs
 Stability Analysis

Routh:

Root-locus:

Bode & Nyquist:

 Routh
0.0007906 1.118126112 22.843112
0.0503 1.043054  
1.10173171 22.843112  
0.00014262    
0    
      22.84788
Kc     0.0007906 1.118129888 8

-4562     0.0503 1.042821  

1.10173915 22.847888  
-0.0003014    
0    
     
Kc    
-4563    
 Root-locus
Root Locus
250

200

150

100

50
Imaginary Axis

-50

-100

-150

Root Locus
-200
5
Kc = 4660
-250
-60 -50 -40 -30 -20 -10 0 10 20 30 40
4
Real Axis

Imaginary Axis

Kc = 0
-1

-2

-3

-4

-5

-1.2 -1 -0.8 -0.6 -0.4 -0.2 0 0.2 0.4 0.6

Real Axis
 Bode (Kc = -4572)
2
Bode Diagram
10

1
10

10
0 AR = 1.0
Magnitude (abs)

-1
10

-2
10

-3
10
0

-90

-180
φ = -180°
Phase (deg)

-270

-360

-450

-540
-2 -1 0 1 2
10 10 10 10 10
Frequency (rad/sec)
 Nyquist (Kc = -4572)
Nyquist Diagram

10

5
Imaginary Axis

-5

-3
x 10 Nyquist Diagram

-10

-15
-5 0 5 10 15 20
Real Axis

Imaginary Axis

-1

-2

-3
-1.002 -1.001 -1 -0.999 -0.998 -0.997
Real Axis
 Unit Step in Set Point (Cgsp)
Cg

Cg

Stable system at Kc > critical Kc

Cg

Sustained oscillatory behavior at

Kc = critical Kc

Unstable system at Kc < critical Kc

 Unit Step in Disturbance (Cg0)
Cg

Cg

Stable system at Kc > critical Kc

Cg

Sustained oscillatory behavior at

Kc = critical Kc

Unstable system at Kc < critical Kc

 Unit Impulse in Set Point (Cgsp)

Stable system at Kc > critical Kc

Sustained oscillatory behavior at Kc =

critical Kc

Unstable system at Kc < critical Kc

 Unit Impulse in Disturbance (Cg0)

Stable system at Kc > critical Kc

Sustained oscillatory behavior at

Kc = critical Kc

Unstable system at Kc < critical Kc

Controller Tuning
 Cohen & Coon

Controller Type Kc τI τD

P -1804.3 --- ---

PI -1575.5 0.525 ---

PID -2362.4 0.467 0.071

 Unit Step
Set Point
P
(Cgsp):
PI
PID

Disturbance (Cg0):

P
PI
PID
 Unit Impulse
Set Point
P
(Cgsp): PI
PID

Disturbance (Cg0):
P
PI
PID
Internal Model Control (IMC)

Controller Type Kc τI τD

PI -320 1.55 ---

PID -375.8 1.68 0.094

 Unit Step
Set Point
(Cgsp):

PI
PID

Disturbance (Cg0): PI
PI
PID
 Unit Impulse
Set Point PI
PI
(Cgsp): PID
PID

Disturbance (Cg0):
PI
PID
 Tyreus-Luyben

Controller Type Kc τI τD

PI -1415.2 3.102 ---

PID -2054.3 3.102 0.224

 Unit Step
Set Point
(Cgsp):

PI
PID

Disturbance (Cg0):
PI
PID
 Unit Impulse
Set Point
(Cgsp): PI
PID

Disturbance (Cg0):
PI
PID
 Ziegler-Nichols

Controller Type Kc τI τD
P -2282.5 --- ---
PI -2054.3 1.175 ---
PID -2739 0.705 0.1763
 Unit Step
Set Point
P
(Cgsp): PI
PID

Disturbance (Cg0):
P
PI
PID
 Unit Impulse
Set Point
(Cgsp): P
PI
PID

Disturbance (Cg0):
P
PI
PID
Fine Tuning
 Unit Step
Set Point
(Cgsp):

Cohen & Coon

IMC
Tyreus-Luyben
Ziegler-Nichols

Disturbance (Cg0):
Cohen & Coon
IMC
Tyreus-Luyben
Ziegler-Nichols
 Unit Impulse
Set Point
(Cgsp): Cohen & Coon
IMC
Tyreus-Luyben
Ziegler-Nichols

Disturbance (Cg0): Cohen & Coon

IMC
Tyreus-Luyben
Ziegler-Nichols
 Ramp
Set Point
(Cgsp): Cohen & Coon
IMC
Tyreus-Luyben
Ziegler-Nichols

Disturbance (Cg0):
Cohen & Coon
IMC
Tyreus-Luyben
Ziegler-Nichols
 Tyreus-Luyben PID Controller
Unit Step in
Disturbance (Cg0): Kc = -2054.3
Kc = -3000
Kc = -1500
Kc = -2500

Unit Impulse
Kc = -2054.3
Disturbance (Cg0): Kc = -3000
Kc = -1500
Kc = -2500
 Conclusions

• Nyquist is the sweetest method for obtaining critical Kc values

• System is stable at -4752 < Kc < 0
• Best controller is PID using the Tyreus-Luyben method
• Fine tuning led to even better results
 Andre 3000

What’s cooler than being cool? ICE-COLD!

 Questions?
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Acknowledgements:
• Dr. V.G.J. Rodgers
• The Classes of ’04,
’05, and ’06 & Jerry