Proceedings of the 9th IFAC Symposium Advances in Control

Education
The International Federation of Automatic Control
Nizhny Novgorod, Russia, June 19-21, 2012

Systems and Control for Biomedical Engineering Students

António Dourado, Alberto Cardoso, Jorge Henriques, César Teixeira

Department of Informatics Engineering
University of Coimbra, Polo II, 3030-290 Coimbra, Portugal
e-mail: {dourado, alberto, jh, cteixei}@dei.uc.pt
Phone: + 351 239 790000, Fax: + 351 239 701266

Abstract: Developments of skills in Systems and Control by Biomedical Engineering Students, a

challenging task for instructors, is discussed. The syllabus and its organization in the University of
Coimbra are described. From PID and fuzzy to optimal control, space has been created inside several
courses mixed with other subjects of biomedical engineering. The approach is based on a “learning-by-
doing” perspective. The syllabus and the practical exercises are presented and commented. The practical
exercises cover most of the topics. ©IFAC 2012.
Keywords: curricula development, biomedical engineering, systems and control, learning strategies,
control education.


1. INTRODUCTION - The general systems concepts introduced by the general

Biomedical Engineering is quite a new engineering field. It is
transdisciplinary, passing by Mathematics, Physics, Chemist
and Biochemist, Physiology, Anatomy, Informatics, Signal
Processing, and also by Systems and Control, Biomedical
Engineering students have distinct characteristics with
respect to other engineering students: they are between
medicine and engineering, or by other words, they are the
engineers of human life and its preservation. They have
usually high-level intellectual capabilities, but need to
develop systems thinking skills. This is the main objective of
systems and control concepts and exercising.
In the University of Coimbra the Biomedical Engineering
degrees (at B.Sc. and M.Sc. levels) include systems and
control concepts spread out in several courses. In this paper
the contents, methods and experiences are described in the
following. Section 2 describes the syllabus supported on the
learning methodology of section 3, plasticized in the
examples of section 4. Bibliography in section 5 and
conclusions complete the presentation.
2. THE ORGANIZATION OF CONCEPTS (SYLLABUS)
systems theory of Bertalanfy (1969) and well developed in
Flood and Carson (1993).
- The description of linear systems by differential equations
and Laplace Transform.
- Transfer function as a tool for systems analysis and
understanding, using the connection between the dynamics
and the transfer function characteristics.
- State space representation, state equations, eigenstructure
and its connections with stability and dynamic properties.
- Modelling of nonlinear systems by differential equations,
singularity points, linearization, and local stability. Phase
curves in state space and their importance as a portrait of
fundamental properties of the nonlinear system.
- Chaotic behaviour of biological and physiological systems
and the Feigenbaum (1979) constant.
Then Matlab©/SIMULINK© environment (Mathworks Inc.)
is extensively used for practical work. Biological and
physiological applications are used whenever possible.

2.2 Neural and Fuzzy Computation

2.1 The basic concepts
The first course where system concepts are introduced is
“Computational Models of Physiological Processes”, at the
5th semester of 6 semesters B.Sc. degree. This is a mandatory
course for all Biomedical Engineering Students and is
intended to develop skills for mathematical modelling and
simulation of the multiplicity of physiological systems in
human body. The first part of the course (15 hour of theory
and 16 hours of exercises) is filled with:
Modelling of complex nonlinear systems by data driven
paradigms such as artificial neural networks and fuzzy rule
based systems is studied in the “Neural and Fuzzy
Computation” course, at M.Sc. level, a specialization course
only mandatory for part of the students (speciality of
Bioinformatics and Clinics Informatics). It includes:
- Artificial Neural Networks (15h): multilayer, radial basis
functions and recurrent architectures with and without time-
delays, and its use as classifiers of large data sets.

978-3-902823-01-4/12/$20.00 © 2012 IFAC 413 10.3182/20120619-3-RU-2024.00107

9th IFAC Symposium Advances in Control Education
Nizhny Novgorod, Russia, June 19-21, 2012
- Fuzzy logic and fuzzy ruled based systems (15h). Building
of fuzzy models from data using clustering (k-means and
subtractive).
- Fuzzy control, the first contact with control the students
have. Experience shows that this is very positive, since fuzzy
control can be taught almost like a game. This creates in
student’s minds an image of control much more attractive
than if they had started with the classical control based on
Laplace transform. The fundamental concepts of control
systems (open-loop, closed-loop, reference, disturbances,
error, etc.) are introduced The students are given a black box
(where a transfer function is inside), apply inputs and read
outputs, try to build up a mental image of the system and then
write the fuzzy rules, defining previously the membership
functions of the antecedents and consequents. Mamdani and
Takagi-Sugeno types are studied and experienced. Usually
the students succeed to get a good controller. The Matlab
Fuzzy Logic toolbox has facilities enabling this exercising.
2.3 Digital and optimal control
The third course where students contact with control is the
“Algorithms for Diagnosis and Self-Regulation”. The “bionic
man” with artificial organs controlled by the central nervous
system, a fusion of biology and electronic, is the motivation
for advanced control theories. The following subjects are
studied:
- Discretization techniques, Z-Transform (review), discrete
transfer function and its recursive identification (5h).
- The synthesis of digital controllers in an “outward-to-
inward” approach: given the desired closed-loop transfer
function, given the process (open loop) discrete transfer
function, derive the digital controller from them to shape the
closed-loop, obeying to the constrains of stability and
realizability. Diophantine equations are introduced and the
discrete PID control is looked as a particular case (5h).
- Pole-zero cancellation controllers: advantages and
drawbacks (the imperfect cancellation of instable poles and
zeros) (5 hours).
- State feedback, in discrete state space, and how it shapes the
closed loop characteristic equation by a proper calculation of
the feedback gains. The regulator problem is treated, and is
faced as a way to surpass the pole-zero cancellation
controllers (5 hours).
- Optimal control is introduced for the regulator problem,
including the Ricatti equation in recursive and steady-state
versions. It is presented as a special case of state feedback (5
hours).
The syllabus organization is illustrated by Fig. 1.
3. LEARNING METHODOLOGY
The systems and control program is extensive, including
most of the control techniques with practical relevance. If
they would be studied with all the details and all
414
mathematical developments, it would not fit in the available
space and most of the students would not be able to absorb
them. Instead, a more “learning – by – doing“ approach is
followed: learn the most important theoretical aspects to
understand the method, implement and practice with it, and if
needed come back to theory. The “learning-by-doing”
approach is not an empirical one, it needs sound
mathematical support, but instead of putting the accent on
abstract theoretical demonstrations, it works for stimulating
the student’s intellectual curiosity by practical work
involving several perceptions. The flexibility of
Matlab/SIMULINK environments allows the fast “mise-en-
oeuvre” and experimentation of controllers following the
cycle: experiment-analyse the results-check with the theory.
This allows the development of a mental image of the field
that supports the development of the student skills, finally the
most important goal of their education.
4. SOME EXPERIMENTAL EXERCISES
In group-working (an education goal by itself), students carry
on computational experiments with several levels of
complexity. Some examples of practical exercises, using the
Matlab and Simulink software, are briefly described in the
following.
4.1 Simulation of the evolution of the population of a
biological species
Defining a biological species (insects, for example) as a
system whose individuals live an integer number of years,
and considering that the population grows with a given
limitation, the population’s temporal evolution is simulated
using a simplified model in the form of the non-linear
difference equation (1) (Flood (1993)),
x k +1 = Ax k (1 - x k ) = f (x k ), x k Î [0,1] (1)
where xk is a fraction of the population’s maximum value in
year k. and A is a positive constant that depends on
environmental conditions (the availability of food, water,
climate, etc.).
The students, after creating the model, simulate it and analyze
the influence of the values of the initial population and of the
constant A on the temporal evolution of the population.
4.2 Simulation of the ingestion and excretion of a drug
The main objectives of this work are to use methods of
numerical integration of functions and to consider numerical
methods to simulate continuous systems modelled by
differential equations. As example, the system considers the
ingestion and excretion of a drug shown in Fig. 2 (Bruce(
2001)).
Figure 2: System of ingestion and excretion of a drug.
9th IFAC Symposium Advances in Control Education
Nizhny Novgorod, Russia, June 19-21, 2012

The drug is taken orally, at a rate u(t), goes to the intestines,
where it reaches a quantity x1(t), and then it is absorbed by
the bloodstream. The bloodstream, where the drug reaches a
quantity x2(t), passes through the kidney (where it is assumed
there is no absorption) that expels the drug at a rate y(t),
passing it into the urine. In this approach, for reasons of
simplicity, other physiological actions are disregarded and
the elimination of the drug by cellular metabolism is ignored.
In medical terminology the process is multi-compartmental.
Assuming the kidney is only one transition element, the
process has only two compartments. Being necessary to find
a compartmental model of the process, an equivalent fluidic
system can be developed, as shown in Fig. 3.
where VL(t) is the lungs volume, P(t) is the differential
pressure between the pressure of the forced ventilation and
the atmospheric pressure, and a and b are coefficients
depending on the total compliance (lungs + chest) and on the
resistance to the flux of the forcing air into the lungs.
The other considered system describes the functioning of the
skeletal muscle using a model with a 2nd order differential
equation (4) ((Bruce (2001)),
dy (t ) d 2 y (t )
Ky (t )  B M  u (t ) (4)
dt dt 2
where y(t) is the output, K the elastic constant, B the viscous
friction constant, M the mass and u(t) the input (applied
force).
Special emphasis is given to the relation between the transfer
function and the state space representations and to the
introduction of feedback control for regulation and tracking
purposes.

4.4 Study of the state space representation of systems and the

Figure 3: Fluidic system equivalent to the ingestion and
excretion of a drug.
Applying the fluidic systems principles, the mass balance of
each compartment provides the differential equations for the
mathematical model of the overall system. Assuming that
x1(t) and x2(t) are the corresponding levels (quantities) and
the fluidic resistances are the following:
dx 1(t )
= -k1x 1(t ) + k1x 2 (t ) + u(t )
dt
dx 2 (t )
= k1x 1(t ) - (k1 + k2 )x 2 (t )
dt
where k1 and k2 are parameters related with the fluidic
resistances R1 and R2, respectively, and u(t) represents the
flux of ingestion of drug.
The model is simulated using different numerical methods
(Euler, Runge-Kutta, etc.) for several operational conditions.
The practical work includes the analysis of the solution’s
sensitivity to the value of the discretization interval
considered by the numerical method.
4.3 Study of the dynamics of artificial ventilation of a patient
This work aims to introduce some basic concepts about linear
and time-invariant systems as the transfer function and the
state space representations, the transient and steady state
response, the poles and zeros, the system’s stability and the
characteristics of first and second-order systems.
One of the case studies is a system modelling the breathing
dynamics of a ventilated patient, given by the following
equation (Bruce (2001)):
· described by the model (6).
VL (t )+ aVL (t ) = bP (t )
phase curves
This work reinforces the study of the state space
representation and introduces the phase plane to analyse
nonlinear systems.
The exercises are based on three case studies: the ingestion
and excretion of a drug (already described); the
interrelationship between the blood glucose and the insulin in
blood; and the epidemiologic study of a population affected
by two competing diseases.
The interrelationship between the blood glucose and the
(2) insulin is described by the model (5) (Marmarelis (2004)),
dG (t )
= -p1[G (t ) - Gb ] - X (t )G (t )
dt (5)
dX (t )
= -p2X (t ) + p3 [I (t ) - I b ]
dt
where G(t) is the plasma glucose concentration, X(t) is the
action of insulin, I(t) is the plasma insulin concentration, Gb
is the baseline plasma glucose concentration, p1 and p2 are the
characteristic parameters describing the kinetics of the
glucose and insulin action and p3 is the parameter that
describes the modulating influence of the insulin action in the
glucose absorption dynamics.
Note that this model does not take into account neither the
insulin pancreatic secretion, induced by the variations of the
plasma glucose concentration, nor the eventual production of
glucose by internal organs. The physiological parameters of
the glucose’s efficiency SG = p1 and the insulin sensitivity
SI=p3/p2 are widely used for clinical purposes.
The third example describes the situation of a population
where coexist two diseases that compete with each other,
(3)

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9th IFAC Symposium Advances in Control Education
Nizhny Novgorod, Russia, June 19-21, 2012

dS error dependence on the considered system order and finally

= -m1I 1S - m2I 2S + d1I 1 + d2I 2 proposes a discrete transfer function for the given time-series.
dt
dI 1 (6)
= m1I 1S - d1I 1 - g I 1I 2 4.6 Development of a fuzzy controller for a process
dt
dI 2 A fuzzy controller is developed and implemented using the
= m2I 2S - d2I 2 + g I 1I 2
dt Matlab Fuzzy Logic toolbox for an experimental benchmark
where S is the fraction of the healthy population and therefore process PT326 (from Feedback). The PT326 process is
susceptible to any disease (an individual cannot have both similar to a hair dryer: air is forced to circulate by a fan
simultaneously), I1 is fraction of the population infected by blower through a tube and heated at the inlet. This is a
the disease 1 and I2 is the fraction of the population infected nonlinear process with a pure time delay, which depends on
by the disease 2. the position of the temperature sensor element and the air
This three order system can be reduced to a second order one, flow rate. The system input is the voltage on the heating
considering that the population is constant and so the device, which consists of a mesh of resistor wires, and the
variables are linked by (7), output, is the outlet air temperature.
Considering mainly the qualitative behavior of the heating
S  I1  I 2  1 (7) process, and based on the fuzzy system theory, students
establish a set of rules in the Mamdani form
resulting in the system (8).
IF (y(k) is OUT ) AND y(k) is (VOUT) THEN u(k) is INP
dI1
 1 I1 (1  I1  I 2 )  1 I1   I1 I 2 where y(k) is the output temperature, y(k)=y(k)-y(k-1) is the
dt (8) variation of the output temperature and u(k) is the voltage
dI 2 supplied to the heating device. The fuzzy sets OUT, VOUT
 2 I 2 (1  I1  I 2 )   2 I 2   I1 I 2
dt and INP are described by linguistics terms, such as
{Negative, Normal, Positive). Although this is not a
This example promotes the study of the singular points of a biomedical device, it can be compared to the heating systems
nonlinear system, the linearization of the system around the of for example an incubator.
singular points and the stability analysis, supported on the
phase curves using the free Matlab pplane application
(http://math.rice.edu/~dfield/index.html) also available in 4.7 Digital Control of a process given by a continuous
Java applet (Polking and Arnold, 1999). Fig. 4 shows a phase transfer function.
plane of (8).
This is the occasion to discuss the analog-to-digital (A/D)
I1 ' = miu1 I1 (1 - I1 - I2) - delta1 I1 - gama I1 I2
I2 ' = miu2 I2 (1 - I1 - I2) - delta2 I2 + gama I1 I2
miu1 = 0.5 delta1 = 0.8
delta2 = 0.2
miu2 = 0.5
gama = 0.5
and digital-to-analog (with zero order hold, ZOH) conversion
as in Fig. 4.
1

0.8

0.6

0.4

0.2

0
I2

-0.2
Figure 5. The closed digital control-loop with ZOH.
-0.4

-0.6
Given the G(s), the students:
-0.8 (i) Develop and implement the controller D(z) of
-1 minimum settling time.
-1 -0.8 -0.6 -0.4 -0.2 0 0.2 0.4 0.6 0.8 1 (ii) Develop and implement a deadbeat controller.
I1
(iii) Derive a controller by pole-zero cancellation,
Figure 4. Phase portrait for the system (8) for given values of considering the closed-loop behavior specified by
the constants. The nonlinear system has 3 singularities with the damping factor and the settling time.
different stability properties (attractor, repelling, saddle
point). 4.8 Discrete State variable feedback of a second order system
given by a continuous state equation.
4.5 Recursive identification of discrete linear systems.
Considering a continuous time process represented in state
A file is given with input and output time series of a system space, considering the ZOH and a given sampling period,
(not known by the student) discretized with a given sampling discrete state feedback is derived and implemented. Stability
frequency. Using the Matlab Systems Identification toolbox, analysis and the closed loop-steady state error are addressed.
each group studies the recursive identification problem, the

416
9th IFAC Symposium Advances in Control Education
Nizhny Novgorod, Russia, June 19-21, 2012
4.9 Optimal control of a discrete system for a finite horizon,
with the recursive solution of the Ricatti equation.
A discrete time process, known to be controllable and
observable, is given. The Linear Quadratic Regulator is
implemented with the study of the relative influence of the Q
(state) and R (input) penalty matrices.
5. BIBLIOGRAPHY OF THE COURSES
The courses are developed accordingly with the instructors’
experience. However there are some books that the students
must use as complementary knowledge. For example
Bertalanfy (1969), Hoppensteadt and Peskin (2000), Khoo
(1999), Ogata (2002), Bronzino (2000), Elizabeth and
Rhodes (2003), Baura (2002), Flood and Carson (2003),
Ross(2004), Hagan and Coll. (1995).
6. STUDENTS FEEDBACK
Students in general express a positive evaluation of the three
courses referred above. The main difficulty arises from the
lack of knowledge in computer programming. Since the
examples are mainly from biomedical problems, they are
stimulated by them and they succeed to overcome these
difficulties. Students have a solid mathematics and physics
background to attain the learning objectives of these courses.
The University has a quality management and control system
with mandatory anonymous answers by the students, every
semester, for each of the individual courses. The average
results for the three courses involving Systems and Control is
usually 4 into 5, meaning a very positive opinion about them.
The students are inquired about several aspects: importance
of the course for their perception of the professional life,
quality of study and bibliographical materials, experienced
quality of learning, coherence between delivered theory and
practical exercises, their involvement in learning activities,
adequacy of the number of students per class, global
appreciation of the lecturers, fairness of evaluation.
7. CONCLUSIONS
At the end, the Biomedical Engineering students of the
University of Coimbra learned, experienced and developed
skills in the main control techniques with practical
rd
st
Mandatory, 3  year, B.Sc. Optional, 1  year, M.Sc.
Computational Models of  Neural and  Fuzzy  Algorithms for Diagnosis
Physiological Processes  Computation
General Systems Theory  Neural networks in 
Differential equations. biomedical applications.
Transfer function. Fuzzy Logic.
State equations. Fuzzy Control.
Nonlinear and chaotic 
systems.
Figure 1. The organization of systems and control curricula in the
Biomedical Engineering Degree at University of Coimbra.
417
importance. Control is very important in the understanding of
the feedback paths in physiological systems. It is decisive in
building artificial organs such as artificial arms and legs, and
in controlling artificial devices such as pacemakers or insulin
injection devices for diabetic patients. Control is in the center
of future medicine.
REFERENCES
Allman Elizabeth S. and John A. Rhodes (2003).
Mathematical Models in Biology: An Introduction by
Cambridge University Press.
Baura G D (2002). System Theory and Practical Applications
of Biomedical Signals, (Biomedical Engineering S.),
John Wiley and Sons.
Bertalanffy, L. (1969). General Systems Theory, George
Brazillier, NY.
Boyd, D.W. (2001). Systems Analysis and Modelling, A
Macro-to-Micro Approach with Multidisciplinary
Applications, Academic Press.
Bronzino, Joseph D. (Editor) (2000). The Biomedical
Engineering Handbook (Electrical Engineering
Handbook), Springer Verlag.
Bruce, Eugene N. (2001). Biomedical Processing and Signal
Modelling, John Wiley and Sons.
Feigenbaum, M.J. (1979)."The Universal Metric Properties of
Nonlinear Transformations." J. Stat. Phys. 21, 669-706.
Flood, R. L. and E. R. Carson (1993). Dealing with
Complexity, An Introduction to the Theory and
Applications of Systems Science, Plenum Press, NY.
Hagan Martin T., H,. B. Demuth and M. H. Beale (1995),
Neural Network Design, PWS Publishing.
Hoppensteadt Frank C., Charles S. Peskin (2000). Modeling
and Simulation in Medicine and the Life Sciences (Texts
in Applied Mathematics), Springer Verlag.
Marmarelis, Vasilis Z. (2004). Nonliner Dynamic Modeling
of Physiological Systems, IEEE Series in Biomedical
Engineering.
Michael Khoo. M. (1999). Physiological Control Systems:
Analysis, Simulation, and Estimation, J. Wiley & Sons.
Ogata, K. (2002). Modern Control Engineering, 4th ed.,
Prentice Hall
Polking J. and David Arnold (1999). Ordinary Differential
Equations using MATLAB, Prentice Hall.
Ross T. (2004). Fuzzy Logic With Engineering Applications,
2nd Ed., McGraw Hill.
st
Optional, 1  year, M.Sc.
 
and Self‐Regulation  
Systems identification.
Digital Control.
Optimal Control.