CH 2

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The study of classical physiology and of many medical specialties is structured
around human physiological systems. (The term classical physiology is used here to
mean the study of whole organs or organ systems as opposed to newer
molecularbased approaches.) For example, cardiologists specialize in the
cardiovascular
system, neurologists in the nervous system, ophthalmologists in the visual system,
nephrologists in the kidneys, pulmonologists in the respiratory system,
gastroenterologists in the digestive system, and endocrinologists in the endocrine
system.
There are medical specialties or subspecialties to cover most physiological systems.
(Another set of medical specialties is based on common tools or approaches,
including surgery, radiology, and anesthesiology, whereas one specialty, pediatrics,
is based
on the type of paFigure 1.1 A classic systems view of a physiological system that
receives an external
input, or stimulus, that evokes an output, or
responsetient.

Figure 1.6 shows an analog model of the muscle skeletal muscle that uses
mechanical elements. The muscle’s force originates at the contractile element, but
this force, Fo, is modified by the muscle mechanical processes before it appears at
the output, F. The internal mechanical processes include the tissue viscosity, a sort
of internal friction, the parallel elastic element which represents the elastic properties
of the
Figure 1.5 An early analog model of the cardiovascular system that used electrical
elements to represent mechanical processes. In this model, voltage is equivalent to
blood pressure and current to blood flow
Figure 1.6 A mechanical analog model of skeletal muscle. The various elements
correspond to specific properties of real muscle.
sarcolemma, and the series elastic element that reflects the elastic behavior of muscle
tendons. In real muscle, these elements are nonlinear, but are often approximated as
linear providing a linearized skeletal muscle model. (For a detailed look at skeletal
muscles, see Devasahayam, 2000.) This basic model of skeletal muscle shown in
Figure 1.6 has been used with additional mechanical elements to construct a
mechanical model of the eye movement system including a pair of extraocular
muscles.
4.1 Electronic Noise Johnson or thermal noise is produced by resistance sources and
the amount of noise generated is related to the resistance and to the temperature: V
kTRBW J = 4 volt
Example 1.5: A 20-mA current flows through a diode (i.e., a semiconductor) and a
200-W resistor. What is the net current noise, in? Assume a bandwidth of 1 MHz (1
¥ 106 Hz). V VVV V T N = + + +◊◊◊ 1 2 2 2 3 2 2 A Hz I qI BW s d = 2 amps V
Hz ( ) A Hz 26 CHAPTER 1 BIOENGINEERING SIGNALS AND SYSTEMS
Solution: Find the noise contributed by the diode using Eq. 1.10, the noise
contributed by the resistor using Eq. 1.9, then combine them using Eq. 1.11. Note
that most of the current noise is coming from the diode, so the addition of the
resistor’s current noise does not contribute much to the diode noise current. The i ii
nT nd nR = += ¥ +¥ =¥ 2 2 15 17 8 -- - 6 4 10 8 5 10 8 1 10 . . . amps i kT BW R nR
= =¥ ( ) = ¥ - - 4 1 7 10 10 200 9 22 10 20 6 9 . . amps i qI BW nd d = =¥ ( )( ) ¥ = ¥
-- - 2 2 1 602 10 20 10 10 8 00 10 19 3 6 8 . . amps
mathematics in this example could be simplified by calculating the square of the
noise current (i.e., not taking the square roots) and using those values to get the total
noise before taking the square roots.

The relative amount of signal and noise present in a waveform is usually quantified
by the signal-to-noise ratio (SNR). As the name implies, this is simply the ratio of
signal to noise, both measured in RMS (root-mean-squared) amplitude. This
measurement is rigorously defined in the next chapter. The SNR is often expressed
in decibels (dB) where: [Eq. 1.12] To convert from decibel scale to a linear scale:
[Eq. 1.13] For example, a SNR of 20 dB means that the RMS value of the signal is
10 times the RMS value of the noise (10(20/20) = 10), +3 dB indicates a ratio of
1.414 (10(3/20) = 1.414), 0 dB means the signal and noise are equal in RMS value,
-3 dB means that the ratio is 1/1.414, and -20 dB means the signal is 1/10 of the
noise in RMS units. Figure 1.12 shows a sinusoidal signal with various amounts of
white noise. Note that is it is difficult to detect the presence of the signal visually
when the SNR is -3 dB, and impossible when the SNR is -10 dB.

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A measuring system exists to provide information about the physical value of some
variable being measured. In simple cases, the system can consist of only a single unit
that gives an output reading or signal according to the magnitude of the unknown
variable applied to it. However, in more complex measurement situations, a
measuring system consists of several separate elements as shown in Figure 1.2.
These components might be contained within one or more boxes, and the boxes
holding individual measurement elements might be either close together or
physically separate. The term measuring instrument is commonly used to describe a
measurement system, whether it contains only one or many elements, and this term
will be widely used throughout this text. The first element in any measuring system
is the primary sensor: this gives an output that is a function of the measurand (the
input applied to it). For most but not all sensors, this function is at least
approximately linear. Some examples of primary sensors are a liquid-in-glass
thermometer, a thermocouple and a strain gauge. In the case of the mercury-in-glass
thermometer, the output reading is given in terms of the level of the mercury, and so
this particular primary sensor is also a complete measurement system in itself.
However, in general, the primary sensor is only part of a measurement system

2.2.6 Sensitivity of measurement The sensitivity of measurement is a measure of the

change in instrument output that occurs when the quantity being measured changes
by a given amount. Thus, sensitivity is the ratio: scale deflection value of measurand
producing deflection The sensitivity of measurement is therefore the slope of the
straight line drawn on Figure 2.6. If, for example, a pressure of 2 bar produces a
deflection of 10 degrees in a pressure transducer, the sensitivity of the instrument is
5 degrees/bar (assuming that the deflection is zero with zero pressure applied)
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2.1 BASIC SIGNALS: THE SINUSOIDAL WAVEFORM Signals are the

foundation of information processing, transmission, and storage. Signals also
provide the interface with physiological systems and are the basis for
communication between biological processes (Figure 2.1). Given the ubiquity of
signals within and outside the body, it should be no surprise that understanding at
least the basics of signals is fundamental to understanding, and interacting with,
biological processes. A few signals are simple and can be defined analytically, that
is as mathematical functions. For example, a sinusoidal signal is defined by the
equation: [Eq. 2.1] where A is the signal amplitude, or more accurately the peak-to-
peak amplitude, wp is the frequency in radians per second, fp is the frequency in
hertz, and T is the period in seconds, and t is time in seconds. Recall that frequency
can be expressed in either radians or hertz (the units formerly known as cycles per
second) and are related by 2p: [Eq. 2.2] Both forms of frequency are used in the text,
and the reader should be familiar with both. The frequency in Hz is also the inverse
of the period, T: [Eq. 2.3] The signal presented in Eq. 2.1 is completely defined by
A and fp (or wp, or T); once you specify these two terms, you have characterized the
sine signal for all time. The sine wave signal is rather boring: if you have seen one
cycle, you have seen them all. Moreover, because the signal is completely defined
by A and fp, if neither the amplitude, A, nor the frequency, fp, changes over time, it
is hard to see how this f T p = 1 w p p p = 2 f xt A t A ft A t T p p ( ) = ( ) = ( ) = Ê
ˈ¯

A general sinusoid (as opposed to a pure sine wave or pure cosine wave) is a sine or
cosine with a general phase term as shown in Eq. 2.5: [Eq. 2.5] where again the
phase, q, would be expressed in degrees even though the frequency descriptor (wpt,
or 2pfpt, or 2pt/T) is expressed in radians or hertz. Many of the sinusoidal signals
described in this text are expressed as in Eq. 2.5. Figure 2.2 shows two sinusoids that
differ by 60 degrees. To convert the difference in phase angle to a difference in time,
note that the phase angle varies through 360 degrees during the course of one period,
T seconds. To calculate the time difference or time delay between the two sinusoids,
td, given the phase angle q: t T [Eq. 2.6] f t T d t f d == == d q q q 360 360 or 360
360 xt A t A ft A t T p p ( ) = - ( ) = - ( ) = - Ê Ë ˆ ¯ cos cos cos wq p q p 2 q 2 xt A
t A ft A t T p p ( ) = + ( ) = + ( ) = + Ê Ë ˆ ¯ sin sin sin wq p q p 2 q 2 or equivalentl
L5
Principle of averaging Many physiological signals are very small. A small signal can
be amplified electronically, but in so doing noise will also be amplified and in many
cases the ‘noise’ may be larger than the signal. By ‘noise’ we mean any signal which
interferes with the signal which is required. It may be electronic noise generated in
the equipment or it may be another physiological signal. The EMG often produces
noise on an ECG record. As was shown in the previous section, differential
amplifiers can be used to reduce interference. Filters can also be used to reduce noise
and interference which has frequency components outside the signal bandwidth. Yet
another common technique is that of averaging. The principle of an averager is
simply that by repeating a measurement many times all the results can be summed
together. The signal will sum in proportion to the number of repetitions, whereas if
the noise is random it will sum more slowly. Consider the problem of determining
the effect of a new drug which is claimed to reduce blood pressure
10.4.5. Screening and interference reduction
A room can be screened to reduce both electric fields and radio-frequency fields but
screening is expensive. The door to the room has to be made of copper and electrical
contacts made all round the edge of the door. Windows cannot be effectively
screened so that screened rooms must be artificially lit at all times. Fortunately, in
nearly all cases, good equipment design and careful use make a screened room
unnecessary. A number of pieces of advice for the reduction of interference can be
given: • Whenever possible use earthed equipment and use screened cables both for
patient connections and the mains supply. A screened cable will remove nearly all
electric field interference. • Do not use fluorescent lights close to a patient if you are
making an ECG/EKG or an EEG recording. Fluorescent lights produce a lot of
electric field interference from the tube and this interference can extend for about 2
m in front of the light. Tungsten lighting is much better. • Do not trail mains supply
leads close to the patient or the patient leads. The magnetic field around the cables
will induce interference. • Avoid making measurements close to an electricity supply
transformer. Even the measurement equipment may contain a transformer so that the
patient should not be placed too close to the equipment. • Computers and monitors
produce interference and should not be placed very close to the patient. • Faulty leads
and badly applied patient electrodes are the most common source of interference. •
If you are involved with the specification of electricity supply wiring then ask that
all the cables be run in earthed metal conduit. • Finally, remember that all
interference falls off in intensity with distance so that to move the place of
measurement may well be the most expedient solution to an interference problem
10.5.2. EEG evoked responses
If any stimulus is presented to the body then it is likely that the EEG will be affected;
if there is a stimulus then there will be a response. However, the response is usually
small and lost in the background EEG, so that the technique of signal averaging must
be used to extract the response from the noise. The technique is widely used for
recording responses to visual and auditory stimuli. Chapter 15 will consider audio-
evoked responses in some detail. Figure 10.15. An EEG response evoked by an
alternating chequerboard pattern visual stimulus. The two upper traces are
successive averages to show that the response is consistent. The lower trace is the
sum of the two upper traces. (Figure provided by Professor Colin Barber, Queen’s
Medical Centre, Nottingham.) Figure 10.15 shows a visual EEG evoked potential
(VEP) recorded in response to an alternating chequerboard stimulus. A VEP can be
recorded in response to a simple repeated flash of light, but a larger response is
usually obtained if a visual pattern is recorded. By alternating the dark and light
squares in a chequerboard pattern a repeated response can be obtained. The response
shown in figure 10.15 is approximately 50 µV in amplitude. This is well above the
thermal noise levels but the ‘noise’ in this case is the EEG. The
electroencephalograph (EEG) is typically 100 µV in amplitude and so our SNR is
less than unity. Averaging can be applied but the constraints are more severe than in
the case of nerve action potential recording.

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The temperature drift is important in the measurement of small pressures such as
bladder or airways’ pressure. In some cases the drift can be greater than the pressure
to be measured. Gain changes are not very important as they can be taken into
account in calibration, but nonlinearity, hysteresis and zero shifts are very difficult
to take into account. A typical practical procedure for the use of a pressure transducer
is: • Make the electrical connection between the transducer and the measurement
equipment. • Connect the pressure lines, with the exception of the patient connection.
• Fill the system with saline and remove all the air bubbles; it may be necessary to
tap and tilt the transducer to dislodge all the bubbles. • Open the transducer to the
atmosphere using the three-way tap. • Zero the bridge and amplifier so that zero
output corresponds to atmospheric pressure. • Close the tap to atmosphere and now
make the patient connection. • Flush a small volume of saline through the system
and check that blood is not entering the system. The system should now be ready for
measurement

18.5. DYNAMIC PERFORMANCE OF TRANSDUCER–CATHETER SYSTEM

The use of a catheter in conjunction with a transducer is the most common method
of measuring blood pressure and other pressures such as the pressure within the
bladder. The addition of a flexible fluid-filled catheter to the relatively rigid
transducer introducessevere problems associated with the dynamic performance of
the system. We will use a simple lumped parameter model, analogous to an electrical
RLC circuit, to explore the dynamic performance problems (this follows an
exposition given in Webster (ed) 1998 Medical Instrumentation: Application and
Design 3rd edn (New York: Wiley) pp 296–300). The model is shown in figure 18.6.
A pressure change at the end of the catheter will cause fluid to move through the
catheter and displace the diaphragm of the transducer. The displacement of the
diaphragm is proportional to the applied pressure. The hydraulic properties that are
important are inertance, resistance and compliance, the electrical analogues of which
are inductance, resistance and capacitance. These properties Copyright © 1999 IOP
Publishing Ltd dx P(t) area a diameter d L piston area A Figure 18.6. Mechanical
model of transducer and catheter. Cc Ct Cd Lc Rc Lt Rt Figure 18.7. Electrical model
of transducer and catheter. are due to the inertia, friction and elasticity within the
system. Figure 18.7 shows the resistance, inertance and compliance per unit length
of the catheter (with subscript c), and for the transducer (with subscript t) and the
compliance of the diaphragm (with subscript d)

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. Doppler ultrasound is able to measure these velocities and is the most widely used
method of measuring blood flow. Chapter 7 dealt with the generation of ultrasound
and its transmission in tissue. We begin now by looking at the Doppler effect for
ultrasound (Evans et al 1991). 19.7.1. The Doppler effect The change in apparent
frequency of a sound source as a result of relative movement of the source and
observer was first described by Christian Doppler in 1842. The pitch change from a
passing train is usually given as a common example of the Doppler effect. In that
case only the source of the sound is moving. However, the effect is also observed if
sound is reflected from a moving target. This is how the effect is used to measure
blood velocity. Moving blood does not spontaneously emit sound, so ultrasound
must be propagated through the tissue to the blood vessel. The red cells are much
smaller than the wavelength of the ultrasound, and behave as elastic spheresin the
ultrasonic pressure field. Each red cell is caused to alter itssize by the pressure field,
and acts as a point source of transmitted ultrasound. The sound transmitted by the
red cell is detected by the receiver. Consideration of the Doppler effect for red cells
is complicated by the fact that the red cell first acts as a moving receiver, and then
as a moving source. We will start by considering these two situations. Consider first
the case of a stationary source and a receiver moving towards the source (figure
19.15). The wavelength of the sound emitted by the source λs is given by λs = c/fs

L 10
20.2.3. Pedobarograph Measurement of the pressure distribution under the feet is a
vital component of the assessment of standing and gait. One way in which to make
the measurements is to construct a two-dimensional matrix of force transducers on
which the subject stands. This technique certainly works, but it is relatively
expensive and complex because a large number of transducers are required. If a
spatial resolution of 2 mm is required over a force plate area of 30 × 30 mm then
225 transducers are required and the associated electronics to interrogate them. An
elegant solution to this problem was suggested by Chodera in 1957. Chodera
suggested the system illustrated in figure 20.4. A thick glass plate is edge illuminated
as shown such that the light will be totally internally reflected within the glass. Total
internal reflection takes place because the refractive index of the glass is higher than
that of the surrounding air (see Snell’s law in section 3.5.1). On top of the glass plate
is a sheet of plastic material whose refractive index is higher than that of the glass.
If this sheet of material makes optical contact with the glass then the total internal
reflection Copyright © 1999 IOP Publishing Ltd Plastic sheet Reflector Glass plate
Fluorescent light Monochrome camera Mirror APPLIED PRESSURE Plastic Glass
Air Figure 20.4. The principle of a pedobarograph which uses an edge-illuminated
glass sheet and a covering plastic sheet to measure pressure distribution
Ch 3
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ELECTRICAL REQUIREMENTS Stimulation Electrodes Electrical stimulation
initiates a functional response by depolarizing the membranes of excitable cells.
Depolarization is achieved by the flow of ionic current between two or more
electrodes, at least one of which is in close proximity to the target tissue. In most
neural applications, electrical stimulation is applied as a series of biphasic current
pulses. Typical pulse waveforms with pulse parameters are shown in Figure 1. Each
pulse has cathodal and anodal phases, with current amplitudes and durations that
result in an overall zero net charge for the pulse (charge-balance). A cathodal current
is reducing at the stimulation electrode, with the direction of electron flow being
from the electrode to the tissue. Anodal indicates an oxidizing current with electron
flow in the opposite direction. The charge delivered is the time integral of the
current, which is simply ic·tc, for a cathodal constant-current pulse of magnitude ic
and pulse width tc. Charge-balance with intramuscular electrodes and electrodes that
interface with the peripheral nervous system is sometimes achieved by a capacitor
discharge circuit, leading to a monophasic, capacitor-coupled waveform, which is
also shown in Figure 1. Current pulses are defined in terms of the charge delivered
in the leading phase (q), the charge density in the leading phase (Qinj), the current
density (I), the pulse width in each phase, and the pulse frequency. The geometric
surface area (GSA) of the electrode is used to define the charge and current densities.
The use of electrochemical surface areas (ESAs) has generally not been useful. The
ESA can vary greatly depending on the method and conditions used in its
measurement, and it is difficult to define for porous electrodes and electrodes with
electroactive coatings (22)

CHARGE-INJECTION MECHANISMS AND ELECTRODES FOR

STIMULATION Electrodes are metallic conductors and reactions at the electrode-
tissue interface are required to mediate the transition from electron flow in the
electrode to ion flow in the tissue. These reactions can be capacitive, involving the
charging and discharging of the electrode-electrolyte double layer, or faradaic, in
which surface-confined species are oxidized and reduced. Capacitive charging can
be either electrostatic, involving purely double-layer ion-electron charge separation
and electrolyte dipole orientation, or electrolytic, involving charge stored across a
thin, high-dielectric-constant oxide at the electrode-electrolyte interface. Faradaic
reactions involve the transfer of an electron across the electrode-electrolyte interface
and require that some species, on the surface of the electrode or in solution, undergo
a change in valence, i.e., are oxidized or reduced. For noble metal electrodes,
primarily Pt and PtIr alloys, the faradaic reactions are confined to a surface
monolayer, and these reactions are often described as pseudocapacitive, although
electron transfer across the interface still occurs (70). Charge can also be stored and
injected into tissue from valence changes in multivalent electrode coatings that
undergo reversible reduction-oxidation (redox) reactions. These coatings, which are
typified by iridium oxide, but include newer materials such as
poly(ethylenedioxythiophene), are mixed conductors, exhibiting both electron and
ion transport within the bulk of the coating. The three-dimensional structure of the
coatings provides more charge for stimulation, but access to this charge is limited
by the rate of electron and ion transport within the coating.

Voltage Transients Voltage transient measurements are frequently used to estimate

the maximum charge that can be injected in a current-controlled stimulation pulse.
For in vitro measurements, the voltage transient is typically recorded in a three-
electrode configuration using a large-area return electrode and a noncurrent-carrying
reference electrode. The voltage transients are analyzed to determine the maximum
polarization, both the most negative (Emc) and most positive (Ema), across the
electrodeelectrolyte interface. These potential extremes are then compared with
established maximum potentials beyond which it is considered unsafe to polarize the
electrode. Examples of maximum potential limits for typical stimulation electrode
materials are provided in Table 2; these are typically water oxidation and reduction
potentials.

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t-A model is presented that represents a large body of data on safety and damage
levels of electrical stimulation. The predictions Manuscript received March 12,
1991; revised September 27, 1991. This work was supported in part by NIH Grant
DC00409 and by FDA orphan product Grant FD-R-000686. The author is with the
House Ear Institute, Los Angeles, CA 90057. IEEE Log Number 9106412. of the
model are consistent with known principles of current flow and known mechanisms
of damage around stimulating electrodes. It is proposed that limits on levels of
electrical stimulation take into account the location of the electrode relative to the
stimulated tissue and these limits can be computed algorithmically from the model.
INTRODUCTION Safety limits for electrical stimulation based on actual data from
animal experiments have led to a bewildering array of apparently conflicting results
for these limits due to the wide variety of stimulating waveforms, electrode sizes,
and charge densities. McCreery et al. [2], [3] have presented one of the most
complete sets of data on safe and unsafe electrical stimulation levels for surface
electrodes on the cortex. They assessed damage to underlying tissue from
stimulation with 400 ps pulses over a range of current densities and electrode shapes
and sizes. Their data are schematically represented in Fig. 1. This figure summarizes
results from dozens of experiments showing the charge and charge densities at which
damage occurs. Observe that both parameters must be specified to assure that the
stimulation is occurring in a region where damage does not occur. We will
demonstrate in this paper that a simple relation can be used to determine these
parameters for safe stimulation. We will discuss the possible biophysical reasons for
this relation, and illustrate its implications for future electrode designs and charge
limits. Previously proposed charge density limits have ranged from 15 to 65
pC/cm’/phase irrespective of electrode area [I]. For small electrode areas, this range
of charge densities would produce stimuli well below the damage limit shown in
McCreery et al.’s data. However, for large electrode areas, these charge densities
would probably produce damage. Thus, a limit purely based on charge density would
be quite conservative for small electrodes but might actually cause stimulation-
induced damage with large electrodes. The boundary which McCreery found
between safe and unsafe charge injections at different charge and charge density
levels can be approximated by the equation where D is charge density in
pCoulombs/cm’/phase and Q is charge in pCoulombs/phase. This equation describes
a family of lines for changing values of k, three of which are shown in Fig. I. When
k = 2, the straight line falls in an area where damage was observed. If this line were
used to define the limit of safe stimulation, some stimuli would be expected to cause
damage. The curve for k = 1.5 defines a set of parameters where no damage was
observed and is used for all computations that follow. Since D = (I7)/A = Q/A where
I is current, T is the duration of each phase of a biphasic pulse, and A is the surface
area of the electrode, (1) can be expressed as log (IT/A) = k - log (IT) which
rearranges to IT = (A 1ok)05. (2) Equation (2) describes the data of McCreery et al.
through a simple relationship between the three major variables in electrical
stimulation: current, pulse duration, and electrode surface area. For disk-shaped
electrodes of diameter d where A = (rd’)/4. (2) can be written as I = (d/(2~))(~
10~)~~

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Mechanical properties of the muscle
Length-tension relationship is an important parameter to explore mechanical
properties of the skeletal muscle. It’s defined as tension values of maximally
stimulated skeletal muscles in different lengths during isometric contraction. It can
be explained by two mechanisms: active and passive length-tension relationships.
The active lengthtension relationship reflects the degree of overlap between actin
and myosin. Too much and too little degrees generate suboptimal tensions whereas
maximal tension is seen in median sarcomere length values. Passive length-tension
relationship reflects the presence of elastic elements within a sarcomere, which
stretch and produce force with increasing length. Length-tension relationship
represents that tension generation in skeletal muscle is a direct function of actin-
myosin overlap (Lieber and Friden, 2000, 2002; Lieber, 2002a,b,c; Frontera and
Ochala, 2015). In fact this definition can be expressed as sarcomeretension
relationship. Although Sir Andrew Huxley offered this physiological invention with
using an isometric contraction set up, it is accepted for all force producing muscle
activities. Knowledge of anatomic lengths of actin and myosin filaments has
important implications on understanding normal movement and treatment strategies
including tendon transfers, stretching and exercise approaches. Altering the length-
tension relationship can have a profound influence on human movements (Lieber
and Friden, 2000; Lieber, 2002a,b,c; Frontera and Ochala, 2015). Length-tension
relationship curves are quite different between single fiber and the whole muscle.
Analysis of single fiber revealed a sharp shaped curve while analysis of whole
muscle revealed more smooth shape due to contribution of muscle, tendon and joints.
However both curves show that at short sarcomere and muscle lengths force
generation is lower. Also, at long sarcomere and muscle lengths force generation is
lower. Therefore the term of ‘mid-range’ have great importance for achieving
optimal muscle performance (Lieber and Friden, 2000; Lieber, 2002a,b,c; Frontera
and Ochala, 2015). Optimal sarcomere length for better muscle function is accepted
as 2.6 μm (Fig. 8.5). When the muscle fiber is highly stretched the sarcomere reaches
the length of 3.65 μm. The myosin filament is 1.65 μm long and the actin filament
is 2.0 μm long and there is no actin-myosin overlap (Fig. 8.6). Thus, m

CH 5
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4. Prototyping a Patient Monitor As an example application of the proposed process,
this section presents the development of the graphical user interface and the
behavioral model of the SC 7000 patient monitor [19]. In this particular case, the
purpose is making a virtual prototype that can be used both to validate an existing
product and to train operators [20]. As usual in real practice, detailed product
specications are not available, so the model has been built on information garnered
from the operating manual and experimentation on the real device. In the
development of a new device, the model would be based on written specications and
interaction with prospective users.
4.1. The Siemens SC 7000 Patient Monitor The Siemens SC 7000 Patient monitor
displays and stores patient parameters and enables operators to set alarms triggered
by the crossing of threshold values. The monitored parameters include ECG,
respiratory rate, pulse oxymetry, and more. In this work, only the functions related
to heart rate and oxygen saturation (SpO2) have been simulated. 4.2. Graphical user
interface The device front panel has a power switch, two LEDs for the power supply,
the screen, twelve xed keys, and a rotary knob incorporating a push button. Some
keys open a menu that is browsed by turning the rotary knob and clicking it to select
an option. In Fig. 1 (left), the red outlines mark the active areas for the interface
widgets of the prototype. Area (1) displays a real-time simulated ECG waveform,
whose instantaneous value is displayed in area (2) along with other parameters.
Areas (3) and (4) are the xed keys alarm limits and all alarms o, and area (5) is the
rotary knob. Areas (6), (7), and (8) are the power button and LEDs. Area (9) displays
the SpO2 waveform
4.3. Modeling device behavior Using the operating manual and experiment on the
real device, the elements of the automaton have been identied as explained in Sec.
3. Figure 2 shows a fragment of the Emucharts model concerning heart monitoring
and oxygen saturation. From the initial menu (INIT), pressing the alarm limits key
(event alarm_lim_key) triggers a transition to mode alarm limits (ALM_LIMITS).
The transition resets variable et, modeling elapsed time since the activation of a
mode. From the alarm limits mode, the user turns the knob right (event knob_right)
to step through menu options, each corresponding to a mode (AUTO_SET,
HBR_ALM, PVC/min_ALM, SpO2_ALM). Turning the knob left (event knob_left)
steps the cursor back. The tick event models the passing of time in discrete steps
(simulating 1 s intervals). Transitions triggered by tick leave the state unchanged up
to sixty time units, and switch to the initial mode above that limit. This models the
timeout mechanism that returns control to the initial menu if no user actions occur
within one minute. Among the various interfaces, special focus has been given to
alarms, particularly to keys alarm limits for alarm management and all alarms ofor
deactivating all active alarms. Animating a prototype makes it possible to perform
what-if analyses under dierent scenarios, possibly following use cases and system-
test plans from requirements specication documents. In the specic case, where the
prototype is actually a virtual replica of a marketed product, interactive animation
was used to reveal behaviors that would be hard to infer from the user manual or the
specications. For example, it was found that in the alarm setting modes it is not
possible to move backward directly from a submenu to the mode’s initial menu
(INIT in the Emucharts diagram), which is somewhat counter-intuitive and
inconvenient. Finally, animation turns a device prototype into a training tool for
medical personnel, providing immediate feedback and increasing condence in the
device

CH 5
L4
2.5 Classification and the Design Process In both the USA and within Europe the
degree of control one applies to the whole life cycle of the device increases with
classification (as illustrated by Table 2.4). The FDA use specific terms for the level
of control, which are worth remembering wherever you intend to work: Class I
means the class of devices that are subject to only the general controls… Class II
means the class of device that is or eventually will be subject to special controls…
Class III means the class of device for which premarket approval is or will be
required
Basically this means that the level of investigation into your design processes before
giving any CE mark, or clearance to market, is negligible for Class I products. Indeed
it is virtually self-regulated. You may be tempted to think that this means you do not
need to do any “real design” but you would be wrong. You have to think about the
situation when something goes wrong: for example, when you are placed in court
defending your product that has just maimed someone, or when you have to defend
your design to an expert designer with no evidence. Self-regulation, therefore, means
you make sure you have the design files in place. The higher the classification, the
“thicker” your design’s file becomes as it will contain more investigations to make
sure it is safe to use. The overall process is the same; it’s the amount of work that
increases. Your company will have to defend its submission to the authorities before
it can be placed on the market. The file has to be bulletproof; the higher the
classification the bigger and faster the bullets. The people that audit your files are
not stupid, they are highly intelligent scientists and engineers so do not try to fool
them – you will fail. Figure 2.8 illustrates the amount of effort required for each
classification. The amount of external control is negligible for Class I products, but
the company’s internal control is significant. For Class III devices the amount of
control exerted by external factors is probably equal to (if not more than) that of your
company. This does not means your hands are tied and you cannot make any design
decisions; it simply means you have to justify them – fully. Hence the amount of
effort you must apply to the design process increases too.

CH 4
L2
10.4.2 Sensors, Amplifiers, and Analog Filters Signals are first detected in the
biological medium such as a cell or on the skin’s surface by using a sensor (see
Chapter 6). A sensor converts a physical measurand into an electric output and
provides an interface between biological systems and electrical recording
instruments. The type of biosignal determines what type of sensor will bE used.
ECGs, for example, are measured with electrodes that have a silver/silver chloride
(Ag/AgCl) interface attached to the body that detects the movement of ions. Arterial
blood pressure is measured with a sensor that detects changes in pressure. It is very
important that the sensor used to detect the biological signal of interest does not
adversely affect the properties and characteristics of the signal it is measuring.
Sensors adapt the signal that is being observed into an electrical analog signal that
can be measured with a data acquisition system. The data acquisition system
converts the analog signal into a calibrated digital signal that can be stored. Digital
signal processing techniques are applied to the stored signal to reduce noise and
extract additional information that can improve understanding of the physiological
meaning of the original parameter.

Why Use an External Offset Voltage-Compensating Network?

Practical operational amplifiers (op-amps) are not ideal devices. Even though they
are designed to amplify signals accurately, real-world op-amps have imperfections,
one of which is input offset voltage. The input offset voltage (VOSV_{OS}VOS)
is the small differential DC voltage that must be applied between the inverting and
non-inverting inputs to make the output voltage zero when no input signal is applied.
This arises due to mismatches in the internal transistors and other fabrication
variations.

Reasons for Offset Compensation:

1. Reduce Output Drift: Without compensation, the offset voltage can cause a
small but significant error in the output, which becomes especially noticeable
in high-gain or precision applications.
2. Improve Accuracy: Offset voltage introduces a systematic error that can
distort signal amplification. Correcting this ensures more accurate and reliable
operation of the circuit.
3. Adapt to High Sensitivity Applications: Circuits like instrumentation
amplifiers or sensors that require accurate low-level signal amplification are
particularly affected by offset voltages.
4. Minimize Long-Term Effects: Offset voltages can be exacerbated by
temperature variations, so compensation improves stability over time and in
varying environmental conditions.

Offset Minimizing Network

An offset minimizing network is an external circuit connected to the op-amp to

correct or nullify the offset voltage. The network typically consists of a
potentiometer and resistors, and it works by introducing a compensating voltage to
counteract the offset voltage.

Components of the Offset Minimizing Network:

 1. Potentiometer (Variable Resistor): Used to fine-tune the compensating
voltage.
2. Fixed Resistors: Used to set the range of adjustment provided by the
potentiometer.
3. Connections to Offset Null Pins: Most practical op-amps (like the 741 op-
amp) include dedicated pins for offset voltage compensation. The
potentiometer is connected between these pins.

How It Works:

1. The potentiometer is adjusted to apply a small compensating voltage at the

input stage of the op-amp.
2. This compensating voltage cancels the input offset voltage by balancing the
differential input.
3. When the output voltage becomes zero (under no input conditions), the offset
voltage has been effectively nullified.

Typical Circuit:

For an op-amp like the 741, the offset minimizing network is connected as follows:

 A potentiometer (e.g., 10 kΩ) is connected between the offset null pins (pins
1 and 5).
 The wiper of the potentiometer is connected to the negative or positive supply
rail, depending on the circuit configuration.
 By adjusting the potentiometer, the offset voltage is canceled.

Conclusion

Using an external offset voltage-compensating network is essential in practical op-

amp circuits to eliminate systematic errors introduced by input offset voltage. This
improves the accuracy and reliability of op-amp-based systems, especially in high-
precision applications. The offset minimizing network is a simple yet effective
solution, leveraging a potentiometer and resistors to balance out the offset.
Autocorrelation and Cross-Correlation

1. Autocorrelation

Autocorrelation is the mathematical tool used to measure the similarity of a signal

with a delayed version of itself over different time lags. It identifies repeating
patterns or periodicities in a signal and is widely used in signal processing, time
series analysis, and system identification.

Mathematical Definition

The autocorrelation function Rxx(τ)R_{xx}(\tau)Rxx(τ) of a signal x(t)x(t)x(t) is

defined as:

Rxx(τ)=∫−∞∞x(t)x(t+τ) dtR_{xx}(\tau) = \int_{-\infty}^{\infty} x(t) x(t + \tau) \,

dtRxx(τ)=∫−∞∞x(t)x(t+τ)dt

Where:

 x(t)x(t)x(t): The original signal.

 τ\tauτ: The time delay (or lag).

Key Points:

 At τ=0\tau = 0τ=0, Rxx(0)R_{xx}(0)Rxx(0) gives the total energy or power

of the signal.
 For periodic signals, Rxx(τ)R_{xx}(\tau)Rxx(τ) exhibits periodic behavior.

Applications:

 Detecting repeating patterns (e.g., in radar, speech, and communication

signals).
 Determining signal delay or alignment.

2. Cross-Correlation

Cross-correlation measures the similarity between two different signals as a function

of time delay (τ\tauτ). It is used to find the time lag at which two signals are most
similar.
Mathematical Definition

The cross-correlation function Rxy(τ)R_{xy}(\tau)Rxy(τ) between two signals

x(t)x(t)x(t) and y(t)y(t)y(t) is defined as:

Rxy(τ)=∫−∞∞x(t)y(t+τ) dtR_{xy}(\tau) = \int_{-\infty}^{\infty} x(t) y(t + \tau) \,

dtRxy(τ)=∫−∞∞x(t)y(t+τ)dt

Where:

 x(t)x(t)x(t): First signal.

 y(t)y(t)y(t): Second signal.
 τ\tauτ: Time delay (or lag).

Key Points:

 When τ\tauτ corresponds to the maximum value of Rxy(τ)R_{xy}(\tau)Rxy

(τ), it indicates the time lag at which x(t)x(t)x(t) and y(t)y(t)y(t) are most
similar.
 Cross-correlation is widely used in applications like signal matching, image
registration, and system identification.

ketch of the Elements of a Measuring Instrument

A measuring instrument generally consists of the following elements:

1. Input Element (Sensor/Transducer):

o Converts the physical quantity being measured (e.g., temperature,
pressure) into an electrical signal.
2. Signal Conditioning Element:
o Amplifies, filters, or modifies the signal from the sensor for further
processing.
3. Output Display or Recording Element:
 o Displays the result in a readable format (e.g., on a screen or as a printed
record).

Here’s a basic block diagram of these elements:

css
Copy code
Physical Quantity → [Sensor/Transducer] → [Signal Conditioning] →
[Display/Output]

Convert x(t)=−5cos⁡(10t)−3sin⁡(10t)x(t) = -5\cos(10t) -

3\sin(10t)x(t)=−5cos(10t)−3sin(10t) into a Single Sinusoidal Wave

A sum of sine and cosine terms can be expressed as a single sinusoidal function in
the form:

x(t)=Asin⁡(10t+ϕ)x(t) = A\sin(10t + \phi)x(t)=Asin(10t+ϕ)

where:

 AAA: Amplitude of the sinusoid.

 ϕ\phiϕ: Phase angle.

Steps to Convert:

1. Find Amplitude AAA:

A=(−5)2+(−3)2=25+9=34A = \sqrt{(-5)^2 + (-3)^2} = \sqrt{25 + 9} =

\sqrt{34}A=(−5)2+(−3)2=25+9=34

2. Find Phase Angle ϕ\phiϕ:

The phase angle ϕ\phiϕ is given by:

ϕ=tan⁡−1(−b−a)=tan⁡−1(−(−3)−(−5))=tan⁡−1(35)\phi = \tan^{-
1}\left(\frac{-b}{-a}\right) = \tan^{-1}\left(\frac{-(-3)}{-(-5)}\right) =
\tan^{-1}\left(\frac{3}{5}\right)ϕ=tan−1(−a−b)=tan−1(−(−5)−(−3)
)=tan−1(53) ϕ≈tan⁡−1(0.6)≈0.540 radians\phi \approx \tan^{-1}(0.6)
\approx 0.540 \, \text{radians}ϕ≈tan−1(0.6)≈0.540radians
 3. Rewrite the Equation:
Substituting AAA and ϕ\phiϕ, the expression becomes:

x(t)=34sin⁡(10t+0.540)x(t) = \sqrt{34} \sin(10t + 0.540)x(t)=34

sin(10t+0.540)

Final Result:

x(t)=34sin⁡(10t+0.540)x(t) = \sqrt{34} \sin(10t + 0.540)x(t)=34sin(10t+0.540)

Let me know if you’d like a graphical illustration or further clarification!

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What is Meant by an Evoked Electric Response?

An evoked electric response refers to the electrical activity generated by the

nervous system in response to a specific stimulus. These responses are typically
recorded from the brain, muscles, or nerves after applying sensory, motor, or
cognitive stimulation.

 Evoked responses are time-locked to a stimulus, meaning they occur in a

predictable time window following the stimulus.
 They can be measured using techniques such as EEG
(Electroencephalography) or EMG (Electromyography).

Types of Evoked Responses

1. Sensory Evoked Potentials (SEPs):

o Generated by the stimulation of sensory pathways (e.g., visual,
auditory, or somatosensory).
o Example: Visual evoked potentials (VEPs) occur in response to visual
stimuli.
2. Motor Evoked Potentials (MEPs):
o Generated when motor pathways are stimulated (e.g., by transcranial
magnetic stimulation).
 3. Cognitive Evoked Potentials:
o Reflect higher-level brain processing in response to specific cognitive
tasks or events (e.g., P300 wave for attention).

How Evoked Responses are Used to Characterize a Physiological Process

Evoked responses provide critical insights into the functionality and health of the
nervous system. Below are ways in which they are utilized:

1. Assessing Neural Pathways

 Evoked responses help in understanding whether sensory or motor pathways

are intact and functioning properly.
 Example: Auditory brainstem responses (ABRs) are used to evaluate hearing
and detect issues in auditory pathways.

2. Diagnosing Neurological Disorders

 Abnormal evoked responses can indicate the presence of disorders such as

multiple sclerosis, stroke, or neuropathy.
 Example: Delayed or reduced VEPs can signify optic nerve damage.

3. Monitoring During Surgery

 Intraoperative monitoring of evoked responses ensures that critical neural

pathways remain intact during procedures like spinal surgeries.
 Example: Monitoring somatosensory evoked potentials (SSEPs) to detect
potential damage to spinal cord pathways.

4. Studying Cognitive and Sensory Processes

 Evoked responses are used in cognitive neuroscience to study brain processes

like perception, attention, and decision-making.
 Example: P300 wave in event-related potentials (ERPs) measures attention
and stimulus processing.

5. Evaluating Development and Recovery

  Evoked responses track the development of neural pathways in infants or the
recovery of function after injury.
 Example: Monitoring VEPs in premature infants to study visual system
development.

Conclusion

An evoked electric response is a valuable tool for assessing the nervous system's
function and diagnosing or monitoring physiological processes. By analyzing the
timing, amplitude, and patterns of these responses, clinicians and researchers can
gain insights into sensory, motor, and cognitive systems, enabling better diagnosis,
treatment, and understanding of various neurological conditions.

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