Bmi - Unit1
Bmi - Unit1
INTRODUCTION:
A knowledge of the structure of the living body and its function is essential for understanding
the functioning of most of the medical instruments. The science of structure of the body is
known as “Anatomy” and that of its function, “Physiology”.
Gross anatomy deals with the study of the structure of the organs as seen by the naked eye on
dissection. It describes the shape, size, components and appearance of the organ under study.
Topographical anatomy deals with the position of the organs in relation to each other, as
they are seen in sections through the body in different planes.
Microscopic anatomy (Histology) is the study of the minute structure of the organs by means
of microscopy.
Cytology is a special field of histology in which the structure, function and development of
the cells are studied.
Similarly, physiology, which relates to the normal function of the organs of the body, can be
classified in different ways. For example:
A biosignal is any signal in living beings that can be continually measured and monitored.
The term biosignal is often used to refer to bioelectrical signals, but it may refer to both
electrical and non-electrical signals. The biosignals are produced by the electrical activity that
arises from the biological activity that takes place within different tissues and organs of the
human body. Biomedical signals are those signals (phenomenon that conveys information)
which are used primarily for extracting information on a biological system under
investigation. The process of extracting information could be as simple as feeling the pulse of
a person on the wrist or as complex as analyzing the structure of internal soft tissues by an
ultrasound scanner.
Bioelectric Signals: These are unique to the biomedical systems. They are generated by
nerve cells and muscle tissues as the result of the changes in the electric currents which are
produced by the sum potential differences across the tissues and organs. Their basic source is
the cell membrane potential which under certain conditions may be excited to generate an
action potential. The electric field generated by the action of many cells constitutes the bio-
electric signal. The most common examples of bioelectric signals are the ECG
(electrocardiographic) and EEG (electroencephalographic) signals.
Biomechanical Signals: These signals originate from some mechanical function of the
biological system. They include all types of motion and displacement signals, pressure and
flow signals etc. The movement of the chest wall in accordance with the respiratory activity
and blood pressure measurements are an example of this type of signal.
Biochemical Signals: The signals which are obtained as a result of chemical measurements
from the living tissue or from samples analyzed in the laboratory. Signals contain information
about the changes in concentration of various chemical agents in the body. The examples are
measurement of partial pressure of carbon-dioxide (pCO2), partial pressure of oxygen (pO2)
and concentration of various ions in the blood.
Biomagnetic Signals: Extremely weak magnetic fields are produced by various organs such
as the brain, heart and lungs. The measurement of these signals provides information which is
not available in other types of bio-signals such bio-electric signals. A typical example is that
of magneto-encephalograph signal from the brain.
Bio-optical Signals: These signals are generated as result of optical functions of the
biological systems, occurring either naturally or induced by the measurement process. For
example, blood oxygenation may be estimated by measuring the transmitted/back scattered
light from a tissue at different wavelengths.
The most common types of methods that are currently used to record biosignals in clinical
research are presented below along with a brief description of their functionality and related
clinical applications.
EEG signals: these types of signals are produced by the electrical activity of the brain cells.
When a neuron fires, an action potential is generated as a result of the exchange of ions that
occurs inside and outside the neuron's cell. This causes an alteration in the electrical charge
from negative to positive and thus generates an ionic current (extracellular current) that is
then propagated through the neuronal axons to other neurons, and as a result an electrical
field is generated. This field is propagated throughout the brain and can be recorded by
electrodes that are placed around the scalp. EEG signals consist of various brain rhythms
(brainwaves) including delta (0.3–4 Hz), theta (4–8 Hz), alpha (8–14 Hz), beta (14–30 Hz),
and gamma (>30 Hz), with each one having a clinical importance in disease and pathological
diagnosis. EEG signals have been extensively used in clinical research to study potential
fluctuations under specific events (i.e., event-related potentials [ERPs]), as well as in various
pathologies including epilepsy, schizophrenia, dyslexia, and dementia.
MEG signals: these types of signals are produced by the magnetic fields that are generated
by the electrical activity of the brain cells. The electrical activity that is generated by the
neuronal triggering produces an extremely weak magnetic field (as a result of intracellular
current flow) that can be only recorded by powerful magnetometers, known as
superconducting quantum interference devices (SQUIDs). SQUIDs are usually placed in
liquid helium and are able to capture the extremely small alterations in the brain's magnetic
field (∼10−15T), when the Earth's magnetic field varies between 10−4 and 10−5T. For this
reason, the MEG examination is performed inside magnetically shielded rooms to shield out
the inference of outside magnetic fields. The main advantage of MEG against EEG is that the
former is not affected by the electrical field's distortion during its propagation through the
skull, scalp, and cerebrospinal fluid. Thus, the MEG yields both higher spatial and temporal
resolution. However, the MEG equipment is very expensive due to its superconducting
technology and is often subject to high noise levels. MEG has been used for the examination
of neocortical epilepsy regions due to its high spatial resolution, amnesia, etc.
EMG signals: these types of signals are produced by the electric currents that are generated
by the muscle contraction. The depolarization and repolarization of the skeletal muscle
produces a difference in the electrical potential within the muscle cells (i.e., an electrical
field), which propagates throughout the muscle fiber. The electrical activity of the selected
muscle is detected by surface electrodes. A needle is often used to stimulate the skeletal
muscles, yielding the single motor unit action potential (SMUAP) with an amplitude of 300–
400 μV. EMG signals are used to detect anomalies in the activity of the muscles, including
myopathy and neuropathy, as well as in biomechanics for the development of body
prosthetics.
EOG signals: these types of signals are produced by the electric potential that is generated
by the cornea and the retinal activity during eye movement. A typical EOG records the
electrical field that is produced by the difference between the cornea's positive potential and
the retina's negative potential, i.e., the corneoretinal potential, with an amplitude from 0.4 to
1 mV. EOG has been used as a method for removing ocular artifacts in other biosignals, such
as EEG, as well as for studying the eye movement in human–computer interaction systems.
Other relevant procedures include the electronystagmography that records the eye movement
during nystagmus.
ECG or EKG signals: these types of signals record the electrical activity that arises from the
depolarization and repolarization activity of the heart. A typical ECG records the P wave as a
result of the right atrium's activation (<80 ms), the QRS complex (<120 ms) as a result of the
depolarization between the left and the right ventricles, the T wave (<160 ms) as a result of
the repolarization of the right and the left ventricles, and finally the U wave as a result of the
repolarization of the interventricular septum. The intervals between the waves can be used as
indications of abnormal heart activity, e.g., a prolonged PR interval from the atrial activation
to the beginning of the ventricular activation might indicate heart failure and a wide QRS
complex might denote both left and right bundle branch block. Furthermore, ECGs have been
widely used for studying arrhythmias, coronary artery disease, and other heart failure
conditions.
Phonocardiography (PCG) signals: these types of acoustic signals record the sounds that
are produced by the heart's beat and the blood flow (murmurs) between the heart valves.
PCGs have the same origins as ECGs, and they have been used to study abnormalities on
heart sound for the detection of heart defects (e.g., cardiomyopathy), as well as for biometric
identification.
Electrocorticography (ECoG) signals: these types of signals can directly capture the
extracellular currents that are produced by the electrical activity of the brain cells within the
cerebral cortex. ECoG signals have been widely used to localize epileptic zones before
epileptic surgery with very high precision and for the localization of activated brain regions
using motor- or somatosensory-evoked potentials through a procedure that is known as
electrical cortical stimulation. ECoG signals yield high temporal resolutions, and their
invasive nature, however, involves surgical operation procedures, a fact that makes it difficult
to obtain with the exception of heavy medical conditions.
In all types of biosignals, the sampling frequency (or sampling rate) and the recording
duration are directly proportional to the size of the acquired data and the speed of data
acquisition process. For the majority of the biosignals, the modern recording systems use
sampling frequencies that may vary from 50 to 500 Hz to 1 kHz and even 10 kHz (i.e.,
10,000 samples per second). According to the signal recording time (e.g., on an hourly basis
or on a daily basis) and the number of bits used for encoding the samples (e.g., 8 bits), the
data size may vary from MB (megabyte) to even GB (gigabyte) of digitized signal data. For
example, the ECG biosensors for patient monitoring can record the activity of the heart for
hours or weeks with sampling rates that vary in 50–250 Hz, yielding huge amounts of
accumulated data (e.g., a system with a sampling rate 250Hz can record more than 21 million
samples per day).
BASIC MEDICAL INSTRUMENTATION SYSTEM:
The majority of the instruments are electrical or electronic systems, although mechanical
systems such as ventilators or spirometers are also employed. Certain characteristic features,
which are common to most instrumentation systems, are also applicable to medical
instrumentation systems.
In the broadest sense, any medical instrument would comprise of the following four basic
functional components:
Measurand: The physical quantity or condition that the instrumentation system measures is
called the measurand. The source for the measurand is the human body which generates a
variety of signals. The measurand may be on the surface of the body (electrocardiogram
potential) or it may be blood pressure in the chambers of the heart.
Another term ‘sensor’ is also used in medical instrumentation systems. Basically, a sensor
converts a physical measurand to an electrical signal. The sensor should be minimally
invasive and interface with the living system with minimum extraction of energy.
Signal Conditioner: Converts the output of the transducer into an electrical quantity suitable
for operation of the display or recording system. Signal conditioners may vary in complexity
from a simple resistance network or impedance matching device to multi-stage amplifiers and
other complex electronic circuitry. Signal conditioning usually include functions such as
amplification, filtering (analog or digital) analog-to-digital and digital-to-analog conversion
or signal transmission circuitry. They help in increasing the sensitivity of instruments by
amplification of the original signal or its transduced form.
Alarm System—with upper and lower adjustable thresholds to indicate when the measurand
goes beyond preset limits.
Data Storage—to maintain the data for future reference. It may be a hard copy on a paper or
on magnetic or semiconductor memories.
In many measurements in the medical field, some form of stimulus or energy is given to the
patient and the effect it has on the patient is measured. The stimulus may be visual in the
form of flash of light or audio tone or direct electrical stimulation of some part of the nervous
system. A typical example is that of recording of the evoked response with EEG machine
when visual/audible stimulus is given to the subject under test.
Medical equipment are primarily used for making measurements of physiological parameters
of the human body and also in some cases a stimulus or some kind of energy is applied to the
human body for diagnosis and treatment. Some of the important factors, which determine the
design of a medical measuring instrument, are:
Measurement Range: Generally, the measurement ranges are quite low compared with non-
medical parameters. Most signals are in the microvolt range.
Frequency Range: Most of the bio-medical signals are in the audio frequency range or
below and that many signals contain dc and very low frequency components.
These general characteristics of physiological signals limit the practical choices available to
designers of medical instruments. Besides, there are some additional constraints, which need
to be considered while designing a measurement system for medical applications.
Inaccessibility of the Signal Source: One of the major problems in making measurements
from a living system is the difficulty in gaining access to the source of the physiological
variable being measured. For example; measurement of intracranial pressure in the brain
requires the placement of a sensor in the brain, which is quite a difficult task. Besides, the
physical size of many sensors may put a constraint for its use on the area of interest.
Evidently, such inaccessible physiological variables must be measured indirectly. The typical
example of making indirect measurement of blood pressure on the brachial artery is that of
using cuff based Korotoff method. In such cases, corrections need to be applied to data that
might have been affected due to the indirect measuring process.
Interference among Physiological Systems: Many feedback loops exist among physiological
systems and many of the interrelationships amongst them contribute to this inherent
variability of physiological signals. In other words, stimulation of one part of a given system
generally affects all other parts of that system in some way. Also, unlike many complex non-
medical systems, a biological system is of such a nature that it is not possible to turn it off
and remove parts of it during measurement procedure to avoid interference from undesirable
physiological signals.
Transducer Interface Problems: All measurement systems are affected in some way by the
presence of the measuring transducer. The problem gets compounded while making
measurement on the living system where the physical presence of the transducer may change
the reading significantly. Also, the presence of a transducer in one system can affect
responses in other systems. Adequate care needs to be taken while designing a measuring
system to ensure that the loading effect of the transducer is minimal on the source of the
measured variable.
High Possibility of Artifacts: The term artifact refers to an undesirable signal that is
extraneous to the physiological variable under measurement. The examples of artifacts are:
50 Hz electrical interference, cross talk and noise generated within the measuring instrument.
A major source of artifacts in medical instruments is due to the movement of the subject.
Many of the transducers are sensitive to the movement and therefore, the movement of the
subject result in generating spurious signals, which may even be large enough to obscure the
signal of interest. This type of situation puts a heavy demand on the signal conditioning part
of the measurement system.
Safe Levels of Applied Energy: Nearly all biomedical measurements require some form of
energy to be applied to the living tissue or some energy gets applied as an incidental
consequence of transducer operation. For example, ultrasonic imaging techniques depend
upon externally applied ultrasound energy to the human body. Safe levels of the various types
of energy on the human subjects are difficult to establish. However, designers of medical
instruments depend upon a large number of studies carried out by numerous researchers,
which establish the threshold of adverse effects by the applied energy.
Reliability Aspects: In case of life saving equipment like defibrillators, their failure to operate
or provide desired output can become a potential life threat for the patient. Therefore,
equipment must be reliable, simple to operate and capable of withstanding physical abuse due
to transportation within the hospital or in the ambulances and exposure to corrosive
chemicals.
Government Regulations: During the initial stages of introduction of technology and a range
of diagnostic and therapeutic devices in the medical field, there was almost no government
control on their design, testing and sales. Situation is rapidly changing and government
regulations are being introduced to ensure that the equipment perform their intended function
and are safe to operate and function. Designers of medical instruments should therefore be
fully conversant with all such regulations on a particular product or system issued by national
and international agencies. It is thus obvious that there are many factors that impose
constraints on the design of medical instruments. In addition to these, there are general
considerations, which need to be considered into the initial design and development of a
medical instrument. These factors are:
Signal Considerations: Type of sensor, sensitivity, range, input impedance, frequency
response, accuracy, linearity, reliability, differential or absolute input.
Environmental Considerations: Signal-to-noise ratio, stability with respect to temperature,
pressure, humidity, acceleration, shock, vibration, radiation etc.
Medical Considerations: Invasive or non-invasive technique, patient discomfort, radiation
and heat dissipation, electrical safety, material toxicity etc.
Economic Considerations: Initial cost, cost and availability of consumables and compatibility
with existing equipment.
Certain types of cells within the body, such as nerve and muscle cells, are encased in a
semipermeable membrane that permits some substances to pass through the membrane while
others are kept out. Bioelectric potentials are generated at a cellular level and the source of
these potentials is ionic in nature. A cell consists of an ionic conductor separated from the
outside environment by a semipermeable membrane which acts as a selective ionic filter to
the ions. This means that some ions can pass through the membrane freely where as others
cannot do so. All living matter is composed of cells of different types. Human cells may vary
from 1 micron to 100 microns in diameter, from 1 mm to 1 m in length, and have a typical
membrane thickness of 0.01 micron.
Surrounding the cells of the body are body fluids, which are ionic and which provide a
conducting medium for electric potentials. The principal ions involved with the phenomena
of producing cell potentials are sodium (Na+), potassium (K+) and chloride (Cl–). The
membrane of excitable cells readily permits the entry of K+ and Cl–but impedes the flow of
Na+ even though there may be a very high concentration gradient of sodium across the cell
membrane.
Since the various ions seek a balance between the inside of the cell and the outside, both
according to concentration and electric charge, the inability of the sodium to penetrate the
membrane results in two conditions.
First, the concentration of sodium ions inside the cell becomes much lower than in the
intercellular fluid outside. Since the sodium ions are positive, this would tend to make the
outside of the cell more positive than the inside.
Second, in an attempt to balance the electric charge, additional potassium ions, which are also
positive, enter the cell, causing a higher concentration of potassium on the inside than on the
outside. This charge balance cannot be achieved, however, because of the concentration
imbalance of potassium ions. Equilibrium is reached with a potential difference across the
membrane, negative on the inside and positive on the outside.
This membrane potential is called the resting potential of the cell and is maintained until
some kind of disturbance upsets the equilibrium. Since measurement of the membrane
potential is generally made from inside the cell with respect to the body fluids, the resting
potential of a cell is given as negative. Research investigators have reported measuring
membrane potentials in various cells ranging from - 60 to - 100 mV.
Figure illustrates in simplified form the cross section of a cell with its resting potential. A cell
in the resting state is said to be polarized.
When a section of the cell membrane is excited by the flow of ionic current or by some form
of externally applied energy, the membrane changes its characteristics and begins to allow
some of the sodium ions to enter. This movement of sodium ions into the cell constitutes an
ionic current flow that further reduces the barrier of the membrane to sodium ions. The net
result is an avalanche effect in which sodium ions literally rush into the cell to try to reach a
balance with the ions outside.
At the same time potassium ions, which were in higher concentration inside the cell during
the resting state, try to leave the cell but are unable to move as rapidly as the sodium ions. As
a result, the cell has a slightly positive potential on the inside due to the imbalance of
potassium ions. This potential is known as the action potential and is approximately + 20 mV.
A cell that has been excited and that displays an action potential is said to be depolarized; the
process of changing from the resting state to the action potential is called depolarization.
Figure 3.2 shows the ionic movements associated with depolarization, and Figure 3.3
illustrates the cross section of a depolarized cell.
Once the rush of sodium ions through the cell membrane has stopped (a new state of
equilibrium is reached), the ionic currents that lowered the barrier to sodium ions are no
longer present and the membrane reverts back to its original, selectively permeable condition,
wherein the passage of sodium ions from the outside to the inside of the cell is again blocked.
However, it would take a long time for a resting potential to develop again.
By an active process, called a sodium pump, the sodium ions are quickly transported to the
outside of the cell, and the cell again becomes polarized and assumes its resting potential.
This process is called repolarization. Although little is known of the exact chemical steps
involved in the sodium pump, it is quite generally believed that sodium is withdrawn against
both charge and concentration gradients supported by some form of high-energy phosphate
compound. The rate of pumping is directly proportional to the sodium concentration in the
cell. It is also believed that the operation of this pump is linked with the influx of potassium
into the cell, as if a cyclic process involving an exchange of sodium for potassium existed.
Figure 3.4 shows a typical action-potential waveform, beginning at the resting potential,
depolarizing, and returning to the resting potential after repolarization. The time scale for the
action potential depends on the type of cell producing the potential. In nerve and muscle
cells, repolarization occurs so rapidly following depolarization that the action potential
appears as a spike of as little as 1 msec total duration. Heart muscle, on the other hand,
repolarizes much more slowly, with the action potential for heart muscle usually lasting from
150 to 300 msec.
Regardless of the method by which a cell is excited or the intensity of the stimulus (provided
it is sufficient to activate the cell), the action potential is always the same for any given cell.
This is known as the all-or-nothing law.
The net height of the action potential is defined as the differences between the potential of
the depolarized membrane at the peak of the action potential and the resting potential.
Following the generation of an action potential, there is a brief period of time during which
the cell cannot respond to any new stimulus. This period, called the absolute refractory
period, lasts about 1 msec in nerve cells.
Following the absolute refractory period, there occurs a relative refractory period, during
which another action potential can be triggered, but a much stronger stimulation is required.
In nerve cells, the relative refractory period lasts several milliseconds. These refractory
periods are believed to be the result of after-potentials that follow an action potential.
When a cell is excited and generates an action potential ionic currents begin to flow. This
Process can, in turn, excite neighboring cells or adjacent areas of the same cell. In the case of
a nerve cell with a long fiber, the action potential is generated over a very small segment of
the fiber's length but is propagated in both directions from the original point of excitation. In
nature, nerve cells are excited only near their input end. As the action potential travels down
the fiber, it cannot re-excite the portion of the fiber immediately upstream, because of the
refractory period that follows the action potential.
The rate at which an action potential moves down a fiber or is propagated from cell to cell is
called the propagation rate. In nerve fibers the propagation rate is also called the nerve
conduction rate, or conduction velocity. This velocity varies widely, depending on the type
and diameter of the nerve fiber. The usual velocity range in nerves is from 20 to 140 meters
per second (m/sec). Propagation through heart muscle is slower, with an average rate from
0.2 to 0.4 m/sec. Special time-delay fibers between the atria and ventricles of the heart cause
action potentials to propagate at an even slower rate, 0.03 to 0.05 m/sec.
The primary characteristics of typical bioelectric signals are given in Table 2.1.
BIO AMPLIFIERS:
Biopotential Amplifiers also called Bio-Amplifiers are specifically designed for processing of
Bio-electric signals as they are low in amplitude. Generally, biological/bioelectric signals
have low amplitude and low frequency. Therefore, to increase the amplitude level of bio-
signals, amplifiers are designed. The outputs from these amplifiers are used for further
analysis and they appear as ECG, EMG, or any bioelectric waveforms. Such amplifiers are
defined as Bio Amplifiers or Biomedical Amplifiers.
Amplifiers are an integral part of electronic devices and modern Instrumentation for
measuring Bio-potentials. As the name indicates, Amplifiers are used to increase the signal
strength while maintaining high fidelity. The measurements include voltages that are at low
levels and high source impedance. To measure Biopotential, electrodes are placed on Human
skin as shown in the Fig. 1. The signals from the Electrodes pass on to the Amplifier stage.
Amplifier helps in minimizing, eliminating most of the signals interfering with the
measurement of Bio-potentials and final readout is obtained. The amplifier provides high
impedance, high CMRR and thereby minimizes loading effects. This is the vital functionality
of Biopotential Amplifiers.
Various stages which represent Biopotential Amplifier is shown in the Fig. The Electrodes
(Bipolar) are placed on the patient’s skin which provide transition between the ionic flow of
currents in biological tissue and electronic flow of current in the Amplifier. The measurement
of Bio-potentials is critical and due to relative movements of electrode and tissue, it gives rise
to electrode offset potential and electrode/tissue impedance. Thus, two interference signals
are generated which are successfully eliminated at later stages of the amplification.
The signal from the electrodes passes on to the pre-amplifier stage which helps in
minimizing, eliminating most of the signals interfering with the measurement of Bio-
potentials. High Pass Filter and Low Pass Filter eliminates interference signals like electrode
Half-cell potentials and Pre-amplifier offset potentials. It also reduces noise amplitude. Bio-
signal should not be distorted or attenuated and hence Filters are used.
In the Isolation Amplifier stage, galvanic decoupling of the patient from the measuring
equipment is served. It prevents Galvanic currents from deteriorating Signal to Noise Ratio
and provides safety to the patient from electrical hazards. Transformer, Optical or Capacitive
Couplers are used in Analog Isolation Amplifiers, to transmit signal through the isolation
barrier. On the other hand, Digital Isolation Amplifiers use Voltage and frequency converter
to digitize the signal before it is transmitted.
Recording of the Bio-potentials in the last stage is done with electrical systems which
produce strong electrical and magnetic fields. Hence the system is capacitively coupled and
the current flows to the ground electrode.
They are majorly used in medical instrumentation systems such as ECG, EMG, CT
scan equipment, Patient hospital monitor.
They are also used in Electromyogram integrator’s, Cardio tachometers, Vector
Cardiograph.
They are used in Bio-telemetry, Holter Recorder and other devices to determine
the specific health condition of a patient.
There are different types of special circuits used as Biopotential Amplifiers or Bio-
Amplifiers. They are:
Differential Amplifier
Operational Amplifier
Instrumentation Amplifier
Chopper Amplifier
Isolation Amplifier
Differential Amplifier:
Biomedical amplifiers employed in the input stage of a biomedical measurement system are
mostly of the differential type. Differential amplifier has three input terminals out of which
one is arranged at the reference potential and the other two are live terminals. These are used
to amplify the difference between the voltages applied to its inputs. The circuits are of two
types.
The differential amplifier is used when it is necessary to measure the voltage difference
between two points, both of them varying in amplitude at different rates and in different
patterns. Heart-generated voltages that are picked up by means of Bioelectrodes on the arms
and legs and brain-generated voltages picked up by the Bioelectrodes on the scalp are typical
examples of signals whose measurements needs the use of differential amplifier.
The ability of the differential amplifier to reject common voltages on its two input leads is
known as Common-mode rejection and is specified as the ratio of common-mode input to
differential input to derive the same response. It is abbreviated as CMRR (Common-mode
rejection ratio). CMRR is an important specification with regard to differential amplifiers and
is usually expressed in decibels.
CMRR for the input stage of biomedical instrumentation systems should be as high as
possible so that only the wanted signals find a way through the amplifier and all unwanted
signals get rejected in the preamplifier stage.
A high rejection ratio is normally achieved by the use of a matched pair of transistors in the
input stage of the preamplifier and a large ‘’tail’’ resistance in the long-tailed pair to provide
maximum negative feedback for in phase signals.
Amplifiers built using either FET’s (Field Effect Transistors) or BJT’s (Bipolar
Junction Transistors):
Input1 of differential amplifier is connected to the base of transistor Q1 and input2 of the
differential is connected to the base of another transistor. VCC and VEE are the two supplies
for differential amplifier. The circuits work proper even with a single supply voltage. If you
want to run the differential amplifier with a single supply then connect VCC to supply
voltage and VEE to ground.
If input signal is applied to the base of transistor Q1 then there is voltage drop across
collector resistor Rc1 so the output of the transistor Q1 is low. When there is no input voltage
to the transistor Q1, the voltage drop across resistor Rc1 is very less as a result output
transistor Q1 is high.
When transistor Q1 is turned on, the current through the emitter resistor Re increases as
emitter current Ie is almost equal to the collector current Ic. As a result, voltage drop across
resistor Re increases and makes emitter of both transistors positive. In this condition
transistor Q2 does not conducts as there is no base voltage. As a result, collector voltage of
transistor Q2 is high. Hence it is clear that the output is produced at the collector of transistor
Q2 when an input is applied to the base of Q1.
Transistors Q1 and Q2 have the exactly same characteristics. The two collector resistors are
equal while the 2rwo emitter resistances Re1 and Re2 are also equal.
The magnitudes of supply voltages +Vcc and -Vee also same. If the input voltages Vs1 and
Vs2 are equal then emitter currents Ie1 and Ie2 are also equal.
Ie = Ie1 + Ie2
Ve = Vb – Vbe.
Vc1 = Vc2 = Vcc – IcRc assuming collector resistances Rc1 = Rc2 =Rc.
These are multistage amplifiers which are interconnected and occupies minimal space even
though it consists of many Transistors, Resistors, and FET’s. They are available in the form
of an Integrated Circuit (IC).
Inverting Operational Amplifier Configuration:
As the open loop DC gain of an operational amplifier is extremely high, we can therefore
afford to lose some of this high gain by connecting a suitable resistor across the amplifier
from the output terminal back to the inverting input terminal to both reduce and control the
overall gain of the amplifier. This then produces and effect known commonly as Negative
Feedback, and thus produces a very stable Operational Amplifier based system.
Negative Feedback is the process of “feeding back” a fraction of the output signal back to
the input, but to make the feedback negative, we must feed it back to the negative or
“inverting input” terminal of the op-amp using an external Feedback Resistor called Rƒ.
This feedback connection between the output and the inverting input terminal forces the
differential input voltage towards zero.
This effect produces a closed loop circuit to the amplifier resulting in the gain of the amplifier
now being called its Closed-loop Gain. Then a closed-loop inverting amplifier uses negative
feedback to accurately control the overall gain of the amplifier, but at a cost in the reduction
of the amplifiers gain.
This negative feedback results in the inverting input terminal having a different signal on it
than the actual input voltage as it will be the sum of the input voltage plus the negative
feedback voltage giving it the label or term of a Summing Point. We must therefore separate
the real input signal from the inverting input by using an Input Resistor, Rin.
As we are not using the positive non-inverting input this is connected to a common ground or
zero voltage terminal as shown below, but the effect of this closed loop feedback circuit
results in the voltage potential at the inverting input being equal to that at the non-inverting
input producing a Virtual Earth summing point because it will be at the same potential as the
grounded reference input.
In this Inverting Amplifier circuit, the operational amplifier is connected with feedback to
produce a closed loop operation. When dealing with operational amplifiers there are two very
important rules to remember about inverting amplifiers, these are: “No current flows into the
input terminal” and that “V1 always equals V2”. However, in real world op-amp circuits both
of these rules are slightly broken.
This is because the junction of the input and feedback signal (X) is at the same potential as
the positive (+) input which is at zero volts or ground then, the junction is a “Virtual Earth”.
Because of this virtual earth node, the input resistance of the amplifier is equal to the value of
the input resistor, Rin and the closed loop gain of the inverting amplifier can be set by the
ratio of the two external resistors.
and this can be transposed to give Vout as:
The negative sign in the equation indicates an inversion of the output signal with respect to
the input as it is 180⁰ out of phase. This is due to the feedback being negative in value.
Non-Inverting Amplifiers:
In this configuration, the input voltage signal, (VIN) is applied directly to the non-inverting
(+) input terminal which means that the output gain of the amplifier becomes “Positive” in
value in contrast to the “Inverting Amplifier” circuit we saw in the last tutorial whose output
gain is negative in value. The result of this is that the output signal is “in-phase” with the
input signal.
Feedback control of the non-inverting operational amplifier is achieved by applying a small
part of the output voltage signal back to the inverting (–) input terminal via a Rƒ – R2 voltage
divider network, again producing negative feedback. This closed-loop configuration produces
a non-inverting amplifier circuit with very good stability, a very high input impedance.
Then using the formula to calculate the output voltage of a potential divider network, we can
calculate the closed-loop voltage gain ( AV ) of the Non-inverting Amplifier as follows:
Then the closed loop voltage gain of a Non-inverting Operational Amplifier will be given
as:
Voltage follower:
In this non-inverting circuit configuration, the input impedance Rin has increased to infinity
and the feedback impedance Rƒ reduced to zero. The output is connected directly back to the
negative inverting input so the feedback is 100% and Vin is exactly equal to Vout giving it a
fixed gain of 1 or unity. As the input voltage Vin is applied to the non-inverting input, the
voltage gain of the amplifier is therefore given as:
Since no current flows into the non-inverting input terminal the input impedance is infinite
(ideal conditions) so zero current will flow through the feedback loop. Thus, any value of
resistance may be placed in the feedback loop without affecting the characteristics of the
circuit as no current flows through it so there is zero voltage drop across it resulting in zero
power loss.
As the input impedance is extremely high, the unity gain buffer (voltage follower) can be
used to provide a large power gain as the extra power comes from the op-amps supply rails
and through the op-amps output to the load and not directly from the input. However, in most
real unity gain buffer circuits there are leakage currents and parasitic capacitances present so
a low value (typically 1kΩ) resistor is required in the feedback loop to help reduce the effects
of these leakage currents providing stability especially if the operational amplifier is of a
current feedback type.
The voltage follower or unity gain buffer is a special and very useful type of non-inverting
amplifier circuit that is commonly used in electronics to isolated circuits from each other.
Differential Amplifiers:
By connecting each input in turn to 0v ground we can use superposition to solve for the
output voltage Vout. Then the transfer function for a Differential Amplifier circuit is given
as:
When resistors, R1 = R2 and R3 = R4 the above transfer function for the differential
amplifier can be simplified to the following expression:
If all the resistors are all of the same ohmic value, that is: R1 = R2 = R3 = R4 then the circuit
will become a Unity Gain Differential Amplifier and the voltage gain of the amplifier will
be exactly one or unity. Then the output expression would simply be Vout = V2 – V1.
If input V1 is higher than input V2 the output voltage sum will be negative, and if V2 is
higher than V1, the output voltage sum will be positive.
One of the most common ways to connect a “Resistive Bridge” commonly called
a Wheatstone Bridge to the input of the amplifier as shown below.
The common-mode rejection for most op-amps is typically between 60 dB and 90 dB. This
may not be enough to reject common-mode noise that is usually encountered in biomedical
measurements. In addition, the input impedance is not very high to handle signals from high
impedance sources. One way to increase the input impedance of the op-amp is to use Field
effect transistors (FET) in the input differential stage. Alternatively, the best solution is to use
an Instrumentation amplifier in the preamplifier stage.
Instrumentation Amplifier:
The differential amplifier part is essential for biomedical sensors; this is because a sensor
produces a signal between its terminals however, in some applications neither terminal may
be connected to the same ground as your measuring circuit hence the terminals may be biased
at a high potential or might be riding on a noise voltage. The differential amplifier fixes this
problem by directly measuring the difference between the sensor’s terminals. The buffered
amplifier provides gain and also prevents the sensor resistance from affecting the resistors in
the op-amp circuit.
Carrier Amplifiers:
To obtain zero frequency response of the dc amplifier and the inherent stability of the
capacitance coupled amplifier, a carrier type of amplifier is generally used. The carrier
amplifier consists of an oscillator and a capacitance coupled amplifier. The oscillator is used
to energize the transducer with an alternating carrier voltage. The transducers, which require
ac excitation, are those whose impedance is not purely resistive. Example can be of a
capacitance-based pressure transducer whose impedance is mainly capacitive with a small
resistive component. The frequency of the excitation voltage is usually around 2.5 kHz.
The transducer shall change the amplitude of the carrier voltage in relation to the changes in
the physiological variable being measured. The output of the transducer therefore, would be
an amplitude modulated (AM) signal (Fig.). The modulated ac signal can then be fed to a
multi-stage capacitance coupled amplifier. The first stage produces amplification of the AM
signal. The second stage is so constructed that it can respond only to signal frequency of the
carrier. It can be further amplified in the following stage. After amplification, the signal is
demodulated in a phase-sensitive demodulator circuit. This helps to extract amplified signal
voltage after the filter circuit. The voltage produced by the demodulator can then be applied
to the driver stage of the writing system.
Carrier amplifiers can be used with a resistance strain gauge transducer such as a
semiconductor strain gauge. When used with pressure gauges, a calibration control is
provided on the carrier amplifier. This enables direct measurements of the blood pressure
from the calibrated graphic recorder.
Lock-in amplifier is a useful version of the carrier technique designed for the measurement of
low-level signals buried in noise. This type of amplifier, by having an extremely narrow-
width output band in which the signal is carried, reduces wideband noise and increases the
signal-to-noise ratio. Thus, the difference between carrier amplifier and lock-in amplifier is
that the former is a general-purpose instrument amplifier while the latter is designed to
measure signals in a noisy background.
In principle, the lock-in amplifier works by synchronizing on a single frequency, called the
reference frequency. This frequency is made to contain the signal of interest. The signal is
modulated by the reference frequency in such a way that all the desired data is at the single
reference frequency whereas the inevitable noise, being broadband, is at all frequencies. This
permits the signal to be recovered from its noisy background.
Chopper Amplifier:
The chopper amplifier is a useful device in the field of medical electronics as it gives another
solution to the problem of achieving adequate low frequency response while avoiding the
drift problem inherent in direct coupled amplifiers. This type of amplifier makes use of a
chopping device, which converts a slowly varying direct current to an alternating form with
amplitude proportional to the input direct current and with phase dependent on the polarity of
the original signal. The alternating voltage is then amplified by a conventional ac amplifier
whose output is rectified back to get an amplified direct current. A chopper amplifier is an
excellent device for signals of narrow bandwidth and reduces the drift problem.
Figure shows a simplified block diagram of a single-ended chopper stabilized amplifier. The
amplifier achieves its ultra-low dc offset voltage and bias current by chopping the low
frequency components of the input signal, amplifying this chopped signal in an ac amplifier
(A1) and then demodulating the output of the ac amplifier. The low frequency components
are derived from the input signal by passing it through the low-pass filter, consisting of R2,
C2 and R2. The chopping signal is generated by the oscillator. The filtered output is then
further amplified in a second stage of dc amplification (A2). High frequency signals, which
are filtered out at the input of the chopper channel, are coupled directly into the second stage
amplifier. The result of this technique is to reduce the dc offsets and drift of the second
amplifier by a factor equal to the gain of the chopper channel. The ac amplifier introduces no
offsets. Minor offsets and bias currents exist due to imperfect chopping, but these are
extremely small. The amplifier modules contain the chopper channel, including switches and
switch-driving oscillator built on the module; only the dc power is supplied externally.
Due to the extremely low dc offset and dc drift associated with the chopper-stabilized
amplifier, the signal resolution is limited only by the noise present in the circuit. Thus, it is
desirable to design the feedback networks and external wiring to minimize the total circuit
noise. When the full bandwidth of the amplifier is not required, it is advisable that a feedback
capacitor be used to limit the overall bandwidth and eliminate as much high frequency noise
as possible. Shielding of feedback components is desirable in chopper amplifiers. It is
particularly necessary in electrically noisy environments. Use of shielded wire for summing
junction leads is also recommended. Typical voltage drift in chopper-stabilised amplifiers is
0.1 mV/°C and current drift as 0.5 pA/°C.
Isolation Amplifiers:
Isolation amplifiers are commonly used for providing protection against leakage currents.
They break the ohmic continuity of electric signals between the input and output of the
amplifier. The isolation includes different supply voltage sources and different grounds on
each side of the isolation barrier.
In a biopotential amplifiers, the main purpose of the isolation amplifier is the protection of
the patient by eliminating the hazard of the electrical shock resulting from the interaction
among patient, amplifier, and other electronic devices in the patient’s environment. It also
adds to the prevention of the line frequency interferences.
Isolation could also be achieved by optical means in which the patient is electrically
connected with neither the hospital line nor the ground line. A separate battery-operated
circuit supplies power to the patient circuit and the signal of interest is converted into light by
a light source (LED). This light falls on a phototransistor on the output side, which converts
the light signal again into an electrical signal (Fig), having its original frequency, amplitude
and linearity. No modulator/demodulator is needed because the signal is transmitted optically
all the way.
The capacitive method (Fig.) uses digital encoding of the input voltage and frequency
modulation to send the signal across a differential capacitive barrier. Separate power supply
is needed on both sides of the barrier. Signals with bandwidths up to 70 kHz can be
conveniently handled in this arrangement.
Advantages:
1. All three types are in common use, though the transformer isolation amplifier is more
popular.
2. Opto-coupled amplifier uses a minimum number of components and is cost effective,
followed by the transformer coupled amplifier. The capacitor coupled amplifier is the
most expensive.
3. Opto-isolated amplifiers offer the lowest isolation voltage (800V continuous) between
input and output; transformer coupled 1200V and capacitance coupled 2200V.
4. Isolation resistance levels are of the order of 10 10, and 1012 ohms for transformer
coupled, opto-coupled and capacitance coupled amplifiers respectively.
5. Gain stability and linearity are best for capacitance coupled versions—0.005%, and
on par for the transformer and opto-coupled amplifier—0.02%.
Electrical isolation is the most commonly used technique to ensure patient protection against
electrical hazards. Instruments such as electrocardiographs, pressure monitors, pressure
transducers, pacemakers and others have been designed to electrically separate the portion of
the circuit to which the patient is connected from the portion of the circuit connected to the ac
power line and ground.
Static characteristics describe the performance of instruments for dc or very low frequency
inputs. The properties of the output for a wide range of constant inputs demonstrate the
quality of the measurement, including nonlinear and statistical effects. Some sensors and
instruments, such as piezoelectric devices, respond only to time-varying inputs and have no
static characteristics.
Dynamic characteristics require the use of differential and/or integral equations to describe
the quality of the measurements. Although dynamic characteristics usually depend on static
characteristics, the nonlinearities and statistical variability are usually ignored for dynamic
inputs, because the differential equations become difficult to solve. Complete characteristics
are approximated by the sum of static and dynamic characteristics. This necessary
oversimplification is frequently responsible for differences between real and ideal instrument
performance.
STATIC CHARACTERISTICS:
Accuracy: This term describes the algebraic difference between the indicated value and the
true or theoretical value of the measurand.
In practice, accuracy is usually expressed as a
percentage of full-scale output or
percent of reading or
± number of digits for digital readouts.
Resolution: It is the smallest quantity being measured which can be detected with certainty
by an instrument. If a non-zero input quantity is slowly increased, the output reading won’t
increase until some minimum change in the input takes place. The minimum change which
causes the change in output is termed resolution. If the measured quantity starts from zero,
the term threshold is synonymous with resolution. Resolution expresses the degree to which
nearly equal values of a quantity can be discriminated.’
Reproducibility: It is the ability of an instrument to give the same output for equal inputs
applied over some period of time. Repeatability is defined as the ability of instrument to
reproduce a group of measurements of same measured quantity, made by same observer,
using same instrument, under same conditions.
Static Sensitivity: It describes transfer ratio of output to input. Static calibration is performed
by holding all inputs constant except one. This one input is varied incrementally over the
normal operating range, resulting in incremental output. Then
The static sensitivity may be constant for only part of the normal operating range of the
instrument, as shown in figure. For input-output data that indicate a straight-line calibration
curve, the slope m and intercept b for the line with minimal sum of the squared differences
between the data points and the line are given by the following equations:
Example: static sensitivity for blood pressure sensor is 50 µV. V-1. mm. Hg-1
Statistical Control: The accuracy of an instrument is not meaningful unless all factors, such
as the environment and the method of use, are considered. Statistical control ensures that
random variations in measured quantities that result from all factors that influence the
measurement process are tolerable. Any systematic errors or bias can be removed by
calibration and correction factors, but random variations pose a more difficult problem.
The measurand and/or the instrument may introduce statistical variations that make outputs
unreproducible. If the cause of this variability cannot be eliminated, then statistical
analysis must be used to determine the error variation. Making multiple measurements and
averaging the results can improve the estimate of the true value.
Zero Drift: Zero drift occurs when all measurements increase or decrease by the same
absolute amount. The slope of the curve is unchanged.
Causes: manufacturing misalignment, variations in ambient temperature, hysteresis vibration,
shock, dc-offset voltage at electrodes
Example: Changes in dc offset voltage at the electrodes in electrocardiograph
Sensitivity Drift: When the slope of the calibration curve changes as a result of interfering
and / or modifying input, a drift in sensitivity occurs.
Causes: manufacturing tolerances, variations in power supply, non-linearity and changes in
the ambient temperature and pressure.
Example: variation in ECG amplifier voltage gain changes due to dc power-supply voltage
variation or change in temperature are examples for sensitivity drift.
Hysteresis: It describes change of output with the same value of input but with a different
history of input variation. For example: hysteresis is observed when the input/output
characteristics for instruments are different for increasing inputs than for decreasing inputs. It
results when some of the energy applied for increasing inputs is not recovered when the input
decreases.
Input Ranges: Minimal resolvable inputs impose a lower bound on the quantity to be
measured. The normal linear operating range specifies maximal or near-maximal inputs that
give linear outputs. Static linear range may be different from dynamic linear range. The
maximal operating range is the largest input without damage to the instrument. Operation in
the upper part of this range is more likely to be nonlinear. These ranges are not always
symmetric with respect to the zero input. Typically operating ranges for blood pressure
sensors have a positive bias, such as +200 mm Hg to -60 mm Hg (+26.6 to -8.0 kPa)
Input Impedance: For every desired input Xd1 that we seek to measure, there is another
implicit input quantity Xd2 such that the product Xd1 * Xd2 has the dimensions of power. The
generalized input impedance ZX is the ratio of the phasor equivalent of a steady state
sinusoidal effort input variable (voltage, force, pressure) to the phasor equivalent of a steady
state sinusoidal flow input variable (current, velocity, flow)
The power P is the time rate of energy transfer from the measurement medium.
To minimize P, when measuring effort variable Xd1 we should make the generalized input
impedance as large as possible.
DYNAMIC CHARACTERISTICS:
Dynamic Error: The difference between the true value of the measured quantity to the value
shown by the measuring instrument under varying conditions.
Speed of response: It is defined as the rapidity of the measurement system that responds to
the changes in the measuring variable. It indicates how active and fast the system is.
Lag: Every system takes at least some time to respond, whatever time it may be to the
changes in the measured variable.
Retardation lag: the response of the measurement begins immediately after the change in
measured quantity has occurred.
Time delay lag: in this case after the application of input, the response of the measurement
system begins with some dead times.
Few medical measurements, such as body temperature, are constant or slowly varying
quantities. Most medical instruments must process signals that are function of time. Response
of Many medical instruments can be described by ordinary linear differential equations. Most
practical instruments have a first or second order response.
The dynamic relation between input x(t) and output y(t) are
Where ai, and bi are constants and these depend on physical and electrical properties of the
system.
Operational transfer function is the ratio (y(D) / x(D)) as a function of the differential
operator D
Frequency transfer function for a linear system is obtained by substituting jω for D in the
transfer function expression,
The order of the system represented by the highest power of the differential equation
This zero-order instrument has ideal dynamic performance, because the output is proportional
to the input for all frequencies and there is no amplitude and phase distortion.
y(t) = K x(t)
transfer function is
𝑦(𝐷) 𝑦(𝑗𝜔)
= 𝑥(𝑗𝜔) = K
𝑥(𝐷)
IC = −IE (A-1)
or
IC + IE = 0 (A-2)
where IC and IE are the currents due to the concentrational and electrical gradi-
ents, respectively.
Concentrational Flux
Consider first the current due to the concentration gradient. which will be
given by
IC = AΦCZF (A-3)
Derivation of the Nernst Equation 209
In words, Equation (A-3) states that the current through the membrane of area
A will be equal to the flux, ΦC, of the ion down the concentration gradient
(number of ions per second per unit area of membrane) multiplied by Z (the
valence of the ion) and F (Faraday’s constant; 96,500 coulombs per mole of
univalent ion). The factor ZF translates the flux of ions into flux of charge and
hence into an electrical current. The flux ΦC for a given ion (call the ion Y,
for example) will depend on the concentration gradient of Y across the mem-
brane (that is, [Y]in − [Y]out) and on the membrane permeability to Y, pY.
Quantitatively, this relation is given by
Note that pY has units of velocity (cm/sec), in order for ΦC to have units of
molecules/sec/cm2 (remember that [Y] has units of molecules/cm3). The
permeability coefficient, pY, is in turn given by
pY = DY/a (A-5)
where DY is the diffusion constant for Y within the membrane and a is the
thickness of the membrane. DY can be expanded to yield
DY = uRT (A-6)
where u is the mobility of the ion within the membrane and RT (the gas con-
stant times the absolute temperature) is the thermal energy available to drive
ion movement. Substituting Equation (A-6) in (A-5) and the result in (A-4)
yields
Membrane
(Y)out (Y)in
Vout Vin
Outside Inside
0 a
Figure A-1 Segment of
E m = V in – Vout membrane separating two
x compartments.
210 Derivation of the Nernst Equation
⎛ a ⎞ ⎛ a ⎞
Φ C ⎜ ∫ d x⎟ = uRT ⎜ ∫ dC ⎟ (A-8)
⎝ o ⎠ ⎝ o ⎠
Here, C stands for the concentration of the ion; therefore, in reference to Figure
A-1, Ca is [Y]in and C0 is [Y]out. Differentiating both sides of Equation (A-8) yields
ΦC dx = uRT dC (A-9)
which can be arranged to give the more general form of Equation (A-7) that we
desire:
⎛ dC ⎞
ΦC = uRT ⎜ ⎟ (A-10)
⎝ dx ⎠
Equation (A-10) can be substituted into Equation (A-3) to give us the ionic cur-
rent due to the concentration gradient.
IE = AΦE ZF (A-11)
The flux, ΦE, of a charged particle through a plane at position x in the presence
of a voltage gradient dV/dx will be
⎛ dV ⎞
ΦE = uZFC ⎜ ⎟ (A-12)
⎝ dx ⎠
Again, u is the mobility of the ion, and C is the concentration of the ion at posi-
tion x. The factor ZFC is then the concentration of charge at the location of the
plane; this is necessary because the voltage gradient dV/dx acts on charge and
ZFC gives the “concentration” of charge at position = x. Equation (A-12) is
analogous to Equation (A-10), except it is the voltage gradient rather than the
concentration gradient that is of interest.
⎛ dC dV ⎞
uAZF ⎜RT + ZFC ⎟ = 0 (A-13)
⎝ dx dx⎠
⎛ dC ⎞ ⎛ dV ⎞
RT ⎜ ⎟ = − ZFC ⎜ ⎟ (A-14)
⎝ dx ⎠ ⎝ dx ⎠
⎛ RT ⎞ ⎛ dC ⎞
⎜− ⎟ ⎜ ⎟ = dV (A-15)
⎝ ZF ⎠ ⎝ C ⎠
This can be solved for V by integrating across the membrane. Using the
nomenclature of Figure A-1, the integrals are
RT dC Vin
[ Y ]in
− = dV (A-16)
ZF [ Y ]out C Vout
RT
(ln [Y] in − ln [Y]out ) = Vin − Vout (A-17)
ZF
or
RT ⎛ [Y]out ⎞
ln ⎜ ⎟ = Vin − Vout = E m (A-18)
ZF ⎝ [Y] in ⎠
Devices that convert ionic potentials into electronic potentials are called electrodes. The
interface of metallic ions in solution with their associated metals results in an electrical
potential that is called the electrode potential. This potential is a result of the difference in
diffusion rates of ions into and out of the metal. Equilibrium is produced by the formation of
a layer of charge at the interface. Bioelectric events have to be picked up from the surface of
the body before they can be put into the amplifier for subsequent record or display. This is
done by using electrodes.
Another source of an electrode potential is the unequal exchange of ions across a membrane
that is semipermeable to a given ion when the membrane separates liquid solutions with
different concentrations of that ion. An equation relating the potential across the membrane
and the two concentrations of the ion is called the Nernst equation and can be stated as
follows:
The activity coefficients, f1, and f2, depend on such factors as the charges of all ions in the
solution and the distance between ions. The product, C1f1, of a concentration and its
associated activity coefficient is called the activity of the ion responsible for the electrode
potential.
In electrodes used for the measurement of bioelectric potentials, the electrode potential
occurs at the interface of a metal and an electrolyte, whereas in biochemical transducers both
membrane barriers and metal electrolyte interfaces are used.
A wide variety of electrodes can be used to measure bioelectric events, all can be classified as
belonging to one of three basic types:
In each case, an electrode potential is developed across the interface, proportional to the
exchange of ions between the metal and the electrolytes of the body. The double layer of
charge at the interface acts as a capacitor. Thus, the equivalent circuit of biopotential
electrode in contact with the body consists of a voltage in series with a resistance-capacitance
network of the type shown in Figure1.
Since measurement of bioelectric potentials requires two electrodes, the voltage measured is
really the difference between the instantaneous potentials of the two electrodes, as shown in
Figure2.
If the two electrodes are of the same type, the difference is usually small and depends
essentially on the actual difference of ionic potential between the two points of the body from
which measurements are being taken. If the two electrodes are different, however, they may
produce a significant dc voltage that can cause current to flow through both electrodes as well
as through the input circuit of the amplifier to which they are connected. The dc voltage due
to the difference in electrode potentials is called the electrode offset voltage. The resulting
current is often mistaken for a true physiological event. Even two electrodes of the same
material may produce a small electrode offset voltage.
In addition to the electrode offset voltage, experiments have shown that the chemical activity
that takes place within an electrode can cause voltage fluctuations to appear without any
physiological input. Such variations may appear as noise on a bioelectric signal. This noise
can be reduced by proper choice of materials or, in most cases, by special treatment, such as
coating the electrodes by some electrolytic method to improve stability. It has been found
that, electrochemically, the silver-silver chloride electrode is very stable.
This type of electrode is prepared by electrolytically coating a piece of pure silver with silver
chloride. The coating is normally done by placing a cleaned piece of silver into a bromide-
free sodium chloride solution. A second piece of silver is also placed in the solution, and the
two are connected to a voltage source such that the electrode to be chloride is made positive
with respect to the other. The silver ions combine with the chloride ions from the salt to
produce neutral silver chloride molecules that coat the silver electrode.
The resistance-capacitance networks shown in Figures1 and 2 represent the impedance of the
electrodes (one of their most important characteristics) as fixed values of resistance and
capacitance. Unfortunately, the impedance is not constant. The impedance is frequency-
dependent because of the effect of the capacitance. Both the electrode potential and the
impedance are varied by an effect called polarization.
Polarization is the result of direct current passing through the metal electrolyte interface. The
effect is much like that of charging a battery with the polarity of the charge opposing the flow
of current that generates the charge. Some electrodes are designed to avoid or reduce
polarization. If the amplifier to which the electrodes are connected has an extremely high
input impedance, the effect of polarization or any other change in electrode impedance
is minimized.
Size and type of electrode are also important in determining the electrode impedance. Larger
electrodes tend to have lower impedances. Surface electrodes generally have impedances of 2
to 10 kΩ, whereas small needle electrodes and microelectrodes have much higher
impedances. For best results in reading or recording the potentials measured by the
electrodes, the input impedance of the amplifier must be several times that of the electrodes.
1. Microelectrodes:
Microelectrodes are electrodes with tips sufficiently small to penetrate a single cell in order to
obtain readings from within the cell. The tip must be small enough to permit penetration
without damaging the cell. This action is usually complicated by the difficulty of accurately
positioning an electrode with respect to a cell.
Metal microelectrodes are formed by electrolytically etching the tip of a fine tungsten or
stainless-steel wire to the desired size. Then the wire is coated almost to the tip with an
insulating material. Some electrolytic processing can also be performed on the tip to lower
the impedance. The metal-ion interface takes place where the metal tip contacts the
electrolytes either inside or outside the cell.
The micropipet type of microelectrode is a glass micropipet with the tip drawn out to the
desired size [usually about 1 micron (now more commonly called micro meter, µm) in
diameter]. The micropipet is filled with an electrolyte compatible with the cellular fluids.
This type of microelectrode has a dual interface. One interface consists of a metal wire in
contact with the electrolyte solution inside the micropipet, while the other is the interface
between the electrolyte inside the pipet and the fluids inside or immediately outside the cell.
Microelectrodes, because of their small surface areas, have impedances well up into the
megohms. For this reason, amplifiers with extremely high impedances are required to avoid
loading the circuit and to minimize the effects of small changes in interface impedance.
2. Body surface recording electrodes
Electrodes used to obtain bioelectric potentials from the surface of the body are found in
many sizes and forms. Although any type of surface electrode can be used to sense EGG,
EEG, or EMG potentials, the larger electrodes are usually associated with EGG, since
localization of the measurement is not important, whereas smaller electrodes are used in EEG
and EMG measurements.
The earliest bioelectric potential measurements used immersion electrodes, which were
simply buckets of saline solution into which the subject placed his hands and feet, one bucket
for each extremity. As might be expected, this type of electrode (Figure 4) presented many
difficulties, such as restricted position of the subject and danger of electrolyte spillage.
A great improvement over the immersion electrodes were the plate electrodes, first
introduced about 1917. Originally, these electrodes were separated from the subject's skin by
cotton or felt pads soaked in a strong saline solution. Later a conductive jelly or paste (an
electrolyte) replaced the soaked pads and metal was allowed to contact the skin through a thin
coat of jelly. Plate electrodes of this type are still in use today. An example is shown in
Figure 5.
Another fairly old type of electrode still in use is the suction-cup electrode shown in Figure 6.
In this type, only the rim actually contacts the skin.
One of the difficulties in using plate electrodes is the possibility of electrode slippage or
movement. This also occurs with the suction-cup electrode after a sufficient length of time. A
number of attempts were made to overcome this problem, including the use of adhesive
backing and a surface resembling a nutmeg grater that penetrates the skin to lower the contact
impedance and reduce the likelihood of slippage.
All the above electrodes suffer from a common problem. They are all sensitive to movement,
some to a greater degree than others. Even the slightest movement changes the thickness of
the thin film of electrolyte between metal and skin and thus causes changes in the electrode
potential and impedance. In many cases, the potential changes are so severe that they
completely block the bioelectric potentials the electrodes attempt to measure.
Later, a new type of electrode, the floating electrode, was introduced in varying forms by
several manufacturers. The principle of this electrode is to practically eliminate movement
artifact by avoiding any direct contact of the metal with the skin. The only conductive path
between metal and skin is the electrolyte paste or jelly, which forms an electrolyte bridge.
Even with the electrode surface held at a right angle with the skin surface, performance is not
impaired as long as the electrolyte bridge maintains contact with both the skin and the metal.
Figure 7 shows a cross section of a floating electrode, and Figure 8 shows a commercially
available configuration of the floating electrode.
Floating electrodes are generally attached to the skin by means of two-sided adhesive collars
(or rings), which adhere to both the plastic surface of the electrode and the skin. Figure 9
shows an electrode in position for biopotential measurement.
Special problems encountered in the monitoring of the ECG of astronauts during long periods
of time, and under conditions of perspiration and considerable movement, led to the
development of spray-on electrodes, in which a small spot of conductive adhesive is sprayed
or painted over the skin, which had previously been treated with an electrolyte coating.
Various types of disposable electrodes have been introduced in recent years to eliminate the
requirement for cleaning and care after each use. An example is shown in Figure 10.
Primarily intended for ECG monitoring, these electrodes can also be used for EEC and EMG
as well. In general, disposable electrodes are of the floating type with simple snap connectors
by which the leads, which are reusable, are attached. Although some disposable electrodes
can be reused several times, their cost is usually low enough that cleaning for reuse is not
warranted. They come pregelled, ready for immediate use.
Special types of surface electrodes have been developed for other applications. For example,
a special ear-clip electrode (Figure11) was developed for use as a reference electrode for
EEG measurements. Scalp surface electrodes for EEG are usually small disks about 7 mm in
diameter or small solder pellets that are placed on the cleaned scalp, using an electrolyte
paste. This type of electrode is shown in Figure12.
3. Needle electrodes
In animal research (and occasionally in man) longer needles are actually inserted into the
brain to obtain localized measurement of potentials from a specific part of the brain. This
process requires longer needles precisely located by means of a map or atlas of the brain.
Sometimes a special instrument, called a stereotaxic instrument, is used to hold the animal's
head and guide the placement of electrodes. Often these electrodes are implanted to permit
repeated measurements over an extended period of time. In this case, a connector is cemented
to the animal's skull and the incision through which the electrodes were implanted is allowed
to heal.
Needle electrodes for EMG- consist merely of fine insulated wires, placed so that their tips,
which are bare, are in contact with the nerve, muscle, or other tissue from which the
measurement is made. The remainder of the wire is covered with some form of insulation to
prevent shorting. Wire electrodes of copper or platinum are often used for EMG pickup from
specific muscles. The wires are either surgically implanted or introduced by means of a
hypodermic needle that is later withdrawn, leaving the wire electrode in place. With this type
of electrode, the metal-electrolyte interface takes place between the uninsulated tip of the
wire and the electrolytes of the body, although the wire is dipped into an electrolyte paste
before insertion in some cases.
The hypodermic needle is sometimes a part of the electrode configuration and is not
withdrawn. Instead, the wires forming the electrodes are carried inside the needle, which
creates the hole necessary for insertion, protects the wires, and acts as a grounded shield. A
single wire inside the needle serves as a unipolar electrode, which measures the potentials at
the point of contact with respect to some indifferent reference. If two wires are placed inside
the needle, the measurement is called bipolar and provides a very localized measurement
between the two wire tips.
Needle electrodes and other types of electrodes that create an interface beneath the surface of
the skin seem to be less susceptible to movement artifacts than surface electrodes, particularly
those of the older types. By making direct contact with the subdermal tissue or the
intercellular fluids, these electrodes also seem to have lower impedances than surface
electrodes of comparable interface area.
The usual method of measuring concentrations of ions or gases is to use one electrode
(sometimes called the indicator or active electrode) that is sensitive to the substance or ion
being measured and to choose the second, or reference electrode, of a type that is insensitive
to that substance.
1. Reference Electrode
A reference electrode is an electrode which has a stable and well-known electrode potential.
Since measurement of electrochemical concentrations simply requires a change of potential
proportional to a change in concentration, the electrode potential of the reference electrode
can be any amount, as long as it is stable and does not respond to any possible changes in the
composition of the solution being measured. Thus, the search for a good reference electrode
is essentially a search for the most stable electrode available.
Two types of electrodes have interfaces sufficiently stable to serve as reference electrodes—
the silver-silver chloride electrode and the calomel electrode.
An equally popular reference electrode is the calomel electrode. Calomel is another name for
mercurous chloride, a chemical combination of mercury and chloride ions. The interface
between mercury and mercurous chloride generates the electrode potential. By placing the
calomel side of the interface in a potassium chloride (KCl) filling solution, an electrolytic
bridge is formed to the sample solution from which the measurement is to be made. Like the
silver-silver chloride electrode, the calomel electrode is very stable over long periods of time
and serves well as a reference electrode in many electrochemical measurements. Also, Uke
the silver-silver chloride electrode, the electrode potential of the calomel electrode depends
on the concentration of KCl. An electrode with a 0.01-mole solution of KCl has an electrode
potential of 0.388 V, whereas a saturated KCl solution (about 3.5 moles) has a potential of
only 0.247 V.
2. The pH Electrode:
Perhaps the most important indicator of chemical balance in the body is the pH of the blood
and other body fluids. The pH is directly related to the hydrogen ion concentration in a fluid.
Specifically, it is the logarithm of the reciprocal of the H+ ion concentration. In equation
form,
The pH is a measure of the acid-base balance of a fluid. A neutral solution (neither acid nor
base) has a pH of 7. Lower pH numbers indicate acidity, whereas higher pH values define a
basic solution. Most human body fluids are slightly basic. The pH of normal arterial blood
ranges between 7.38 and 7.42. The pH of venous blood is 7.35, because of the extra CO2.
Because a thin glass membrane allows passage of only hydrogen ions in the form of H3O+, a
glass electrode provides a membrane interface for hydrogen. The principle is illustrated in
Figure 15. Inside the glass bulb is a highly acidic buffer solution. Measurement of the
potential across the glass interface is achieved by placing a silver-silver chloride electrode in
the solution inside the glass bulb and a calomel or silver-silver chloride reference electrode in
the solution in which the pH is being measured. In the measurement of pH and, in fact, any
electrochemical measurement, each of the two electrodes required to obtain the measurement
is called a half-cell. The electrode potential for a half-cell is sometimes called the half-cell
potential. For pH measurement, the glass electrode with the silver-silver chloride electrode
inside the bulb is considered one half-cell, while the calomel reference electrode constitutes
the other half-cell.
The type of glass used for the membrane has much to do with the pH response of the
electrode. Special hydroscopic glass that readily absorbs water provides the best pH response.
Modern pH electrodes have impedances ranging from 50 to 500 megohms (MΩ). Thus, the
input of the meter that measures the potential difference between the glass electrode and the
reference electrode must have an extremely high input impedance. Most pH meters employ
electrometer inputs.
The other more important physiological chemical measurements are the partial pressures of
oxygen and carbon dioxide in the blood. The partial pressure of a dissolved gas is the
contribution of that gas to the total pressure of all dissolved gases in the blood. The partial
pressure of a gas is proportional to the quantity of that gas in the blood.
The partial pressure of oxygen, PO2, often called oxygen tension, can be measured both in
vitro and in vivo. The basic principle is shown in Figure 17. A fine piece of platinum or some
other noble metal wire, embedded in glass for insulation purposes, with only the tip exposed,
is placed in an electrolyte into which oxygen is allowed to diffuse.
If a voltage of about 0.7 V is applied between the platinum wire and a reference electrode
(also placed into the electrolyte), with the platinum wire negative, reduction of the oxygen
takes place at the platinum cathode. As a result, an oxidation-reduction current proportional
to the partial pressure of the diffused oxygen can be measured. The electrolyte is generally
sealed into the chamber that holds the platinum wire and the reference electrode by means of
a membrane across which the dissolved oxygen can diffuse from the blood.
The platinum cathode and the reference electrode can be integrated into a single unit (the
Clark electrode). This electrode can be placed in a cuvette of blood for in vitro
measurements, or a micro version can be placed at the tip of a catheter for insertion into
various parts of the heart or vascular system for direct in vivo measurements.
One of the problems inherent in this method of measuring PO2 is the fact that the reduction
process actually removes a finite amount of the oxygen from the immediate vicinity of the
cathode. By careful design and use of proper procedures, modern PO2 electrodes have been
able to reduce this potential source of error to a minimum. Another apparent error in PO2
measurement is a gradual reduction of current with time. This effect, generally called aging,
has also been minimized in modern PO2 electrodes.
The measurement of the partial pressure of carbon dioxide, P C02, makes use of the fact that
there is a linear relationship between the logarithm of the PC02 and the pH of a solution. Since
other factors also influence the pH, measurement of PC02 is essentially accomplished by
surrounding a pH electrode with a membrane selectively permeable to CO2. A modern,
improved type of PC02 electrode is called the Severinghaus electrode.
In this type of electrode, the membrane permeable to the CO2 is made of Teflon, which is not
permeable to other ions that might affect the pH. The space between the Teflon and the glass
contains a matrix consisting of thin cellophane, glass wool, or sheer nylon. This matrix serves
as the support for an aqueous bicarbonate layer into which the CO2 gas molecules can diffuse.
One of the difficulties with older types of CO2 electrodes is the length of time required for the
CO2 molecules to diffuse and thus obtain a reading. The principal advantage of the
Severinghaus-type electrode is the more rapid reading that can be obtained because of the
improved membrane and bicarbonate layer.
In some applications, measurements of PO2 and PC02 are combined into a single electrode that
also includes a common reference half-cell. Such a combination electrode is shown in
diagram form in Figure 18.
Just as the glass electrode provides a semipermeable membrane for the hydrogen ion in the
pH electrode, other materials can be used to form membranes that are semipermeable to other
specific ions. In each case, measurement of the ion concentration is accomplished by
measurement of potentials across a membrane that has the correct degree of permeability to
the specific ion to be measured.
The permeability should be sufficient to permit rapid establishment of the electrode potential.
Both liquid and solid membranes are used for specific ions. As in the case of the pH
electrode, a silver-silver chloride interface is usually provided on the electrode side of the
membrane, and a standard reference electrode serves as the other half-cell in the solution.
Figure 4.19 shows a solid-state electrode of the type used for measurement of fluoride ions.
Figure 4.20 shows three specific ion electrodes along with a pH glass electrode. The sodium
electrode in Figure 4.20(a) is commonly used to determine sodium ion activity in blood and
other physiological solutions. The cationic electrode (b) is used when studying alkaline metal
ions or enzymes. The ammonia electrode (d) is designed for determinations of ammonia
dissolved in aqueous solutions.
Figure 21 is a diagram showing the construction of a flow-through type of electrode. This is a
liquid-membrane, specific-ion electrode. One of the difficulties encountered in the
measurement of specific ions is the effect of other ions in the solution. In cases where more
than one type of membrane could be selected for measurement of a certain ion, the choice of
membrane actually used might well depend on other ions that may be expected. In fact, some
specific-ion electrodes can be used in measurement of a given ion only in the absence of
certain other ions.
For measurement of divalent ions, a liquid membrane is often used for ion exchange. In this
case, the exchanger is usually a salt of an organophosphoric acid, which shows a high degree
of specificity to the ion being measured. A calcium chloride solution bridges the membrane
to the silver-silver chloride electrode. Electrodes with membranes of solid materials are also
used for measurement of divalent ions.
Cell organization:
Regardless of the type of cell, all cells have some similarities in features. These include the
cytoplasm, cell membrane, ribosomes, and DNA and RNA. Eukaryotic cells have a large
assortment of structures and organelles.