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SENSORS TECHNOLOGY SERIES

EDITOR-IN-CHIEF’S PREFACE

In recent years the interface between the life sciences and the physical sciences has become inhabited by
researchers and practitioners with knowledge and expertise in both areas. This is a very welcome trend
because traditionally it has been difficult for the physical scientist to appreciate the needs of the life
scientist or medical practitioner, and equally difficult for the biomedical community to ascertain what
might be possible in physical terms. Happily, this gulf is rapidly being filled. In particular, the develop-
ment of instruments based on physical, chemical, and biological principles has burgeoned. Inevitably,
as with all things, there are downsides, the predominant one in the medical context being related to
cost, which for some installations can represent several millions of dollars.
However, rather more modest analytical instruments require sensors of various types as well, and
this volume presents a selection of these, complete with detailed background material on the scientific
and technical principles relevant to each. Such multifaceted work represents a major ongoing interna-
tional endeavor and, as such, merits more comprehensive bibliographical material than do some of the
more mature topics in other volumes of the series. The descriptive material and relevant bibliographies
in the present compilation have been provided by an author list of leading scientists in their various
specialties assembled by the volume editor, Deric Jones, who has drawn upon his experience as Head of
Medical Electronics & Physics at the Medical School of St. Bartholomew’s Hospital in the University
of London. These authors have in turn drawn upon their own experiences to present authoritative
reviews of sensors ranging from basic devices for measuring temperature and flow, through both ion-
izing and nonionizing radiation, to transducers for ultrasound, chemical, and biological sensing.

J. Watson
Editor-in-Chief
July 2010

ABOUT THE EDITOR-IN-CHIEF

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Joseph Watson is an electrical engineering graduate of the University of Nottingham, England,

and the Massachusetts Institute of Technology. He has published books and papers in various areas

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including electronic circuit design, nucleonics, biomedical electronics, and gas sensors and has been
a visiting professor at the University of Calgary, Canada, and the University of California, Davis and
Santa Barbara. Dr. Watson has held various consultancies with firms in the United States, Canada, and
Japan and since retirement from the University of Wales, Swansea, has continued as chairman of the
UK-based Gas Analysis and Sensing Group and as editor-in-chief for the Sensors Technology Series
for Momentum Press.
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PREFACE

BACKGROUND
In 400 b.c. the Greek physician Hippocrates placed his hand on a patient’s forehead and used the sense
of touch to estimate body temperature. The five human senses were effectively the only sensors available
to the “father of medicine” and his descendents until the seventeenth century when the first objective
biomedical sensor in the form of a crude thermometer was devised. However, it was only toward the
end of the nineteenth century that developments in science made possible significant advances in bio-
medical sensor technology. The twentieth century and the modern era of biomedical technology may
have been ushered in when, in November 1895, Wilhelm Röntgen astonished the medical profession
and the world with an X-ray image of his wife’s hand that he obtained using photographic film as a sen-
sor. Twenty-four centuries after Hippocrates, sensors now extend the range of human senses to make
possible diagnostic and therapeutic techniques that the ancient Greeks could never have envisioned.
Almost all modern biomedical measurement and imaging systems depend upon sensors of one kind or
another, although in many cases they are not immediately evident, often being hidden deep within the
medical instrument. Today it is quite common for there to be a number of sensors embedded within
the same medical device; for example, the ubiquitous hospital blood gas analyzer will routinely incor-
porate more than half a dozen sensors, one for each gas and substance to be analyzed.

WHAT IS A SENSOR?
The broadest and simplest definition of a sensor is “anything that responds to an input of interest.”
However, a general-purpose dictionary definition is “a device that detects or measures some condi-
tion or property and records, indicates, or otherwise responds to the information received.” Although
this is an excellent everyday definition, for biomedical engineering and medical physics purposes it is
too imprecise. A device that merely “detects some condition or property,” presumably by registering
the presence or absence of a physical quantity with a simple yes-or-no response, would be called a
“detector,” not a sensor. Although detectors have important uses in medicine, especially as the basis of
alarms, they are not generally regarded as sensors. For practical biomedical applications a sensor is bet-
applicable copyright law.

ter defined as “a device that responds to a physical input of interest with a recordable functionally related
output that is usually electrical or optical.” In a biomedical context, of course, the term physical input is
taken to include chemical and biochemical quantities and concentrations. A device with an electrical
output satisfies the “records or indicates” criterion in the general dictionary definition because electri-
cal signals can be amplified and processed readily to give a display on a monitor, an output on a chart

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recorder, or an input to a digital data storage system. Sometimes a sensor’s optical output signals are
the required output—in imaging, for example—but any optical output signal can usually be converted
fairly easily into an electrical signal by means of a photosensor.
It is the requirement that the output be functionally related to the physical quantity of the input
that distinguishes a sensor from a yes–no detector. The most desirable functional relationship is a
simple linear one, whereby a doubling of the input physical quantity results in a doubling of the elec-
trical or optical output. Such a relationship usually leads to a relatively simple calibration procedure.
Unfortunately, many common and widely utilized sensors do not exhibit such linear behavior—
a thermistor for temperature measurement, for example—but nevertheless they can still be made into
useful practical devices by using suitable, if more elaborate, calibration methods (see Chapter 1).
The terms sensor and transducer are often used synonymously, although there are times when this
may not be appropriate. It seems to be generally accepted in science and technology that a working
definition of a transducer is “a device that converts one form of energy into another, the latter often
being electrical.” A sensor usually meets this criterion and can therefore also be described as a trans-
ducer. Even sensors of biochemical quantities or concentrations are somehow converting chemical
energy into electrical or optical energy. However, a transducer, unlike a sensor, does not necessarily
have an electrical or optical output that is intended to be recordable and also functionally related
to its input. An example of this is in ultrasonic imaging (see Chapter 6), where the same probe has
two quite separate functions: (1) to generate the ultrasonic waves that enter the human body and
(2) to respond to, or sense, the ultrasonic echoes from tissue interfaces within the body. In the first case
the probe is acting as a transducer, converting a short pulse of electrical energy into ultrasonic mechani-
cal energy; in the second case the probe acts as a sensor, converting the incident ultrasonic mechanical
energy in the echo into an electrical signal that is processed to give the recorded image. On the basis
of this distinction, transducers can sometimes be regarded as components of sensors. For example, a
diaphragm in a microphone or a pressure sensor converts sound or pressure energy into strain energy in
the diaphragm; a second transducer stage is required to convert this strain energy into recordable elec-
trical energy in order to make a complete sound or pressure sensor. The use of the word sensor allows a
distinction to be made between a device that gives a measurable recordable output that is functionally
related to changes in a physical quantity at its input, and a device for converting one form of energy
into another—a transducer, which may not necessarily have the properties of a sensor.

SCOPE OF THIS VOLUME

This volume includes a wide range of topics in biomedical engineering and medical physics. However,
the subject of biomedical sensors has grown very rapidly in the last three decades and now encompasses
such a huge field that even a “comprehensive” treatment of this sensor technology must, of necessity,
be selective. The choice of topics was influenced principally by their clinical relevance and also to some
extent by the contents of a long-established graduate-taught master’s course at the Medical School of
St. Bartholomew’s Hospital, London, UK, that the editor organized. It was decided to include sensors
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associated with the measurement of temperature, fluid flow, radiation (including ionizing radiation, non-
ionizing radiation, and ultrasound), and also chemical and biochemical sensors, including biosensors.
Those sensors associated with purely mechanical physical quantities have not been treated as primary
subjects in this volume. Hence, sensors for the measurement of position, force, pressure, and acceleration,
which are all of particular importance in the field of biomechanics, have been left for the present.

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The aim here is to emphasize the technological principles and the practical applications of bio-
medical sensors rather than the theoretical concepts. The treatments in the chapters usually include
details of the technical principles of the sensor together with those of any associated peripheral devices
essential for registering the response of the sensor. Examples of the practical applications of the systems
associated with the sensors have been included, but detailed discussions of the operations of complete
systems have been avoided. Generally the volume concentrates on sensors that are currently used in
practice or are likely to be used in the near future. Research laboratory techniques that are speculative
or a long way from being practically viable in a clinical context have not been included. Some chapters,
where appropriate, contain critical comparisons of manufacturers’ sensor data.

READERSHIP
This volume is intended to provide a good initial introduction and reference source for biomedical
engineers and medical physicists who need to become acquainted with new fields and topics. It should
act as a reliable guide to the bewildering array of more specialized literature and texts on the subject.
The contents should be accessible to a broad range of professionals in biomedicine, including practic-
ing experienced biomedical engineers, medical physicists, clinical technologists, and clinicians working
in a hospital or other health care environment.
Academics in higher education institutions will find the book an invaluable resource to further their
scholarship and advance research projects on sensors and other medical devices. In addition, students should
benefit from a well-written, advanced textbook suitable for those final-year undergraduate, postgraduate,
and research students aiming to pursue a career in the field of medical physics or biomedical engineering.
Engineers and applied physicists working for health care providers or for the pharmaceutical and
medical instrumentation industries will find in this volume a rich source of relevant information. It
also contains essential tools to help solve practical problems encountered in both routine applications
and the challenges of advanced development work.

THE CONTENTS
The majority of the distinguished authors who have contributed to Biomedical Sensors have had
decades of practical experience in biomedical engineering and medical physics. Moreover, the authors
have well-established international reputations and many are world-renowned experts in their fields.
The chapters are organized according to the measurand being considered, that is, the physical
quantity being sensed and measured (e.g., temperature, ionizing radiation, or chemical concentration).
The first chapter deals with the measurement of the temperature of the human body. Temperature
has been used by physicians since the earliest times for the diagnosis and monitoring of disease. Given
its fundamental importance, it is surprising that there have been so few comprehensive reviews of the
subject. It is almost as if it is taken for granted that anyone can measure body temperature accurately
if required. This chapter shows that this is not necessarily true, particularly as there are now so many
applicable copyright law.

possible techniques, some intended for specific applications, that the choice of an appropriate method
to give accurate reliable results is often not easy. Chapter 1 provides a timely overview of modern
clinical thermometry and gives a critical assessment of the accuracy and applicability of the various
methods available to the physician, surgeon, parents, and others for whom assessing the temperature
of the human body is of vital importance.

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Chapter 2 is primarily concerned with the most important liquid in the body, which is, of course,
blood. The measurement of blood velocity and blood flow in arteries and veins is a major activ-
ity for large numbers of biomedical engineers and medical physicists. The quantitative estimation of
blood flow in the limbs and in various organs is of great value in many diagnostic investigations, and
advances in the subject have made significant contributions to cardiology. The chapter provides a com-
prehensive review of the traditional flow measurement techniques, such as indicator dilution methods,
plethysmography, and ultrasound for arteries and veins. It also covers more modern techniques such as
ultrasonic Doppler methods in cardiology and functional magnetic resonance imaging (MRI) in the
brain. More advanced topics, such as the use of contrast agents in ultrasonic imaging and MRI in the
quantitative analysis of dynamic processes are also discussed. The chapter ends with a brief overview of
the measurement of flow in other fluids, including urine, saliva, tears, and gastric acids.
Chapter 3, on respiratory flow sensors, considers another fluid, namely, the gas that flows out of
and into the human lung. It requires the use of quite specialized techniques that are different from
those outlined in Chapter 2 for liquids. Every large hospital has a pulmonary function laboratory,
because respiratory disease is one of the most significant public health burdens in developed countries.
Indeed, respiratory diseases account for about one-third of all deaths in the United States. It might be
thought that the measurement of airflow is relatively simple, but there are many technical challenges
associated with the application of flow sensors in pulmonary medicine. These are dealt with in an
exemplary manner in this chapter.
Chapter 4 deals comprehensively with ionizing radiation sensors in medicine, a field that is
primarily the preserve of medical physicists, but also engages numerous engineers in the design, devel-
opment, and maintenance of medical X-ray equipment. The importance of ionizing radiation can be
judged from the fact that it is likely that two-thirds or more of all the clinical engineers and scientists
working in hospital environments are employed in X-ray or other ionizing radiation–related activities
in diagnostic imaging, radiotherapy, nuclear medicine, and radiation protection. The chapter gives
an overview of the basic requirements for sensing ionizing radiation, the interactions with materials,
and the criteria for assessing the performance of the sensors. It goes on to treat sensors for dosim-
etry ranging from semiconductors and radiographic film to diamond and outlines their advantages
and disadvantages. Next, sensors for imaging are reviewed, including radiographic film and flat-panel
detectors, while the characteristics of various scintillator materials for sensors are also outlined. Specific
applications and advances in imaging in computed tomography (CT), mammography, single photon
emission computed tomography (SPECT), and positron emission tomography (PET) are also covered.
The final part deals with sensors for ionizing radiation spectroscopy and concludes with examples of
detector selection in a series of case studies.
Chapter 5 deals with nonionizing electromagnetic radiation and radiometric and photometric
measurements. Lasers have played an important role in biomedicine for more than three decades,
finding significant applications in ophthalmology, surgery, and photodynamic therapy for cancer
treatment. In Europe, recent directives on the use of artificial optical radiation in the workplace are
being implemented, while in the United States, the Food and Drug Administration (FDA) Center for
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Devices and Radiological Health produces similar guidance notes. There is also an increasing use of
ultraviolet (UV) light therapy for the treatment of eczema and hyperbilirubinemia in newborn babies,
up to 60% of whom may suffer from this condition. This authoritative chapter is timely, as there is a
growing need to understand the challenges faced in obtaining accurate dosimetry measurements with
nonionizing radiation, particularly when it is required to make comparisons with other treatment

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centers. There is an explanation of radiometric and photometric terms and a review of measurement
sensors. Radiometric sensors for the measurement of UV irradiance in phototherapy treatment and
their application are discussed. The chapter ends with a section on the objective measurement of solar
radiation at the earth’s surface and, in particular, the measurement of sun-burning UV radiation, a
topic of some importance with the increasing incidence of skin cancer worldwide.
Ultrasonic imaging was originally developed in the 1960s to replace potentially damaging X-rays
in fetal imaging. It now finds applications not only in obstetrics, but in a wide range of disciplines from
cardiology to ophthalmology and gastroenterology. Chapter 6 reviews in depth the probes that gener-
ate and sense the ultrasonic signals that enter the human body in ultrasonic imaging. It complements
the sections on ultrasonic flow measurements in Chapter 2. The principles of operation of the probes
are outlined and various practical electrical and acoustical models of the sensors are developed. The
construction of single-element probes and multielement arrays is considered and the characteristics of
various modern piezoelectric materials used to make the probes are compared. Focusing principles and
performance criteria are established, followed by some examples of the clinical applications of phased
and linear arrays. Finally, advanced topics such as multimode operation and the construction of two-
dimensional arrays are considered.
The measurement of the concentrations of the various chemical components of blood is of great
importance in the diagnosis and treatment of disease. Blood gas analyzers are among the most signifi-
cant of medical instruments and operate 24 hours a day, every day, in all major hospitals. Gas sensors
also perform a vital role in anesthesia, measuring accurately the concentrations of the anesthetic agents.
Chapter 7 is a comprehensive overview of the principles of the sensors used to measure these and other
chemical compounds. Electrochemical sensors for the measurement of pH, pO2 (the partial pressure of
oxygen), and pCO2 (the partial pressure of carbon dioxide) in blood both noninvasively and invasively
are described. Advanced miniature microelectromechanical systems (MEMS) for sensing blood pO2 and
pCO2 and similar ion-selective field effect transistors (ISFETs) for pH are covered. Optical fiber chemi-
cal sensors for pH, pCO2, and invasive and noninvasive blood oximetry are reviewed. The principles of
gas phase sensors for the real-time measurement of the concentrations of oxygen, carbon dioxide, and
anesthetic gases in respiratory medicine and anesthesia are outlined. There is also a review of a variety of
methods for blood glucose sensing from optical and electrochemical sensors to biosensors. Some of the
latter part of this section complements the following chapter on biosensors. Finally, a highly sensitive
acoustic chemical sensor is described that makes use of a quartz crystal microbalance coated with zeolite
to detect acetone in the breath for the diagnosis of diabetes and for other clinical analyses.
Biosensors have evolved from the marriage of two disciplines: optoelectronics technology, exem-
plified by microcircuits and optical fibers, and molecular biology. They are among the most exciting
and challenging developments in analytical devices and have the potential to make continuous mea-
surements of blood chemistry at the bedside or, by means of a chip on a catheter, in a patient’s vein.
They incorporate a biological recognition element that interacts with a target molecule to provide a
highly selective sensor. Drugs, metabolites, proteins, and nucleic acids are all targets for biosensors.
Chapter 8 introduces and reviews enzyme-based biosensors—in particular, those based on glucose
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oxidase, used to estimate blood glucose, and urease for the estimation of blood urea. Enzyme immo-
bilization techniques are described, from physical entrapment and chemical immobilization to surface
adsorption. Optical biosensors, including optical fibers, surface plasmon resonance, and attenuated
total reflection types are covered. Modified electrochemical biosensors that can be used for home glu-
cose monitoring are also described. Microfabricated enzyme-linked field effect transistors (ENFETs),

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whole cell biosensors, and nanobiosensors are discussed. Biosensors have enormous potential, but
there are also formidable challenges for practical utilization, which are outlined clearly in this chapter.
The problems include robustness and lifetime and operational stability, but these are being resolved
using a variety of sensors, formatting techniques, and MEMS.
Medical thermography is the ultimate noninvasive investigative technique in which clinically
relevant information is obtained without any contact with the patient and without the use of pen-
etrating radiation. It is the subject of the final chapter and uses infrared (IR) radiation that is passively
emitted by the human body. Medical thermography is a fine example of “swords into plowshares”
technology transfer, because most of the significant advances in the challenging field of IR imaging
have been made for military purposes. Thermography is unique in providing quantitative informa-
tion on inflammatory processes (e.g., in rheumatic diseases), and modern cameras are even capable of
detecting infection in passengers at airport gates. In addition, skin diseases, nerve injuries, industrial
and sports injuries, and disruptions to the peripheral circulation have all been investigated using IR
imaging. This chapter complements Chapter 5, in that it describes a practical application of IR radi-
ometry. It begins with an historical overview of IR detection and imaging and the development of early
thermographic cameras. The IR spectrum and its subdivisions and the laws governing the emission of
IR radiation are then described. Next, IR camera characteristics and the measurement of IR radiation
using IR thermometers and thermal imagers are reviewed, followed by an outline of the development
of modern focal-plane imaging arrays. Finally, the characteristics of a variety of sensors, from minia-
ture bolometers to photon detectors, are described and figures of merit for assessing thermal camera
performance are discussed.
The design, manufacture, distribution, and maintenance of sensors and the biomedical systems
that depend on them are of immense and growing commercial significance. Multimillion-dollar com-
panies, such as the biomedical divisions of General Electric, Philips, and Siemens, together with scores
of other smaller enterprises, all base their prosperity on sensors, since virtually all their biomedical
products depend critically on the reliable functioning of sensors of one kind or another.
Advanced biomedical sensors represent a commendable application of cutting-edge technology
for the benefit of humanity. The practice of modern medicine would be impossible without them.
The authors of this volume have communicated not only their consummate expertise, but also their
enthusiasm for the subject. Readers will find here a rich source of practical knowledge and, it is hoped,
the inspiration to make their own contributions to this rapidly expanding and important field.

ACKNOWLEDGMENTS
It is a pleasure to acknowledge the encouragement of Stuart J. Meldrum of the Norfolk and Norwich
University Hospital, United Kingdom, and Michael R. Neuman of Michigan Technological University
in the initial stages of this project. I am grateful to Stuart Meldrum for reading and providing invalu-
able comments on the manuscript of Chapter 3. I should also like to express my gratitude to all the
distinguished authors who have interrupted their busy schedules to contribute to this volume. With-
applicable copyright law.

out them it would not exist. The original concept for the “Comprehensive Sensor Technology” series
came from Joe Watson, the series editor. His steadfast enthusiasm, determination, and tenacity have

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overcome many obstacles to ensure that the series is being published. I am deeply indebted to him for
his sound advice, for his unfailing support, and for much more. Finally, I would like to thank my wife,
Jennifer, for her forbearance and patience.

Deric P. Jones
Editor
Biomedical Engineering
School of Engineering & Mathematical Sciences
City University
Northampton Square, London
July 14, 2010

ABOUT THE EDITOR

Professor Deric Powell Jones BSc DIC PhD was born in Monmouthshire,
South Wales, and received the degrees of BSc in physics and PhD in the super-
conductivity of alloys from Imperial College, London. He worked as a medical
physicist at St. Bartholomew’s Hospital and then as a lecturer at the Medi-
cal School. During more than twenty-five years spent at St. Bartholomew’s he
became a reader in the University of London and head of Medical Electronics
and Physics in the Medical School. His research interests include the appli-
cation of opto-electronic techniques in anesthesia and surgery and also the
development of new techniques for physiological measurements in respiration
and ophthalmology. He is a fellow of the UK Institute of Physics and of the UK Institute of Physics
and Engineering in Medicine and a chartered engineer and a senior member of the Institute of Elec-
trical and Electronics Engineers. Professor Jones is currently affiliated to the Biomedical Engineering
Department at City University, London.
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CHAPTER 1

BIOMEDICAL SENSORS
TEMPERATURE SENSOR TECHNOLOGY

P. A. Kyriacou
School of Engineering and Mathematical Sciences
City University, London, UK

The clinical thermometer ranks in importance with the stethoscope. A doctor without his ther-
mometer is like a sailor without his compass.

—Family Physician, 1882

1.1. INTRODUCTION
Human body temperature is of vital importance to the well-being of the person and therefore it is
routinely monitored to indicate the state of the person’s health. Despite the fact that temperature
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Celsius thermometer (attached to a barometer) made by J. G. Hasselström, Stockholm, late

eighteenth century.

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