Medical INSTRUMENTATION Shahall and

MEDICAL
INSTRUMENTATION Shahall and —
John G. Webster, Editor Toe nm eller
MEDICAL INSTRUMENTATION
Application and Design
MEDICAL INSTRUMENTATION
Application and Design
FOURTH EDITION
John G. Webster, Editor
Contributing Authors
John W. Clark, Jr.

Rice University
Michael R. Neuman
Michigan Technological University
Walter H. Olson
Medtronic, Inc.
Robert A. Peura
Worcester Polytechnic Institute
Frank P. Primiano, Jr.

Consultant
Melvin P. Siedband
University of Wisconsin-Madison
John G. Webster
University of Wisconsin-Madison
Lawrence A. Wheeler
Nutritional Computing Concepts
@)
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Library of Congress Cataloging-in-Publication Data
Medical instrumentation : application and design / John G. Webster, editor ; contributing

authors, John W. Clark Jr... . [et al.]. — 4th ed.
p.;cm.
Includes bibliographical references and index.
ISBN 978-0-471-67600-3 (cloth)
1. Medical instruments and apparatus. 2. Physiological apparatus. I. Webster, John G.,
1932— II. Clark, John W. (John William), 1936—
[DNLM: 1. Equipment and Supplies. 2. Biomedical Engineering — instrumentation.
3. Equipment Design. W 26 M4898 2009]
R856.M376 2009
610.28-dce22
2008042917
ISBN-13 978-0471-67600-3
Printed in the United States of America
10987654321
PREFACE
Medical Instrumentation: Application and Design, Fourth Edition, is written
for a senior to graduate-level course in biomedical engineering. It describes the
principles, applications, and design of the medical instruments most commonly
used in hospitals. Because equipment changes with time, we have stressed
fundamental principles of operation and general types of equipment, avoiding
detailed descriptions and photographs of specific models. Furthermore, be-
cause biomedical engineering is an interdisciplinary field requiring good
communication with health-care personnel, we have provided some applica-
tions for each type of instrument. However, to keep the book to a reasonable
length, we have omitted much of the physiology.
Most of those who use this text have had an introductory course in
chemistry, are familiar with mathematics through differential equations,
have a strong background in physics, and have taken courses in electric circuits
and electronics. However, readers without this background will gain much
from the descriptive material and should find this text a valuable reference. In
addition, we recommend reading background material from an inexpensive
physiology text, such as W. F. Ganong’s Review of Medical Physiology, 22nd
edition (New York: McGraw-Hill, 2005).
EMPHASIS ON DESIGN
Throughout the book, we emphasize design. A scientist or engineer who has

some background in electronics and instrumentation will glean enough infor-
mation, in many of the areas we address, to be able to design medical
instruments. This ability should be especially valuable in those situations—
so frequently encountered—where special instruments that are not commer-
cially available are required.
PEDAGOGY
The book provides 300 homework problems, located at the end of each
chapter, plus 64 in-text worked examples. Problems are designed to cover a
Vv
vi PREFACE
wide variety of applications ranging from analysis of the waves of the electro-
cardiogram to circuit design of biopotential amplifiers and identification of
electric safety hazards.
REFERENCES
Rather than giving an exhaustive list of references, we have provided a list of
review articles and books that can serve as a point of departure for further
study on any given topic.
ORGANIZATION
Each chapter has been carefully reviewed and updated for the fourth edition,
and many new examples and references are included.
Chapter 1 covers general concepts that are applicable to all instrumen-

tation systems, including on the commercial development of medical instru-
ments, on biostatistics, and on the regulation of medical devices. Chapter 2
describes basic sensors, and Chapter 3 presents the design of amplifiers for
them. Chapters 4 through 6 deal with biopotentials, tracing the topic from
the origin of biopotentials, through electrodes, to the special amplifier
design required.
Chapters 7 and 8 cover the measurement of cardiovascular dynamics—

pressure, sound, flow, and volume of blood. Chapter 9 presents the measure-
ment of respiratory dynamics—pressure, flow, and concentration of gases.
Chapter 10 describes the developing field of biosensors: sensors that

measure chemical concentrations within the body via catheters or implants.
Chapter 11 describes that area in the hospital where the greatest number of
measurements is made, the clinical laboratory. Chapter 12 starts with general
concepts of medical imaging and shows their applications to x-ray techniques,
magnetic resonance imaging, positron emission tomography, and Doppler
ultrasonic images.
Chapter 13 deals with devices used in therapy, such as the pacemaker,

defibrillator, cochlear prosthesis, transcutaneous electrical nerve stimulation,
implantable automatic defibrillators, the total artificial heart, lithotripsy, infant
radiant warmers, drug infusion pumps, and anesthesia machines. Chapter 14
presents a guide both to electric safety in the hospital and to minimization of
hazards.
We have used the recommended International System of Units (SI)

throughout this book. In the case of units of pressure, we have presented
both the commonly used millimeters of mercury and its SI unit, the pascal. To
help the reader follow the trend toward employing SI units, the Appendix
provides the most common conversion factors. The Appendix also provides a
number of physical constants used in the book and a list of abbreviations.
A Solutions Manual containing complete solutions to all problems is
available free to adopters of this text.
PREFACE Vv
ACKNOWLEDGMENTS
We would like to thank the reviewers of previous editions.
First Edition Reviewers
David Arnett, Pennsylvania State University
Robert B. Northrup, University of Connecticut (Starrs)

Kenneth C. Mylrea, University of Arizona
Curran S. Swift, Jowa State University
Second Edition Reviewers

Jonathan Newell, Rensselaer Polytechnic Institute
Robert B. Northrup, University of Connecticut (Storrs)
Third Edition Reviewers
Noel Thompson, Stanford University
W. Ed Hammond, Duke University
Robert B. Northrup, University of Connecticut

Richard Jendrucko, University of Tennessee, Knoxville
Fourth Edition Reviewers
Paul J. Benkeser, Georgia Institute of Technology

Lawrence V. Hmurcik, University of Bridgeport
Art Koblasz, Georgia Institute of Technology
Anant Madabhushi, Rutgers University
Andrew Mason, Michigan State University
Ken Meissner, Texas A&M University

Peter Molnar, Clemson University
Homer Nazeran, The University of Texas at El Paso

John A. Pearce, The University of Texas at Austin
Nadine Barrie Smith, The Pennsylvania State University
The authors welcome your suggestions for improvement of subsequent print-

ings and editions.
John G. Webster
LIST OF SYMBOLS
This list gives single-letter symbols for quantities, without subscripts or

modifiers. Symbols for physical constants are given in Appendix A.1, multi-
letter symbols in Appendix A.4, and chemical symbols in Appendix A.5.
Symbol Quantity Introduced in Section

a Absorplivily 10.3
a Activity 5.2
a Coefficient 1.10
a Lead vector 6.2
A Absorbance 10.3
A Area 2.2
A Coefficient 1.9
A Gain 3.1
A Percent 1.7
b Coefficient 1.9
5 Intercept 1.9
B Coefficient 1.10
B Percent 1.9
B Viscous friction 1.10
B Magnetic flux density 8.3
c Coefficient 7A3
c Specific heat 8.1
c Velocity of sound 8.4
Cc Capacitance 1.10
Cc Compliance 73
Cc Concentration 10.3
Cc Contrast 12.1
d Derivative 1.10
d Diameter 1.10
d Distance 4.1
D Density 12.4
D Detector responsivity 2.17
(Continued )
xX
LIST OF SYMBOLS

D didt 1.10
D Diameter 5.8
D Diffusing capacity 98
D Distance 4.4
E emf 27
E Energy 2.13
E Exposure 12.4
E Irradiance 217
E Modulus of elasticity 73
f Force 2.6
f Frequency 1.10
f Function 4.2
F Filter transmission 217
F Flow 73
F Force 2.2
F Fraction 12.1
F Molar fraction 93
g Conductance/area 4.1
G Conductance 2.9
G Form factor 24
G Gage factor 2.2
G Gain 17
h Height 713
A Feedback gain 17
i Current 2.6
i Current 3.7
i Intensity 10.3
j +(-1)'? 1.10
J Number of standard deviations 12.1
k Constant 6.7
k Piezoelectric constant 2.6
K Constant 1.10
K Number 12.1
K Sensitivity 1.10
K Solubility product 53
K Spring constant 1.10
L Inductance 24
L Inertance 73
L Length 2.2
L Line-source response 12.10
m Average number 121
m Mass 73
m Slope 1.9
M Mass 1.10
M Measured values 12.2
M Modulation 12.1
M Cardiac vector 6.2
n Number 1.8
LIST OF SYMBOLS xi
Symbol
Quantity
Introduced in Section
Sobek eH RR SSE ECTS OP PENNANT TAA FT OOS AS yoy wt Sees
Refractive index
Noise equivalent bandwidth
Number
Turns ratio
Change in pressure
Probability
Power
Pressure
Projection
Charge
Rate of heat
Change in volume llow
Heat content
Volume flow
Correlation coefficient
Radius
Resistance/length
Range
Ratio
Resistance
Standard deviation
Modulation transfer function
Saturation
Slew rate
Source outpul
Thickness
Time
Interval
Temperature
Transmittance
Velocity
Work function
Molar uptake
Voltage
Change in volume
Voltage
Volume
Power
Weight
Weighting factor
Constant
Distance
Input
Chemical species
Effort variable
Value
Constant
2.14
12.3
5.3
3.13
9.1
12.1
1.9
73
12.8
2.6
8.1
9.1
8.2
9.1
1.8
73
4.2
8.4
10.3
1.10
1.8
12.2
10.1
3.11
217
5.8
1.10
1.10
2.8
11.1
4.2
12.6
9.1
1.10
9.1
1.10
2.2
2.10
10.3
12.8
10.3
2.4
17
9.1
1.9
1.8
10.3
(Continued )
xii LIST OF SYMBOLS
y Output 17
Y Admittance 1.9
Y Flow variable 1.9
Y Value 18
Zz Distance 4.1
Z Atomic number 12.6
Z Impedance 1.9
Greek Letters

a Polytropic constant 9.5
a Thermistor coefficient 2.9
a Thermoelectric sensitivity 2.8
B Thermistor constant 2.9
A Deviation 10.3
g Emissivity 2.10
g Dielectric constant 2.5
c Damping ratio 1.10
n Viscosily 73
0 Angle 2.14
A Logarithmic decrement 1.10
A Wavelength 2.10
i Attenuation coefficient 12.8
bb Mobility 5.2
bb Permeability 2.4
i Poisson’s ratio 2.2
p Density 73
p Mole density 9.1
p Resistivity 2.2
a Conductance 13.4
a Conductivity/distance 4.7
o Variance 12.1
T Time constant 1.10
@ Number of photons 12.6
o Phase shift 1.10
@ Divergence 8.4
® Potential 4.6
@ Frequency 1.10
CONTENTS
Preface v
List of Symbols ix
BASIC CONCEPTS OF
MEDICAL INSTRUMENTATION 1
Walter H. Olson
L1 Terminology of Medicine and Medical Devices 4

12 Generalized Medical Instrumentation System 5
13 Alternative Operational Modes 7
14 Medical Measurement Constraints 9
15 Classifications of Biomedical Instruments 12
16 Interfering and Modifying Inputs 12
L7 Compensation Techniques 13
18 Biostatistics 16
19 Generalized Static Characteristics 19
1.10 Generalized Dynamic Characteristics 25
111 Design Criteria 35
1.12 Commercial Medical Instrumentation Development Process 37
1.13 Regulation of Medical Devices 39

Problems 42
References 43
2 BASIC SENSORS AND PRINCIPLES 45

Robert A. Peura and John G. Webster
2.1 Displacement Measurements 45
2.2 Resistive Sensors 46
2.3 Bridge Circuits 53
2.4 Inductive Sensors 53
2.5 Capacitive Sensors 56
2.6 Piezoelectric Sensors 58
2.7 Temperature Measurements 62

2.8 Thermocouples 63
XIV
CONTENTS
29 Thermistors 66
2.10 Radiation Thermometry 69
2.11 Fiber-Optic Temperature Sensors 74
2.12 Optical Measurements 74
2.13 Radiation Sources 75
2.14 Geometrical and Fiber Optics 79
2.15 Optical Filters 82
2.16 Radiation Sensors 83
217 Optical Combinations 86

Problems 87
References 88
5 AMPLIFIERS AND SIGNAL PROCESSING 91

John G. Webster
3.1 Ideal Op Amps 91
3.2 Inverting Amplifiers 93
3.3 Noninverting Amplifiers 96
3.4 Differential Amplifiers 97

3.5 Comparators 100
3.6 Rectifiers 102
3.7 Logarithmic Amplifiers 103
3.8 Integrators 104
3.9 Differentiators 107
3.10 Active Filters 108
3.11 Frequency Response 110
3.12 Offset Voltage 112
3.13. Bias Current 114
3.14 Input and Output Resistance 115
3.15 Phase-Sensitive Demodulators 117
3.16 Timers 120
3.17. Microcomputers in Medical Instrumentation 122

Problems 123
References 125
4 THE ORIGIN OF BIOPOTENTIALS 126

John W. Clark, Jr.
4.1 Electrical Activity of Excitable Cells 126
4.2 Volume-Conductor Fields 135
43 Functional Organization of the Peripheral
Nervous System 138

4.4 The Electroneurogram 140
45
4.6
4.7
48
49
CONTENTS
The Electromyogram 144
The Electrocardiogram 147

The Electroretinogram 158
The Electroencephalogram 163

The Magnetoencephalogram 181
Problems 182
References 186
XV
BIOPOTENTIAL ELECTRODES 189

Michael R. Neuman
5.1 The Electrode—Electrolyte Interface 189
5.2 Polarization 192
53 Polarizable and Nonpolarizable Electrodes 196
5.4 Electrode Behavior and Circuit Models 202
55 The Electrode—Skin Interface and Motion Artifact 205
5.6 Body-Surface Recording Electrodes 209
5.7 Internal Electrodes 215
5.8 Electrode Arrays 220
5.9 Microelectrodes 222
5.10 Electrodes for Electric Stimulation of Tissue 231
5.11 Practical Hints in Using Electrodes 233
Problems 235
References 239
6 BIOPOTENTIAL AMPLIFIERS 241
Michael R. Neuman
6.1
6.3
6.4
6.5
6.6
6.7
6.8
6.9
6.10
Basic Requirements 241
The Electrocardiograph 243
Problems Frequently Encountered 254
Transient Protection 264
Common-Mode and Other Interference-Reduction

Circuits 266
Amplifiers for Other Biopotential Signals 269
Example of a Biopotential Preamplifier 274
Other Biopotential Signal Processors 275
Cardiac Monitors 282
Biotelemetry 287
Problems 288
References 291
CONTENTS
BLOOD PRESSURE AND SOUND 293

7A
7.2
7.3
74
75
7.6
7.7
78
79
7.10
7AL
7.12
7.13
7.14
Robert A. Peura
Direct Measurements 295
Harmonic Analysis of Blood-Pressure

Waveforms 300
Dynamic Properties of Pressure-Measurement

Systems 301
Measurement of System Response 308
Effects of System Parameters on Response 310
Bandwidth Requirements for Measuring

Blood Pressure 311
Typical Pressure-Waveform Distortion 311
Systems for Measuring Venous Pressure 313
Heart Sounds 314

Phonocardiography 318
Cardiac Catheterization 318
Effects of Potential and Kinetic Energy on

Pressure Measurements 323
Indirect Measurements of Blood Pressure 325
Tonometry 330
Problems 335
References 336
MEASUREMENT OF FLOW AND VOLUME

OF BLOOD 338
John G. Webster
8.1
8.2
8.3
8.4
8.5
8.6
8.7
Indicator-Dilution Method That Uses

Continuous Infusion 338
Indicator-Dilution Method That Uses

Rapid Injection 341
Electromagnetic Flowmeters 344
Ultrasonic Flowmeters 350

Thermal-Convection Velocity Sensors 361
Chamber Plethysmography 364
Electrical-Impedance Plethysmography 366
Photoplethysmography 372
Problems 374
References 375
CONTENTS
MEASUREMENTS OF THE
RESPIRATORY SYSTEM 377

Frank P. Primiano, Jr.
9.1 Modeling the Respiratory System 378
9.2 Measurement of Pressure 385
9.3 Measurement of Gas-Flow 388
9.4 Lung Volume 396
9.5 Respiratory Plethysmography 404
9.6 Some Tests of Respiratory Mechanics 411
9.7 Measurement of Gas Concentration 425
98 Some Tests of Gas Transport 436
Problems 443
References 446
10 cremicat siosensors 449
Robert A. Peura
10.1. Blood-Gas and Acid-Base Physiology 451
10.2 Electrochemical Sensors 453
10.3 Chemical Fibrosensors 461
10.4 Ton-Selective Field-Effect Transistor 475
10.5 Immunologically Sensitive Field-Effect
Transistor 478
10.6 Noninvasive Blood-Gas Monitoring 479
10.7 Blood-Glucose Sensors 486
10.8 Electronic Noses 492
10.9 Lab-on-a-Chip 493
10.10 Summary 494
Problems 495
References 495
1 1 CLINICAL LABORATORY
INSTRUMENTATION 498
Lawrence A. Wheeler
111
11.2
113
11.4
Spectrophotometry 499
Automated Chemical Analyzers 508
Chromatology 512
Electrophoresis 515
CONTENTS
11.5 Hematology 517

Problems 526
References 527
1 2 MEDICAL IMAGING SYSTEMS 528
Melvin P. Siedband
12.1 Information Content of an Image 528
12.2. Modulation Transfer Function 535
12.3 Noise-Equivalent Bandwidth 536
12.4 — Television Systems 537
12.5 Radiography 540
12.6 Computed Radiography 549
12.7. Computed Tomography 553
12.88 Magnetic Resonance Imaging 561
12.9 Nuclear Medicine 566
12.10 Single-Photon Emission Computed
Tomography 572
12.11 Positron Emission Tomography 573
12.12 Ultrasonography 576
12.13 Contrast Agents 585
Problems 587
References 589
1 5 THERAPEUTIC AND PROSTHETIC DEVICES 590
Michael R. Neuman
13.1. Cardiac Pacemakers and Other Electric
Stimulators 590
13.2. Defibrillators and Cardioverters 606
13.3. Mechanical Cardiovascular Orthotic
and Prosthetic Devices 611
13.4 Hemodialysis 615
13.5 Lithotripsy 618
13.6 Ventilators 619
13.7. Infant Incubators 622
13.8 Drug Delivery Devices 624
13.9 Surgical Instruments 629
13.10 Therapeutic Applications of the Laser 632
Problems 633
References 635
CONTENTS
1 4 ELECTRICAL SAFETY
xix
638
Walter H. Olson
141 “Physiological Effects of Electricity 639
14.2 Important Susceptibility Parameters 641
143 = Distribution of Electric Power 646
14.4 Macroshock Hazards 650
14.5 Microshock Hazards 653
146 ~~ Electrical-Safety Codes and Standards 658
14.7. Basic Approaches to Protection Against Shock 659
14.8 — Protection: Power Distribution 660
14.9 Protection: Equipment Design 663
14.10 Electrical-Safety Analyzers 667
14.11 Testing the Electric System 667
14.12 Tests of Electric Appliances 669
Conclusion 673
Problems 673
References 674
APPENDIX 676
A.l Physical Constants 676
A2 International System of Units (SI) Prefixes
(Thompson and Taylor, 2008) 676
A3 International System of Units
(Thompson and Taylor, 2008) 677
A4 Abbreviations 678
AS Chemical Elements 681
INDEX 683
BASIC CONCEPTS OF MEDICAL

INSTRUMENTATION
Walter H. Olson
The invention, prototype design, product development, clinical testing, regu-

latory approval, manufacturing, marketing, and sale of a new medical instru-
ment add up to acomplex, expensive, and lengthy process. Very few new ideas
survive the practical requirements, human barriers, and inevitable setbacks of
this arduous process. Usually there is one person who is the “champion” of a
truly new medical instrument or device. This person—who is not necessarily
the inventor—must have a clear vision of the final new product and exactly how
it will be used. Most importantly, this person must have the commitment and
persistence to overcome unexpected technical problems, convince the
naysayers, and cope with the bureaucratic apparatus that is genuinely needed
to protect patients.
One of five inventors’ stories from New Medical Devices: Invention,

Development and Use (Eckelman, 1988) is reprinted here to illustrate this
process. The automated biochemical analyzer uses spectrophotometric meth-
ods in a continuous-flow system to measure the amount of many clinically
important substances in blood or urine samples (Section 11.2).
Development of Technicon’s Auto Analyzer

Epwin C. WHITEHEAD
In 1950 Alan Moritz, chairman of the department of pathology at Case

Western Reserve University and an old friend of mine, wrote to tell me about
Leonard Skeggs, a young man in his department who had developed an
instrument that Technicon might be interested in. I was out of my New York
office on a prolonged trip, and my father, cofounder with me of Technicon
Corporation, opened the letter. He wrote to Dr. Moritz saying that Tech-
nicon was always interested in new developments and enclosed a four-page
confidential disclosure form. Not surprisingly, Dr. Moritz thought that
Technicon was not really interested in Skeggs’s instrument, and my father
dismissed the matter as routine.
2
1 BASIC CONCEPTS OF MEDICAL INSTRUMENTATION
Three years later Ray Roesch, Technicon’s only salesman at the

time, was visiting Joseph Kahn at the Cleveland Veterans Administration
Hospital. Dr. Kahn asked Ray why Technicon had turned down Skeggs’s
invention. Ray responded that he had never heard of it and asked, “What
invention?” Kahn replied, “A machine to automate chemical analysis.”
When Ray called me and asked why I had turned Skeggs’s idea down, I said
I had not heard of it either. When he told me that Skeggs’s idea was to
automate clinical chemistry, my reaction was, “Wow! Let’s look at it and
make sure Skeggs doesn’t get away.”
That weekend, Ray Roesch loaded some laboratory equipment in his

station wagon and drove Leonard Skeggs and his wife Jean to New York. At
Technicon, Skeggs set up a simple device consisting of a peristaltic pump to
draw the specimen sample and reagent streams through the system, a
continuous dialyzer to remove protein molecules that might interfere
with the specimen-reagent reaction, and a spectrophotometer equipped
with a flow cell to monitor the reaction. This device demonstrated the
validity of the idea, and we promptly entered negotiations with Skeggs for a
license to patent the Auto Analyzer. We agreed on an initial payment of
$6,000 and royalties of 3 percent after a certain number of units had been
sold.
After Technicon “turned-down”’ the project in 1950, Skeggs had made

arrangements first with the Heinecke Instrument Co. and then the Harshaw
Chemical Co. to sell his device. Both companies erroneously assumed that
the instrument was a finished product. However, neither company had been
able to sell a single instrument from 1950 until 1953. This was not surprising,
because Skeggs’s original instrument required an expensive development
process to make it rugged and reliable, and to modify the original, manual
chemical assays. Technicon spent 3 years refining the simple model devel-
oped by Skeggs into a commercially viable continuous-flow analyzer.
A number of problems unique to the Auto Analyzer had to be over-

come. Because the analyzer pumps a continuous-flow stream of reagents
interrupted by specimen samples, one basic problem was the interaction
between specimen samples. This problem was alleviated by introducing air
bubbles as physical barriers between samples. However, specimen carry-
over in continuous-flow analyzers remains sensitive to the formation and
size of bubbles, the inside diameter of the tubing through which fluids flow,
the pattern of peristaltic pumping action, and other factors.
Development of the Auto Analyzer was financed internally at Techni-
con. In 1953 Technicon had ongoing business of less than $10 million per
year: automatic tissue processors and Slide filing cabinets for histology
laboratories, automatic fraction collectors for chromatography, and porta-
ble respirators for polio patients. Until it went public in 1969, Technicon had
neither borrowed money nor sold equity. Thus, Technicon’s patent on
Skegg’s original invention was central to the development of the Auto
Analyzer. Without patent protection, Technicon could never have afforded
to pursue the expensive development of this device.
1 BASIC CONCEPTS OF MEDICAL INSTRUMENTATION 3
Early in the instrument’s development, I recognized that traditional

marketing techniques suitable for most laboratory instruments would not
work for something as revolutionary as the Auto Analyzer. At that time,
laboratory instruments were usually sold by catalog salesmen or by mail
from specification sheets listing instrument specifications, price, and perhaps
product benefits. In contrast, we decided that Technicon had to market the
Auto Analyzer as a complete system—instrument, reagents, and instruction.
Technicon’s marketing strategy has been to promote the Auto Analyzer

at professional meetings and through scientific papers and journal articles.
Technicon employs only direct salesmen. The company has never used
agents or distributors, except in countries where the market is too small to
support direct sales.
To introduce technology as radical as the Auto Analyzer into conserv-

ative clinical laboratories, Technicon decided to perform clinical evalua-
tions. Although unusual at that time, such evaluations have since become
commonplace. An important condition of the clinical evaluations was
Technicon’s insistence that the laboratory conducting the evaluation call
a meeting of its local professional society to announce the results. Such
meetings generally resulted in an enthusiastic endorsement of the Auto
Analyzer by the laboratory director. I believe this technique had much to do
with the rapid market acceptance of the Auto Analyzer.
Other unusual marketing strategies enployed by Technicon to promote

the Auto Analyzer included symposia and training courses. Technicon
sponsored about 25 symposia on techniques in automated analytical
chemistry. The symposia were generally 3-day affairs, attracting between
1,000 and 4,500 scientists, and were held in most of the major countries of
the world including the United States.
Because we realized that market acceptance of the Auto Analyzer could
be irreparably damaged by incompetent users, Technicon set up a broad-
scale training program. We insisted that purchasers of Auto Analyzers come
to our training centers located around the world for a 1-week course of
instruction. I estimate that we have trained about 50,000 people to use Auto
Analyzers.
Introduction of Technicon’s continuous-flow Auto Analyzer in 1957

profoundly changed the character of the clinical laboratory, allowing
a hundredfold increase in the number of laboratory tests performed over
a 10-year period. When we began to develop the Auto Analyzer in 1953, I
estimated a potential market of 250 units. Currently, more than 50,000 Auto
Analyzer Channels are estimated to be in use around the world.
In reviewing the 35-year history of the Auto Analyzer, I have come to

the conclusion that several factors significantly influenced our success. First,
the Auto Analyzer allowed both an enormous improvement in the quality of
laboratory test results and an enormous reduction in the cost of doing
chemical analysis. Second, physicians began to realize that accurate labo-
ratory data are useful in diagnosis. Last, reimbursement policies increased
the availability of health care.
4 1 BASIC CONCEPTS OF MEDICAL INSTRUMENTATION
(Reprinted with permission from New Medical Devices, Invention, Devel-

opment and Use, (c) 1988 by the National Academy of Sciences. Published
by National Academy Press, Washington, D.C.)
This success story demonstrates that important new ideas rarely flow
smoothly to widespread clinical use. There are probably 100 untold failure
stories for each success story! New inventions usually are made by the wrong
person with the wrong contacts and experience, in the wrong place at the
wrong time. It is important to understand the difference between a crude
feasibility prototype and a well-developed, reliable, manufacturable product.
Patents are important to protect ideas during the development process and to
provide incentives for making the financial investments needed. Many devices
have failed because they were too hard to use, reliability and ruggedness were
inadequate, marketing was misdirected, user education was lacking, or service
was poor and/or slow.
An evolutionary product is a new model of an existing product that adds

new features, improves the technology, and reduces the cost of production. A
revolutionary new product either solves a totally new problem or uses a new
principle or concept to solve an old problem in a better way that displaces old
methods. A medical instrument that improves screening, diagnosis, or mon-
itoring may not add value by improving patient outcome unless improvements
in the application of therapy occur as a result of using the medical instrument.
1.1 TERMINOLOGY OF MEDICINE AND MEDICAL DEVICES
Most biomedical engineers learn the physical sciences first m the context of
traditional engineering, physics, or chemistry. When they become interested in
medicine, they usually take at least a basic course in physiology, which does not
describe disease or pathologic terminology. The book Medical Terminology:
An Illustrated Guide (Cohen, 2004) is recommended. It emphasizes the Latin
and Greek roots in a workbook format (with answers) that includes clinical
case studies, flash cards, and simple, clear illustrations. An unabridged medical
dictionary such as Dorland’s Illustrated Medical Dictionary, 30th ed. (Dorland,
2003), is often useful. Physicians frequently use abbreviations and acronyms
that are difficult to look up, and ambiguity or errors result. Six references on
medical abbreviations are given (Cohen, 2004; Davis, 2001; Firkin and Whit-
worth, 1996; Haber, 1988; Hamilton and Guides, 1988; Heister, 1989). Medical
eponyms are widely used to describe diseases and syndromes by the name of
the person who first identified them. Refer to Dictionary of Medical Eponyms
(Firkin and Whitworth, 1996).
The name used to describe a medical instrument or device should be

informative, consistent, and brief. The annual Health Devices Sourcebook
1.2 GENERALIZED MEDICALINSTRUMENTATION SYSTEM 5
(Anonymous, 2007) is a directory of U.S. and Canadian medical device products,

trade names, manufacturers, and related services. This book uses internationally
accepted nomenclature and a numerical coding system for over 5000 product
categories. The Product Development Directory (1996) lists all specific medical
products by the FDA standard product category name since enactment of the
Medical Devices Amendments in April 1976. The Encyclopedia of Medical
Devices and Instrumentation (Webster, 2006) has many detailed descriptions. But
beware of borrowing medical terminology to describe technical aspects of devices
or instruments. Confounding ambiguities can result.
Recent information on medical instrumentation can be found by searching

World Wide Web servers such as www.google.com or www.uspto.gov, Library
Online Catalogs, and journal electronic databases such as Engineering Village,
Science Citation Index, and PubMed.
1.2 GENERALIZED MEDICAL INSTRUMENTATION SYSTEM
Every instrumentation system has at least some of the functional components

shown in Figure 1.1. The primary flow of information 1s from left to night.
Elements and relationships depicted by dashed lines are not essential. The
major difference between this system of medical instrumentation and
Perceptible
capa
a
So Shani
electric,
“oromher:
energy
Figure 1.1 Generalized instrumentation system The sensor converts energy

or information from the measurand to another form (usually electric). This
signal is then processed and displayed so that humans can perceive the
information. Elements and connections shown by dashed lines are optional
for some applications.
conventional instrumentation systems is that the source of the signals is living

tissue or energy applied to living tissue.
MEASURAND
The physical quantity, property, or condition that the system measures is called
the measurand. The accessibility of the measurand is important because it may
be internal (blood pressure), it may be on the body surface (electrocardiogram
potential), it may emanate from the body (infrared radiation), or it may be
derived from a tissue sample (such as blood or a biopsy) that is removed from
the body. Most medically important measurands can be grouped in the
following categories: biopotential, pressure, flow, dimensions (imaging), dis-
placement (velocity, acceleration, and force), impedance, temperature, and
chemical concentrations. The measurand may be localized to a specific organ
or anatomical structure.
SENSOR
Generally, the term transducer is defined as a device that converts one form of
energy to another. A sensor converts a physical measurand to an electric
output. The sensor should respond only to the form of energy present in the
measurand, to the exclusion of all others. The sensor should interface with the
living system in a way that minimizes the energy extracted, while being
minimally invasive. Many sensors have a primary sensing element such as a
diaphragm, which converts pressure to displacement. A variable-conversion
element, such as a strain gage, then converts displacement to an electric
voltage. Sometimes the sensitivity of the sensor can be adjusted over a
wide range by altering the primary sensing element. Many variable-conversion
elements need external electric power to obtain a sensor output.
SIGNAL CONDITIONING
Usually the sensor output cannot be directly coupled to the display device.
Simple signal conditioners may only amplify and filter the signal or merely
match the impedance of the sensor to the display. Often sensor outputs are
converted to digital form and then processed by specialized digital circuits or a
microcomputer (Tompkins and Webster, 1981), For example. signal filtering
may reduce undesirable sensor signals. It may also average repetitive signals to
reduce noise, or it may convert information from the time domain to the
frequency domain.
OUTPUT DISPLAY
The results of the measurement process must be displayed in a form that the
human operator can perceive. The best form for the display may be numerical
or graphical, discrete or continuous, permanent or temporary—depending on
1.3 ALTERNATIVE OPERATIONAL MODES 7
the particular measurand and how the operator will use the information.
Although most displays rely on our visual sense, some information (Doppler
ultrasonic signals, for example) is best perceived by other senses (here, the
auditory sense). User controls and the output display should conform to the
Human Factors Engineering Guidelines and Preferred Practices for the Design
of Medical Devices (AAMI, 1993).
AUXILIARY ELEMENTS
A calibration signal with the properties of the measurand should be applied to

the sensor input or as early in the signal-processing chain as possible. Many
forms of control and feedback may be required to elicit the measurand, to
adjust the sensor and signal conditioner, and to direct the flow of output for
display, storage, or transmission. Control and feedback may be automatic or
manual. Data may be stored briefly to meet the requirements of signal
conditioning or to enable the operator to examine data that precede alarm
conditions. Alternatively, data may be stored before signal conditioning, so
that different processing schemes can be utilized. Conventional principles of
communications can often be used to transmit data to remote displays at
nurses’ stations, medical centers, or medical data-processing facilities.
1.3. ALTERNATIVE OPERATIONAL MODES
DIRECT-INDIRECT MODES
Often the desired measurand can be interfaced directly to a sensor because the
measurand is readily accessible or because acceptable invasive procedures are
available. When the desired measurand is not accessible, we can use either
another measurand that bears a known relation to the desired one or some
form of energy or material that interacts with the desired measurand to
generate a new measurand that is accessible. Examples include cardiac
output (volume of blood pumped per minute by the heart), determined
from measurements of respiration and blood gas concentration or from dye
dilution; morphology of internal organs, determined from x-ray shadows;
and pulmonary volumes, determined from variations in thoracic impedance
plethysmography.
SAMPLING AND CONTINUOUS MODES
Some measurands—such as body temperature and ion concentrations—

change so slowly that they may be sampled infrequently. Other quantities—
such as the electrocardiogram and respiratory gas flow—may require
continuous monitoring. The frequency content of the measurand, the objective
of the measurement, the condition of the patient, and the potential liability of
the physician all influence how often medical data are acquired. Many data that
are collected may go unused.
GENERATING AND MODULATING SENSORS
Generating sensors produce their signal output from energy taken directly
from the measurand, whereas modulating sensors use the measurand to alter
the flow of energy from an external source in a way that affects the output of
the sensor. For example, a photovoltaic cell is a generating sensor because it
provides an output voltage related to its irradiation, without any additional
external energy source. However, a photoconductive cell is a modulating
sensor; to measure its change in resistance with irradiation, we must apply
external energy to the sensor.
ANALOG AND DIGITAL MODES
Signals that carry measurement information are either analog, meaning

continuous and able to take on any value within the dynamic range, or
digital, meaning discrete and able to take on only a finite number of different
values. Most currently available sensors operate in the analog mode, al-
though some inherently digital measuring devices have been developed.
Increased use of digital signal processing has required concurrent use of
analog-to-digital and digital-to-analog converters to interface computers
with analog sensors and analog display devices. Researchers have developed
indirect digital sensors that use analog primary sensing elements and digital
variable-conversion elements (optical shaft encoders). Also quasi-digital
sensors, such as quartz-crystal thermometers, give outputs with variable
frequency, pulse rate, or pulse duration that are easily converted to digital
signals.
The advantages of the digital mode of operation include greater accuracy,

repeatability, reliability, and immunity to noise. Furthermore, periodic cali-
bration is usually not required. Digital numerical displays are replacing many
analog meter movements because of their greater accuracy and readability.
Many clinicians, however, prefer analog displays when they are determining
whether a physiological variable is within certain limits and when they are
looking at a parameter that can change quickly, such as beat-to-beat heart
rate. In the latter case, digital displays often change numbers so quickly that
they are very difficult and annoying to observe.
REAL-TIME AND DELAYED-TIME MODES

Of course sensors must acquire signals in real time as the signals actually
occur. The output of the measurement system may not display the result
immediately, however, because some types of signal processing, such as
averaging and transformations, need considerable input before any results
can be produced. Often such short delays are acceptable unless urgent
1.4 MEDICAL MEASUREMENT CONSTRAINTS 9
feedback and control tasks depend on the output. In the case of some
measurements, such as cell cultures, several days may be required before
an output is obtained.
1.4 MEDICAL MEASUREMENT CONSTRAINTS
The medical instrumentation described throughout this book is designed to

measure various medical and physiological parameters. The principal mea-
surement and frequency ranges for each parameter are major factors that
affect the design of all the instrument components shown in Figure 1.1. To get a
brief overview of typical medical parameter magnitude and frequency ranges,
refer to Table 1.1. Shown here are approximate ranges that are intended to
include normal and abnormal values. Most of the parameter measurement
ranges are quite low compared with nonmedical parameters. Note, for exam-
ple, that most voltages are in the microvolt range and that pressures are low
(about 100 mm Hg = 1.93 psi = 13.3 kPa). Also note that all the signals listed
are in the audio-frequency range or below and that many signals contain direct
current (dc) and very low frequencies. These general properties of medical
parameters limit the practical choices available to designers for all aspects of
instrument design.
Many crucial variables in living systems are inaccessible because the

proper measurand-sensor interface cannot be obtained without damaging
the system. Unlike many complex physical systems, a biological system is
of such a nature that it is not possible to turn it off and remove parts of it during
the measurement procedure. Even if interference from other physiological
systems can be avoided, the physical size of many sensors prohibits the
formation of a proper interface. Either such inaccessible variables must be
measured indirectly, or corrections must be applied to data that are affected by
the measurement process. The cardiac output is an important measurement
that is obviously quite inaccessible.
Variables measured from the human body or from animals are seldom
deterministic. Most measured quantities vary with time, even when all con-
trollable factors are fixed. Many medical measurements vary widely among
normal patients, even when conditions are similar. This inherent variability has
been documented at the molecular and organ levels, and even for the whole
body. Many internal anatomical variations accompany the obvious external
differences among patients. Large tolerances on physiological measurements
are partly the result of interactions among many physiological systems. Many
feedback loops exist among physiological systems, and many of the interre-
lationships are poorly understood. It is seldom feasible to control or neutralize
the effects of these other systems on the measured variable. The most common
method of coping with this variability is to assume empirical statistical and
probabilistic distribution functions. Single measurements are then compared
with these norms (see Section 1.8).
Table 1.1
Medical and Physiological Parameters
Parameter or
Principal Measurement Signal Frequency Standard Sensor
Measuring Technique Range of Parameter Range, Hz or Method

Ballistocardiography 0-7 mg dce—40 Accelerometer,
(BCG) strain gage
0-100 wm dce—40 Displacement linear
variable differential
transformer (LVDT)
Bladder pressure 1-100 cm H,0 de-10 Strain-gage manometer
Blood flow 1-300 mls de-20 Flowmeter
(electromagnetic or
ultrasonic)
Blood pressure, arterial
Direct 10-400 mm Hg de-50 Strain-gage manometer
Indirect 25-400 mm Hg dc-60 Cuff, auscultation
Blood pressure, venous 0-50 mm Hg de-50. Strain gage
Blood gases
Po, 30-100 mm Hg de-2 Specific electrode,
: volumetric or
manometric
Poo, 40-100 mm Hg de-2 Specific electrode,
: volumetric or
manometric
Pn, 1-3 mm Hg de-2 Specific electrode,
: volumetric or
manometric
Poo 01-0.4 mm Hg de-2 Specific electrode,
volumetric or
manometric
Blood pH 6.8-7.8 pH units de-2 Specific electrade
Cardiac output 4-25 liter/min de-20 Dye dilution, Fick
Electrocardiography 0.5-4 mV 0.01-250 Skin electrodes
(ECG)
Electroencephalography 5-300 wV de-150 Scalp electrodes
(EEG)
(Electrocorticography 10-5000 pV de-150 Brain-surface or depth
and brain depth) electrodes
Electrogastrography 10-1000 pV de-1 Skin-surface electrodes
(EGG)
0.5-80 mV de-1 Stomach-surflace
electrodes
Electromyography 0.1-5 mV de-10,000 Needle electrodes
(EMG)
Eye potentials
Electro-oculogram (EOG)
Electroretinogram (ERG)
Galvanic skin response

(GSR)
Gastric pH.
50-3500 WV
0-900 wV
1-500 kO.
3-13 pH units
de—50
de—50
0.01-1
de-1
Contact electrodes
Contact electrodes
Skin electrodes
pH electrode; antimony
electrode
1.4 MEDICAL MEASUREMENT CONSTRAINTS 11
Table 1.1 (Continued)
Parameter or Principal Measurement Signal Frequency Standard Sensor
Measuring Technique Range of Parameter Range, Hz or Method
Gastrointestinal pressure 0-100 cm H,O de-10 Strain-gage manometer
Gastrointestinal forces 1-50 g de-1 Displacement system,

LVDT
Nerve potentials 0.01-3 mV de-10,000 Surface or needle

electrodes
Phonocardiography Dynamic range 5-2000 Microphone
80 dB, threshold
about 100 wPa
Plethysmography Varies with organ de-30 Displacement chamber

(volume change) measured or impedance change
Circulatory 0-30 ml de-30 Displacement chamber
or impedance change
Respiratory functions 0-600 liter/min dce—40 Pneumotachograph
Pneumotachography head and differential
(flow rate) pressure
Respiratory rate 2-50 breaths/min 0.1-10 Strain gage on chest,
impedance, nasal
thermistor
Tidal volume 50-1000 ml/breath 0.1-10 Above methods
Temperature of body 32-40°C de-0.1 Themistor,
90-104 °F thermocouple
Source: Revised from Medical Engineering. C. D. Ray (ed.). Copyright © 1974 by Year Book
Medical
Publishers, Inc., Chicago. Used by permission.
Nearly all biomedical measurements depend either on some form of

energy being applied to the living tissue or on some energy being applied
as an incidental consequence of sensor operation. X-ray and ultrasonic imaging
techniques and electromagnetic or Doppler ultrasonic blood flowmeters
depend on externally applied energy interacting with living tissue. Safe levels
of these various types of energy are difficult to establish, because many
mechanisms of tissue damage are not well understood. A fetus is particularly
vulnerable during the early stages of development. The heating of tissue is one
effect that must be limited, because even reversible physiological changes can
affect measurements. Damage to tissue at the molecular level has been
demonstrated in some instances at surprisingly low energy levels.
Operation of instruments in the medical environment imposes important

additional constraints. Equipment must be reliable, easy to operate, and
capable of withstanding physical abuse and exposure to corrosive chemicals.
Electronic equipment must be designed to minimize electric-shock hazards
(Chapter 14). The safety of patients and medical personnel must be considered
in all phases of the design and testing of instruments. The Medical Device
Amendments of 1976 and the Safe Medical Devices Act of 1990 amend the
Federal Food, Drug, and Cosmetics Act to provide for the safety and effec-
tiveness of medical devices intended for human use (Section 1.13).
1.5 CLASSIFICATIONS OF BIOMEDICAL INSTRUMENTS

The study of biomedical instruments can be approached from at least four
viewpoints. Techniques of biomedical measurement can be grouped according
to the guantity that is sensed, such as pressure, flow, or temperature. One
advantage of this classification is that it makes different methods for measuring
any quantity easy to compare.
A second classification scheme uses the principle of transduction, such as

resistive, inductive, capacitive, ultrasonic, or electrochemical. Different appli-
cations of each principle can be used to strengthen understanding of each
concept; also, new applications may be readily apparent.
Measurement techniques can be studied separately for each organ system,

such as the cardiovascular, pulmonary, nervous, and endocrine systems. This
approach isolates all important measurements for specialists who need to know
only about a specific area, but it results im considerable overlap of quantities
sensed and principles of transduction.
Finally. biomedical instruments can be classified according to the clinical

medicine specialties, such as pediatrics, obstetrics, cardiology, or radiology.
This approach is valuable for medical personnel who are interested in special-
ized instruments. Of course, certain measurements—such as blood pressure—
are important to many different medical specialties.
1.6 INTERFERING AND MODIFYING INPUTS
Desired inputs are the measurands that the instrument is designed to isolate.
Interfering inputs are quantities that inadvertently affect the instrument as a
consequence of the principles used to acquire and process the desired inputs. If
spatial or temporal isolation of the measurand is incomplete, the interfering
input can even be the same quantity as the desired input. Modifying inputs
are undesired quantities that indirectly affect the output by altering the
performance of the instrument itself. Modifying inputs can affect processing
of either desired or interfering inputs. Some undesirable quantities can act as
both a modifying input and an interfering input.
A typical electrocardiographic recording system, shown in Figure 1.2, will

serve to illustrate these concepts. The desired input is the electrocardiographic
voltage Vecg that appears between the two electrodes on the body surface. One
interfering input is 60 Hz noise voltage induced in the shaded loop by
environmental alternating current (ac) magnetic fields. The desired and the
interfering voltages are in series, so both components appear at the input to the
14.7. COMPENSATION TECHNIQUES 13
Electrodes
60-HE
ad Mee
| field
Be => Basal
oN Differential
mail
Displacement o ==
cHTrents
Figure 1.2 Simplified electrocardiographic recording system Two possible

interfering inputs are stray magnetic fields and capacitively coupled noise.
Orientation of patient cables and changes in electrode-skin impedance are two
possible modifying inputs. Z; and Z, represent the electrode-skin interface
impedances.
differential amplifier. Also, the difference between the capacitively coupled

displacement currents flowing through each electrode and the body to ground
causes an interfering voltage to appear across Zpoay between the two electro-
des and two interfering voltages across Z, and Z3, the electrode impedances.
An example of a modifying input is the orientation of the patient cables. If
the plane of the cables is parallel to the ac magnetic field. magnetically
introduced interference is zero. If the plane of the cables is perpendicular
to the ac magnetic field, magnetically introduced interference is maximal.
1.7 COMPENSATION TECHNIQUES

The effects of most interfering and modifying inputs can be reduced or
eliminated either by altering the design of essential instrument components
or by adding new components designed to offset the undesired inputs. The
former alternative is preferred when it is feasible, because the result is usually
simpler. Unfortunately, designers of instruments can only rarely eliminate the

actual source of the undesired inputs. We shall discuss several compensation
methods for eliminating the effects of interfering and modifying inputs.
INHERENT INSENSITIVITY
If all instrument components are inherently sensitive only to desired inputs,

then interfering and modifying inputs obviously have no effect. For the
electrocardiograph an example is the twisting of the electrode wires to reduce
the number of magnetic flux lines that cut the shaded loop im Figure 1.2.
The voltage of the induced noise is proportional to the area of that loop. The
effects of electrode motion can be reduced by techniques described in
Section 5.5.
NEGATIVE FEEDBACK
When a modifying input cannot be avoided, then improved instrument

performance requires a strategy that makes the output less dependent on
the transfer function Gg. The negative feedback method takes a portion of the
output, H;, at any instant of time and feeds it back to the input of the
instrument. This output-dependent signal is subtracted from the input, and
the difference becomes the effective system input. For input xq and output y,
we can write
(xg — Hiy}Gy = y (1.1)

xaGqg= y(l + HrGa) (1.2)
G,
y= TH (1.3)
Gq usually includes amplification, so H;Gy “> 1 and y = (1/H;)(xq}. This well-

known relationship shows that only the feedback element, H;, determines the
output for a given input. Of course, this strategy fails if H; is also affected by
modifying inputs. Usually the feedback device carries less power, so it is
more accurate and linear. Less input-signal power is also needed for this
feedback scheme, so less loading occurs. The major disadvantage of using this
feedback principle is that dynamic instability leading to oscillations can occur,
particularly if Gg contains time delays. The study of feedback systems is a
well-developed discipline that cannot be pursued further here (Kuo and
Golnaraghi, 2003).
SIGNAL FILTERING
A filter separates signals according to their frequencies. Most filters accom-

plish this by attenuating the part of the signal that is in one or more frequency
bands. A more general definition for a filter is “‘a device or program that
14.7. COMPENSATION TECHNIQUES 15
separates data, signals, or material in accordance with specified criteria”’

(IEEE, 1997).
Filters may be inserted at the instrument input, at some point within the
instrument, or at the output of the instrument. In fact, the limitations of
people's senses may be used to filter unwanted signal components coming from
display devices. An example is the utilization of flicker fusion for rapidly
changing images from a real-time ultrasonic scanner.
Input filtering blocks interfering and modifying inputs but does not alter
the desired input. Filter elements may be distinct devices that block or pass all
inputs, or they may be embodied in a single device that selectively blocks only
undesired inputs. Many designers do not use input filters that are electric
circuits but use instead mechanical, pneumatic, thermal, or electromagnetic
principles to block out undesired environmental inputs. For example, instru-
ments are often shock-mounted to filter vibrations that affect sensitive
instrument components. Electromagnetic shielding is often used to block
interfering electric and magnetic fields, such as those indicated in Figure 1.2.
Electronic filters are often incorporated at some intermediate stage within

the instrument. To facilitate filtering based on differences in frequency, mixers
and modulators are used to shift desired and/or undesired signals to another
frequency range where filtering is more effective. Digital computers are
used to filter signals on the basis of template-matching techniques and various
time-domain signal properties. These filters may even have time- or signal-
dependent criteria for isolating the desired signal.
Output filtering is possible, though it is usually more difficult because

desired and undesired output signals are superimposed. The selectivity needed
may be easier to achieve with higher-level output signals.
OPPOSING INPUTS
When interfermg and/or modifying inputs cannot be filtered, additional
interfering inputs can be used to cancel undesired output components. These
extra intentional inputs may be the same as those to be canceled. In general,
the unavoidable and the added opposing inputs can be quite different, as long
as the two output components are equal so that cancellation results. The two
outputs must cancel despite variations in all the unavoidable interfering
inputs and variations in the desired inputs. The actual cancellation of
undesired output components can be implemented either before or after
the desired and undesired outputs are combined. Indeed, either the inten-
tional or the unavoidable interfering input signal might be processed by Gq.
The method of opposing inputs can also be used to cancel the effects of
modifying inputs.
Automatic real-time corrections are implied for the method of opposing

inputs just described. Actually, output corrections are often calculated manu-
ally or by computer methods and applied after data are collected. This requires
quantitative knowledge of the interfering and/or modifying input at the time of
the measurement and also of how these inputs affect the output. This method is
usually cumbersome, loses real-time information, and is often used only for
rather static interfering inputs, such as temperature and atmospheric pressure.
Anexample of using the opposing-input method is to intentionally induce
a voltage from the same 60 Hz magnetic field present m Figure 1.2 to be
amplified and inverted until cancellation of the 60 Hz interference in
the output is achieved. An obvious disadvantage of this method is that the
amplifier gain has to be adjusted whenever the geometry of the shaded loop in
Figure 1.2 changes. In electronic circuits that must operate over a wide
temperature range, thermistors (temperature-dependent resistors) are often
used to counteract unavoidable temperature-dependent changes in character-
istics of active circuit elements, such as transistors and integrated circuits.
1.8 BIOSTATISTICS
The application of statistics to medical data is used to design experiments and

clinical studies; to summarize, explore, analyze, and present data; to draw
inferences from data by estimation or hypothesis testing; to evaluate diagnostic
procedures; and to assist clinical decision making (Dawson-Saunders and
Trapp, 2004).
Medical research studies can be observational studies, wherein character-

istics of one or more groups of patients are observed and recorded, or
experimental intervention studies, wherein the effect of a medical procedure
or treatment is investigated. The simplest observational studies are case-series
studies that describe some characteristics of a group. These studies are without
control subjects, in order only to identify questions for further research. Case-
control observational studies use individuals selected because they have (or do
not have) some outcome or disease and then look backward to find possible
causes or risk factors. Cross-sectional observational studies analyze character-
istics of patients at one particular time to determine the status of a disease or
condition. Cohort observational studies prospectively ask whether a particular
characteristic is a precursor or risk factor for an outcome or disease. Exper-
imental clinical trials are controlled if the outcome for patients administered a
drug, device, or procedure is compared to the outcome for patients given a
placebo or another accepted treatment. The trials are uncontrolled if there is
no such comparison. Concurrent controls are best, because patients are
selected in the same way and for the same time period. Double-blind study
with randomized selection of patients to treatment options is preferred,
because this design minimizes investigator and patient bias. Medical outcome
studies show cost-effective improvements in patient health are increasingly
required prior to adoption and reimbursement for new medical technologies
(Anonymous, 2001).
Quantitative data are measured on a continuous or discrete numerical

scale with some precision. Qualitative data values that fit into categories are
measured on nominal scales that show the names of the categories. An ordinal
4.8 BIOSTATISTICS 17
scale is used when the categories exhibit an inherent order. Descriptive

statistics are useful to summarize data and their attributes. Distributions of
empirical or theoretical data reflect the values of a variable or characteristic
and the frequency of occurrence of those values.
Measures of the middle, or central tendency, include the well-known

mean, which is the sum of observed values divided by the number of observa-
tions. The mean, found as follows,
yuk (1.4)
n
works best as the measure of central tendency for symmetric distributions. The
median is the value for which half the observations are smaller and half are
larger; it is used for skewed numerical data or ordinal data. The mode is the
observation that occurs most frequently; it is used for bimodal distributions.
The geometric mean (GM) is the nth root of the product of the observations:
GM = (/X}X0X3---X, (1.5)
It is used with data on a logarithmic scale.
Measures of spread or dispersion of data describe the variation in the

observations. The range, which is the difference between the largest and
smallest observations, is used to emphasize extreme values. The standard
deviation is a measure of the spread of data about the mean. It is computed as
follows:
p= [Ee XY (1.6)
n—-1
It is used with the mean for symmetric distributions of numerical data.

Regardless of the type of symmetric distribution, at least 75% of the values
always lie between X — 2s and X + 2s. The coefficient of variation (CV) is
calculated as follows:
cv = (=) (100%) (17)
It standardizes the variation, making it possible to compare two numerical

distributions that are measured on different scales. A percentile gives the
percentage of a distribution that is less than or equal to the percentile number;
it may be used with the median for ordinal data or skewed numerical data. The
interquartile range is the difference between the 25th and 75th percentiles, so
it describes the central 50% of a distribution with any shape. The standard
error of the mean (SEM) (i.e., standard deviation of the mean), ss = s/n — 1,
expresses the variability to be expected among the means in future samples,
whereas the standard deviation describes the variability to be expected among

individuals in future samples.
EXAMPLE 1.1 ‘Your samples from a population are 1, 1, 3, 5, 5. Estimate

the mean X, the standard deviation s, and the standard deviation of the mean
Sz.
ANSWER Mean_X = (sum of values)/(number of values) = (1 + 14+3+45+

5/5 =3 standard deviation s = {[(1- 3% + 1-37 4+ (3-37 4 (5-37 4
(5-3) /6- bP" = 16/4)'? =2 standard deviation of mean sz=
si¥n—1=2/¥5—-1=1.
Often we need to study relationships between two numerical character-

istics. The correlation coefficient r is a measure of the relationship between
numerical variables X and Y for paired observations.
SO HM 7) (18)
Die xP YU vy
The correlation coefficient ranges from — 1 for a negative linear relationship to

+1 for a positive linear relationship; 0 indicates that there is no linear
relationship between X and Y. The correlation coefficient is independent of
the units employed to measure the variables, which can be different. Like the
standard deviation, the correlation coefficient is strongly mfluenced by out-
lying values. Because the correlation coefficient measures only a straight-line
relationship, it may be small for a strong curvilinear relationship. Of course, a
high correlation does not imply a cause-and-effect relationship between the
variables.
Estimation and hypothesis testing are two ways to make an inference

about a value in a population of subjects from a set of observations drawn
from a sample of such subjects. In estimation, confidence intervals are
calculated for a statistic such as the mean. The confidence imtervals indi-
cate that a percentage—say 95%—of such confidence intervals contain the
true value of the population mean. The confidence imtervals indicate the
degree of confidence we can have that they contain the true mean. Hypothe-
sis testing reveals whether the sample gives enough evidence for us to reject
the null hypothesis, which is usually cast as a statement that expresses the
opposite of what we think is true. A P-value is the probability of obtaining, if
the null hypothesis is true, a result that is at least as extreme as the one
observed. The P-value indicates how often the observed difference would
occur by chance alone if, indeed, nothing but chance were affecting the
outcome. Recent trends favor using estimation and confidence intervals
rather than hypothesis testing.
Methods for measuring the accuracy of a diagnostic procedure use three

pieces of information. The sensitivity [TP/(TP + FN)] of a test is the probability
1.9 GENERALIZED STATIC CHARACTERISTICS 19
of its yielding true positive (TP) results in patients who actually have the disease.
A test with high sensitivity has a low false-negative (FN) rate. The specificity
[TN/(TN + FP)]of a test is the probability of its yielding negative results in
patients who do not have the disease. A test with high specificity has a low false-
positive (FP) rate; it does not give a false positive (FP) result in many patients
who do not have the disease. The third piece of information is the prior
probability, or prevalence [(TP + FN)/(TN + TP + FN + FP)] of the condition
prior to the test (all diseased persons divided by all persons). There are several
methods for revising the probability that a patient has a condition on the basis of
the results of a diagnostic test. Taking into consideration the results of a
diagnostic procedure is only one part of the complex clinical decision-making
process. Decision tree analysis and other forms of decision analysis that include
economic implications are also used in an effort to make optimal decisions
(Webster, 2004).
1.9 GENERALIZED STATIC CHARACTERISTICS
To enable purchasers to compare commercially available instruments and

evaluate new instrument designs, quantitative criteria for the performance of
instruments are needed. These criteria must clearly specify how well an
instrument measures the desired input and how much the output depends
on interfering and modifying inputs. Characteristics of instrument perform-
ance are usually subdivided into two classes on the basis of the frequency of the
input signals.
Static characteristics describe the performance of instruments for de or

very low frequency inputs. The properties of the output for a wide range of
constant inputs demonstrate the quality of the measurement, including non-
linear and statistical effects. Some sensors and instruments, such as piezo-
electric 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.
ACCURACY
The accuracy of a single measured quantity is the difference between the true
value and the measured value divided by the true value. This ratio is usually
expressed as a percent. Because the true value is seldom available, the
accepted true value or reference value should be traceable to the National

Institute of Standards and Technology.
The accuracy usually varies over the normal range of the quantity
measured, usually decreases as the full-scale value of the quantity decreases
on amultirange instrument, and also often varies with the frequency of desired,
interfering, and modifying inputs. Accuracy is a measure of the total error
without regard to the type or source of the error. The possibility that the
measurement is low and that it is high are assumed to be equal. The accuracy
can be expressed as percent of reading, percent of full scale, + number of digits
for digital readouts, or +1/2 the smallest division on an analog scale. Often the
accuracy is expressed as a sum of these, for example, on a digital device,
+0.01% of reading +0.015% of full-scale +1 digit. If accuracy is expressed
simply as a percentage, full scale is usually assumed. Some instrument manu-
facturers specify accuracy only for a limited period of time.
PRECISION
The precision of a measurement expresses the number of distinguishable

alternatives from which a given result is selected. For example, a meter
that displays a reading of 2.434 V is more precise than one that displays a
reading of 2.43 V. High-precision measurements do not imply high accuracy,
however, because precision makes no comparison to the true value.
RESOLUTION
The smallest incremental quantity that can be measured with certainty is the
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
The ability of an instrument to give the same output for equal inputs applied
over some period of time is called reproducibility or repeatability. Reproduc-
ibility does not imply accuracy. For example, a broken digital clock with an
AM or PM indicator gives very reproducible values that are accurate only once
a day.
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.
STATIC SENSITIVITY
A static calibration is performed by holding all inputs (desired, interfering, and

modifying) constant except one. This one input is varied incrementally over the
normal operating range, resulting in a range of incremental outputs. The static
sensitivity of an instrument or system is the ratio of the incremental output
quantity to the incremental input quantity. This ratio is the static component of Gg
for desired inputs within the range of the incremental inputs. The incremental
slope can be obtained from either the secant between two adjacent points or the
tangent to one point on the calibration curve. The static sensitivity may be
constant for only part of the normal operating range of the instrument, as shown in
Figure 1.3(a). For input-output data that indicate a straight-line calibration curve,
the slope m and intercept b for the line with the minimal sum of the squared
differences between data points and the line are given by the following equations:
m = DRX ~ ONY) (19)

ndixg — Qoxa)
ny - (Sxu)
y=mxy+hb (1.11)
b (1.10)
where nis the total number of points and each sum is for all ” points. The static
sensitivity for modulating sensors is usually given per volt of excitation,
because the output voltage is proportional to the excitation voltage. For
example, the static sensitivity for a blood-pressure sensor containing a
strain-gage bridge might be 50 4V - V7! mm Hg".
ZERO DRIFT
Interfering and/or modifying inputs can affect the static calibration curve shown
in Figure 1.3(a) in several ways. Zero drift has occurred when all output values
increase or decrease by the same absolute amount. The slope of the sensitivity
curve is unchanged, but the output-axis intercept increases or decreases as
shown in Figure 1.3(b). The following factors can cause zero drift: manufacturing
misalignment, variations in ambient temperature, hysteresis, vibration, shock,
and sensitivity to forces from undesired directions. A change in the de-offset
voltage at the electrodes in the electrocardiograph example in Figure 1.2 is an
example of zero drift. Slow changes in the de-offset voltage do not cause a
v (Output
Y= tiny +b
xy Unpury
Characteristic with zero and sensitivity drift
Total error due to drift

y¥ (Output
Design characteristic
+ Sensitivity
drift
.
*
i
Aero irllt *
oe?
a®
oe? =
+ Zero —Sensitivity drifi
drift
| 44 (lnpur}
Figure 1.3 (a) Static-sensitivity curve that relates desired input xg to output y.
Static sensitivity may be constant for only a limited range of inputs. (b) Static
sensitivity: zero drift and sensitivity drift. Dotted lines indicate that zero drift
and sensitivity drift can be negative. [Part (b) modified from Measurement
Systems: Application and Design, E. O. Doebelin. Copyright © 1990 by
McGraw-Hill, Inc. Used with permission of McGraw-Hill Book Co.]
problem, because the ECG amplifier is ac-coupled. Fast changes due to motion
of the subject do cause low-frequency artifact to appear at the output.
SENSITIVITY DRIFT
When the slope of the calibration curve changes as a result of an interfering and/
or modifying input, a drift in sensitivity results. Sensitivity drift causes error
that is proportional to the magnitude of the input. The slope of the calibration
curve can either increase or decrease, as indicated in Figure 1.3(b). Sensitivity
drift can result from manufacturing tolerances, variations in power supply,
nonlinearities, and changes in ambient temperature and pressure. Variations
in the electrocardiograph-amplifier voltage gain as a result of fluctuations in de

power-supply voltage or change in temperature are examples of sensitivity drift.
LINEARITY
Asystem or element is linear if it has properties such that if y, is the response to

x, and y2 is the response to x2, then y; + ys is the response to x, + x2, and Ky, is
the response to Kx,. These two requirements for system linearity are restated
in Figure 1.4(a).
They are clearly satisfied for an instrument with a calibration curve that isa
straight line.
:¥A;‘
Mi Lincar ¥I Cy vg! Lincar (yy ey
———
System system
and and
42 Linear ¥ Ay aittad Rey
ate es ss] =
aystern Svstem
(in)
Leasl-squanes
= strnght line
bv (Outputt
| ay {input}
Point at which
AS of reading = BS of full seale
(b)
Figure 1.4 (a) Basic definition of linearity for a system or element. The same
linear system or element is shown four times for different inputs. (b) A
graphical illustration of independent nonlinearity equals tA % of the reading,
or +B% of full scale, whichever is greater (that is, whichever permits the larger
error). [Part (b) modified from Measurement Systems: Application and Design,
E. O. Doebelin. Copyright © 1990 by McGraw-Hill, Inc. Used with permission
of McGraw-Hill Book Co.]
Keep in mind, however, that high accuracy does not necessarily imply
linearity. In practice, no instrument has a perfect linear response, so a measure
of deviation from linearity is needed. Independent nonlinearity expresses the
maximal deviation of poimts from the least-squares fitted line as either +A % of
the reading or 4B% of full scale, whichever is greater (that is, whichever
permits the larger error). This linearity specification is shown in Figure 1.4(b).
For up-scale readings, the percent-of-reading figure is desirable because most
errors are proportional to the reading. For small readings near zero, however,
percentage of full scale is more realistic because it is not feasible to test for
small percent-of-reading deviations near zero. All data points must fall inside
the “funnel’’ shown in Figure 1.4(b). For most instruments that are essentially
linear, if other sources of error are minimal, the accuracy is equal to the
nonlinearity.
INPUT RANGES
Several maximal ranges of allowed input quantities are applicable for various
conditions. Minimal resolvable inputs impose a lower bound on the quantity to
be measured. The normal linear operating range specifies the maximal or near-
maximal inputs that give linear outputs.
The static linear range and the dynamic linear range may be different.
The maximal operating range is the largest input that does not damage the
instrument. Operation in the upper part of this range is more likely to be
nonlinear. Finally, storage conditions specify environmental and interfering
input limits that should not be exceeded when the instrument is not being used.
These ranges are not always symmetric with respect to zero input, particularly
for storage conditions. Typical 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
Because biomedical sensors and instruments usually convert nonelectric

quantities into voltage or current, we introduce a generalized concept of input
impedance. This is necessary so that we can properly evaluate the degree to
which instruments disturb the quantity being measured. For every desired
input Xq that we seek to measure, there is another implicit input quantity X qo
such that the product Xa: Xa has the dimensions of power. This product
represents the instantaneous rate at which energy is transferred across the
tissue—sensor interface. The generalized input impedance Z, 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).
_ Xa _ effort variable
'= Xn” flow variable (1.12)

1.10 GENERALIZED DYNAMIC CHARACTERISTICS 25
The power P is the time rate of energy transfer from the measurement
medium.
xX?
P=XyXn = > =Z,Xy (1.13)
To minimize P, when measuring effort variables Xq1, we should make the

generalized input impedance as large as possible. This is usually achieved by
minimizing the flow variable. However, most instruments function by meas-
uring minute values of the flow variable. so the flow variable cannot be reduced
to zero. On the other hand, when we are measuring flow variables Xj ., small
input impedance is needed to minimize P. The loading caused by measuring
devices depends on the magnitude of the input impedance |Z,| compared
with the magnitude of the source impedance |Z,| for the desired input.
Unfortunately, biological source impedances are usually unknown, variable,
and difficult to measure and control. Thus the instrument designer must usually
focus on maximizing the input impedance Z, for effort-variable measurement.
When the measurand 1s a flow variable mstead of an effort variable, it is more
convenient to use the admittance Y, = 1/Z, than the impedance.
1.10 GENERALIZED DYNAMIC CHARACTERISTICS
Only a few medical measurements, such as body temperature, are constant or

slowly varying quantities. Most medical instruments must process signals that
are functions of time. It is this time-varying property of medical signals that
requires us to consider dynamic instrument characteristics. Differential or
integral equations are required to relate dynamic inputs to dynamic outputs
for continuous systems. Fortunately, many engineering instruments can be
described by ordinary linear differential equations with constant coefficients.
The input x(7) is related to the output y(¢} according to the following equation:
d"y dy _
On Fin bo Fatt aoy(t} = bn
d"x
arm
dx
$e $b
+ box(t} (1.14)
where the constants a,(i = 0,1,....2} and bj(j =0,1,...,m) depend on the
physical and electric parameters of the system. By introducing the differential
operator D* = d*(\/dt*, we can write this equation as
(a,D" + ---+a,;D + agjy(t) = (b,D” + +--+ 5) D + bojx(t} (1.15)
Readers familiar with Laplace transforms may recognize that D can

be replaced by the Laplace parameter s to obtain the equation relating the
transforms Y(s) and X(s). This is a linear differential equation, because
the linear properties stated in Figure 1.4(a) are assumed and the coefficients
a; and b; are not functions of time or the input x(z). The equation is ordinary,
because there is only one independent variable y. Essentially such properties
mean that the instrument’s methods of acquiring and analyzing the signals do
not change as a function of time or the quantity of input. For example, an
autoranging instrument may violate these conditions.
Most practical instruments are described by differential equations of zero,

first, or second order; thus 7 = 0, 1, 2, and derivatives of the input are usually
absent, so m = 0.
The input x(t) can be classified as transient, periodic, or random. No

general restrictions are placed on x(1), although, for particular applications,
bounds on amplitude and frequency content are usually assumed. Solutions for
the differential equation depend on the input classifications. The step function
is the most common transient input for instrumentation. Sinusoids are the most
common periodic function to use because, through the Fourier-series expan-
sion, any periodic function can be approximated by a sum of sinusoids. Band-
limited white noise (uniform-power spectral content) is a common random
input because one can test instrument performance for all frequencies in a
particular bandwidth.
TRANSFER FUNCTIONS
The transfer function for a linear instrument or system expresses the relation-
ship between the input signal and the output signal mathematically. If the
transfer function is known, the output can be predicted for any input. The
operational transfer function is the ratio y(D)\/x(D} as a function of the
differential operator D.
= 1.16
X(D) a, D" +---+a,D +4 ag ( )
This form of the transfer function is particularly useful for transient inputs.
For linear systems, the output for transient inputs, which occur only once and
do not repeat, is usually expressed directly as a function of time, y(t), which is
the solution to the differential equation.
The frequency transfer function for a linear system is obtained by substi-

tuting jw for D in (1.16).
YU) _ din( joy" + bio) + bo

X(jo} — an( joy" +---ay{ jo} +a
(1.17)
where j = +W—1 and wis the angular frequency in radians per second. The
input is usually given as x(t} = A, sin (wf), and all transients are assumed to
have died out. The output y(f) is a sinusoid with the same frequency, but
the amplitude and phase depend on «; that is, y(t) = B(w) sin [wf + d(e)].
The frequency transfer function is a complex quantity having a magnitude
that is the ratio of the magnitude of the output to the magnitude of the
input and a phase angle ¢ that is the phase of the output y(t) minus the phase
of the input x(t). The phase angle for most instruments is negative. We do
not usually express the output of the system as y(r) for each frequency,
because we know that it is just a sinusoid with a particular magnitude and
phase. Instead, the amplitude ratio and the phase angle are given separately
as functions of frequency.
The dynamic characteristics of instruments are illustrated below by

examples of zero-, first-. and second-order linear instruments for step and
sinusoidal inputs.
ZERO-ORDER INSTRUMENT
The simplest nontrivial form of the differential equation results when all the a’s
and b’s are zero except ay and bo.
ayylt} = ox(t) (1.18)
This is an algebraic equation, so
yD) _ Yio) _ by
x(D) X{(jw} ap
= K =static sensitivity (1.19)
where the single constant K replaces the two constants ay and bo. This zero-
order instrument has ideal dynamic performance, because the output is
proportional to the input for all frequencies and there is no amplitude or
phase distortion.
A linear potentiometer is a good example of a zero-order instrument. Figure

1.5 shows that if the potentiometer has pure uniform resistance, then the output
voltage y(A) is directly proportional to the input displacement x(1), with no time
delay for any frequency of input. In practice, at high frequencies, some parasitic
capacitance and inductance might cause slight distortion. Also, low-resistance
circuits connected to the output can load this simple zero-order instrument.
FIRST-ORDER INSTRUMENT
If the instrument contains a single energy-storage element, then a first-order

derivative of y(t) is required in the differential equation.
dy(f}
dt
ay + agy(t} = box(f} (1.20)
This equation can be written in terms of the differential operator D as

(cD + y(t) = Kx(t} (1.21)
where K = bo/ap = Static sensitivity, and t = a, /a) = time constant.

Output y
a
E+
et
a) E ———ior
: ‘Slope =
r¥
<. r O-
D Tnyratx
(al (bh)
with Log #) Y(fau
sealed
K-£.
7L
ss -
t Lag seale a
(c} (a)
aly .
? SV—_—_— -
> —— Log scale a)
a _“g
Figure 1.5 (a) A linear potentiometer, an example of a zero-order system.

(b) Linear static characteristic for this system. (c) Step response is proportional
to input. (d) Sinusoidal frequency response is constant with zero phase shift.
Exponential functions offer solutions to this equation when appropriate

constants are chosen. The operational transfer function is
y{D} K
x(D) 1+tD
(1.22)
and the frequency transfer function is
Yo) KK -
X(jo) 1+ jot Vireo /? = arctan (-ot/1) (1.23)
The RC low-pass filter circuit shown in Figure 1.6(a) is an example of a

first-order instrument. The input is the voltage x(7), and the output is the
voltage y(t) across the capacitor. The first-order differential equation for this

Ovltput yi
o——_\ A, A —__5
+
win) C= wi Slope =K = 1
: Inpuat xis
(a) (bj
aun Log y | Fj!
| scale] [XL joa]
I
l
|
I
|
i a, my Log scale co
(ch (cl)
att a
Figure 1.6 (a) A low-pass RC filter. an example of a first-order instrument.

(b) Static sensitivity for constant inputs. (c) Step response for large time
constants (t,,} and small time constants (ts). (d) Sinusoidal frequency response
for large and small time constants.
circuit is RC|dy(1)/dt] + y(f) = Kx(t}. The static-sensitivity curve given in

Figure 1.6(b) shows that static outputs are equal to static inputs. This is
verified by the differential equation because, for static conditions, dy/dt = 0.
The step response in Figure 1.6(c) is exponential with a time constant
t=RC.
y(t} = K(1- el) (1.24)
The smaller the time constant, the faster the output approaches the input. For
sinusoids, (1.23) and Figure 1.6(d) show that the magnitude of the output
decreases as frequency increases. For larger time constants, this decrease
occurs at lower frequency.
When w =1/t, the magnitude is 1/2 = 0.707 times smaller, and the
phase angle is —45°. This particular frequency w is known as the corner, cutoff,
or break frequency. Figure 1.6(d) verifies that this is a low-pass filter; low-
frequency sinusoids are not severely attenuated, whereas high-frequency
sinusoids produce very little output voltage. The ordinate of the frequency-
response magnitude in Figure 1.6(d) is usually plotted on a log scale and
may be given in units of decibels (dB), which are defined as dB = 20
logi)/¥ (ja) /X(jo)|. A mercury-in-glass thermometer is another example
of a low-pass first-order instrument.
EXAMPLE 1.2 A first-order low-pass instrument has a time constant of

20 ms. Find the maximal sinusoidal input frequency that will keep output
error due to frequency response less than 5%. Find the phase angle at this
frequency.
ANSWER
Yijo) K
X(jw) 14 jet
KK
——_| = ——— = 0.95K
i + jot] Vita
(wr? + 1}(0.95P =1
»>___ 1~ (0,95)
(0.95) (20 x 10-3)°
w= 164 rad/s
@
=5~ = 2.62 Hz
o= tan"! (=) = —18.2°
If R and C in Figure 1.6(a) are interchanged, the circuit becomes another

first-order instrument known as a high-pass filter. The static characteristic is
zero for all values of input, and the step response jumps immediately to the step
voltage but decays exponentially toward zero as time increases. Thus
y(t) = Ke-“*., Low-frequency sinusoids are severely attenuated, whereas
high-frequency sinusoids are little attenuated. The sinusoidal transfer function
is Y(jo){X(jo) = jot/(L + jor).
EXAMPLE 1.3. From a 2 kV source in series with a 20 kQ resistor,

calculate the time required to charge a 100 wF defibrillator capacitor to
19kV
ANSWER Circuit is shown in Figure 1.6(a). Use (1.24) ve = V — Ve7#C
1900 V = 2000 V — 2000-V - & mamanynoi0-7F

100 V = —2000V - ¢. MOE
0.05 = eM
t
~ 20-F
t= 5.995
In 0.05 =
SECOND-ORDER INSTRUMENT
An instrument is second order if a second-order differential equation is

required to describe its dynamic response.
al 2) a, a0 + avy(t) — boxtt) (1.25)
Many medical instruments are second order or higher, and low pass. Further-
more, many higher-order instruments can be approximated by second-order
characteristics if some simplifying assumptions can be made. The four con-
stants in (1.25) can be reduced to three new ones that have physical
significance:
F 4 25D y(t) = Kxit} (1.26)
wt
a On
where
K =— =static sensitivity, output units divided by input units

a
On = i= =undamped natural frequency, rad/s
2
a::::
c= = damping ratio, dimensionless
2. /AgQ4
Again exponential functions offer solutions to this equation, although the

exact form of the solution varies as the damping ratio becomes greater than,
equal to, or less than unity. The operational transfer function is
yD) K
x(D) D? 2¢D (1.27)

st +1
oO On
and the frequency transfer function is
Yio) _ K
X(jo) (jofony + 2¢jofo,) +1
K ae (1.28)
—————————————._ /¢ = arctan ——_
[L— (wfeny’P + 420% fo hten = nfo
A mechanical force-measuring instrument illustrates the properties of a

second-order instrument (Doebelin, 1990). Mass, spring, and viscous-damping
elements oppose the applied input force x(‘), and the output is the resulting
displacement y(t) of the movable mass attached to the spring [Figure 1.7(a)]. If
the natural frequency of the spring is much greater than the frequency
components in the input, the dynamic effect of the spring can be included
by adding one-third of the spring’s mass to the mass of the moving elements to
obtain the equivalent total mass M.
‘Ohuitput Input
displacement force x(r}
Output vir)
ta) tb Inpur xf}

Resonance
att Log |) jen .
scale] [Ni jag
i= BS ee eo SE
ae — U5
———} - | - ———————_—-
ic} t tah i, Lag scale a
o iy
Log scale do
} - 180°
Figure 1.7 (a) Force-measuring spring scale, an example of a second-order
instrument. (b) Static sensitivity. (c) Step response for overdamped case ¢ = 2,
critically damped case ¢ = 1, underdamped case ¢ = 0.5. (d) Sinusoidal steady-
state frequency response, ¢ = 2, ¢=1, ¢ =0.5. [Part (a) modified from Mea-
surement Systems: Application and Design, E. O. Doebelin. Copyright © 1990
by McGraw-Hill, Inc. Used with permission of McGraw-Hill Book Co.]
Hooke’s law for linear springs is assumed, so the spring constant is K,. Dry
friction is neglected and perfect viscous friction is assumed, with constant B.
To eliminate gravitational force from the equation, we adjust the scale

until y = 0 when x = 0. Then the sum of the forces equals the product of mass
and acceleration.
x(f) — poo — K,y(t) = ue (1.29)
This equation has the same form as (1.26) when the static sensitivity, un-
damped natural frequency, and damping ratio are defined in terms of K,, B,
and M, as follows:
1
Kaz (1.30)
@, = \/K,/M (1.31)
B
c= 2JKM (1.32)
The static response is y(f} = Kx(t}, as shown in Figure 1.7(b). The step
response can have three forms, depending on the damping ratio. For a
unit-step input, these three forms are
Overdamped, ¢ > 1:
yl = SENET olson
270 1
4h Vv e Lok VPA ont +K
2f/e-1 (1.33)
Critically damped, ¢ = 1:
y(t} = -(14+ @,t)Ke" + K (1.34)
Underdamped, ¢ < 1:
en sent
y(t) = een 1- Cont +4) +K

¢@ =aresin ¥1— 2 (1.35)
Examples of these three step responses are represented in Figure 1.7(c). Only
for damping ratios less than unity does the step response overshoot the final
value. Equation (1.35) shows that the frequency of the oscillations in the
underdamped response in Figure 1.7(c) is the damped natural frequency
(4 = Wy 1/1 — ¢?. A practical compromise between rapid rise time and minimal
overshoot is a damping ratio of about 0.7.
EXAMPLE 1.4 For underdamped second-order instruments, find the damp-

ing ratio ¢ from the step response.
ANSWER To obtain the maximums for the underdamped response, we take

the derivative of (1.35) and set it to zero. For ¢ < 0.3 we approximate positive
maximums when the sine argument equals 37/2, 77/2, and so forth. This
occurs at
L= 3af2—o and hil = Tnf2—o (1.36)
ony l—? Onl —?
The ratio of the first positive overshoot y, to the second positive overshoot yn41
[Figure 1.7(c)] is
_ nfl — ¢
YK ( vn, ae 2)
Kos ( co, BULA 2)

1 ~~ e On 1 ~~ e
= exp 20g
1-¢
in a 28
Yn 1-2 (1.37)
where A is defined as logarithmic decrement. Solving for ¢ yields
-_A (1.38)
Vf 47? +N?
For sinusoidal steady-state responses, the frequency transfer function

(1.28) and Figure 1.7(d) show that low-pass frequency responses result. The
rate of decline in the amplitude frequency response is twice the rate of that
decline for first-order instruments. Note that resonance phenomena can
occur if the damping ratio is too small. Also note that the output phase
lag can be as much as 180°, whereas for single-order instruments, the maximal
phase lag is 90°.
4.11. DESIGN CRITERIA 35
TIME DELAY
Instrument elements that give an output that is exactly the same as the input,
except that it is delayed in time by ty, are defined as time-delay elements. The
mathematical expression for these elements is
VQ =K,(f—ta}, t> (1.39)
These elements may also be called analog delay lines, transport lags, or dead
times. Although first-order and second-order instruments have negative phase
angles that imply time delays, the phase angle varies with frequency, so the
delay is not constant for all frequencies. For time delays, the static character-
istic is the constant K, the step response is specified by (1.39), and the
sinusoidal frequency response for magnitude and phase is
Y(jo) _ —jatq
Time delays are present in transmission lines (electric, mechanical, hydraulic
blood vessels, and pneumatic respiratory tubing), magnetic tape recorders, and
some digital signal-processing schemes. Usually these time delays are to be
avoided, especially in instruments or systems that involve feedback, because
undesired oscillations may result.
If the instrument is used strictly for measurement and is not part of a

feedback-control system, then some time delay is usually acceptable. The
transfer function for undistorted signal reproduction with time delay becomes
Y{(jo)/X(jo) = Kf-wtg. Our previous study of time-delay elements shows
that the output magnitude is K times the input magnitude for all frequencies
and that the phase lag increases linearly with frequency.
The transfer-function requirements concern the overall instrument trans-

fer function. The overall transfer function of linear elements connected in
series is the product of the transfer functions for the individual elements. Many
combinations of nonlinear elements can produce the overall linear transfer
function required. Various forms of modulation and demodulation are used,
and unavoidable sensor nonlinearities can sometimes be compensated for by
other instrument elements.
1.11 DESIGN CRITERIA
As shown, many factors affect the design of biomedical instruments. The

factors that impose constraints on the design are of course different for
each type of instrument. However, some of the general requirements
can be categorized as signal, environmental, medical, and economic factors.
Sensitivity
anne
Differential
, orabsolute mput
— Signal = [put impedance
factors Transient and
frequency response:
Accuracy
Linsaraty
Reliability
Initial
4 instrument
Specificiey design
Signil-to-noise ratio . +
ae =a bedi temperature,
{ale PCT wridily. pressure, *
factors an obi ee a Se
vibration, radkatian
‘Power requirements 1
Mauinting size, ship Final
insirusmiest
Measurand 4 r desis
;t
Invasiveir man-invasive
Tissne-senson : FG
Inferface requirements al
Medical Material toxicity | er
factors Electric safery q
sper and
heat dissipation Producti
Patient discomfon “™m
A
Cost
Availability
; Warral
Lge se ietes ———_ Consumable J
mars requirements
Compatibility with
existing equipment
Figure 1.8 Design process for medical instruments Choice and design of
instruments are affected by signal factors and also by environmental, medical,
and economic factors. (Revised from Transducers for Biomedical Measure-
ments: Application and Design, R. S. C. Cobbold. Copyright © 1974, John
Wiley and Sons, Inc. Used by permission of John Wiley and Sons, Inc.)
Figure 1.8 shows how these factors are incorporated into the initial design and
development of an instrument.
Note that the type of sensor selected usually determines the signal-
processing equipment needed, so an instrument specification includes more
than just what type of sensor to use. To obtain a final design, some compro-
mises in specifications are usually required. Actual tests on a prototype are
always needed before final design decisions can be made. Changes in
1.12 COMMERCIAL MEDICAL INSTRUMENTATION 37
performance and interaction of the elements in a complex instrument often

dictate design modifications. Good designs are frequently the result of many
compromises throughout the development of the instrument. In Chapter 2, we
shall examine basic methods of sensing biomedical quantities to ensure that
many sensor design alternatives are considered (King and Fries, 2009).
1.12 COMMERCIAL MEDICAL INSTRUMENTATION

DEVELOPMENT PROCESS
A commercial medical instrument project has many phases, and the size of the
team needed grows as the project progresses. Ideas often come from people
working where health care is delivered, because clinical needs are most evident
there. Physicians, nurses, clinical engineers, and sales personnel are therefore
good sources of ideas. Industry engineers and marketing personnel should
spend time in hospitals observing how their products are actually being used
(and misused). Unsolicited inventions are often presented to industry. Most
companies have one or more people who are responsible for evaluating new
ideas, so it is very important for those who want to propose a new idea to be in
contact with a person who can understand the idea and who has the authority
to proceed with a detailed evaluation. A simple, signed nondisclosure agree-
ment is adequate (but essential) to protect patent rights when detailed ideas
are discussed.
At this early stage even the best ideas are crudely defined, and they are
often not appreciated until at least a preliminary feasibility analysis is done.
The feasibility analysis and written product description should consider the
medical need for the product, its technical feasibility. and how well it fits with
the company’s current or planned product lines and sales methods. Determin-
ing medical feasibility entails examining the clinical need for the product,
including patient indications, number of patients, clinical specialty, and exactly
how, why, and by whom the device will be utilized. Marketing research and
analysis can be useful for evolutionary products but are not reliable for
revolutionary products, especially when a change in medical practice is
required. Technical feasibility analysis should include a description of the
core technologies needed, suitability of existing or readily modifiable compo-
nents, breakthroughs or inventions required, systems analysis, and preliminary
cost estimates. A functional prototype that includes the sensor, primary signal
processing elements, and other new or unique components should be built and
tested on animals and humans as early as possible. The manufacturing
feasibility analysis should be done early, when major alternative technologies
can still be selected. A brief business plan should assess financial aspects,
personnel requirements, competition, patents, standards, manufacturing re-
quirements, sales and service requirements, and the time schedule for the
project. Experience has shown that abbreviating the feasibility phase or adding
features after this phase usually causes disasters later. A detailed feasibility
review should be required at the end of this phase. If the results are not clearly
favorable, the project should be abandoned or the feasibility phase should be
continued.
After a favorable feasibility review is complete, a detailed product speci-

fication must be written to describe all the product features. Included should be
numerical values for performance, many internal testing requirements, user
interface requirements, environmental testing requirements, and even the size,
weight, and color of the instrument. The product specification should say
everything about “what” is required but nothing about “how” it is to be
achieved. This gives design engineers important flexibility. The product
specification is used by design and development engineers. test equipment
design engineers, quality assurance engineers, and manufacturing engineers
throughout the product life cycle. The product specification remains a confi-
dential document in most companies; only the main external performance
specifications appear in user technical manuals and promotional materials.
Design and development uses the product specification to make a manu-

facturable prototype. For most instruments, functions must be partitioned into
hardware and software before detailed design can begin. Circuit diagrams,
detailed software requirements, and mechanical designs are made by means of
computer-aided-design (CAD) tools that allow such detailed simulations of
functional operation that there is little need for “‘breadboard” prototypes.
Design reviews focus on systems issues and problems that the company may
encounter in meeting the product specification. True prototypes that are very
similar to the final product are thus developed much earlier and can be used by
test, design assurance, and manufacturing engineers. These prototypes are also
tested on animals or human subjects to verify expected operation and per-
formance at a few clinical testing centers. Data from these clinical feasibility
trials (including repeated observations of users) should be studied closely,
because design flaws that cause user frustration or errors must be discovered at
this critical stage. A final design review should include test results for all
specifications. clinical results including subjective user feedback. an assess-
ment of manufacturability, and more detailed cost estimates.
Production engineers must be involved throughout the design and devel-

opment process to avoid a redesign for manufacturability. Special production
equipment usually has a long lead time. Many fixtures and automatic tests must
be designed. All final documents that describe how the product 1s made must
be released by the design and development engineers. Any changes made after
the final design review must be authorized via an engineering change order
(ECO). Small production runs are usually needed to discover problems and
improve efficiency. Mast medical instruments and devices are not produced in
high volume, as consumer products are, so full automation of production is not
cost-effective. Even after full production begins, some ECOs may be needed to
correct problems that occur in the field. Any failures of medical devices must
be documented, along with the corrective action taken.
Throughout the product life cycle, which includes the period after the
product is no longer offered for sale, technical support for user questions and
1.13 REGULATION OF MEDICAL DEVICES 39
problems must be provided. Successful companies must be committed to

repairing or replacing their products throughout the entire expected lifetime
of the product.
1.13 REGULATION OF MEDICAL DEVICES
In 1976 the United States Congress passed what are known as the Medical
Device Amendments (Public Law 94-295) to the Federal Food, Drug, and
Cosmetics Act that dates back to the 1930s. In the Safe Medical Devices Act of
1990, further amendments were made (Pacela, 1991). The primary purpose was
to ensure the safety and efficacy of new medical devices prior to marketing of
the device. The law’s definition of the term medical device is “any item
promoted for a medical purpose that does not rely on chemical action to
achieve its intended effect’? (Kessler et al., 1987). Medical devices were
classified in two ways. First. the division of such devices into Class I. II. and
IU was based on the principle that devices that pose greater potential hazards
should be subject to more regulatory requirements. Second, seven categories
were established: preamendment, postamendment, substantially equivalent,
implant, custom, investigational, and transitional (Enderle et a/., 2005).
The seven categories into which medical devices are divided are described
in Table 1.2, which also includes classification rules and examples. Software
used in medical devices has become an area of increasing concern; several
serious accidents have been traced to software bugs (Murfitt, 1990). Increased
requirements for maintaining traceability of devices to the ultimate customer,
postmarketing surveillance for life-sustaining and life-supporting implants,
and hospital reporting requirements for adverse incidents were added to the
law in 1990.
Class I general controls. Manufacturers are required to perform

registration, premarketing notification, record keeping. labeling. reporting
of adverse experiences, and good manufacturing practices. These controls
apply to all three classes.
Class IT performance standards. These standards were to be

defined by the federal government, but the complexity of procedures
called for in the amendments and the enormity of the task have resulted in
little progress having been made toward defining the 800 standards
needed. The result has been overreliance on the postamendment “sub-
stantial equivalence”? known as the 510(k) process.
Class Il premarketing approval. Such approval is required for

devices used in supporting or sustaining human life and preventing
impairment of human health. The FDA has extensively regulated these
devices by requiring manufacturers to prove their safety and effectiveness
prior to market release.
40 1
Table 1.2 FDA Medical Device Categories
BASIC CONCEPTS OF MEDICAL INSTRUMENTATION
Category Description
Classification Rules
Examples
Devices on the
market before
May 28, 1976,
when the
Medical Device
Amendments
were enacled.
Preamendment
devices (or
old devices)
Postamendment
devices (or
Devices put on the

market after
new devices) May 28, 1976.

Substantially Postamendment
equivalent devices that are
devices substantially
equivalent to
preamendment
devices.
Devices are assigned to 1

of 3 classes. A
presumption exists that
preamendment devices
should be placed in
Class I unless their
safely and effectiveness
cannol be ensured
without the greater
regulation afforded by
Classes II and Il. A
manufacturer may
petition the FDA for
teclassification.
Unless shown to be
substantially equivalent
to a device that was on
the market before the
amendments took
effect, these devices are
automatically placed in
Class IIL A
manufacturer may
petition the FDA for
reclassification,
Devices are assigned to the

same class as their
preamendment
counterparts and subject
to the same
requirements. If and
when the FDA requires
testing and approval of
preamendment devices,
their substantially
equivalent counterparts
will also be subject to
testing and approval.
Analog electrocardiog-
raphy machine; elec-
trohydraulic
lithotriptor;
contraceplive
intrauterine device
and accessories; infant
radiant warmer;
contraceplive tubal
occlusion device;
automated heparin
analyzer; automated
differential cell
counter; automated
blood-cell separator;
transabdominal
aminoscope.
Magnetic resonance im-

ager; extracorporeal
shock-wave lithotrip-
tor; absorbable
sponge; YAG laser;
AIDS-antibody test
kit; hydrophilic contact
lenses; percutaneous
catheter for
transluminal coronary
angioplasty;
implantable
defibrillator; bone-
growth stimulator;
alpha-fetoprotein RIA
kit; hepatitis B-
antibody detection kit.
Digital
electrocardiography
machines; YAG lasers
for certain uses;
tampons; ELISA
diagnostic kits; devices
used to test for drug
abuse.
1.13 REGULATION OF MEDICAL DEVICES 41

Table 1.2 (Continued)
Category Description Classification Rules Examples
Implanted Devices that are Devices are assumed to Phrenic-nerve stimulator;
devices inserted into a require placement in pacemaker pulse
Custom devices
Investigational
devices
Transitional
devices
Devices not
Unapproved
Devices that were
surgically Class III unless a less-

formed or regulated class will
natural body ensure safely and
cavily and effectiveness.
intended to
remain there for
> 30 days.
Devices are exempt from

premarketing testing
and performance
standards but are
subject to general
controls.
generally
available to
other licensed
practitioners and
not available in
finished form.
Product must be
specifically
designed fora
particular
patient and may
not be offered
for general
commercial
distribution.
Devices are exempt if an
Investigational Device
Exemption has been
granted.
devices
undergoing
clinical
investigation
under the
authority of an
Investigational
Device
Exemption.
Devices are automatically
assigned to Class LI but
may be reclassified in
Class Lor LL.
regulated as
drugs before
enactment of the
statute but are
now defined as
medical devices.
generator; intracardiac
patch; vena cava
clamp.
Dentures; orthopedic
shoes.
Artificial heart; ultrasonic

hyperthermia
equipment; DNA
probes; laser
angioplasty devices;
positron emission
tomography machines.
Antibiotic susceptibility
disks; bone
heterografts;
gonorrhea diagnostic
products; injectable
silicone; intraocular
lenses; surgical
sulures; soft contact
lenses.
Source: Reprinted with permission from The New England Journal of Medicine 317(6), 357-366,
1987.
PROBLEMS
1.1 Find the independent nonlinearity, as defined in Figure 1.4(b), for the
following set of inputs and outputs from a nearly linear system. Instrument was
designed for an output equal to twice the input. Full scale is 20.
Inputs 0.50 1.50 2.00 5.00 10.00

Outputs 0.90 3.05 400 9.90 20.50
1.2 Find the correlation coefficient r for the set of five inputs and outputs
given in Problem 1.1.
1.3 Derive the operational transfer function and the sinusoidal transfer
function for an RC high-pass filter. Plot the step response and the complete
frequency response (magnitude and phase).
1.4 A first-order low-pass instrument must measure hummingbird wing

displacements (assume sinusoidal) with frequency content up to 100 Hz
with an amplitude inaccuracy of less than 5%. What is the maximal allowable
time constant for the instrument? What is the phase angle at 50 Hz and at
100 Hz?
1.5 A mercury thermometer has a cylindrical capillary tube with an internal

diameter of 0.2 mm. If the volume of the thermometer and that of the bulb are
not affected by temperature, what volume must the bulb have if a sensitivity of
2mm/"C is to be obtained? Assume operation near 24°C. Assume that the stem
volume is negligible compared with the bulb internal volume. Differential
expansion coefficient of Hg = 1,82 x 10-4+ml/(ml-*C).
1.6 For the spring scale shown in Figure 1.7(a), find the transfer function when
the mass is negligible.
1.7 Find the time constant from the following differential equation, given that
x is the input, y is the output, and a through / are constants.
dy
“a
+bxtethy=e® + fe +8
18 A low-pass first-order instrument has a time constant of 20 ms. Find the

frequency, in hertz, of the input at which the output will be 93% of the dc output.
Find the phase angle at this frequency.
1.9 A second-order instrument has a damping ratio of 0.4 and an undamped

natural frequency of 85 Hz. Sketch the step response, and give numerical values
for the amplitude and time of the first two positive maxima. Assume that the
input goes from 0 to 1 and that the static sensitivity is 10.
1.10 Consider an underdamped second-order system with step response as

shown in Figure 1.7(c). A different way to define logarithmic decrement is
T=
Yn4vi
REFERENCES 43
Here 7 refers not to the number of positive peaks shown in Figure 1.7(c) but to
both positive and negative peaks. That is, 7 increases by 1 for each half cycle.
Derive an equation for the damping ratio ¢ in terms of this different definition
of logarithmic decrement.
REFERENCES
Anonymous, Designers Handbook: Medical Electronics. A Resource and Buyers Guide for
Medical
Electronics Engineering and Design, 3rd ed. Santa Monica, CA: Canon Communications,
Inc.1994.
Anonymous, Health Devices Sourcebook. Plymouth Meeting, PA: ECRI, 2007.
Anonymous, [uman Factors Engineering Guidelines and Preferred Practices for the Design of
Medical Devices, 2nd ed. Arlington, VA: ANSI/AAMI HE48, 1993.
Anonymous, Medical Outcomes and Guidelines Sourcebook. New York, NY: Faulkner and Gray,
Inc., 2001.
Anonymous, Product Development Directory. Montvale, NJ: Medical Economics Co., 1996.
Bronzino, J. D. (ed.), The Biomedical Engineering Handbook, 3rd ed. Boca Raton, FL: CRC
Press,
2006.
Brush, L. C., The Guide to Biomedical Standards, 21st ed. Brea, CA: Quest Publishing Co.,
1999.
Cobbold, R. S. C., Transducers for Biomedical Measurements: Principles and Applications. New
York: Wiley, 1974.
Cohen, B. J., Medical Terminology: An Illustrated Guide, 4th ed. Philadelphia: Lippincott, 2004.
Cromwell, L., F. J. Weibell, and E. A. Pfeiffer, Biomedical Instrumentation and Measurements,

2nd
ed. Englewood Cliffs, NJ: Prentice-Hall, 1980.
Davis, N. M., Medical Abbreviations: 15,000 Conveniences at the Expense of Communication

and
Safety, 10th ed. Huntington Valley, PA: Neil M. Davis Associates, 2001.
Dawson-Saunders, B., and R. G. Trapp, Basic and Clinical Biostatistics. 4th ed. Norwalk, CT:
Appleton & Lange, 2004.
Doebelin, E. O., Measurement Systems: Application and Design, 4th ed. New York:
McGraw-Hill,
1990.
Dorland, N. W. (ed.), Dorland’s Mustrated Medical Dictionary, 30th ed. Philadelphia: Saunders,
2003.
Ekelman, K. B., New Medical Devices: Invention, Development, and Use. Washington, DC:
National Academy Press, 1988.
Enderle, J. D., 8. M. Blanchard, and J. D. Bronzino, Introduction to Biomedical Engineering, 2nd

ed., San Diego: Academic, 2005.
Firkin, B. G., and J. A. Whitworth, Dictionary of Medical Eponyms, 2nd ed. Park Ridge, NJ:
Parthenon, 1996.
Geddes, L. A., and L. E. Baker, Principles of Applied Biomedical Instrumentation, 3rd ed. New
York: Wiley, 1989.
Haber, K., Common Abbreviations in Clinical Medicine. New York: Raven Press, 1988.
Hamilton, B., and B. Guides, Medical Acronyms, Symbols and Abbreviations, 2nd ed. New York:
Neal-Schuman, 1988.
Heister, R., Dictionary of Abbreviations in Medical Sciences. New York: Springer, 1989.
Institute of Electrical and Electronics Engineers (IEEE), IEEE Standard Dictionary of Electrical
and Electronic Terms, 6th ed. Piscataway, NJ: Institute of Electrical and Electronics
Engineers, 1997.
Jacobson, B., and J. G. Webster, Medicine and Clinical Engineering. Englewood Cliffs, NJ:
Prentice-Hall, 1977.
Kessler, D. A., “The federal regulation of medical devices.’ N. Engl. J. Med., 1987, 317(6), 357—
366.
King, P. H., and R. C. Fries, Design of Biomedical Devices and Systems, 2"! ed. Boca Raton,
FL:
CRC Press, 2009.
Kuo, B., and F. Golnaraghi, Automatic Control Systems, 8th ed. New York: Wiley, 2003.
Murfitt, R. R., “United States government regulation of medical device software: A review.” J.
Med. Eng. Technol., 1990, 14(3), 111-113.
Pacela, A. F. (ed.), “Safe medical devices law: Sweeping changes for hospitals and the
standards
industry,” Biomed. Safety and Stand. Special Supplement No. 12, February 1991.
Rabbitt, J. T., and P. A. Bergh, The ISO 9000 Book, 2nd ed. White Plains, NY: Quality
Resources,
1994.
Ray, C. D. (ed.), Medical Engineering. Chicago: Year Book, 1974.
Scott, D., and J. G. Webster, “Development phases for medical devices.” Med. Instrum., 1986,
20(1), 48-52.
Stanaszek, M. J., The Inverted Medical Dictionary, 2nd ed. Lancaster, PA: Technomic Publishing
Co., 1991.
Tompkins, W. J., and J. G. Webster (eds.), Design of Microcomputer-Based Medical Instrumen-

tation. Englewood Cliffs, NJ: Prentice-Hall, 1981.
Webster, J. G. (ed.), Bioinstrumentation. Hoboken NJ: Wiley, 2004.
Webster, J. G. (ed.), Encyclopedia of Medical Devices and Instrumentation, 2nd ed. Vols. 1-6.
New
York: Wiley, 2006.
Webster, J. G.,and A.M. Cook (eds.), Clinical Engineering: Principles and Practices. Englewood
Cliffs, NJ: Prentice-Hall, 1979.
2
BASIC SENSORS AND
PRINCIPLES
Robert A. Peura and John G. Webster
This chapter deals with basic mechanisms and principles of the sensors used in
a number of medical instruments. A transducer is a device that converts energy
from one form to another. A sensor converts a physical parameter to an electric
output. An actuator converts an electric signal to a physical output. An electric
output from the sensor is normally desirable because of the advantages it gives
in further signal processing (Pallas-Areny and Webster, 2001). As we shall see
in this chapter, there are many methods used to convert physiological events to
electric signals. Dimensional changes may be measured by variations in
resistance, inductance, capacitance, and piezoelectric effect. Thermistors
and thermocouples are employed to measure body temperatures. Electro-
magnetic-radiation sensors include thermal and photon detectors. In our
discussion of the design of medical instruments in the following chapters,
we shall use the principles described in this chapter (Togawa et al., 1997).
2.1 DISPLACEMENT MEASUREMENTS
The physician and biomedical researcher are interested in measuring the size,
shape, and position of the organs and tissues of the body. Variations in these
parameters are important in discriminating normal from abnormal function.
Displacement sensors can be used in both direct and indirect systems of
measurement. Direct measurements of displacement are used to determine
the change in diameter of blood vessels and the changes in volume and shape of
cardiac chambers.
Indirect measurements of displacement are used to quantify movements of

liquids through heart valves. An example is the movement of a microphone
diaphragm that detects the movement of the heart indirectly and the resulting
heart murmurs.
Here we will describe the following types of displacement-sensitive

measurement methods: resistive, inductive, capacitive, and piezoelectric
(Nyce, 2004).
45
46 2 BASICSENSORS AND PRINCIPLES
2.2 RESISTIVE SENSORS
POTENTIOMETERS
Figure 2.1 shows three types of potentiometric devices for measuring displace-
ment. The potentiometer shown in Figure 2.1(a) measures translational dis-
placements from 2 to 500 mm. Rotational displacements ranging from 10° to
more than 50° are detected as shown in Figure 2.1(b) and (c). The resistance
elements (composed of wire-wound, carbon-film, metal-film, conducting-
plastic, or ceramic material) may be excited by either dc or ac voltages. These
potentiometers produce a linear output (within 0.01% of full scale) as a function
of displacement, provided that the potentiometer is not electrically loaded.
The resolution of these potentiometers is a function of the construction. It

is possible to achieve a continuous stepless conversion of resistance for low-
resistance values up to 10 © by utilizing a straight piece of wire. For greater
variations in resistance, from several ohms to several megohms, the resistance
wire is wound on a mandrel or card. The variation in resistance is thereby not
continuous, but rather stepwise, because the wiper moves from one turn of
wire to the next. The fundamental limitation of the resolution is a function of
the wire spacing, which may be as small as 20 zm. The frictional and inertial
components of these potentiometers should be low in order to minimize
dynamic distortion of the system.
STRAIN GAGES
When a fine wire (25 ym) is strained within its elastic limit, the wire’s resistance
changes because of changes in the diameter, length, and resistivity. The
resulting strain gages may be used to measure extremely small displacements,
on the order of nanometers. The following derivation shows how each of these
parameters influences the resistance change. The basic equation for the
+
+O
~
+ ‘i
a
O,
i
+] -
(a) Translational Cb} Single dum to) Multtturn
Figure 2.1. Three types of potentiometric devices for measuring displace-

ments (a) Translational. (b) Single-turn, (c) Multiturn. (From Measurement
Systems: Application and Design, by E. O. Doebelin. Copyright © 1990 by
McGraw-Hill, Inc. Used with permission of McGraw-Hill Book Co.)
2.2 RESISTIVE SENSORS 47
resistance R of a wire with resistivity o (ohm-meter), length L (meters), and

cross-sectional area A (meter squared) is given by
pL
R=— 2.1
= (2.1)
The differential change in R is found by taking the differential
pd 2 dp
dR= > — pA~LdA+ L— a (2.2)
We shall modify this expression so that it represents finite changes in the

parameters and is also a function of standard mechanical coefficients. Thus
dividing members of (2.2) by corresponding members of (2.1) and introducing
incremental values, we get
AR AL AA. Ap
RL atp (23)
Poisson’s ratio jz. relates the change in diameter AD to the change in length:
AD/D = — AL/L. Substituting this into the center term of (2.3) yields
AR A
(142 we + =? (2.4)
—_ be p
Dimensional Piezoresistive
effect effect
Note that the change in resistance is a function of changes in dimension—

length (AL/L} and area (2;,AL/L)—plus the change in resistivity due to
strain-induced changes in the lattice structure of the material, Ap/e. The gage
factor G, found by dividing (2.4) by AL/L, is useful in comparing various
strain-gage materials.
— ARIR _ 4 Dele. (2.5)
~ arn tH air
Table 2.1 gives the gage factors and temperature coefficient of resistivity of various
strain-gage materials. Note that the gage factor for semiconductor materials is
approximately 50 to 70 times that of the metals.
Also note that the gage factor for metals is primarily a function of
dimensional effects. For most metals, 4 = 0.3 and thus G is at least 1.6,
whereas for semiconductors, the piezoresistive effect is dominant. The desir-
able feature of higher gage factors for semiconductor devices is offset by their
greater resistivity-temperature coefficient.
Designs for instruments that use semiconductor materials must incorpo-

rate temperature compensation.
Strain gages can be classified as either unbonded or bonded. An unbonded

strain-gage unit is shown in Figure 2.2(a). The four sets of strain-sensitive wires
48 2
BASIC SENSORS AND PRINCIPLES
Table 2.1 Properties of Strain-Gage Materials
Temperature
Coefficient of
Resistivity
Material Composition (%) Gage Factor ec-1_1075)
Constantan Nigs, Cuss 21 +2
(advance)
Isoelastic Nigg, Crg 3.52 to 3.6 +17
(Mn, Si, Mo)4
Fes)
Karma Niz4, Crag, Fes 21 +2
Cus
Manganin Cuga, Mnp, Nig 0.3 to 0.47 +2
Alloy 479 Plo, Wg 3.6 to 4.4 +24
Nickel Pure —12 to —20 670
Nichrome V Nigo, Cra 2.1 to 2.63 10
Silicon (p type) 100 to 170 70 to 700
Silicon (n type) —100 to —140 70 to 700
Germanium (p type) 102
Germanium (n type) —150
Source: From R. S.C. Cobbold, Transducers for Biomedical Measurements, 1974, John Wiley &
Sons, Inc.. Used with permission of John Wiley & Sons, Inc., New York.
are connected to form a Wheatstone bridge, as shown in Figure 2.2(b). These

wires are mounted under stress between the frame and the movable armature
such that preload is greater than any expected external compressive load. This
is necessary to avoid putting the wires in compression. This type of sensor may
be used for converting blood pressure to diaphragm movement, to resistance
change, then to an electric signal.
A bonded strain-gage element, consisting of a metallic wire, etched foil,

vacuum-deposited film, or semiconductor bar, is cemented to the strained
surface. Figure 2.3 shows typical bonded strain gages. The deviation from
linearity is approximately 1%. One method of temperature compensation for
the natural temperature sensitivity of bonded strain gages involves using a
second strain gage as a dummy element that is also exposed to the temperature
variation, but not to strain. When possible, the four-arm bridge shown in
Figure 2.2 should be used, because it not only provides temperature compen-
sation but also yields four times greater output if all four arms contain active
gages. Four bonded metal strain gages can be used on cantilever beams to
measure bite force in dental research (Dechow, 2006).
Strain-gage technology advanced in the 1960s with the introduction of the

semiconductor strain-gage element, which has the advantage of having a high
gage factor, as shown in Table 2.1. However, it is more temperature sensitive
and inherently more nonlinear than metal strain gages because the piezo-
resistive effect varies with strain. Semiconductor elements can be used as
Diaplragin
— Amarin
Strain-gage wires
(b}
Figure 2.2. (a) Unbonded strain-gage pressure sensor. The diaphragm is

directly coupled by an armature to an unbonded strain-gage system. With
increasing pressure, the strain on gage pair B and C is increased, while that on
gage pair A and D is decreased. (b) Wheatstone bridge with four active
elements: R,; = B, Ry = A, R3 =D, and Ry =C when the unbonded strain
gage is connected for translational motion. Resistor R, and potentiometer Ry
are used to initially balance the bridge, V; is the applied voltage, and Av, is the
output voltage on a voltmeter or similar device with an internal resistance of Rj.
Helical
Le Ful
wine
Boirck rng:
P Backing
«ay thy ic]
Figure 2.3 Typical bonded strain-gage units (a) resistance-wire type, (b) foil
type, (c) helical-wire type. Arrows above units show direction of maximal
sensitivity to strain. [Parts (a) and (b) are modified from Instrumentation in
Scientific Research, K. S. Lion. Copyright © 1959 by McGraw-Hill, Inc. Used
with permission of McGraw-Hill Book Co.]
bonded, unbonded, or integrated strain-gage units. These integrated devices

can be constructed with either silicon or germanium p or 7 type as the substrate
that forms the structural member. The opposite-type material is diffused into
the substrate. Opposite signs for the gage factor result for n- and p-type
substrate gages. A large gage factor can be attained with lightly doped
material. Figure 2.4 shows typical semiconductor strain-gage units.
- iE —- p -— Top vi
AC SSS a bp view
oe (=
diffused
layer TZ =
~
a
a Cross-sectional view
n-type Si
plane
Diffused
Top view
Figure 2.4 Typical semiconductor strain-gage units (a) unbonded, uniformly

doped, (b) diffused p-type gage, (c) integrated pressure sensor, (d) integrated
cantilever-beam force sensor. (From Transducers for Medical Measurements:
Application and Design, R. S. C. Cobbold. Copyright © 1974, John Wiley &
Sons, Inc. Reprinted by permission of John Wiley & Sons, Inc.)
dem
To patient
Ty cahing
Silicon chip
Electrical cable
Figure 2.5 Isolation in a disposable blood-pressure sensor Disposable blood-

pressure sensors are made of clear plastic so air bubbles are easily seen. Saline
flows from an intravenous (IV) bag through the clear IV tubing and the sensor
to the patient. This flushes blood out of the tip of the indwelling catheter to
prevent clotting. A lever can open or close the flush valve. The silicon chip has
a silicon diaphragm with a four-resistor Wheatstone bridge diffused into it. Its
electrical connections are protected from the saline by a compliant silicone
elastomer gel, which also provides electrical isolation. This prevents electric
shock from the sensor to the patient and prevents destructive currents during
defibrillation from the patient to the silicon chip.
The integrated-type sensor has an advantage in that a pressure sensor can

be fabricated by using a silicon substrate for the structural member of the
diaphragm. The gages are diffused directly onto the diaphragm. When pressure
is applied to the diaphragm, a radial stress component occurs at the edge. The
sign of this component is opposite to that of the tangential stress component
near the center. The placement of the eight diffused strain-gage units shown in
Figure 2.4(c) gives high sensitivity and good temperature compensation
(Cobbold, 1974). Figure 2.5 shows a disposable blood-pressure sensor that
uses an integrated silicon chip. Silicon strain-gage pressure sensors can be
placed on the tip of a catheter and inserted directly into the blood, resulting in
more accurate measurements and faster response times (Korites, 1987).
Elastic-resistance strain gages are extensively used in biomedical applica-

tions, especially in cardiovascular and respiratory dimensional and plethysmo-
graphic (volume-measuring) determinations. These systems normally consist of a
narrow silicone-rubber tube [0.5 mm inner diameter (ID), 2 mm outer diameter
(OD)] from 3 to 25 cm long and filled with mercury or with an electrolyte or
conductive paste. The ends of the tube are sealed with electrodes (amalgamated
copper, silver, or platinum). As the tube stretches, the diameter of the tube
decreases and the length increases, causing the resistance to increase. The
resistance per unit length of typical gages is approximately 0.02 to 2 O/em. These
units measure much higher displacements than other gages.
The elastic strain gage is linear within 1% for 10% of maximal extension.
As the extension is increased to 30% of maximum, the nonlinearity reaches 4%
of full scale. The initial nonlinearity (dead band) is ascribed to slackness of the
unit. Long-term creep is a property of the rubber tubing. This is not a problem
for dynamic measurements.
Operational problems include maintaining a good contact between the mer-

cury and the electrodes, ensuring continuity of the mercury column, and controll-
ing the drift in resistance due to a relatively large gage temperature coefficient.
In addition, accurate calibration is difficult because of the mass-elasticity and
stress-strain relations of the tissue—strain-gage complex. The low value of resist-
ance Means more power is required to operate these strain-gage units.
Lawton and Collins (1959) determined the static and dynamic response of
elastic strain gages. They found that the amplitude and phase were constant up
to 10 Hz. Significant distortion occurred for frequencies greater than 30 Hz.
Cobbold (1974) indicated that a problem not fully appreciated is that the gage
does not distend fully during pulsations when diameter of the vessel is being
measured. The mass of the gage and its finite mechanical resistance can cause it
to dig into the vessel wall as the vessel expands, so it can give a reading several
times lower than that measured using ultrasonic or cineangiographic methods.
Hokanson et al. (1975) described an electrically calibrated mercury-in-

rubber strain gage. Lead-wire errors are common with these devices because of
the low resistance of the strain gage. In Hokanson’s design, the problem was
eliminated by effectively placing the strain gage at the corners of the mea-
surement bridge. A constant-current source causes an output that is linear for
large changes in gage resistance. Figure 2.6 shows the device and its output
when applied to the human calf.
MeV) ib Leen
Figure 2.6 Mercury-in-rubber strain-gage plethysmography (a) Four-lead
gage applied to human calf, (b) Bridge output for venous-occlusion plethys-
mography. (c) Bridge output for arterial-pulse plethysmography. [Part (a) is
based on D. E. Hokanson, D. S. Sumner, and D. E. Strandness, Jr., “An
electrically calibrated plethysmograph for direct measurement of limb blood
flow.” 1975, BME-22, 25-29; used with permission of JEEE Trans. Biomed.
Eng., 1975, New York.]
2.4 INDUCTIVE SENSORS 53
2.3. BRIDGE CIRCUITS
The Wheatstone bridge circuit is ideal for measuring small changes in resist-
ance. Figure 2.2(b) shows a Wheatstone bridge with an applied dc voltage of +;
and a readout meter Av, with internal resistance R;. It can be shown by the
voltage-divider approach that Aw, is zero—that is, the bridge is balanced—
when R,/Rs = Ra/R3.
Resistance-type sensors may be connected in one or more arms of a bridge

circuit. The variation in resistance can be detected by measuring At, with a
differential amplifier feeding an analog-to-digital converter (ADC), which
feeds a computer.
Assume that all values of resistance of the bridge are initially equal to Ro
and that Ry «< R;. An increase in resistance, AR, of all resistances still results in
a balanced bridge. However, if R, and Rz increase by AR, and R, and Ry
decrease by AR, then
Av, = AR 2.6)
Uy = R, Vi (2.
Because of the symmetry a similar expression results if Ro and R4 increase by
AR and R,; and R3 decrease by AR. Note that (2.6), for the four-active-arm
bridge, shows that Aw, is linearly related to AR. A nonlinearity in AR/Rp is
present even when Ry/R; = 0.
It is common practice to incorporate a balancing scheme in the bridge
circuit [see Figure 2.2(b)]. Resistor Ry, and potentiometer R, are used to
change the initial resistance of one or more arms. This arrangement brings the
bridge into balance so that zero voltage output results from ‘“‘zero” (or base-
level) input of the measured parameter.
To minimize loading effects, R, is approximately 10 times the resistance of

the bridge leg, and R, limits the maximal adjustment. Strain-gage applications
normally use a value of R, = 25 times the resistance of the bridge leg.
Alternating-current (ac) balancing circuits are more complicated because a
reactive as well as a resistive imbalance must be compensated.
2.4 INDUCTIVE SENSORS
An inductance LZ can be used to measure displacement by varying any three of

the coil parameters:
L=nGu (2.7)
where
n=number of turns of coil
G=geometric form factor
i =effective permeability of the medium
Each of these parameters can be changed by mechanical means.

| te
o r mo be
, Ey Ez
e
uch
Figure 2.7 Inductive displacement sensors (a) self-inductance, (b) mutual

inductance, (c) differential transformer.
Figure 2.7 shows (a) self-inductance, (b) mutual-inductance, and (c) differ-
ential transformer types of inductive displacement sensors. It is usually possible to
convert a mutual-inductance system into a self-inductance system by series of
parallel connections of the coils. Note in Figure 2.7 that the mutual-inductance
device (b) becomesaself-inductance device (a) whenterminals b-c are connected.
An inductive sensor has an advantage in not being affected by the

dielectric properties of its environment. However, it may be affected by
external magnetic fields due to the proximity of magnetic materials.
The variable-inductance method employing a single displaceable core is

shown in Figure 2.7(a). This device works on the principle that alterations in
the self-inductance of a coil may be produced by changing the geometric form
factor or the movement of a magnetic core within the coil. The change in
inductance for this device is not linearly related to displacement. The fact that
these devices have low power requirements and produce large variations in
inductance makes them attractive for radiotelemetry applications.
The mutual-inductance sensor employs two separate coils and uses the varia-
tion in their mutual magnetic coupling to measure displacement [Figure 2.7(b)].
Cobbold (1974) describes the application of these devices in measuring cardiac
dimensions, monitoring infant respiration, and ascertaining arterial diameters.
Van Citters (1966) provides a good description of applications of mutual

inductance transformers in measuring changes in dimension of internal organs
(kidney, major blood vessels, and left ventricle). The induced voltage in the
secondary coil is a function of the geometry of the coils (separation and axial
alignment), the number of primary and secondary turns, and the frequency and
amplitude of the excitation voltage. The induced voltage in the secondary coil
is anonlinear function of the separation of the coils. In order to maximize the
output signal, a frequency is selected that causes the secondary coil (tuned
circuit) to be in resonance. The output voltage is detected with standard
demodulator and amplifier circuits.
The linear variable differential transformer (LVDT) is widely used in

physiological research and clinical medicine to measure pressure, displacement,
and force (Kesavan and Reddy, 2006). As shown in Figure 2.7(c), the LVDT is
composed of a primary coil (terminals a—b) and two secondary coils (c-e andd-e)
connected in series. The coupling between these two coils is changed by the
2.4 INDUCTIVE SENSORS 55
motion of a high-permeability alloy slug between them. The two secondary

coils are connected in opposition in order to achieve a wider region of linearity.
The primary coil is sinusoidally excited, with a frequency between 60 Hz

and 20 kHz. The alternating magnetic field induces nearly equal voltages 1,.
and ty. in the secondary coils. The output voltage tq = toe — tac. When the
slug is symmetrically placed, the two secondary voltages are equal and the
output signal is zero.
Linear variable differential transformer characteristics include linearity

over a large range, a change of phase by 180° when the core passes through the
center position, and saturation on the ends. Specifications of commercially
available LVDTs include sensitivities on the order of 0.5 to 2 mV for a
displacement of 0.01 mm/V of primary voltage, full-scale displacement of
0.1 to 250 mm, and linearity of +0.25%. Sensitivity for LVDTs is much higher
than that for strain gages.
A disadvantage of the LVDT is that it requires more complex signal-

processing instrumentation. Figure 2.8 shows that essentially the same
U
x
Displacsment
Positive
ogalive
ta}
Positive
Megalive
(bi
Figure 2.8 (a) As x moves through the null position, the phase changes 180°,
while the magnitude of 2 is proportional to the magnitude of x. (b) An
ordinary rectifier demodulator cannot distinguish between (a) and (b), so a
phase-sensitive demodulator is required.
magnitude of output voltage results from two very different input displace-
ments. The direction of displacement may be determined by using the fact that
there is a 180° phase shift when the core passes through the null position. A
phase-sensitive demodulator is used to determine the direction of displace-
ment. Figure 3.17 shows a ring-demodulator system that could be used with the
LVDT.
2.5 CAPACITIVE SENSORS
The capacitance between two parallel plates of area A separated by distance

Xx is
A
C= me 2.8
Eg6, x ( )
where & is the dielectric constant of free space (Appendix A.1) and ¢, is the
relative dielectric constant of the insulator (1.0 for air) (Bowman and Meindl,
1988). In principle it is possible to monitor displacement by changing any of
the three parameters ¢,, A, or x. However, the method that is easiest to
implement and that is most commonly used is to change the separation
between the plates.
The sensitivity K of a capacitive sensor to changes in plate separation Ax is

found by differentiating (2.8).
AC A
K= i = —Eoey 2 (2.9)
Note that the sensitivity increases as the plate separation decreases.
By substituting (2.8) into (2.9), we can develop an expression showing that
the percent change in C about any neutral point is equal to the per-unit change
in x for small displacements. Thus
dC —-C
dex (2.10)
or
dC —dx
The capacitance microphone shown in Figure 2.9 is an excellent example of a

relatively simple method for detecting variation in capacitance (Doebelin,
1990; Cobbold, 1974). This is a de-excited circuit, so no current flows when the
capacitor is stationary (with separation xo), and thus + = £. A change in
2.5 CAPACITIVE SENSORS 57
r=
T
Figure 2.9 Capacitance sensor for measuring dynamic displacement
changes.
Ud
position Ax = x; — x9 produces a voltage v) = — E. The output voltage V, is

related to x, by
Vol joo) _ (Efxo) jor
2.12
Xi (jo) jott 1 (2.12)
where t= RC = Repe,A/Xo.
Typically, R is 1 MO or higher, and thus the readout device must have a

high (10 MO or higher) input impedance.
For wr 1, Vo(jo)/X1( jo) = E/xo, which is a constant. However, the
response drops off for low frequencies, and it is zero when w = 0. Thus (2.12)
describes a high-pass filter. This frequency response is quite adequate for a
microphone that does not measure sound pressures at frequencies below
20 Hz. However, it is inadequate for measuring most physiological variables
because of their low-frequency components.
Compliant plastics of different dielectric constants may be placed between foil

layers to form a capacitive mat to be placed on a bed. Patient movement generates
charge, which is amplified and filtered to display respiratory movements from the
lungs and ballistographic movements from the heart (Alihanka er al, 1982).
A capacitance sensor can be fabricated from layers of mica insulators

sandwiched between corrugated metal layers. Applied pressure flattens the
corrugations and moves the metallic plates closer to each other, thus increasing
the capacitance. The sensor is not damaged by large overloads, because flattening
of the corrugations does not cause the metal to yield. The sensor measures the
pressure between the foot and the shoe (Patel er al., 1989). Tsoukalas et al. (2006)
describe micromachined silicon capacitive sensors and their electronic interfaces.
EXAMPLE 2.1 For a 1 cm? capacitance sensor, R is 100 MQ. Calculate x,

the plate spacing required to pass sound frequencies above 20 Hz.
ANSWER From the corner frequency, C = 1/27fR = 1/(2720 = 10°) =

80pF From (2.8) we can calculate x given the value of C.
_ &&A (8.854 x 10771 x 104) 5

x= = 30 x 10-2 =111x10m=111 ym
2.6 PIEZOELECTRIC SENSORS
Piezoelectric sensors are used to measure physiological displacements and

record heart sounds. Piezoelectric materials generate an electric potential
when mechanically strained, and conversely an electric potential can cause
physical deformation of the material. The principle of operation is that when
an asymmetrical crystal lattice is distorted, a charge reorientation takes place,
causing a relative displacement of negative and positive charges. The displaced
internal charges induce surface charges of opposite polarity on opposite sides
of the crystal. Surface charge can be determined by measuring the difference in
voltage between electrodes attached to the surfaces.
Initially, we assume infinite leakage resistance. Then, the total induced

charge gq is directly proportional to the applied force f.
q=kf (2.13)
where & is the piezoelectric constant, C/N. The change in voltage can be found
by assuming that the system acts like a parallel-plate capacitor where the
voltage «# across the capacitor is charge g divided by capacitance C. Then, by
substitution of (2.8), we get
_ kf _ kfx
ew C= ion A (2.14)
Tables of piezoelectric constants are given in the literature (Lion, 1959; and
Cobbold, 1974).
Typical values for k are 2.3 pC/N for quartz and 140 pC/N for barium
titanate. For a piezoelectric sensor of 1 cm* area and 1 mm thickness with an
applied force due to a 10 g weight, the output voltage # is 0.23 mV and 14 mV
for the quartz and barium titanate crystals, respectively.
There are various modes of operation of piezoelectric sensors, depending

on the material and the crystallographic orientation of the plate (Lion, 1959).
These modes include the thickness or longitudinal compression, transversal
compression, thickness-shear action, and face-shear action.
Also available are piezoelectric polymeric films, such as polyvinylidene

fluoride (PVDF) (Hennig, 1988; Webster, 1988). These films are very thin,
lightweight and pliant, and they can be cut easily and adapted to uneven
surfaces. The low mechanical quality factor does not permit resonance appli-
cations, but it permits acoustical broadband applications for microphones and
loudspeakers.
Piezoelectric materials have a high but finite resistance. As a consequence,

if a static deflection x is applied, the charge leaks through the leakage resistor
(on the order of 100GQ). It is obviously quite important that the input
impedance of the external voltage-measuring device be an order of magnitude
higher than that of the piezoelectric sensor. It would be helpful to look at the
2.6 PIEZOELECTRIC SENSORS 59
¢ Anagti lier
RAR RAR, + R= aR,

CaC+C.+¢,
(hi
Figure 2.10 (a) Equivalent circuit of piezoelectric sensor, where R, = sensor

leakage resistance, C, = sensor capacitance, C, = cable capacitance, Cy =
amplifier input capacitance, R, = amplifier input resistance, and g = charge
generator. (b) Modified equivalent circuit with current generator replacing
charge generator. (From Measurement Systems: Application and Design, by E.
O. Doebelin. Copyright © 1990 by McGraw-Hill, Inc. Used with permission of
McGraw-Hill Book Co.)
equivalent circuit for the piezoelectric sensor [Figure 2.10(a)] in order to

quantify its dynamic-response characteristics.
This circuit has a charge generator g defined by
q = Kx (2.15)
where where
K=proportionality constant, C/m

x = deflection
The circuit may be simplified by converting the charge generator to a

current generator, i,.
. _ dq Ke
The modified circuit is shown in Figure 2.10(b), where the resistances and
capacitances have been combined. Assuming that the amplifier does not draw
any current, we then have
i, =ict+ip (2.17)
Yo = te = | fi dt (2.18)
0 FCS C Cc .
. dity ax %
or
V,(jo) _ Ky jot
X(jo) jett+1 (2.20)
where
K,=K/C (sensitivity, V/m)

t= RC (time constant)
EXAMPLE 2.2 A piezoelectric sensor has C = 500 pF. The sensor leakage
resistance is 10 GQ. The amplifier input impedance is 5 MQ. What is the low-
corner frequency?
ANSWER We may use the modified equivalent circuit of the piezoelectric

sensor given in Figure 2.10(b) for this calculation.
fre = Uf (22RC) = 1/[2n(5 = 10°}(500 x 107-17}] = 64 Hz
Note that by increasing the input impedance of the amplifier by a factor of 100,
we can lower the low-corner frequency to 0.64 Hz.
EXAMPLE 2.3 For a piezoelectric sensor plus cable that has 1 nF capaci-
tance, design a voltage amplifier (not a charge amplifier) by using only one
noninverting amplifier that has a gain of 10. It should handle a charge of 1 pC
generated by the carotid pulse without saturation. It should not drift into
saturation because of bias currents. It should have a frequency response from
0.05 to 100 Hz. Add the minimal number of extra components to achieve the
design specifications.
ANSWER Calculate the voltage from V = Q/C = 1yC/1nF=1kV. Be-

cause this is too high, add a shunt capacitor C,=1F to achieve 1.0 V.
Allow for a gain of 10. To achieve low-corner frequency, add shunt
2.6 PIEZOELECTRIC SENSORS 61
Avil
¥ Teme } r a
Imercasing T .
Increasing =
Figure 2.11 Sensor response to a step displacement (From Doebelin, E. O.

1990. Measurement Systems: Application and Design, New York: McGraw-
Hill.)
R, = 1/2af,C = 1/22(0.05}(1 pF) = 3.2 MO. To achieve gain of +10 in a
noninverting amplifier, select Rp =10kQ and Ri =11.1k0. To achieve
high-corner frequency, Cp = 1/27f, Rp = 1/27(100}(10kO} = 160 nF.
Figure 2.11 shows the voltage-output response of a piezoelectric sensor to

a step displacement x. The output decays exponentially because of the finite
internal resistance of the piezoelectric material. At time equal to T the force is
released, and a displacement restoration results that is equal to and opposite of
the original displacement. This causes a sudden decrease in voltage of magni-
tude Kx/C, with a resulting undershoot equal to the decay prior to the release
of the displacement. The decay and undershoot can be minimized by increas-
ing the time constant, t = RC. The simplest approach to increasing tis to add a
parallel capacitor. However, doing so reduces the sensitivity in the midband
frequencies according to (2.20).
Another approach to improving the low-frequency response is to use the

charge amplifier described in Section 3.8.
Because of its mechanical resonance, the high-frequency equivalent

circuit for a piezoelectric sensor is complex. This effect can be represented
by adding a series RLC circuit in parallel with the sensor capacitance and
leakage resistance. Figure 2.12 shows the high-frequency equivalent circuit
and its frequency response. Note that in some applications—for example, in
the case of crystal filters—the mechanical resonance is useful for accurate
frequency control.
Piezoelectric sensors are used quite extensively in cardiology for external

(body-surface) and internal (intracardiac) phonocardiography. They are also
used in the detection of Korotkoff sounds in blood-pressure measurements
(Chapter 7). Additional applications of piezoelectric sensors involve their use in
measurements of physiological accelerations. A piezoelectric sensor and circuit
can measure the acceleration due to human movements and provide an estimate
of energy expenditure (Servais et al, 1984). Section 8.4 describes ultrasonic
blood-flow meters in which the piezoelectric element operating at mechanical
resonance emits and senses high-frequency sounds. Li and Su (2006) describe
piezoelectric sensors as sensitive mass sensors to detect and measure a broad
variety of biomedical analytes in both gas and liquid phases based on the
adsorption and/or desorption of target analyte(s) on the sensor surface.
e, ja OR 3
Mechanical
utpol Volkan Pesaran Sa
Inpad Farce
zi Frequency
Figure 2.12. (a) High-frequency circuit model for piezoelectric sensor. R, is

the sensor leakage resistance and C, is the capacitance. Lm, Cm, and Ry
represent the mechanical system, (b) Piezoelectric sensor frequency response.
(From Transducers for Biomedical Measurements: Principles and Applications,
by R. S. C. Cobbold. Copyright (c) 1974, John Wiley and Sons, Inc. Reprinted
by permission of John Wiley and Sons, Inc.)
2.7. TEMPERATURE MEASUREMENTS
A patient’s body temperature gives the physician important information about

the physiological state of the individual. External body temperature is one of
many parameters used to evaluate patients in shock, because the reduced
blood pressure of a person in circulatory shock results in low blood flow to the
periphery. A drop in the big-toe temperature is a good early clinical warning of
shock. Infections, on the other hand, are usually reflected by an increase in
body temperature, with a hot, flushed skin and loss of fluids. Increased
ventilation, perspiration, and blood flow to the skin result when high fevers
destroy temperature-sensitive enzymes and proteins. Anesthesia decreases
body temperature by depressing the thermal regulatory center. In fact,
physicians routinely induce hypothermia in surgical cases in which they
wish to decrease a patient’s metabolic processes and blood circulation.
In pediatrics, special heated incubators are used for stabilizing the body
temperature of infants. Accurate monitoring of temperature and regulatory
2.8 THERMOCOUPLES 63
control systems are used to maintain a desirable ambient temperature for the
infant.
In the study of arthritis, physicians have shown that temperatures of joints

are closely correlated with the amount of local inflammation. The increased
blood flow due to arthritis and chronic inflammation can be detected by
thermal measurements.
The specific site of body-temperature recording must be selected carefully

so that it truly reflects the patient’s temperature. Also, environmental changes
and artifacts can cause misleading readings. For example, the skin and oral-
mucosa temperature of a patient seldom reflects true body-core temperature.
The following types of thermally sensitive methods of measurement will be

described here: thermocouples, thermistors, and radiation and fiber-optic
detectors (Samaras, 2006). The voltage across a p—n junction changes about
2mV/°C so temperature sensors that use this principle are available (Togawa,
2006).
2.8 THERMOCOUPLES
Thermoelectric thermometry is based on the discovery of Seebeck in 1821. He

observed that an electromotive force (emf) exists across a junction of two
dissimilar metals. This phenomenon is due to the sum of two independent
effects. The first effect, discovered by Peltier, is an emf due solely to the contact
of two unlike metals and the junction temperature. The net Peltier emf is
roughly proportional to the difference between the temperatures of the two
junctions. The second effect, credited to Thomson (Lord Kelvin), is an emf due
to the temperature gradients along each single conductor. The net Thomson
emf is proportional to the difference between the squares of the absolute
junction temperatures (T, and T,). The magnitudes of the Peltier and Thom-
son emfs can be derived from thermodynamic principles (Anonymous, 1974),
and either may predominate, depending on the metals chosen.
Knowledge of these two effects is not generally useful in practical appli-
cations, so empirical calibration data are usually curve fitted with a power
series expansion that yields the Seebeck voltage,
1
E=aT+>bT’ + vo (2.21)
where T is in degrees Celsius and the reference junction is maintained at 0°C.

Figure 2.13(a) is a thermocouple circuit with two dissimilar metals, A and
B, at two different temperatures, 7,, and 7>. The net emf at terminals c-d is a
function of the difference between the temperatures at the two junctions and
the properties of the two metals. In the practical situation, one junction is held
at a constant known temperature (by an ice bath or controlled oven) for a
reference in order to determine the desired or unknown temperature.
la} ib) ic)
E, +E
(cdl)
Figure 2.13 Thermocouplecircuits (a) Peltier emf, (b) law of homogeneous

circuits, (c) law of intermediate metals, (d) law of intermediate temperatures.
An understanding of the three empirical thermocouple laws leads to using

them properly. The first law, homogeneous circuits, states that in a circuit
composed of a single homogeneous metal, one cannot maintain an electric
current by the application of heat alone. In Figure 2.13(b), the net emf at c-d is
the same as in Figure 2.13(a), regardless of the fact that a temperature
distribution (73) exists along one of the wires (A).
The second law, intermediate metals, states that the net emf in a circuit
consisting of an interconnection of a number of unlike metals, maintained at
the same temperature, is zero. The practical implication of this principle is that
lead wires may be attached to the thermocouple without affecting the accuracy
of the measured emf, provided that the newly formed junctions are at the same
temperature [Figure 2.13(c)].
The third law, successive or intermediate temperatures, is illustrated in
Figure 2.13(d), where emf F, is generated when two dissimilar metals have
junctions at temperatures T, and 7> and emf £> results for temperatures T> and
T3. It follows that an emf £, + £, results at c-d when the junctions are at
temperatures T, and 73. This principle makes it possible for calibration curves
derived for a given reference-junction temperature to be used to determine the
calibration curves for another reference temperature.
The thermoelectric sensitivity a (also called the thermoelectric power or the

Seebeck coefficient) is found by differentiating (2.21) with respect to 7. Then
dE
a= apa atbT + (2.22)
2.8 THERMOCOUPLES 65
Oise c
£¥ oA 1h :
Ry Ay
rp Wy
= PS
+i
Ss
L_ —:
| er ons: | + 1 1
Thermocouple
Figure 2.14 The LT1025 electronic cold junction and the hot junction of the
thermocouple yield a voltage that is amplified by an inverting amplifier.
Note that @ is not a constant but varies (usually increases) with temperature.
The sensitivities of common thermocouples range from 6.5 to 80 V/°C at
20°C, with accuracies from 4% to 1%.
For accurate readings, the reference junction should be kept in a triple-

point-of-water device the temperature of which is 0.01 + 0.0005 °C (Doebelin,
1990). Normally the accuracy of a properly constructed ice bath, 0.05 °C with a
reproducibility of 0.001°C is all that is necessary. Temperature-controlled
ovens can maintain a reference temperature to within +0,4°C. Figure 2.14
shows that modern thermocouple signal conditioners contain an electronic
cold junction (Tompkins and Webster, 1988; Sheingold, 1980).
Increased sensitivity may be achieved by connecting a number of ther-

mocouples in series, all of them measuring the same temperature and using the
same reference junction. An arrangement of multiple-junction thermocouples
is referred to as a thermopile. Parallel combinations may be used to measure
average temperature.
It is easy to obtain a direct readout of the thermocouple voltage using a

digital voltmeter. Chart recordings may be secured by using a self-balancing
potentiometer system. The linearity of this latter device is dependent only
on the thermocouple and potentiometer; it is independent of the other
circuitry.
Thermocouples have the following advantages: fast response time (time

constant as small as 1 ms), small size (down to 12m diameter), ease of
fabrication, and long-term stability. Their disadvantages are small output
voltage, low sensitivity, and the need for a reference temperature.
Numerous examples of the use of thermocouples in biomedical re-

search are given in the literature (Wren, 2006). Thermocouples can be
made small in size, so they can be inserted into catheters and hypodermic
needles.
2.9 THERMISTORS
Thermistors are semiconductors made of ceramic materials that are thermal

resistors with a high negative temperature coefficient. These materials react to
temperature changes in a way that is opposite to the way metals react to such
changes. The resistance of thermistors decreases as temperature increases and
increases as temperature decreases (Melo, 2006).
Sapoff (1971) reviewed the various types of thermistors that have been
found to be most suitable for biomedical use. The resistivity of thermistor
semiconductors used for biomedical applications is between 0.1 and 100 0O-m.
These devices are small in size (they can be made less than 0.5 mm in
diameter), have a relatively large sensitivity to temperature changes (—3 to
—5%/°C), and have excellent long-term stability characteristics (40.2% of
nominal resistance value per year).
Figure 2.15(a) shows a typical family of resistance-versus-temperature

characteristics of thermistors. These properties are measured for the
100
Resisiance ratio, RR.
Woltaga, 'y
O03]
30 (S100) §Sth 00 : nto i 1 10.0)

Temperature, 0 Cums, much
Figure 2.15 (a) Typical thermistor zero-power resistance ratio-temperature

characteristics for various materials. (b) Thermistor voltage-versus-current
characteristic for a thermistor in air and water. The diagonal lines with a positive
slope give linear resistance values and show the degree of thermistor linearity at
low currents. The intersection of the thermistor curves and the diagonal lines
with negative slope give the device power dissipation. Point A is the maximal
current value for no appreciable self-heat. Point B is the peak voltage. Point Cis
the maximal safe continuous current in air. [Part (b) is from Thermistor Manual,
EMC-6, © 1974, Fenwal Electronics, Framingham, MA. Used by permission.]
2.9 THERMISTORS 67
thermistor operated at a very small amount of power such that there is

negligible self-heating. This resistance is commonly referred to as zero-power
resistance. The empirical relationship between the thermistor resistance R, and
absolute temperature T in kelvin (K) (the SI unit kelvin does not use a degree
sign) is
R, = Roel to-T Tl (2.23)
where
= material constant for thermistor, K

To = standard reference temperature, K
The value of # increases slightly with temperature. However, this does not
present a problem over the limited temperature spans for biomedical work
(10°C to 20°C). £, also known as the characteristic temperature, is in the range
of 2500 to 5000 K. It is usually about 4000 K.
The temperature coefficient a can be found by differentiating (2.23) with

respect to T and dividing by R,. Thus
1 dR, B
C= apa A lBK) (2.24)
Note from (2.24) that w is a nonlinear function of temperature. This non-
linearity is also reflected in Figure 2.15(a).
The voltage-versus-current characteristics of thermistors, as shown in

Figure 2.15(b), are linear up to the point at which self-heating becomes a
problem. When there is large self-heating, the thermistor voltage drop de-
creases as the current increases. This portion of the curve displays a negative-
resistance characteristic.
In the linear portion, Ohm’s law applies and the current is directly
proportional to the applied voltage. The temperature of the thermistor is
that of its surroundings. However, at higher currents a point is reached,
because of increased current flow, at which the heat generated in the thermis-
tor raises the temperature of the thermistor above ambient. At the peak of the
wi characteristic, the incremental resistance is zero, and for higher currents a
negative-resistance relationship occurs. Operations in this region render the
device vulnerable to thermal destruction.
Figure 2.15(b) shows the difference in the self-heat regions for a thermistor
in water and air due to the differences in thermal resistance of air and water.
The principle of variation in thermal resistance can be used to measure blood
velocity, as described in Section 8.5.
EXAMPLE 2.4 Sketch typical thermistor «i characteristics with and with-

out a heat sink. Explain why there is a difference.
ANSWER | Figure 2.15(b) shows typical thermistor #i characteristics in water

and air. For low currents Ohm’s law applies, and the current is directly
proportional to the applied voltage in both cases. The thermistor temperature
is close to ambient. The system with water can reach higher current levels and still
remain in a linear portion of the v7 curve since the water keeps the thermistor
close to ambient temperature. Eventually the thermistor-water combination will
self-heat and a negative-resistance relationship will result. In the same manner,
the heat sink keeps the thermistor temperature close to ambient at higher current
levels and yields characteristics similar to Figure 2.15(b).
EXAMPLE 2.5 For a thermistor assume self-heating < 0.1°C, voltage — 5 V,

dissipation coefficient (DC}=2.0mW/"C. Calculate minimum thermistor
resistance.
ANSWER
PVR
“DC DC
v2 ¥
~ AT(D.C) 0.1°C(0.002 WC}
AT
R = 125,000 0
Choose next larger available size = 500,000 0
The current-time characteristics of a thermistor are important in any

dynamic analysis of the system. When a step change in voltage is applied to a
series circuit consisting of a resistor and a thermistor, a current flows. The time
delay for the current to reach its maximal value is a function of the voltage
applied, the mass of the thermistor, and the value of the series-circuit resist-
ance. Time delays from milliseconds to several minutes are possible with
thermistor circuits. Similar time delays occur when the temperature surround-
ing the thermistor is changed in a step fashion.
Various circuit schemes for linearizing the resistance-versus-temperature

characteristics of thermistors have been proposed (Cobbold, 1974; Doebelin,
1990). Modern instruments use microcomputers to correct for nonlinearities,
rather than the former circuit schemes.
The circuitry used for thermistor readout is essentially the same as for
conductive sensors, and many of the same techniques apply. Bridge circuits
give high sensitivity and good accuracy. The bridge circuit shown in Figure
2.2(b) could be used with R; = R, and R, = the thermistor resistance at the
midscale value.
Very small differences in temperature can be found using a differential-

temperature bridge. It is often necessary to measure such minute differences in
biological work. An example is the need to determine the temperature
difference between two organs or between multiple sites in the same organ.
2.10 RADIATION THERMOMETRY 69
A dc differential bridge can achieve a linearity of better than 1% of full-

scale output when bead thermistors matched to within +1% of each other at
25 °C are used. The de stability of this bridge is not normally a problem,
because the output voltage of the bridge—even for temperature differences of
0.01%—is larger than the de drift of good integrated-circuit operational
amplifiers (Cobbold, 1974).
Operational-amplifier circuits may be used to measure the current in a

thermistor as a function of temperature. In essence, this circuit applies a
constant voltage to the thermistor and monitors its current with a current-to-
voltage converter.
Various shapes of thermistors are available: beads, chips, rods, and

washers (Sapoff, 1971). The glass-encapsulated bead thermistor is the one
most commonly used in biomedical applications. The glass coating protects
the sensing element from the hostile environment of the body without
significantly affecting the thermal response time of the system. The small
size of these thermistors makes possible their placement at the tip of catheters
or hypodermic needles. The thermodilution-catheter system discussed in
Section 8.2 employs a four-lumen catheter with a thermistor located near
the catheter tip.
An additional application of thermistors is in the clinical measurement of

oral temperature. Thermistor probes with disposable sheaths are presently
used, but these exhibit a first-order step response as shown in Figure 1.6(c). To
yield the oral temperature prior to stabilization, a fixed correction of about
1°C is added to the probe temperature when the rate of change of probe
temperature decreases below 0.1 °C/s.
A problem with thermistor neonatal skin surface temperature-monitoring

instruments is that the probes fall off. Thermal contact with the skin can be
monitored by applying a 14s pulse every 4.5 min and monitoring the resultant
temperature rise (Re and Neuman, 1991).
2.10 RADIATION THERMOMETRY
The basis of radiation thermometry is that there is a known relationship

between the surface temperature of an object and its radiant power. This
principle makes it possible to measure the temperature of a body without
physical contact with it. Medical thermography is a technique whereby the
temperature distribution of the body is mapped with a sensitivity of a few
tenths of a kelvin. It is based on the recognition that skin temperature can vary
from place to place depending on the cellular or circulatory processes occur-
ring at each location in the body. Thermography has been used for the early
detection of breast cancer, but the method is controversial. It has also been
used for determining the location and extent of arthritic disturbances, for
gauging the depth of tissue destruction from frostbite and burns, and for
detecting various peripheral circulatory disorders (venous thrombosis, carotid
artery occlusions, and so forth) (Qi, 2006). Here we shall deal with the basic
principles of thermal radiation and detector systems.
Every body that is above absolute zero radiates electromagnetic power,

the amount being dependent on the body’s temperature and physical propert-
ies. For objects at room temperature, the spectrum is predominantly in the far-
and extreme-far-infrared regions.
A blackbody is an ideal thermal radiator; as such, it absorbs all incident

radiation and emits the maximal possible thermal radiation. The radiation
emitted from a body is given by Planck’s law multiplied by emissivity ¢. This
expression relates the radiant flux per unit area per unit wavelength W, at a
wavelength A (wm) and is stated as
_ eC 2
where
C; = 3.74 « 100 (W-pm*/cm?)

Cy = 1.4410" (um-K}
T =blackbody temperature, K
é=emissivity, the extent by which a surface deviates from a blackbody
(=1)
Figure 2.16(a) shows a plot of (2.25), the spectral radiant emittance versus
wavelength for a blackbody at 300 K.
Wien’s displacement law gives the wavelength 4,, for which W, is a

maximum. It can simply be found by differentiating (2.25) and setting this
to zero.
2898
hn =
mT
(wm) (2.26)
Figure 2.16(a) indicates 1, = 9.66 um (T = 300K). Note from (2.25) that the
maximal level of spectral emittance increases with T, and from (2.26) that A is
inversely related to 7.
The total radiant power W,, can be found by integrating the area under the
curve. This expression is known as the Stefan—Boltzmann law.
W,=eoT! (Wiem?) (2.27)
where o is the Stefan—Boltzmann constant (see Appendix).
It is of interest to examine how the percentage of total radiant power varies

with wavelength for room-temperature objects. This parameter, plotted in
Figure 2.14(a), is found by dividing [; W,d by the total radiant power W,
(2.27). Note that approximately 80% of the total radiant power is found in the
wavelength band from 4 to 25 wm.
ay LCS
4,,= 3h pm 4
00312
1.008
AME
TA
Speveral madinnt ccnitance, Wee yuo
Sh Total poaver
5 ith 1s 20 23
Wavelength, Ui
Fused silica
1
Sapphire
Arsenid trisulfide
‘Thallium
bromide
boli
ay
Percent transmission
1
O
I iM CK)
(by Wavelength, psn
| AIL thenmeal chetectors
3 1 =a
=|
=
es a
z 20
iio 3) Me SB se FoR
Wavelength, sm
Figure 2.16 (a) Spectral radiant emittance versus wavelength for a blackbody
at 300 K on the left vertical axis; percentage of total energy on the right vertical
axis. (b) Spectral transmission for a number of optical materials. (c) Spectral
sensitivity of photon and thermal detectors. [Part (a) is from Transducers for
Biomedical Measurements: Principles and Applications, R. 8. C. Cobbold.
Copyright © 1974, John Wiley & Sons, Inc. Reprinted by permission of John
Wiley & Sons, Inc. Parts (b) and (c) are from Measurement Systems: Applica-
tion and Design, E. O. Doebelin. Copyright © 1990 by McGraw-Hill, Inc. Used
with permission of McGraw-Hill Book Co.]
Determining the effect of changes in surface emissivity with wavelength is

important in order to accurately determine the temperature of a given source.
It can be shown that for 7 = 300K and }4=3ym, a 5% change in ¢ is
equivalent to a temperature change of approximately 1°C. Variations in ¢
with A should be found in the case of absolute-temperature determinations,
but they are less significant when relative temperature is desired, provided that
é remains constant over the surface area being measured. The data relating the
variation of ¢ with A for human skin are not consistent and show variations as
large as 5% from unity over the 4 span from 2 to 6 mm (Cobbold, 1974).
The lenses used in infrared instruments must be carefully selected for their
infrared spectral properties. Special materials must be chosen because stan-
dard glass used for the visible spectrum does not pass wavelengths longer than
2m. On the other hand, some materials (such as arsenic trisulfide) readily
pass infrared and not visible light. Figure 2.16(b) shows the spectral transmis-
sion for a number of optical materials.
Infrared detectors and instrument systems must be designed with a high

sensitivity because of the weak signals. These devices must have a short
response time and appropriate wavelength-bandwidth requirements that
match the radiation source. Thermal and photon detectors are used as infrared
detectors. The detectors are of two types, both of which are described in
Section 2.16. The thermal detector has low sensitivity and responds to all
wavelengths, as shown in Figure 2.16(c), whereas quantum detectors respond
only to a limited wavelength band.
Suitable instrumentation must be used to amplify, process, and display

these weak signals from radiation detectors. Most radiometers make use of a
beam-chopper system to interrupt the radiation at a fixed rate (several hundred
hertz). This arrangement allows the use of high-gain ac amplifiers without the
inherent problems of stability associated with dc amplifiers. In addition,
comparison of reference sources and techniques of temperature compensation
are more applicable to ac-instrumentation systems.
Figure 2.17 shows a typical chopped-beam radiation-thermometer system

(Cobbold, 1974). A mirror focuses the radiation on the detector. However, a
blackened chopper interrupts the radiation beam at a constant rate. The output
of the detector circuit is a series of pulses with amplitude dependent on the
strength of the radiation source. This ac signal is amplified, while the mean
value, which is subject to drift, is blocked. A reference-phase signal, used to
synchronize the phase-sensitive demodulator (Section 3.15), is generated in a
special circuit consisting of a light source and detector. The signal is then
filtered to provide a dc signal proportional to the target temperature. This
signal can then be displayed or recorded. Infrared microscopes have also been
designed using these techniques.
Figure 2.18 shows one application of radiation thermometry is an instru-

ment that determines the internal or core body temperature of the human by
measuring the magnitude of infrared radiation emitted from the tympanic
membrane and surrounding ear canal. The tympanic membrane and hypo-
thalamus are perfused by the same vasculature. The hypothalamus is the
IR dkerksctur
it
Fare | ge arun, | eee =
——* Gimpieiier Petes Ee | te
demmadalator
Filter
helio
“3 Ketercnc:
plese
Debectir
Fleck
Chopper
bhache
Tenperabare = 7
Figure 2.17. Stationary chopped-beam radiation thermometer (From Trans-

ducers for Biomedical Measurements: Principles and Applications, by R. S. C.
Cobbold. Copyright (c) 1974, John Wiley and Sons, Inc. Reprinted by permis-
sion of John Wiley and Sons, Inc.)
Shutter
Far Ambient sensor
IR i La rt | = Micro
T, MUX ag | Processor
( > Ty a Ee
k Amp. v
h Sensor Digital
Waveguide Window Shutter display
switch
Figure 2.18 The infrared thermometer opens a shutter to expose the sensor
to radiation from the tympanic membrane. [From J. G. Webster (ed.), Bio-
instrumentation, New York: John Wiley & Sons, 2004.]
body’s main thermostat, which regulates the core body temperature. This
approach has advantages over using mercury thermometers, thermocouples,
or thermistors. The standard temperature-measuring techniques measure the
temperature of the sensor, not that of the subject. The sensor must be in
contact with the patient long enough for its temperature to become the same
as, or close to, that of the subject whose temperature is being measured.
However, the infrared thermometry device detects emitted energy that is
proportional to the actual temperature of the subject. There is negligible
thermal time constant for the pyroelectric sensor (Fraden, 1997). The infrared
tympanic temperature-monitoring system has a response time in the order of
0.1 s and an accuracy of approximately 0.1°C. A disposable sanitary probe
cover is used to prevent cross-contamination from patient to patient. Ear
thermometry offers several clinical benefits over taking sublingual (oral) or
rectal measurements. Response is rapid, and readings can be obtained
independent of user technique and degree of patient activity or cooperation

(Fraden, 1991).
Infrared tympanic temperature-monitoring systems require a calibration

target in order to maintain their high accuracy.
2.11 FIBER-OPTIC TEMPERATURE SENSORS
Figure 2.19 shows the details of a GaAs semiconductor temperature probe

(Samaras, 2006). A small prism-shaped sample of single-crystal undoped GaAs
is epoxied at the ends of two side-by-side optical fibers. The sensors and fibers
can be quite small, compatible with biological implantation after being
sheathed. One fiber transmits light from a light-emitting diode source to
the sensor, where it is passed through the GaAs and collected by the other
fiber for detection in the readout instrument. Some of the optical power
traveling through the semiconductor is absorbed, by the process of raising
valence-band electrons, across the forbidden energy gap into the conduction
band. Because the forbidden energy gap is a sensitive function of the material’s
temperature, the amount of power absorbed increases with temperature.
This nonmetallic probe is particularly suited for temperature measure-

ment in the strong electromagnetic heating fields used in heating tissue for
cancer therapy or in patient rewarming.
Epoxy
\y
Transmit fiber
0.25 mm
—
Receive fiber _
Gavks sensor
Figure 2.19 Details of the fiber-sensor arrangement for the GaAs semi-
conductor temperature probe.
2.12 OPTICAL MEASUREMENTS

Optical systems are widely used in medical diagnosis. The most common use
occurs in the clinical-chemistry lab, in which technicians analyze samples of
blood and other tissues removed from the body. Optical instruments are also
used during cardiac catheterization to measure the oxygen saturation of
hemoglobin and to measure cardiac output.
2.13 RADIATION SOURCES 75
Sample
Source —- Filter + Detector
day
Filters Lenses
| U ml) 7
Lamp Cuvette Photo tube
ib)
,r
Light- i ia m1
emitting i Photatransistor
diode . —_ a ig
hal
Chvente
qc)
Figure 2.20 (a) General block diagram of an optical instrument. (b) Highest
efficiency is obtained by using an intense lamp and lenses to gather and focus
the light on the sample in the cuvette, and a sensitive detector. (c) Solid-state
lamps and detectors may simplify the system.
Figure 2.20(a) shows that the usual optical instrument has a source, filter,
and detector. Figure 2.20(b) shows a common arrangement of components.
Figure 2.20(c) shows that in some cases, the function of source, filter, sample,
and detector may be accomplished by solid-state components.
The remainder of this chapter is divided into sections that deal with
sources, geometrical optics, filters, detectors, and combinations thereof.
2.13 RADIATION SOURCES
TUNGSTEN LAMPS
Incandescent tungsten-wire filament lamps are the most commonly used

sources of radiation. Their radiant output varies with temperature and wave-
length, as given by (2.25). For 4 < 1m, tungsten has an emissivity of about
0.4 and thus emits about 40% of what it would if the emissivity were 1.0.
The relative-output spectrum shown in Figure 2.21(a) is only slightly altered.
For higher temperatures, A,,, the maximal wavelength of the radiant-output
GaAs Wat 2000 K
Wat 200)
Kelative source
1 j i 1 fa
ia} 200 500 bon 2000 S000
Loe Crowe
lass
1i1
thy S00) A) ei) Sah)
i (hen 4
a. | 34
BE
eg pe 4 ! !
is} 200 Sih 1000 200) =H)
V¥BOYOR
Rigs
210 _ ee ae
5 War 3000) R87, Si
&
ay
es
as War SERIO RS W at 3000 K, Ge, InSb

ead jer pe Pa oo
i) a0 500 TODO 2000) S00)
Wavelength. om
Figure 2.21 Spectral characteristics of sources, filters, detectors, and combina-

tions thereof (a) Light sources: tungsten (W) at 3000 K has a broad spectral
output. At 2000 K, output is lower at all wavelengths and peak output shifts to
longer wavelengths. Light-emitting diodes yield a narrow spectral output with
GaAs in the infrared, GaP in the red, and GaAsP in the green. Monochromatic
outputs from common lasers are shown by dashed lines: Ar, 515 nm; HeNe, 633
nm; ruby, 693 nm; Nd, 1064 nm; CO; (not shown), 10,600 nm. (b) Filters: A
Corning 5-56 glass filter passes a blue wavelength band. A Kodak 87 gelatin
filter passes infrared and blocks visible wavelengths. Germanium lenses pass
long wavelengths that cannot be passed by glass. Hemoglobin Hb and oxy-
hemoglobin HbO pass equally at 805 nm and have maximal difference at
660 nm. (c) Detectors: The S4 response is a typical phototube response. The
eye has a relatively narrow response, with colors indicated by VBGYOR. CdS
plus a filter has a response that closely matches that of the eye. Si p—1 junctions
are widely used. PbS is a sensitive infrared detector. InSb is useful in far
infrared. Note: These are only relative responses. Peak responses of different
detectors differ by 10’. (d) Combination: Indicated curves from (a), (b), and (c)
are multiplied at each wavelength to yield (d), which shows how well source,
filter, and detector are matched. (e) Photon energy: If it is less than 1 eV, it is
too weak to cause current flow in Si p—7 junctions.
2.13 RADIATION SOURCES 77
curves, shifts to a shorter wavelength, as given by (2.26) and as shown in Figure

2.21(a).
Low temperatures, then, yield a reddish color (infrared lamps), whereas

high temperatures yield a bluish color (photoflood lamps). The total radiation
is given by (2.27). Hence the radiant output increases rapidly with temperature,
as do the efficiency, the evaporation of tungsten, and the blackening of the
glass bulb. The life of the filament is thus drastically shortened by higher
temperatures.
Filaments are usually coiled to increase their emissivity and efficiency. For
use in instruments, short linear coils may be arranged within a compact, nearly
square area lying in a single plane. To produce a source of uniform radiant
output over a substantial area, ribbon filaments may be used.
Tungsten-halogen lamps have iodine or bromine added to the gases

normally used to fill the bulb. The small quartz bulbs operate at temperatures
above 250°C and usually require cooling by a blower. The halogen combines
with tungsten at the wall. The resulting gas migrates back to the filament,
where it decomposes and deposits tungsten on the filament. As a result, these
lamps maintain more than 90% of their initial radiant output throughout their
life. The radiant output of a conventional lamp, on the other hand, declines as
much as 50% over its lifetime.
ARC DISCHARGES
The fluorescent lamp is filled with a low-pressure Ar—Hg mixture. Electrons

are accelerated and collide with the gas atoms, which are raised to an excited
level. As a given atom’s electron undergoes a transition from a higher level to a
lower level, the atom emits a quantum of energy. The energy per quantum
E=hw = he/d, where h = Planck’s constant, » = frequency, c = velocity of
light, and 4 = wavelength.
Because the strongest transition of the mercury atom corresponds to

about 5 eV, Figure 2.21(e) shows the resulting wavelength to be about
250 nm. A phosphor on the inside of the glass bulb absorbs this ultraviolet
radiation and emits light of longer, visible wavelengths. The fluorescent
lamp has low radiant output per unit area, so it is not used in optical
instruments. However, it can be rapidly turned on and off in about 20 us,
so it is used in the fachistoscope (which presents brief stimuli to the eye) used
in measurements of visual perception. Other low-pressure discharge lamps
include the glow lamp (such as the neon lamp), the sodium-vapor lamp, and
the laser.
High-pressure discharge lamps are more important for optical instruments

because the arc is compact and the radiant output per unit area is high. The
carbon arc has been in use for the longest time, but it has largely been replaced
by the mercury lamp (bluish-green color), the sodium lamp (yellow color), and
the xenon lamp (white color). These lamps usually have a clear quartz bulb
with electrodes at both ends of the spherical bulb. The zirconium arc lamp
provides an intense point source.
Voltage, ¥
Figure 2.22 Forward characteristics for p—7 junctions. Ordinary silicon diodes
have a band gap of 1.1 eV and are inefficient radiators in the near-infrared
range. GaAs has a band gap of 1.44 eV and radiates at 900 nm. GaP has a band
gap of 2.26 eV and radiates at 700 nm.
LIGHT-EMITTING DIODES (LEDS)
Light-emitting diodes are p-n junction devices that are optimized for radiant
output. The ordinary silicon p—n junction characteristic shown in Figure 2.22 emits
radiant power when a current (typically 20 mA) passes in the forward direction.
Spontaneous recombination of injected hole and electron pairs results in the
emission of radiation. Because the silicon band gap is 1.1 eV, the wavelength is at
about 1100 nm. The silicon device is not efficient. However, GaAs has a slightly
higher band gap, as shown in Figure 2.22, and therefore radiates at 900 nm, as
shown in Figure 2.21(a). Although the output is not visible, the efficiency is high
and the GaAs device is widely used. It can be switched in less than 10 ns.
Figure 2.21(c) and Figure 2.21(e) show that, in order to produce visible
light, the band gap of a p-7 junction must exceed 1.9 eV. The GaP LED in
Figure 2.22 has a band gap of 2.26 eV, requires a larger forward-bias voltage
than silicon diodes, and is electroluminescent at 700 nm, as shown in Figure
2.21(a). It is an efficient visible LED and produces a bright red light. The
GaAsP LEDs make use of a special phosphor that absorbs two photons at one
wavelength and emits a single photon at a shorter wavelength. The GaAs is Si
doped to emit radiation at 940 nm. Power at this wavelength is absorbed by the
phosphor coating that emits green light at 540 nm, as shown in Figure 2.21(a).
The decay time of the phosphor is about 1 ms.
Light-emitting diodes are compact, rugged, economical, and nearly mono-

chromatic. They are widely used in a variety of medical, transportation, and
industrial circuits. A variety of circuits are available for LEDs and photo-
detectors using either steady or modulated radiation.
LASERS
Laser (light amplification by stimulated emission of radiation) action can occur

in GaAs. The end faces that are perpendicular to the p—v junction are polished
2.14 GEOMETRICAL AND FIBER OPTICS 79
to serve as partial mirrors, thus forming a resonant optical cavity. The forward
current pumps a large population of the molecules to an excited energy level.
Radiation incident on the molecules causes the production of additional
radiation that is identical in character. This phenomenon, known as stimulated
emission, is produced by the feedback from the mirrors. Laser output is highly
monochromatic, collimated (parallel), and phase coherent. However, p—1
junction lasers are not widely used because they operate in the infrared
and require current densities of 10° A/cm? or more, thus necessitating pulsed
(10-100 ns) operation rather than continuous wave (CW).
The most common laser is the He-Ne laser that operates at 633 nm in the
red region, as shown in Figure 2.21(a). The laser is operated by a low-pressure
arc similar to a neon sign and provides up to 100 mW. Partially reflective
mirrors at each end provide the resonant optical cavity and laser action.
Argon lasers provide the highest continuous-power levels (1-15 W) in the

visible part of the spectrum at 515 nm [Figure 2.21(a)]. This high-power output
permits photocoagulation of blood vessels in the eyes of patients suffering
from diabetic retinopathy.
CO) lasers provide 50-500 W of CW output power and are used for cutting
plastics, rubber, and metals up to 1 cm thick.
Two solid-state lasers—both usually operated in the pulsed mode—are

widely used. The lasers are pumped by firing a flash tube that is wound around
them. The ruby laser has a moderate (1 mJ) output in the red region of the
spectrum at 693 nm, as shown in Figure 2.21(a). The neodymium in yttrium
aluminum garnet (Nd: YAG) laser has a high (2 W/mm’) output in the infrared
region at 1064 nm, as shown in Figure 2.21(a).
The most important medical use of the laser has been to mend tears in the
retina. A typical photocoagulator uses a pulsed ruby laser with a controllable
output. It is focused on a tear in the retina. The heat dissipated by the pulse forms
a burn, which, on healing, develops scar tissue that mends the original tear.
Section 13.10 provides further information on therapeutic applications of lasers.
Safety to the eye should be considered with respect to some light sources. It is
safe to look at a 100 W frosted light bulb for long periods of time. However,
looking at clear incandescent lamps, the sun, high-pressure arc sources, or lasers
can cause burns on the retina. Protective eyewear worn by the physician to protect
against lasers usually consists of a set of filters that attenuate at the specific
wavelengths emitted by the laser but transmit as much visible radiation as possible.
2.14 GEOMETRICAL AND FIBER OPTICS

GEOMETRICAL OPTICS
There are a number of geometric factors that modify the power transmitted
between the source and the detector. In Figure 2.20(b), the most obvious
optical elements are the lenses. The lamp emits radiation in all directions. The

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MEDICAL

INSTRUMENTATION Shahall and —

John G. Webster, Editor Toe nm eller

John G. Webster, Editor

John W. Clark, Jr.

Frank P. Primiano, Jr.

JOHN WILEY & SONS, INC.

VP & EXECUTIVE PUBLISHER Don Fowley

ASSOCIATE PUBLISHER Dan Sayre

SENIOR PRODUCTION EDITOR Nicole Repasky

DESIGNER Kevin Murphy

PRODUCTION MANAGEMENT SERVICES Thomson Digital

MEDIA EDITOR Lauren Sapira

COVER PHOTO to come

This book is printed on acid free paper. 6

Library of Congress Cataloging-in-Publication Data

Medical instrumentation : application and design / John G. Webster, editor ; contributing

Throughout the book, we emphasize design. A scientist or engineer who has

Chapter 1 covers general concepts that are applicable to all instrumen-

Chapters 7 and 8 cover the measurement of cardiovascular dynamics—

Chapter 10 describes the developing field of biosensors: sensors that

Chapter 13 deals with devices used in therapy, such as the pacemaker,

We have used the recommended International System of Units (SI)

First Edition Reviewers

David Arnett, Pennsylvania State University

Robert B. Northrup, University of Connecticut (Starrs)

Curran S. Swift, Jowa State University

Second Edition Reviewers

Third Edition Reviewers

Noel Thompson, Stanford University

W. Ed Hammond, Duke University

Robert B. Northrup, University of Connecticut

Fourth Edition Reviewers

Paul J. Benkeser, Georgia Institute of Technology

Art Koblasz, Georgia Institute of Technology

Anant Madabhushi, Rutgers University

Andrew Mason, Michigan State University

Ken Meissner, Texas A&M University

Homer Nazeran, The University of Texas at El Paso

The authors welcome your suggestions for improvement of subsequent print-

This list gives single-letter symbols for quantities, without subscripts or

Symbol Quantity Introduced in Section

Symbol Quantity Introduced in Section

Sobek eH RR SSE ECTS OP PENNANT TAA FT OOS AS yoy wt Sees

Symbol Quantity Introduced in Section

L1 Terminology of Medicine and Medical Devices 4

13 Alternative Operational Modes 7

14 Medical Measurement Constraints 9

15 Classifications of Biomedical Instruments 12

16 Interfering and Modifying Inputs 12

19 Generalized Static Characteristics 19

1.10 Generalized Dynamic Characteristics 25

111 Design Criteria 35

1.12 Commercial Medical Instrumentation Development Process 37

1.13 Regulation of Medical Devices 39

2 BASIC SENSORS AND PRINCIPLES 45

2.1 Displacement Measurements 45

2.2 Resistive Sensors 46

2.3 Bridge Circuits 53

2.4 Inductive Sensors 53

2.5 Capacitive Sensors 56

2.6 Piezoelectric Sensors 58

2.7 Temperature Measurements 62