`
`]
`
`HANDBOOK
`
`Editor-in-Chief
`JOSEPH D. BRONZINO
`Trinity College
`Hartford, Connecticut
`
`©CRCPRESS
`
`•. IEEE PRESS
`
`A CRC Handbook Published in Cooperation with IEEE Press
`
`Petitioner Apple Inc. – Ex. 1019, cover p. 1
`
`
`
`Library of Congress Cataloging-in-Publication Data
`
`The biomedical engineering handbook/ editor-in-chief, Joseph D. Bronzino.
`p. cm. -
`(The electrical engineering handbook series)
`Includes bibliographical references and index.
`ISBN 0-8493-8346-3
`1. Biomedical engineering-Handbooks, manuals, etc.
`Joseph D., 1937-
`.
`II. Series.
`[DNLM: 1. Biomedical Engineering-handbooks. QT 29 B615 1995]
`R856.15.B86 1995
`610 '.28-dc20
`· DNLM/DLC
`For Library of Congress
`
`I. Bronzino,
`
`95-6294
`CIP
`
`This book contains information obtained from authentic and highly regarded sources. Reprinted material is quoted
`with permission, and sources are indicated. A wide variety of references are listed. Reasonable efforts have been made
`to publish reliable data and information, but the author and the publisher cannot assume responsibility for the valid(cid:173)
`ity of all materials or for the consequences of their use.
`Neither this book nor any part may be reproduced or transmitted in any form or by any means, electronic or
`mechanical, including photocopying, microfilming, and recording, or by any information storage or retrieval system,
`without prior permission in writing from the publisher.
`All rights reserved. Authorization to photocopy items for internal or personal use, or the personal or internal use
`of specific clients, may be granted by CRC Press, Inc., provided that $.50 per page photocopied is paid directly to Copy(cid:173)
`right Clearance Center, 27 Congress Street, .Salem, MA 0 1970, USA. The fee code for users of the Transactional
`Reporting Service is ISBN 0-8493-8346-3/95/ $0.00+$.50. The fee is subject to change without notice. For organiza(cid:173)
`tions that have been granted a photocopy license by the CCC, a separate system of payment has been arranged.
`CRC Press, Inc:s consent does not extend to copying for general distribution, for promotion, for creating new works,
`or for resale. Specific permission must be obtained in writing from CRC Press, Inc. for such copying.
`Direct all inquiries to CRC Press, Inc., 2000 Corporate Blvd. N.W., Boca Raton, Florida 33431.
`
`© 1995 by CRC Press, Inc.
`
`No claim to original U.S. Government works
`International Standard Book Number 0-8493-8346-3
`Library of Congress Card Number 95-6294
`Printed in the United States of America 1 2 3 4 5 6 7 8 9 0
`Printed on acid-free paper
`
`Petitioner Apple Inc. – Ex. 1019, cover p. 2
`
`
`
`Introduction
`
`In the 20th century, technological innovation has progressed at such an accelerated pace that it has
`permeated almost every facet of our lives. This is especially true in the field of medicine and the de(cid:173)
`livery of health care services. Today, in most developed countries, the modern hospital has emerged
`as the center of a technologically sophisticated health care system serviced by an equally technolog(cid:173)
`ically sophisticated staff.
`With almost continual technological innovation driving medkal care, engineering professionals
`have become intimately involved in many medical ventures. As a result, the discipline of biomedical
`engineering has emerged as an integrating medium for two dynamic professions, medicine and en(cid:173)
`gineering. In the process, biomedical engineers have beco~e actively involved in the design, devel(cid:173)
`opment, and utilization of materials, devices (such as ultrasonic lithotripsy, pacemakers, etc.), and
`techniques (such as signal and image processing, artificial intelligence, etc.) for clinical research, as
`well as the diagnosis and treatment of patients. Thus many biomedical engineers now serve as mem(cid:173)
`bers of health care delivery teams seeking new solutions for the difficult health care problems con(cid:173)
`fronting our society. The purpose of this handbook is to provide a central core of knowledge from those
`fields encompassed by the discipline of biomedical engineering. Before.presenting this detailed infor(cid:173)
`mation, it is important to provide a sense of the evolution of the modern health care system and
`identify the diverse activities biomedical engineers perform to assist in the diagnosis and treatment
`of patients.
`
`Evolution of the Modern Health Care System
`
`Before 1900, medicine had little to offer the average citizen, since its resources consisted mainly of
`the physician, his education, and his "little black bag." In general, physicians seemed to be in short
`supply, but the shortage had rather different causes than the current crisis in the availability of health
`care professionals. Although the costs of obtaining medical training were relatively low, the demand
`for doctors' services also was very small, since many of the services provided by the physician also
`could be obtained from experienced amateurs in the community. The home was typically the site
`for treatment and recuperation, and relatives and neighbors constituted an able and willing nursing
`staff. Babies were delivered by midwives, and those illnesses not cured by home remedies were left
`to run their natural, albeit frequently fatal, course. The contrast with contemporary health care prac(cid:173)
`tices·, in which specialized physicians and nurses located within the hospital provide critical diag(cid:173)
`nostic and. treatment services, is dramatic
`The changes that have occurred within medical science originated in the rapid developments that
`took place in the applied sciences ( chemistry, physics, engineering, microbiology, physiology, phar(cid:173)
`macology, etc.) at the turn of the century. This process of development was chara~terized by intense
`
`iii
`
`Petitioner Apple Inc. – Ex. 1019, p. iii
`
`
`
`interdisciplinary cross-fertilization, which provided an environment in which medical research was
`able to take giant strides in developing techniques for the diagnosis and treatment of disease. For
`example, in 1903, Willem Einthoven, the Dutch physiologist, devised the first electrocardiograph to
`measure the electrical activity of the heart. In applying discoveries in the physical sciences to the
`analysis of a biologic process, he initiated a new age in both cardiovascular medicine and electrical
`measurement techniques.
`New discoveries in medical sciences followed one another like intermediates in a chain reaction.
`However, the· most significant innovation for clinical medicine was the development of x-rays. These
`"new kinds of rays:' as their discoverer W. K. Roentgen described them in 1895, opened the "inner
`man" to medical inspection. Initially, x-rays were used to diagnose bone fractures and dislocations,
`and in the process, x-ray machines became commonplace in most urban hospitals. Separate de(cid:173)
`partments of radiology were established, and their influence spread to other departments through(cid:173)
`out the hospi-tal. By the 1930s, x-ray visualization of practically all organ systems of the body had
`been made possible through the use of barium salts and a wide variety of radiopaque materials.
`X-ray technology gave physicians a powerful tool that, for the first time, permitted accurate di(cid:173)
`agnosis of a wide variety of diseases and injuries. Moreover, since x-ray machines were too cum(cid:173)
`bersome and expensive for local doctors and clinics, they had to be placed in health care centers or
`hospitals. Once there, x-ray technology essentially triggered the transformation of the hospital from
`a passive receptacle for the sick to an active curative institution for all members of society.
`For economic reasons, the centralization of health care services became essential because of many
`other important technological innovations appearing on the medical scene. However, hospitals re(cid:173)
`mained institutions to dread, and it was not until the introduction of sulfanilamide in th~ mid-1930s
`and penicillin in the early 1940s that the main danger of hospitalization, i.e., cross-infection among
`patients, was significantly reduced. With these new drugs in their arsenals, surgeons were permitted
`to perform their operations without prohibitive morbidity and mortality due to infection. Further(cid:173)
`more, even though the different blood groups and their incompatibility. were discovered in 1900 and
`sodium citrate was used in 1913 to prevent clotting, full development of blood banks was not prac(cid:173)
`tical until the 1930s, when technology provided adequate refrigeration. Until that time, "fresh"
`donors were bled and the blood transfused while it was still warm.
`Once these surgical suites were established, the employment of specifically designed pieces of
`medical technology assisted in further advancing the development of complex surgical procedures.
`For example, the Drinker respirator was introduced in 1927 and the first heart-lung bypass in 1939.
`By the 1940s, medical procedures heavily dependent on medical technology, such as cardiac
`catheterization and angiography ( the use-of a cannula threaded through an arm vein and into the
`heart with the injection of radiopaque dye for the x-ray visualization of lung and heart vessels and
`valves), were developed. As a result, accurate diagnosis of congenital and acquired heart disease
`(mainly valve disorders due to rheumatic fever) became possible, and a new era of cardiac and vas(cid:173)
`cular surgery was established.
`Following World War II, technological advances were spurred on by efforts to develop superior
`weapon systems and establish habitats in space and on the ocean floor. As a by-product of these ef(cid:173)
`forts, the development of medical devices accelerated and the medical profession benefited greatly
`from this rapid surge of"technological finds:' Consider the following examples:
`
`1. Advances in solid-state electronics made it possible to map the subtle behavior of the funda(cid:173)
`mental unit of the central nervous system-the neuron-as well as to monitor various phys(cid:173)
`iologic parameters, such as the electrocardiogram, of patients in intensive care units.
`2. New prosthetic devices became a goal of engineers involved in providing the disabled with
`tools to improve their quality of life.
`3. Nuclear medicine-an outgrowth of the atomic age-emerged as a powerful and effective
`approach in detecting and treating specific physiologic abnormalities.
`
`iv
`
`Petitioner Apple Inc. – Ex. 1019, p. iv
`
`
`
`4. Diagnostic ultrasound based on sonar technology became so widely accepted that ultrasonic
`studies are now part of the routine diagnostic workup in many medical specialties.
`s. "Spare parts" surgery also became commonplace. Technologists were encouraged to provide
`cardiac assist devices, such as artificial heart valves and artificial blood vessels, and the artifi(cid:173)
`cial heart program was launched to develop a replacement for a defective or diseased human
`heart.
`6. Advances in materials have made the development of disposable medical devices, such as
`needles and thermometers, as well as implantable drug delivery systems, a reality.
`7. Computers similar to those developed to control the flight plans of the Apollo capsule were
`used to store, process, and cross-check medical records, to monitor patient status in inten(cid:173)
`sive care units, and to provide sophisticated statistical diagnoses of potential diseases corre(cid:173)
`lated with specific sets of patient symptoms.
`8. Development of the first computer-based medical instrument, the computerized axial to(cid:173)
`mography scanner, revolutionized clinical approaches to noninvasive diagnostic imaging
`procedures, which now include magnetic resonance imaging and positron emission tomog(cid:173)
`raphy as well.
`
`The impact of these discoveries and many others has been profound. The health care system con(cid:173)
`sisting primarily of the "horse and buggy" physician is gone forever, replaced by a technologically
`sophisticated clinical staff operating primarily in "m.odern" hospitals designed to accommodate the
`new medical technology. This evolutionary process continues, with advances in biotechnology and
`tissue engineering altering the very nature of the health care delivery system itself.
`
`The Field of Biomedical Engineering
`Today, many of the problems confronting health professionals are of extreme interest to engineers
`because they involve the design and practical application of medical devices and systems-processes
`that are fundamental to engineering practice. These medically related design problems can range
`from very complex large-scale constructs, such as the design and implementation of automated clin(cid:173)
`ical laboratories, multiphasic screening facilities (i.e., centers that permit many clinical tests to be
`conducted), and hospital information systems, to the creation of relatively small and "simple" de(cid:173)
`vices, such as recording electrodes and biosensors, that may be used to monitor the activity of spe(cid:173)
`cific physiologic processes in either a research or clinical setting. They encompass the many com(cid:173)
`plexities of remote monitoring and telemetry, including the requirements of emergency vehicles,
`operating rooms, and intensive care units. The American health care system, therefore, encompasses
`many problems that represent challenges to certain members of the engineering profession called
`biomedical engineers.
`
`Biomedical Engineering: A Definition
`Although what is included in the field of biomedical engineering is considered by many to be quite
`clear, there are some disagreements about its definition. For example, consider the terms biomedical
`engineering, bioengineering, and clinical ( or medical) engineering which have been defined in Pacela's
`Bioengineering Education Directory [ Quest Publishing Co., 1990]. While Pacela defines bioengineer(cid:173)
`ing as the broad umbrella term used to describe this entire field, bioengineering is u.sually defined as
`a basic research-oriented activity closely related to biotechnology and genetic engineering, i.e., the
`modification of animal or plant cells, or parts of cells, to improve plants or animals or to develop
`new microorganisms for beneficial ends. In the food industry, for example, this has meant the im(cid:173)
`provement of strains of yeast for fermentation. In agriculture, bioengineers may be concerned with
`the improvement of crop yields by treatment of plants with organisms to reduce frost damage. It is
`dear that bioengineers of the future will have a tremendous impact on the quality of human life, the
`potential of this specialty is difficult to imagine. Consider the following activities of bioengineers:
`
`V
`
`Petitioner Apple Inc. – Ex. 1019, p. v
`
`
`
`• Development of improved species of plants and animals for food production
`• Invention of new medical diagnostic tests for diseases
`• Production of synthetic vaccines from clone cells
`• Bioenvironmental engineering to protect human, animal, and plant life from toxicants and
`pollutants
`• Study of protein-surface interactions
`• Modeling of the growth kinetics of yeast and hybridoma cells
`• Research in immobilized enzyme technology
`• Development of therapeutic proteins and monoclonal antibodies
`
`In reviewing the above-mentioned terms, however, biomedical engineering appears to have the
`most comprehensive meaning. Biomedical engineers apply electrical, mechanical, chemical, optical,
`and other engineering principles to understand, modify, or control biologic (i.e., human and ani(cid:173)
`mal) systems, a's well as design and manufacture products that can monitor physiologic. functions
`and assist in the diagnosis and treatment of patients. When biomedical engineers'work within a hos(cid:173)
`pital or clinic, they are more properly called clinical engineers.
`
`Activities of Biomedical Engineers
`The breadth of activity of biomedical engineers is significant. The field has moved significantly from
`being concerned primarily with the development of medical devices in the 1950s and 1960s and to
`include a more wide-ranging set of activities. As illustrated below, the field of biomedical engineer(cid:173)
`ing now includes many new career areas, each of which is presented in this Handbook. These areas
`include
`
`• Application of engineering system analysis (physiologic modeling, simulation, and control)
`to biologic problems
`• Detection, measurement, and monitoring of physiologic signals (i.e., biosensors and biomed-
`ical instrumentation)
`• Diagnostic interpretation via signal-processing techniques of bioelectric data
`-· Therapeutic and rehabilitation procedures and devices (rehabilitation engineering)
`• Devices for replacement or augmentation of bodily functions (artificial organs)
`• Computer analysis of patient-related data and clinical decision making (i.e., medical infor(cid:173)
`matics and artificial intelligence)
`• Medical imaging, i.e., the graphic display of anatomic detail or physiologic function
`• The creation of new biologic products (i.e., biotechnology and tissue engineering)
`
`Typical pursuits of biomedical engineers, therefore, include
`
`• Research in new materials for implanted artificial organs
`• Development of new diagnostic instruments for blood analysis
`• Computer modeling of the function of the human heart
`• Writing software for analysis of medical research data
`• Analysis of medical device hazards for safety and efficacy
`• Development of new diagnostic imaging systems
`• Design of telemetry systems for patient monitoring
`• Design of biomedical sensors for measurement of human physiologic systems variables
`• Development of expert systems for diagnosis of diseases
`• Design of closed-loop control systems for drug administration
`
`vi
`
`Petitioner Apple Inc. – Ex. 1019, p. vi
`
`
`
`• Modeling of the physiologic systems of the human body
`• Design of instrumentation for sports medicine
`• Development of new dental materials
`• Design of communication aids for the handicapped
`• Study of pulmonary fluid dynamics
`• Study of the biomechanics of the human body
`• Development of material to be used as replacement for human skin
`
`Biomedical engineering, then, is an interdisciplinary branch of engineering that ranges from the(cid:173)
`oretical, nonexperimental undertakings to state-of-the-art applications. It can encompass research,
`development, implementation, and operation. Accordingly, like medical practice itself, it is unlikely
`thqt any single person can acquire expertise that encompasses the entire field. Yet, because of the in(cid:173)
`terdisciplinary nature of this activity, there is considerable interplay and overlapping of interest and
`effort between them. For example, biomedical engineers engaged in the development ofbiosensors
`may interact with those interested in prosthetic devices to develop a means to detect and use the
`same bioelectric signal to power a prosthetic device. Those engaged in automating the clinical chem(cid:173)
`istry laboratory may collaborate with those developing expert systems to assist clinicians in making
`decisions based on specific laboratory data. The possibilities are endless.
`Perhaps a greater potential benefit occurring from the use of biomedical engineering is identifi(cid:173)
`cation of the problems and needs of our present health care system that can be solved using exist(cid:173)
`ing engineering technology and systems methodology. Consequently, the field of biomedical engi(cid:173)
`neering offers hope in the continuing battle to provide high-quality health care at a reasonable cost;
`and if properly directed toward solving problems related to preventive medical approaches, ambu(cid:173)
`latory care services, and the like, biomedical engineers can provide the tools and techniques to make
`our health care system more effective and efficient.
`
`Joseph D. Bronzino
`Editor-in-Chief
`
`vii
`
`Petitioner Apple Inc. – Ex. 1019, p. vii
`
`
`
`The Discipline of Biomedical Engineering
`
`Biomechanics
`Study of static
`andfluid
`mechanics
`associated with
`physiologic
`systems
`
`Physiologic Modeling
`Simulation and Control
`Use of computer
`simulations to develop
`an understanding of
`physiologic relationships
`
`Rehabilitation
`Engineering
`Design and development
`of therapeutic and
`rehabilitation devices
`and procedures
`
`Medical Imaging
`To provide graphic
`displays of anatomic
`detail and physiologic
`function
`
`Biologic Effects
`of
`Electromagnetic
`Fields
`Study of the
`effects of
`electromagnetic
`fields on
`biologic tissue
`
`Biomaterials
`Design and development
`of bioimplantable
`materials
`
`Biomedical
`Instrumentation
`To monitor and measure
`physiologic events;
`involves development
`of biosensors
`
`Prosthetic Devices and
`Artificial Organs
`Design and development
`of devices for replacement
`or augmentation of bodily
`function
`
`Biotechnology
`To create or modify
`biologic material
`for beneficial ends,
`including tissue
`engineering
`
`Biosensors
`Detection of biologic
`events and their
`conversion to electrical
`signals
`
`Medical and Biologic
`Analysis
`To detect, classify, and
`analyze bioelectric
`signals
`
`Medical Informatics
`Of patient-related data,
`interpret results and
`assist in clinical
`decision making,
`including expert
`systems and neural
`networks
`
`Clinical Engineering
`Design and development of
`clinically related facilities,
`devices, systems, and
`procedures
`
`Petitioner Apple Inc. – Ex. 1019, p. viii
`
`
`
`52
`
`Optical Sensors
`
`52.1 Instrumentation ...................................... 765
`Light Source • Optical Element • Photodetectors • Signal Processing
`52.2 Optical Fibers ................................ ; ........ 766
`Probe Configurations • Optical Fiber Sensors • Indicator-Mediated
`Transducers
`52.3 General Principles of Optical Sensing ..................... 767
`Evanescent Wave Spectroscopy • Surface Plasmon Resonance
`52.4 Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 769
`Oximetry • Blood Gases • Glucose Sensors • Immunosensors
`·
`
`Yitzhak Mendelson
`Worcester Polytechnic Institute
`
`Optical methods are among the oldest and best-established techniques for sensing biochemical
`analytes. Instrumentation for optical measurements generally consists of a light source, a number
`of optical components to generate a light beam with specific characteristics and to direct this light
`to some modulating agent, and a photodetector for processing the optical signal. The central part
`of an optical sensor is the modulating component, and a major part of this chapter will focus on
`how to exploit the interaction of an analyte with optical radiation in order to obtairi essential
`biochemical information.
`The number of publications in the field of optical sensors for biomedical applications has grown
`significantly during the past two decades. Numerous scientific reviews and historical perspectives
`have been published, and the reader interested in this rapidly growing field is advised to consult these
`sources for additional details. This chapter will emphasiz~ the basic concept of typical optical sensors
`intended for continuous in vivo monitoring of biochemical variables, concentrating on those
`sensors which have generally progressed beyond the initial feasibility stage and reached the promis(cid:173)
`ing stage of practical development or commercialization.
`Optical sensors are usually based on optical fibers or on planar waveguides. Generally, there are
`three distinctive methods for quantitative optical sensing at surfaces:
`
`1. The analyte directly affects the optical properties of a waveguide, such as evanescent waves
`( electromagnetic waves generated in the medium outside the optical waveguide when light
`is reflected from within) or surface plasmons (resonances induced by an evanescent wave in
`a thin film deposited on a waveguide surface).
`2. An optical fiber is used as a plain transducer to guide light to a remote sample and return
`light from the sample to the detection system. Changes in the intrinsic optical properties of
`the medium itself are sensed by an external spectrophotometer.
`3. An indicator or chemical reagent placed inside, or on, a polymeric support near the tip of the
`optical fiber is used as a mediator to produce an observable optical signal. Typically, conven(cid:173)
`tional techniques, such as absorption spectroscopy and fluorimetry, are employed to measure
`changes in the optical signal.
`
`764
`
`0-8493-8346-3/95/$0.00+$.50
`© 1995 by CRC Press, Inc.
`
`Petitioner Apple Inc. – Ex. 1019, p. 764
`
`
`
`Optical Sensors
`52.1 Instrumentation
`
`765
`
`The actual implementation of instrumentation designed to interface with optical sensors will vary
`greatly depending on the type of optical sensor used and its intended application. A block diagram
`of a generic instrument is illustrated in Fig. 52.1. The basic building blocks of such an instrument
`are the light source, various optical elements, and photodetectors.
`
`Light Source
`A wide selection of light sources are available for optical sensor applications. These include: highly
`coherent gas and semiconductor diode lasers, broad spectral band incandescent lamps, and narrow(cid:173)
`band, solid-state, light-emitting diodes (LEDs). The important requirement of a light source is
`obviously good stability. In certain applications, for example in portable instrumentation, LEDs
`have significant advantages over other light sources because they are small and inexpensive, con(cid:173)
`sume low power, produce selective wavelengths, and are easy to work with. In contrast, tungsten
`lamps produce a broader range of wavelengths, higher intensity, and better stability but require a .
`sizable power supply and can cause heating problems inside the apparatus.
`
`Optical Elements
`Various optical elements are used routinely to manipulate light in optical instrumentation. These
`include lenses, mirrors, light choppers,beam splitters, and couplers for directing the light from the
`light source into the small aperture of a fiber optic sensor or a specific area on a waveguide surface
`and collecting the light from the sensor before it is processed by the photodetector. For wavelength
`selection, optical filters, prisms, and diffraction gratings are the most common components used to
`provide a narrow bandwidth of excitation when a broadwidth light source is utilized.
`
`Photodetectors
`In choosing photodetectors for optical sensors, a number of factors must be considered. These
`include sensitivity, detectivity, noise, spectral response, and response time. Photomultipliers and
`
`I
`FILTER+
`
`--------(cid:144)-----Y---i-
`
`LENS
`
`BEAM
`SPUTTER
`
`FILTER
`
`FIGURE 52.1 General diagram representing the basic building blocks of an optical instrument
`for optical sensor applications.
`
`Petitioner Apple Inc. – Ex. 1019, p. 765
`
`
`
`Biomedical Sensors
`
`766
`semiconductor quantum photodetectors, such as photoconductors and photodiodes, are both suit(cid:173)
`able. The choice, however, is somewhat dependent on the wavelength region of interest. Generally,
`both give adequate performance. Photodiodes are usually more attractive because of the compact(cid:173)
`ness and simplicity of the circuitry involved.
`Typically, two photodetectors are used in optical instrumentation because it is often necessary to
`include a_separate reference detector to track fluctuations in source intensity and temperature. By
`taking a ratio between the two detector readings, whereby a part of the light that is not affected by
`the measurement variable is used for correcting any optical variations in the measurement system,
`a more accurate and stable measurement can be obtained.
`
`Signal Processing
`Typically, th~ signal obtained from a photodetector provides a voltage or a current proportional to
`the measured light intensity. Therefore, either simple analog computing circuitry (e.g., a current(cid:173)
`to-voltage converter) or direct connection to a programmable gain voltage stage is appropriate.
`Usually, the output from a photodetector is connected directly to a preamplifier before it is applied
`to sampling and analog-to-digital conversion circuitry residing inside a computer.
`Quite often two different wavelengths oflight are utilized to perform a specific measurement. One
`wavelength is usually sensitive to changes in the species being measured, and the other wavelength
`is unaffected by changes in the analyte concentration. In this manner, the unaffected wavelength is
`used as a reference to compensate for fluctuations in instrumentation over time. In other applica(cid:173)
`tions, additional discriminations, such as pulse excitation or electronic background subtraction
`utilizing synchronized lock-in amplifier detection, are useful, allowing improved selectivity and
`enhanced signal-to-noise ratio.
`
`52.2 Optical Fibers
`Several types of biomedical measurements can be made by using either plain optical fibers as a
`remote device for detecting changes in the spectral properties of tissue and blood or optical fibers
`tightly coupled to various indicator-mediated transducers. The measurement relies either on direct
`illumination of a sample through the endface of the fiber or by excitation of a coating on the side
`wall surface through evanescent wave coupling. In both cases, sensing takes place in a region out(cid:173)
`side the optical fiber itself. Light emanating from the fiber end is scattered or fluoresced back into
`the fiber, allowing measurement of the returning light as an indication of the optical absorption or
`fluorescence of the sample at the fiber optic tip.
`Optical fibers are based on the principle of total internal reflection. Incident light is transmitted
`through the fiber if it strikes the cladding at an angle greater than the so-c<!,lled critical angle, so that
`it is totally internally reflected at the core/ cladding interface. A typical instrument for performing fiber
`optic sensing consists of a light source, an optical coupling arrangement, the fiber optic light guide
`with or without the necessary sensing medium incorporated at the distal tip, and a light detector.
`A variety of high-quality optical fibers are available commercially for biomedical sensor applica(cid:173)
`tions, depending on the analytic wavelength desired. These include plastic, glass, and quartz fibers
`which cover the optical spectrum from the UV through the visible to the near IR region. On one
`hand, plastic optical fibers have a larger aperture and are strong, inexpensive, flexible, and easy to
`work with but have poor UV transmission below 400 nm. On the other hand, glass and quartz fibers
`have low attenuation and better transmission in the UV but have small apertures, are fragile, and
`present a potential risk in in vivo applications.
`
`Probe Configurations
`There are many different ways to implement fiber optic sensors. Most fiber optic chemical sensors
`employ either a single-fiber configuration, where light travels to and from the sensing tip in one
`
`Petitioner Apple Inc. – Ex. 1019, p. 766
`
`
`
`Optical Sensors
`
`767
`
`fiber, or a double-fiber configuration, where separate optical fibers are used for illumination and
`detection. A single fiber optic configuration offers the most compact and potentially least expensive
`implementation. However, additional challenges in instrumentation are involved in separating the
`illuminating signal from the composite signal returning for processing.
`The design of intravascular catheters require special considerations related to the sterility and bio(cid:173)
`compatibility of the sensor. For example, intravascular fiberoptic sensors must be sterilizable and
`their material nonthrombogenic and resistant to platelet and protein deposition. Therefore, these
`catheters are typically made of materials covalently bound with heparin or antiplatelet agents. The
`catheter is normally introduced into the jugular vein via a peripheral cut-down and a slow heparin
`flush is maintained until it is removed from the blood.
`
`Optical Fiber Sensors
`Advantages cited for fiber optic sensors include their small size and low cost. In contrast to electri(cid:173)
`cal measurements, where the difference of two absolute potentials must be measured, fiber optics
`are self-contained and do not require an external reference signal. Because the signal is optical, there
`is no electrical risk to the patient, and there is no direct interference from surrounding electric or
`magnetic fields. Chemical analysis can be performed in real-time with almost an instantaneous
`respons