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Biomedical Engineering
The second edition of this popular introductory undergraduate textbook uses
theory, examples, applications, and a problem-solving approach to convey the
impact of biomedical engineering. Updates throughout the book highlight the
important advances made over recent years, including iPS cells, microRNA,
nanomedicine, imaging technology, biosensors, and drug delivery systems, giving
students a modern description of the various subfields of biomedical engineering.
Highlight features:

■ All of the molecular biology, cellular biology, and human physiology back-
ground that students need to understand the context in which biomedical
engineers’ work is provided.
■ Mathematical treatments are boxed for students who wish to apply them to
engineering analysis.
■ An expanded set of profiles in biomedical engineering showcase the broad
range of career paths open to students who make biomedical engineering their
calling.
■ Over 200 quantitative and qualitative exercises, many new to this edition, are
included at the end of chapters to consolidate learning.

W. Mark Saltzman is the Goizueta Professor of Chemical and Biomedical

Engineering at Yale University, and was the founding Chair of the Yale Depart-
ment of Biomedical Engineering. He has taught numerous courses on topics in
biomedical engineering in the last three decades, and has been widely recognised
for his excellence in research and teaching. He is a Fellow of the American
Institute for Medical and Biological Engineering, and a Fellow of the Biomedical
Engineering Society. He is also the recipient of the 2014 Mines Medal and has
been elected to the Institute of Medicine of the National Academies.

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“This book sets a gold standard for textbooks in biomedical engineering. It is

beautifully and clearly written, and explains all aspects, old and very new, of
biomedical engineering in ways that are both exciting to the reader as well as easy
to understand.”
Robert Langer, Massachusetts Institute of Technology
“This textbook is a wonderful summary of the field of biomedical engineering—
a must have for any faculty member teaching an introductory BME course! As
usual, Professor Saltzman has provided rich context and broad examples; he does
an excellent job of weaving in valuable scenarios that are realistic, yet interesting—
a great tool for engaging students! There are many creative and useful features to
the text: the figures and illustrations provide much value to understanding the
material, the problem sets offer both conceptual and quantitative review of the
material, and the “Key Concepts and Definitions” and “Useful Links” sections at
the end of each chapter are very practical for a student new to the field of BME.
Of particular note, the “Profiles in BME” vignettes for each chapter add a personal
touch and serve to connect students to role models who are real people (with real
stories) making an impact on the world.”
Christine E. Schmidt, University of Florida
“This is an excellent book that covers the fundamentals of a broad array of specific
fields within biomedical engineering. This textbook will certainly be adopted by
many introductory biomedical engineering courses due to its meaningful organiza-
tion, clear writing, illuminative figures, and variety of problems for students to
work through. Its breadth and scope will stimulate all readers. Once again, Mark
Saltzman has accomplished a major achievement by providing such a comprehen-
sive text for students and educators alike.”
Melissa Krebs, Colorado School of Mines
“This is a truly exceptional textbook. It is completely up-to-date and comprehen-
sive, yet it is so readable that you can dip in at any page and find something that
grabs you. It is designed for undergraduate students, and is a tremendous resource
for course development—but equally, it is one of those essential bookshelf books,
the one you will turn to when you need ‘to brush up on your biology’, or ‘get your
head straight on the engineering stuff’. A must for anyone interested in the very
far-reaching field of biomedical engineering.”
Quentin Pankhurst, University College London

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CAMBRIDGE TEXTS IN BIOMEDICAL ENGINEERING

Series editors
W. Mark Saltzman, Yale University
Shu Chien, University of California, San Diego

Series Advisors
Jerry Collins, Alabama A & M University
Robert Malkin, Duke University
Kathy Ferrara, University of California, Davis
Nicholas Peppas, University of Texas, Austin
Roger Kamm, Massachusetts Institute of Technology
Masaaki Sato, Tohoku University, Japan
Christine Schmidt, University of Florida
George Truskey, Duke University
Douglas Lauffenburger, Massachusetts Institute of Technology

Cambridge Texts in Biomedical Engineering provide a forum for high-quality

textbooks targeted at undergraduate and graduate courses in biomedical
engineering. It covers a broad range of biomedical engineering topics from
introductory texts to advanced topics, including biomechanics, physiology,
biomedical instrumentation, imaging, signals and systems, cell engineering, and
bioinformatics, as well as other relevant subjects, with a blending of theory and
practice. While aiming primarily at biomedical engineering students, this series is
also suitable for courses in broader disciplines in engineering, the life sciences
and medicine.

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Biomedical
Engineering
Bridging Medicine and
Technology

W. Mark Saltzman
Yale University

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University Printing House, Cambridge CB2 8BS, United Kingdom

Cambridge University Press is part of the University of Cambridge.

It furthers the University’s mission by disseminating knowledge in the pursuit of

education, learning and research at the highest international levels of excellence.

www.cambridge.org
Information on this title: www.cambridge.org/9781107037199

© W. Mark Saltzman 2009, 2015

This publication is in copyright. Subject to statutory exception

and to the provisions of relevant collective licensing agreements,
no reproduction of any part may take place without the written
permission of Cambridge University Press.

First published 2009

Second edition 2015

Printed in the United Kingdom by Bell and Bain Ltd

A catalogue record for this publication is available from the British Library

Library of Congress Cataloguing in Publication data

Saltzman, W. Mark, author.
Biomedical engineering : bridging medicine and technology / W. Mark Saltzman. – Second edition.
p. ; cm.
Includes bibliographical references and index.
ISBN 978-1-107-03719-9 (Hardback)
I. Title.
[DNLM: 1. Biomedical Engineering. QT 36]
R856
610.28–dc23 2014043725

ISBN 978-1-107-03719-9 Hardback

Additional resources for this publication at www.cambridge.org/saltzman

Cambridge University Press has no responsibility for the persistence or accuracy of

URLs for external or third-party internet websites referred to in this publication,
and does not guarantee that any content on such websites is, or will remain,
accurate or appropriate.

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To Noa and Zach and Alex

There is no luckier, happier father on earth than I.

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ix

Contents

Preface page xv
Acknowledgments xix
Abbreviations and Acronyms xxi

1 Introduction: What Is Biomedical Engineering? 1

1.1 Prelude 1
1.2 Engineering in modern medicine 4
1.3 What is biomedical engineering? 8
1.4 Biomedical engineering in the future 23
1.5 How to use this book 26
PROF ILES I N BME : THE A UTH OR, W. MARK SAL TZMA N 28

PART 1 MOLECULAR AND CELLULAR PRINCIPLES

2 Biomolecular Principles 37
2.1 Prelude 37
2.2 Bonding between atoms and molecules 39
2.3 Water: The medium of life 43
2.4 Biochemical energetics 45
2.5 Importance of pH 50
2.6 Macromolecules: Polymers of biological importance 58
2.7 Lipids 72
PROF ILES I N BME : TIF FAN EE GREEN MA CK EY 80

3 Biomolecular Principles: Nucleic Acids 94

3.1 Prelude 94
3.2 Overview: Genetics and inheritance 99
3.3 Molecular basis of genetics 106
3.4 The central dogma: Transcription and translation 116
3.5 Control of gene expression 123
3.6 Recombinant DNA technology 128
PROF ILES I N BME : LAU RA L IPTA I 143

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x Contents

4 Biomolecular Principles: Proteins 160

4.1 Prelude 160
4.2 Protein structure 162
4.3 Modification and processing of polypeptides 171
4.4 Enzymes 175
PR OFI LES IN B ME: BR ENDA K. MA NN 182

5 Cellular Principles 190

5.1 Prelude 190
5.2 Cell structure and function 192
5.3 ECM 196
5.4 Molecules in the cell membrane 198
5.5 Cell proliferation 206
5.6 Cell differentiation and stem cells 210
5.7 Cell death 213
5.8 Cell culture technology 214
PROFI LES IN BME: E.E. “ JAC K” R IC HAR DS I I 219

PART 2 PHYSIOLOGICAL PRINCIPLES

6 Communication Systems in the Body 231
6.1 Prelude 231
6.2 Signaling fundamentals 237
6.3 The nervous system 242
6.4 The endocrine system 251
6.5 The adaptive immune system 256
6.6 Connections to biomedical engineering 265
PR OFI LES IN B ME: DOU GLAS LAUF FEN BU RGE R 268

7 Engineering Balances: Respiration and Digestion 280

7.1 Prelude 280
7.2 Introduction to mass balances 281
7.3 Respiratory physiology 295
7.4 Digestion and metabolism 313
PROFI LES IN BME: DAN L UO 331

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xi Contents

8 Circulation 341
8.1 Prelude 341
8.2 The circulating fluid 342
8.3 The blood vessels 345
8.4 The heart 361
PR OF ILES I N BME : CU RTI S G. N EASO N 368

9 Removal of Molecules from the Body 377

9.1 Prelude 377
9.2 Examples of elimination of molecules from the body 379
9.3 Biotransformation and biliary excretion 383
9.4 Elimination of molecules by the kidneys 385

PART 3 BIOMEDICAL ENGINEERING

10 Biomechanics 413
10.1 Prelude 413
10.2 Mechanical properties of materials 415
10.3 Mechanical properties of tissues and organs 424
10.4 Cellular mechanics 433
PROF ILES I N BME : WALT BAX TER 438

11 Bioinstrumentation 448
11.1 Prelude 448
11.2 Overview of measurement systems 451
11.3 Types of sensors 453
11.4 Instruments in medical practice 463
11.5 Instruments in the research laboratory 478
11.6 Biosensors 482
11.7 Biomicroelectromechanical systems and lab-on-a-chip devices 484
PR OF ILES I N BME : BI LL HAWK INS 488

12 Bioimaging 497
12.1 Prelude 497
12.2 X-rays and CT 501
12.3 Ultrasound imaging 508
12.4 Nuclear medicine 513

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12.5 Optical bioimaging 520

12.6 MRI 524
12.7 Image processing and analysis 527
PR OFI L E S I N B M E : REB E C CA R I CH AR DS- KOR T UM 535

13 Biomolecular Engineering I: Biotechnology 544

13.1 Prelude 544
13.2 Drug delivery 546
13.3 Tissue engineering 559
13.4 Nanobiotechnology 567
13.5 Other areas of biomolecular engineering 574
PR OFI L E S I N B M E : ROB E R T L ANG E R 577

14 Biomolecular Engineering II: Engineering of Immunity 588

14.1 Prelude 588
14.2 Antigens, Abs, and mAbs 590
14.3 What are Abs? 592
14.4 How can specific Abs be manufactured? 597
14.5 Clinical uses of Abs 600
14.6 Vaccines 603
PROFI LES IN BME: ELIAH R. S HAMI R 618

15 Biomaterials and Artificial Organs 626

15.1 Prelude 626
15.2 Biomaterials 627
15.3 Hemodialysis 634
15.4 Membrane oxygenators 643
15.5 Artificial heart 645
15.6 Biohybrid artificial organs 650
PROFI LES IN BME: ELIAS QUIJAN O 659

16 Biomedical Engineering and Cancer 666

16.1 Prelude 666
16.2 Introduction to cancer 667
16.3 Surgery 669
16.4 Radiation therapy 671
16.5 Chemotherapy 680

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16.6 Hormonal and biological therapies 686

16.7 Systems biology, biomedical engineering, and cancer 691
PR OF ILES I N BME : KAT IE SER R ANO 699

Appendix A Physiological Parameters 705

Appendix B Chemical Parameters 715
Appendix C Units and Conversion Factors 721
Index 723
Color plate section is between pages 360 and 361.

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Preface

The field of biomedical engineering has expanded markedly in the past 15 years.
This growth is supported by advances in biological science, which have created
new opportunities for development of tools for diagnosis of and therapy for human
disease. This book is designed as a textbook for an introductory course in
biomedical engineering. The text was written to be accessible for most entering
college students. In short, the book presents some of the basic science knowledge
used by biomedical engineers and illustrates the first steps in applying this
knowledge to solve problems in human medicine.
Biomedical engineering now encompasses a range of fields of specialization
including bioinstrumentation, bioimaging, biomechanics, biomaterials, and bio-
molecular engineering. Most undergraduate students majoring in biomedical
engineering are faced with a decision, early in their program of study, regarding
the subfield in which they would like to specialize. Each subfield has a set of
course requirements, which can be supplemented by wise selection of elective and
supporting coursework. Also, many young students of biomedical engineering use
independent research projects as a source of inspiration and preparation but have
difficulty identifying research areas that are right for them. Therefore, a second
goal of this book is to link knowledge of basic science and engineering to current
research, and the accompanying opportunities to create new medical products, in
each subfield.
As a general introduction, this textbook assembles foundational resources from
molecular and cellular biology and physiology and relates this science to various
subspecialties of biomedical engineering. The first two parts of the book present
basic information in molecular/cellular biology and human physiology; quantita-
tive concepts are stressed in these sections. Comprehension of these basic life
science principles provides the context in which biomedical engineers interact and
innovate. The third part of the book introduces the subspecialties in biomedical
engineering and emphasizes – through examples and profiles of people in the
field – the types of problems biomedical engineers solve. Organization of the
chapters into these three major parts allows course instructors and students to
customize their usage of some or all of the chapters depending on the background
of the students and the availability of other course offerings in the curriculum.

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xvi Preface

WHICH STUDENTS PROFIT FROM THIS BOOK?

A significant number of students come to college with a clear idea of pursuing a
career in biomedical engineering. Of course, these students benefit tremendously
from a rigorous overview of the field, ideally provided in their first year. Most of
these students leave the course even more certain about their choice of career.
Many of them jump right into independent study or research projects: This
overview of the diverse applications of biomedical engineering provides them
with the information that they need to select research projects—or future
courses—that will move them in the right direction.
I have also found this material to be interesting to engineering students who are
trying to decide which of the engineering degree programs is right for them. The
material in this textbook might also be used to introduce undeclared or undecided
engineering majors to the field of biomedical engineering. Students enter college
with varying degrees of competence in science and math. Some do not know what
biomedical engineering encompasses and whether they have the adequate second-
ary education training to succeed. Exposure to the topics presented here may
inspire some of these students to further their studies in biomedical engineering.
Also, I encourage instructors to make their course accessible to students who are
not likely to become engineering majors; biomedical technology is increasingly
important to the life of all educated citizens. I have taught courses in this subject to
freshmen at three different universities over the past 25 years; students with a variety
of intended majors always enroll in the course (mathematics, history, economics,
English, fine arts, and anthropology majors have participated in the past few years).
In fact, it is these students who appear to be most changed by the experience.

TO THE INSTRUCTOR
Teachers of courses directed to early undergraduates in biomedical engineering
struggle against competing forces: The diverse backgrounds of the students pull
you to start from first principles, and the rapid progress of the field pushes you to
cover more and more topics. To address this, I have presented more material than
I am capable of covering in a one-semester course for freshmen students. In a
typical 13-week semester, I find that only 12–13 of the 16 chapters can be covered
comfortably. Assuming that this will be true for your situation as well,
I recommend that you assess the level of experience of your students and decide
which chapters are most valuable in creating a coherent and satisfying course.
Many students arrive at college with a sophisticated understanding of cellular and
molecular biology; therefore, I do not cover Part 1 (Chapters 2–5) in detail.
Condensing this early material allows me to include almost all of the other
chapters. Part 1 is still available to the student, of course, and most of them profit
from reading these chapters, as they need as the course progresses, even if the

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Modular approaches to teaching an introductory course in biomedical engineering using this text
Week of the Comprehensive Applications Physiology Cellular engineering
course approach emphasis emphasis emphasis
1 Chap. 1 and 2 Chap. 1 Chap. 1 Chap. 1

2 Chap. 3 and 4 Chap. 2–5 Chap. 2–4 Chap. 2 and 3

(selected) (selected)

3 Chap. 5 Chap. 10 Chap. 5 Chap. 4

4 Chap. 7 Chap. 10 and 11 Chap. 6 Chap. 5

5 Chap. 8 Chap. 11 Chap. 7 Chap. 6–9 (selected)

6 Chap. 9 Chap. 12 Chap. 8 Chap. 10

7 Midterm review Midterm review Midterm review Midterm review

8 Chap. 10 Chap. 2–5 Chap. 9 Chap. 11

(selected)

9 Chap. 11 Chap. 13 Chap. 10 Chap. 12

10 Chap. 12 Chap. 14 Chap. 11 and 12 Chap. 13

11 Chap. 13 and 14 Chap. 15 Chap. 13 Chap. 14

12 Chap. 15 Chap. 16 Chap. 14 Chap. 15

13 Chap. 16 Chap. 16 Chap. 15 Chap. 16

details are not covered in lecture. In courses that emphasize biomedical engineer-
ing, and not the biological sciences, the instructor might want to cover only Part
3 of the book and use the previous parts as reference material.
Some examples of approaches for arranging the chapters into semester-long
courses that emphasize different aspects of biomedical engineering are presented
in the preceding table.

WHAT IS NEW IN THE SECOND EDITION

The second edition builds on the strengths of the first edition, but adds new
material that will be helpful to students and instructors. Each chapter has been
updated, with new text added to highlight important advances in biomedical
engineering since the first edition appeared in 2009. The second edition includes
new information reflecting recent advances in biological science (such as iPS cells
and microRNA), as well as advances in engineering and technology (such as
nanomedicine, biosensors, imaging technology, and drug delivery systems). Each
chapter has also been revised to improve readability. More qualitative and

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xviii Preface

quantitative practice material—in the form of Questions and Problems—has been

added to each chapter. Overall, there are 20% more Questions and Problems in the
second edition. Finally, the popular Profiles in BME sections have been updated
and expanded, with new profiles describing additional biomedical engineers,
representing a broad range of career paths and diverse interests.

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Acknowledgments

I have many people to thank, for encouragement and direct participation. It is a

long list, and undoubtedly incomplete. For the past 12 years, I have been
immersed in a milieu rich in creativity and industriousness. So I profited from
brushes and asides, from long conversations and wisdom overheard. I thank my
colleagues and friends at Yale University for providing intellectual stimulation,
personal support, and inspiration.
I thank the Whitaker Foundation for their generous financial support of the first
edition, which made it possible for me to transform notes and notions into text.
I am particularly grateful to Jack Linehan, who has been a steady source of
inspiration and advice to me. I thank Kyle Vanderlick, Dean of the School of
Engineering and Applied Sciences at Yale, for creating the space I needed to
complete this second edition.
I thank Peter Gordon of Cambridge University Press, who has been the most
stalwart supporter of this project. Peter is everything one could hope for in an
editor: He is wise, generous with praise, and direct (yet kind) with criticism.
Thankfully, he is also patient. I thank Michelle Carey for her brilliant support,
which was even more substantial in the preparation of this second edition. What a
pleasure, to be an author for Cambridge University Press.
I thank Veronique Tran for her help in the inception of this project, her critical
assistance in overall organization of the book, and her work on early versions of
Chapters 2, 6, and 11. It was Veronique who urged this project forward at the start,
and it would not have happened without her effort and enthusiasm. I thank
Lawrence Staib, who co-authored Chapter 12 and shaped it into one of my favorite
chapters in the book. I thank Rachael Sirianni, who continues to amaze me with
the breadth of her talents: Rachael’s photography enhances every chapter.
I burdened generous friends; each of them read part of the manuscript carefully
and provided thoughtful edits and suggestions, making each chapter better, more
readable. I thank Ian Suydam (Chapter 2), Kim Woodrow (Chapter 3), Michael
Caplan (Chapter 5), Parwiz Abrahimi (Chapter 6), Michelle Kelly (Chapter 7),
Peter Aronson (Chapter 9), Deepak Vashishith (Chapter 10), Themis Kyriakides
(Chapter 15), and Kathryn Miller-Jensen (Chapter 16).
I am grateful to my co-instructors in Physiological Systems (BENG 350) at
Yale, who have been exceptional colleagues and patient, enthusiastic teachers of

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xx Acknowledgments

physiology. The influence of Michael Caplan, Elizabeth Holt, Walter Boron,

Emile Boulpaep, Peter Aronson, and Stuart Campbell can be felt in Chapters 5,
6, 7, 8, 9, and 10, respectively. I have profited from their examples as teachers.
A number of people contributed essential administrative and research support—
tracking down papers and facts, producing figures, proofreading, and creating and
solving homework problems. For their work on the first edition, I thank Tiffanee
Green, Michael Henry, Kofi Buaku Atsina, Florence Kwo, and Salvador Joel
Nunez Gastelum. Two special people did this and much more: Audrey Lin and
Jennifer Saucier-Sawyer proofread, edited, pursued figures (and permissions for
figures), and managed to keep binders, drafts, and sticky notes organized. More
than this, they smiled at every obstacle, accommodated every idea, and remained
positive as I missed deadlines. Without Audrey’s expert help in the final push on
the first edition—and her never-say-no generosity—this text would still be in
binders. For the second edition, I thank Anthony Bianchi, Julie Chang, and Elias
Quijano. Anthony and Julie persevered through the final flurry of edits and
proofreading, with good spirits and exceptional attention to detail. This new
edition would not have been possible without Elias’s continuous help over the
past two years. I am so impressed with Elias, who teaches me something new
about patience, generosity, common sense, and biomedical engineering each day.
Something remarkable happened between the first and second edition. I got
married! Thank you, Christina, for being my partner and friend and for inspiring
me to shine, in your eyes. Your quiet strength and boundless spirit are constant
sources of inspiration to me.

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Abbreviations and Acronyms

3D- three-dimensional
3DCRT three-dimensional conformal radiation therapy
Ab antibody
ADA adenosine deaminase deficiency
ADH anti-diuretic hormone
ADP adenosine diphosphate
AIDS acquired immune deficiency syndrome
AML acute myeloid leukemia
APC antigen presenting cell
ATP adenosine-50 -triphosphate
AV atrioventricular
BBB blood–brain barrier
BCG bacillus Calmette–Guérin
BME biomedical engineering
BMR basal metabolic rate
BSA bovine serum albumin
CABG coronary artery bypass graft
CLL chronic lymphocytic leukemia
CT computed tomography
DAG diacylglycerol
DNA deoxyribonucleic acid
EBRT external beam radiation therapy
ECF extracellular fluid
ECG electrocardiography, electrocardiogram
ECM extracellular matrix
EGF epidermal growth factor
EGFR epidermal growth factor receptor
EVAc poly(ethylene-co-vinyl acetate)
FBR foreign body response
FDA U.S. Food and Drug Administration
fMRI functional magnetic resonance imaging
GFR glomerular filtration rate
GFP green fluorescent protein

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xxii Abbreviations and Acronyms

HIV human immunodeficiency virus

HPV human papillomavirus
HSC hematopoietic stem cells
HUVEC human umbilical vein endothelial cells
ICAM intercellular adhesion molecule
Ig immunoglobulin
IL-2 interleukin 2
IMRT intensity-modulated radiation therapy
IR infrared
IRS insulin receptor substrate
ISF interstitial fluid
LDL low-density lipoprotein
mAbs monoclonal antibodies
MHC major histocompatibility complex
MRI magnetic resonance imaging
MW molecular weight
NHL non-Hodgkin’s lymphoma
NMR nuclear magnetic resonance
PAH para-aminohippuric acid
PAN polyacrylonitrile
PCR polymerase chain reaction
PDMS polydimethylsiloxane
PE polyethylene
PEG poly(ethylene glycol)
PET positron emission tomography or poly(ethylene terephthalate)
PEU polyurethane
pHEMA poly(2-hydroxymethacrylate)
PIP3 phosphatidylinositol 3,4,5-trisphosphate
PKB protein kinase B
PLGA poly(lactide-co-glycolide)
pMMA poly(methyl methacrylate)
PP polypropylene
PS polystyrene
PSA prostate specific antigen
PSu polysulphone
PTFE poly(tetrafluoroethylene)
PVC poly(vinyl chloride)
PVP poly(vinyl pyrrolidone)
RBC red blood cell

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xxiii Abbreviations and Acronyms

RF radio frequency
RGD three peptide sequence of arginine (R), glycine (G), and aspartic
acid (D)
RNA ribonucleic acid
RPF renal plasma flow
rRNA ribosomal RNA
RSV respiratory syncytial virus
RTK receptor tyrosine kinase
SA sinoatrial
SARS Severe Acute Respiratory Syndrome
SGOT serum glutamic oxaloacetic transaminase
siRNA small interfering RNA
sMRI structural magnetic resonance imaging
SPECT single photon emission computed tomography
TIL tumor-infiltrating lymphocytes
tRNA transfer RNA
UV-VIS ultraviolet-visible spectroscopy
VEGF vascular endothelial cell growth factor
WBC white blood cells
WHO World Health Organization

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