Immunoassay Handbook - Theory and Applications of Ligand Binding, ELISA and Related Techniques

1056 Pages·2013·38.38 MB·English

by  Wild

The Immunoassay Handbook
Theory and applications of ligand binding,
ELISA and related techniques
Fourth Edition
Edited by
David Wild
Associate Editors
Rhys John, Chris Sheehan,
Steve Binder and Jianwen He
AMSTERDAM (cid:127) BOSTON (cid:127) HEIDELBERG (cid:127) LONDON (cid:127) NEW YORK (cid:127) OXFORD (cid:127) PARIS (cid:127) SAN DIEGO (cid:127) SAN FRANCISCO (cid:127) SINGAPORE (cid:127) SYDNEY (cid:127) TOKYO
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Fourth Edition 2013
© 2013, 2005 David G. Wild. Published by Elsevier Ltd. All rights reserved.
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First Edition published by Macmillan Press (Basingstoke, UK) and Stockton Press (New York, USA) 1994
Second Edition published by Nature Publishing 2001
Notice
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instructions or ideas contained in the material herein
British Library Cataloguing in Publication Data
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ISBN: 978-0-08-097037-0
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While every care has been taken in compiling the information contained in this publication, the publishers
and editor accept no responsibility for any errors or omissions.
The reference intervals provided in this book are for specific methods, determined at a particular time, and
using a single population of patients. Because of the inherent variability of immunoassays, they should not be
applied to clinical situations.
Therapeutic and toxic doses, and therapeutic ranges for drugs are only provided as a guide. They are not for
clinical use.
Printed and bound in Great Britain
13 14 15 16 17 10 9 8 7 6 5 4 3 2 1
Cover Credit: Rajeev Doshi
(cid:3)
Preface
“There’s a place….” (((John Lennon and Paul McCartney, without purification. The most sensitive commercial ana-
1963). lyzers in hospital laboratories attain this level of specificity
and sensitivity routinely. Research immunoassays have
First thing in the morning, I walk to the Dee estuary, detected concentrations as low as 10−21 mol, the concen-
which lies between England and Wales, to gain a clearer tration of a bucketful of chemical dispersed across all the
perspective on the day ahead and organize my thoughts. world’s oceans, and immunoassays are now an important
I stroll along a footpath by a hedgerow and cross a track tool in the investigation of pollution, a negative conse-
where a steam railway once pounded down a long aban- quence of man’s interaction with nature.
doned route. I listen to birds singing in the trees and walk The core elements of immunoassays have undergone
onto a cliff top with a view of the Welsh hills across the many incremental changes. Immunoassay signals have
estuary, which is home to thousands of wading birds in the transitioned from radioactive to enzymatic to chemilumi-
winter. nescent, antibodies have progressed from polyclonal to
As I take my morning constitutional, I often think about monoclonal to recombinant, and protein assays have con-
immunoassays and how best to present them in this book. verted from competitive to immunometric. In just one
All around me, I can see how our ancestors have been 10-year period, separation methods evolved from antibody
harnessing nature for centuries. My neighbor’s dogs are a precipitation and centrifugation, through centrifugation of
product of selective breeding, as are the cows and sheep. latex particles, to magnetic separation of paramagnetic
The estuary attracts birds because the river was channeled particles, diverging into microtiter plate washing in some
to provide a constant supply of cooling water to a power sectors. In the same period, homogeneous assays appeared
station, creating large expanses of food-rich tidal mudflats that do not require a separation at all. Advances in automa-
and salt marsh. Seaward, I can see the ferries to Ireland tion have traced another innovation pathway, documented
passing a wind farm. I realize that I am continuing this for posterity in the technology sections of the four editions
human compulsion to take advantage of nature, even as I of this book. The diversity of technical approaches in use
walk. During the Spring, I can prompt a vocal response today indicates that immunoassays are far from being a
from hidden warblers by playing mp3 versions of their mature technology.
songs through the powerful but tiny speakers on my A rapid pace of change has resulted from pushing the
iPhone. integration of biochemistry and engineering to the limit,
I find myself wondering: where do immunoassays rank made possible by the combined efforts of thousands of
on the scale of human technological achievement, which is engineers, biochemists, chemists, clinical chemists, physi-
all based on our understanding of the natural world? cists, mathematicians, doctors, programmers, marketers,
They are based on a broad and deep scientific knowl- accountants, managers, and business strategists. The indus-
edge in physics, chemistry, and biology. The engineering try has provided employment for an estimated 100,000
and biochemistry have become highly complex, and the manufacturing workers. What has been the broader eco-
pace of innovation is faster than in many industries, nomic impact?
including automobiles, construction, pharmaceuticals, and The invention of immunoassay is almost unknown to
protection of the environment. The dual application of the general public, in contrast to the breaking of the
cutting-edge biochemistry andd engineering places immu- genetic code in the same decade. But the immunoassay
noassay into a select subgroup of highly advanced biotech- business is considerably larger in dollar terms than all
nology products. DNA-related businesses combined. Att the time of writing,
Edward Jenner discovered the process of vaccination in immunoassay sales (at least $20 billion pa) correspond to
1796, exploiting the natural process of immunity for the 70% of global computer and video game sales revenues.
first time. Immunoassay, as defined in this book, was Although the immunoassay market is dwarfed by the
invented in the 1950s, building on earlier applications of sales of pharmaceuticals, many of the latest biological
antibodies as reagents to quantify molecules in blood sam- drugs now transforming medicine are based on advances in
ples. Since antibodies resulted from millions of years of monoclonal antibody bioengineering that have their roots
evolution in animals, as part of the body’s defense against in immunoassay research and development, documented
parasites, bacteria, viruses, toxins, and other hazards, why since the first edition of this book.
not adopt them to provide assays of exquisite specificity Immunoassays have had a profound influence on medi-
and sensitivity? This book explains how it is done. cine, explained in the final section (part 9) of the book.
Immunoassays are remarkable examples of biotechnol- The pivotal role of immunoassays in clinical diagnosis and
ogy. Using a minute quantity of an immunized animal’s follow-up remains their primary contribution to society,
blood, an immunoassay can detect and quantify 1 part in much influencing the effectiveness and cost of medical
1,000,000,000,000 of a substance in a complex sample, treatment, which is the largest budgetary expenditure
xi
xii Preface
category in developed world economies. This edition has was 1% inspiration and 99% perspiration, with large teams
been extensively revised to reflect recent changes in clini- working together as immunoassay systems became ever
cal practice related to immunoassays. more complex. The last immunoassay development pro-
This book is only possible because many experts made gram I worked on involved three large development teams
time in their busy schedules to write about the theory and in the USA and the UK, with a budget of $250 million.
applications of the extensive range of immunoassays Only someone who has worked on a new product intro-
described, including glimpses at what is on the drawing duction can understand how demanding the process is and
board for the future. Because of the pace of innovation and how deep the satisfaction when the first customers express
the competitive spirit in the immunoassay industry and their delight with the outcome.
academia, we have all experienced ups and downs in our If you enjoy reading about the application of science,
careers and had mixed feelings when our peers have made you have come to the right place. Immunoassay provides a
breathtaking leaps forward. But we have each been grateful master class in the life cycle of a technology business that
to play a small part in immunoassay history. I am deeply is still unfolding.
grateful to the many contributors, past and present, for Just a brief note on nomenclature. In The Immunoassay
their commitment to immunoassay education through the Handbook, assays are described either as competitive or immu-
pages of this book. nometric most of the time. I like the term “competitive”
The fourth edition has involved a team of more than because it has a strong descriptive element that helps new-
90 authors, with 12 new chapters and significant revisions comers to remember how these assays work. However, it is
made to most of the existing chapters. Some of the original not universally accepted as a scientific description, as some-
book authors have retired. Their chapters have been times the tracer is added after the antibody has had time to
revised in this edition by new leaders in their fields, and in bind to analyte in the sample. I also have a bias toward
some chapters, we have brought together experts from dif- “immunometric” because the somewhat negative connota-
ferent institutions because of their complementary knowl- tions of “noncompetitive” or “reagent excess” belie their
edge and experience. In a handful of cases, chapters written superior performance compared to their competitive coun-
by intellectual giants of the field that received great acclaim terparts. I also think the popular term for the immunomet-
when the book was first published have been retained with ric format “sandwich assay” is potentially misleading,
minimal changes because of their high reputation and although it is descriptive, as competitive immunoassays may
timeless content. These chapters are still used for refer- also have three or more layers of molecules bound together.
ence as breathtaking new technologies, such as digital Having justified the use of these terms in the book, I must
ELISA, are developed for the future. In total, 124 authors, also point out that although most immunometric assays are
past and present, contributed material to this edition. also noncompetitive, the term immunometric was origi-
There has been no let up in the pace of innovation since nally introduced to describe any immunoassay that uses a
the previous edition of The Immunoassay Handbook was labeled antibody, and there are some assays that are com-
published in 2005. Many believed that the publication of petitive and use labeled antibodies. In these cases, the assays
the human genome would signal the end of immunoassays are described in the book as competitive rather than immu-
as the dominant medical research tool, as researchers nometric. I hope the experts will forgive these attempts to
prepared to switch from analysis of proteins to genes. simplify and unify nomenclature in order to standardize the
I thought that the third edition might be the last. But the book across a range of fields that have sometimes developed
surprising finding that there are only about 25,000 genes independently. Many times in the book you will see the
in the human genome has brought the spotlight back onto term sandwich alongside immunometric because in some
immunoassays, as the genes code for multiple variants of applications it is much more commonly used.
proteins. In the field of proteomics, immunoassays can ELISA is a term used in its correct context in the book.
help to trace metabolic pathways and control mechanisms It describes solid-phase immunoassays with enzyme-based
in cells, to understand how genes can control so many labels. This is a subset of immunoassays that became
intricate biological functions and how gene expression is prominent when radioactive labels fell out of favor. But the
controlled. In this edition of The Immunoassay Handbook, majority of immunoassays performed on hospital analyzers
the fields of immunohistochemistry and immunocyto- now have chemiluminescent labels, because of their
chemistry have been added, as they are closely related to improved reagent stability and the need for signal genera-
immunoassay in life science research. tion to occur quickly. So ELISA should not be used as a
A tool that threatened to topple immunoassay from its generic term for all immunoassays.
high perch was mass spectrometry, which has been refined This book is packed with information about immunoas-
to the point where it can analyze protein mixtures with says. The contributing authors have condensed an amaz-
great specificity, using a more direct approach than immu- ing amount of information into their chapters without
noassay. But for generating an assay that can be used to making the subject indigestible. They have taken the time
screen large numbers of samples at low cost with compara- to tell the story of immunoassay in an accessible way, so
tively cheap equipment, immunoassay continues to reign that readers at all levels can be let into its secrets. The col-
supreme. laboration between the experts writing in this book contin-
What this book shows is that when industry and aca- ues the spirit that began when Rosalyn Yalow and Solomon
demia work together there is no end to the sparkling bril- Berson, who refused to patent their invention, trained the
liance of the innovation that can be achieved. Again and founders of the immunoassay industry, leading to its rapid
again, incremental improvements have been made that growth (see FOREWORD). The authors of this book, from
moved the field forward. Much of the time, the innovation industry, medicine and academia, have set a wonderful
Preface xiii
example by sacrificing their time and passing on their As I return from the estuary and climb the gentle incline to
knowledge and experience in a digestible form. my house, I reflect on 25 satisfying years working on this
I hope you find this book a welcome source of informa- book, from the first edition to the fourth, as the immunoas-
tion and insight and discover for yourself something new say field has taken me on an exciting and rewarding journey.
and exciting in the field of immunoassay and its many
applications. If you do, you will be continuing a long tradi- David Wild,
tion of scientific fascination with this intriguing subject. [email protected]
Contents
Foreword ix 2.10 Lab-on-a-Chip,Micro-andNanoscale
Preface xi ImmunoassaySystems,andMicroarrays 175
Acknowledgements xv Simon Rattle, Oliver Hofmann, Christopher P. Price,
ListofContributors xvii Larry J. Kricka, David Wild
AbouttheEditors xxi 2.11 ImmunologicalBiosensors 203
Jason Reed, James K. Gimzewski
1 2.12 SurfacePlasmonResonanceinBinding
P A R T Site,Kinetic,andConcentration
Analyses 209
Immunoassay Fundamentals
Robert Karlsson
1.1 HowtoUseThisBook 3 2.13 MeasurementofSingleProteinMolecules
UsingDigitalELISA 223
David Wild
David M. Rissin, David H. Wilson, David C. Duffy
1.2 ImmunoassayforBeginners 7
David Wild
1.3 ImmunoassayPerformanceMeasures 11 3
P A R T
Chris Davies
Immunoassay Components
2
P A R T 3.1 Antibodies 245
Eryl Liddell
Immunoassay Configurations
3.2 SignalGenerationandDetection
2.1 PrinciplesofCompetitiveand Systems(ExcludingHomogeneous
ImmunometricAssays(IncludingELISA) 29 Assays) 267
Chris Davies Ian Weeks, Larry J. Kricka, David Wild
2.2 Non-competitiveImmunoassaysforSmall 3.3 SeparationSystems 287
Molecules—theAnti-complexandSelective David Wild, Wlad Kusnezow
AntibodySystems 61 3.4 ConjugationMethods 301
Colin H. Self, Stephen Thompson, Theresa Street, Kelly J. Alastair H. Dent
Lamb, Gordon Duffin, John L. Dessi, Maggie Turnbull 3.5 StandardizationandCalibration 315
2.3 HomogeneousImmunoassays 67 David Wild, Chris Sheehan
Edwin F. Ullman 3.6 CalibrationCurveFitting 323
2.4 LateralFlowImmunoassaySystems: John Dunn, David Wild
EvolutionfromtheCurrentStateofthe
ArttotheNextGenerationofHighly
Sensitive,QuantitativeRapidAssays 89 4
P A R T
Brendan O’Farrell
2.5 AmbientAnalyteAssay 109 Related Techniques
Roger Ekins
4.1 TheFoundationsofImmunochemistry 339
2.6 FreeAnalyteImmunoassay 123
Robert F. Ritchie
Nic D. Christofides
4.2 Immunohistochemistryand
2.7 QualitativeImmunoassay—Featuresand
Immunocytochemistry 357
Design 139
Simon Renshaw
Jianwen He, Simon Parker
2.8 DetectionofAntibodiesRelevantto
InfectiousDisease 149 5
P A R T
Steven Binder, Jennifer A. Isler
2.9 Microsphere-BasedMultiplexImmunoassays: Immunoassay Development
DevelopmentandApplicationsUsing
Luminex®xMAP®Technology 157 5.1 PracticalGuidetoELISADevelopment 381
Sherry A. Dunbar, Michaela R. Hoffmeyer Jianwen He
v
vi Contents
5.2 Method Evaluation—A Practical Guide 395 7.10 ADVIA Centaur® XP 567
Chris Sheehan, Jianwen He, Mari Smith Jean Metzar
5.3 Interferences in Immunoassay 403 7.11 IMMULITE® and IMMULITE 1000 571
Jason Y. Park, Larry J. Kricka Arthur L. Babson
5.4 Immunoassay Development in the In Vitro 7.12 Immulite® 2000 and Immulite 2000 XPi 575
Diagnostic Industry 417 Arthur L. Babson
Doug Brandt, Steve Figard 7.13 VITROS® ECiQ Immunodiagnostic System,
VITROS® 3600 Immunodiagnostic System,
and VITROS® 5600 Integrated System 579
6
John W. Backus, David Wild
P A R T
7.14 VITROS® Immuno-Rate and MicroTiptm
Immunoassay Implementation Assays 585
John W. Backus, Susan J. Danielson, David A. Hilborn
6.1 Sample Collection, Including Participant
7.15 Access 2 589
Preparation and Sample Handling 427
Katherine M. Leith
Colin Wilde, Dorothée Out, Sara Johnson,
7.16 DxI 600 and DxI 800 597
Douglas A. Granger
Katherine M. Leith
6.2 Quality Assurance 441
7.17 Elecsys® Immunoassay Systems 603
Catharine M. Sturgeon
Mary Beth Myers
6.3 Point-of-Care Testing 455
7.18 PRISMtm 609
James H. Nichols
Dinesh Shah, Jim Stewart
6.4 Choosing an Automated Immunoassay
7.19 Phadia Laboratory Systems 617
System 465
Angela Gore, Gareth Evans, Mats Rilvën
Lori J. Sokoll
Daniel W. Chan
8
6.5 Immunoassay Troubleshooting Guide 469 P A R T
David Wild, Jianwen He
Immunoassay Applications other than
Clinical Chemistry
7
P A R T
8.1 Immunoassay Applications in Veterinary
Diagnostics 623
Immunoassay Product Technology
Thomas P. O’Connor, Jr., John Lawrence, Philip Andersen,
7.1 Introduction to Immunoassay Product Valerie Leathers, Erwin Workman
Technology in Clinical Diagnostic 8.2 Ligand Binding Assays in Drug
Testing 509 Development 647
David Wild, Chris Sheehan, Steve Binder Jeffrey M. Sailstad, Ronald R. Bowsher, Omar F. Laterza,
7.2 Market Trends 517 William Nowatzke
David Huckle
7.3 Lateral Flow and Consumer 9
P A R T
Diagnostics 533
Sarah Tiplady Immunoassay Clinical Applications
7.4 Consumer Diagnostics—Clearblue (Human)
Pregnancy and Fertility Testing 537
Sarah Tiplady 9.1 Clinical Concepts 661
7.5 The Triage® System 541 Chris Davies
Thomas I. Koshy, Kenneth F. Buechler 9.2 Thyroid 673
7.6 Stratus® CS Acute Caretm STAT Fluorometric Rhys John, Nic Christofides, Carole A. Spencer, David Wild
Analyzer 545 9.3 The Adrenal Cortex 695
Amy Sarli, W.N. McLellan Les Perry, Sami Medbak
7.7 IMx® 549 9.4 Bone and Calcium Metabolism 705
Kent Ford William D. Fraser, Kay W. Colston, John C. Stevenson
7.8 AxSYM® 555 9.5 Infertility 721
Theresa Donahoe Michael J. Wheeler
7.9 Abbott ARCHITECT® Family of 9.6 I n Vitro Fertilization and Embryo Transfer
Analyzers 561 (IVF-ET) 735
Frank A. Quinn, David A. Armbruster Richard Fleming, Sherry Faye
Contents vii
9.7 Hirsutism and Virilization in the 9.16 Gastrointestinal Tract 891
Female 745 Arne Røseth, Richard Chapman, Radra Ramachandran,
Michael J. Wheeler Chris Sheehan
9.8 Pregnancy 757 9.17 Hepatitis 901
Kevin Spencer, Tim Chard Ravi Kaul
9.9 Growth and Growth Hormone 9.18 HIV-1 and HIV-2: Causative Agents of
Deficiency 777 AIDS 913
Gill Rumsby, Peter Hindmarsh, Michael Preece, Catherine A. Brennan, Sushil G. Devare
Jane Pringle 9.19 Viral Diseases 919
9.10 Diabetes Mellitus 783 Carey-Ann D. Burnham, Christopher Doern, Steven R Binder
Penny Clark, Tim McDonald 9.20 Bacterial Diseases 929
9.11 Hematology 795 Carey-Ann D. Burnham, Christopher Doern, Steven R. Binder
Katy Evans, Zane Amenhotep, Derek Dawson, 9.21 Parasites and Fungi 939
Harry Waters, John Ardern
Steven R. Binder, Patrice D. Sarfati
9.12 Cardiac Markers 817 9.22 Therapeutic Drug Monitoring (TDM) 945
Deborah French, Alan H.B. Wu Philip A. Routledge, Alun D. Hutchings
9.13 Cancer Markers 833 9.23 Drugs of Abuse 963
Hoon H. Sunwoo, Mavanur R. Suresh Alun D. Hutchings, Brian Widdop
9.14 Allergy 857
Marcos Alcocer, Lars Yman
Index 989
9.15 Autoimmune Disease 869
David F. Keren
Color version of figures in this book can be found at www.immunoassayhandbook.com
1
P A R T
IMMUNOASSAY FUNDAMENTALS
How to Use This Book
C H A P T E R
1.1
David Wild ([email protected])
The Immunoassay Handbook is a comprehensive source only the bound fraction results in a measurable signal from
of information about immunoassays and their applications. the label. Homogeneous immunoassays are designed to
This chapter explains how the book is structured to help discriminate bound from unbound label without requiring
you find the information you need. a separation, by a range of ingenious approaches. This
simplifies assay automation. They can be competitive or
immunometric. This is an innovative area, receiving con-
Using the Index
siderable attention from researchers.
2.4 Lateral flow immunoassay systems. This type of
In the index, if a page reference is in bold type, the topic is immunoassay is widely used and deserves a special chapter.
usually explained in more detail. A well-known example is the home pregnancy test. The
format is used in point-of-care, forensic, environmental,
and food applications. A key characteristic is accomplish-
Book Structure
ment of the mechanical steps, including separation, on an
inert test strip through capillary action without interven-
The book content is separated into parts, each one build- tion by the user. This is a field that is the subject of inten-
ing on the previous body of information. sive development activity.
2.5 Ambient analyte immunoassay. Professor Roger
Ekins applied immunoassay theory to achieve something
PART 1 – IMMUNOASSAY
that intuitively sounds impossible: a quantitative assay
FUNDAMENTALS
that is independent of the sample volume. Small, immobi-
1.2 Immunoassay for beginners is a good place to start lized microdots of antibody sample the analyte in solution,
for newcomers, explaining the basic principles of rather like a thermometer measuring the surrounding
immunoassay. temperature without affecting it.
1.3 Immunoassay performance measures explains the 2.6 Free analyte immunoassay. This is a special family
terminology and methodology that define the performance of assay formats, designed to measure free analyte in blood
of an immunoassay. samples, i.e., the fraction that is not bound to carrier pro-
tein. This is important if the free analyte is the metaboli-
cally active fraction. Free thyroxine is the best known
PART 2 – IMMUNOASSAY
example, with a free fraction of just 0.02% of the total.
CONFIGURATIONS
2.7 Qualitative immunoassays—features and design.
2.1 Principles of competitive and immunometric assays As immunoassays have evolved to meet specific clinical
(including ELISA). Nearly all immunoassays are competi- needs, qualitative tests that give a yes/no answer have
tive or immunometric in configuration. They are explained become more common. Home pregnancy tests are qualita-
in the same chapter because they share some common tive as are some blood-screening tests, which sometimes
characteristics. ELISA (Enzyme-Linked Immunosorbent also have a gray zone between the positive and negative
Assay) is a subgroup of immunometric assays although the classification areas. Although qualitative immunoassays are
term is sometimes used loosely (but incorrectly) to describe simple for the user, they have unique design requirements,
any immunoassay. Immunometric assays are commonly because the test provides clinical interpretation, rather
known as sandwich assays because the analyte becomes than simply the analyte concentration.
sandwiched between the two antibodies (the capture and 2.8 Detection of antibodies relevant to infectious dis-
labeled antibodies). ease. Conventional immunoassays utilize antibodies to
2.2 Non-competitive immunoassays for small mole- “fish” for complementary antigens: the target analytes.
cules. Usually the competitive assay configuration is used The same principles apply when antibodies are the targets,
for small molecules, such as steroid hormones and many and antigens are used as the “bait,” but in practice anti-
drugs, because of the technical difficulties involved in cre- body assays have unique challenges. In a conventional
ating an antibody sandwich with the relatively small ana- immunoassay, the developer can select a clone or pool of
lyte between them. But immunometric assays have antibodies to engineer the desired assay performance char-
significant performance advantages. This chapter explains acteristics. But in an antibody assay, the antibody popula-
how immunometric assay performance can be achieved tions may be highly variable between samples.
with low-molecular-weight analytes by creating a pseudo- 2.9 Microsphere-based multiplex immunoassays: devel-
immunometric assay format. opment and applications using Luminex® xMAP® tech-
2.3 Homogeneous immunoassays. Conventional immu- nology. Luminex pioneered the use of antibody-coated
noassays are heterogeneous, relying on separation of mate- microspheres and cell sorting, and this is now an important
rial bound to antibody from the unbound material, so that immunoassay class, with many applications.
© 2013 David G. Wild. Published by Elsevier Ltd. All rights reserved. 3
http://dx.doi.org/10.1016/B978-0-08-097037-0.00001-4