Engineering Biosensors - Kinetics and Design Applications

418 Pages·2002·16.42 MB·English

by  Sadana

Engineering Biosensors:
Kinetics and Design
Applications
Ajit Sadana
Chemical Engineering Department
University of Mississippi
University, Mississippi
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This book is dedicated to my parents,
Dr. J. C. Sadana and Mrs. Jinder Sadana, to whom I owe more than
they will ever know.
PREFACE
Biosensors are becoming increasingly important bioanalytical tools in the
pharmaceutical, biotechnology, food, and other consumer-oriented indus-
tries. Although well developed in Europe, this technology has only recently
begun to generate interest in the United States and is developing slowly. Much
research is now being directed toward the development of biosensors that are
versatile, economical, and simple to use.
There is a critical need to provide a better understanding of the mode of
operation of biosensors with the goal being to improve its stability, specificity,
response time, regenerability, and robustness. Diffusional limitations are
invariably present in biosensors because of their construction and principle of
operation. A better knowledge of the kinetics involved in the binding and
dissociation assays of the biosensors will provide valuable physical insights
into the nature of the biomolecular interactions sensed by the biosensors. In
addition to these kinetics, knowledge regarding the nature of the sensor
surface is an important consideration in the design. However, this aspect is
sadly overlooked in many texts and publications dealing with biosensors. The
main aim of this book is to address the kinetics involved in analyte-receptor
binding using a novel mathematical approach calledfractals. We will attempt
to model the binding and dissociation of an analyte and a receptor using
examples obtained from literature using fractal analysis. In doing so, we wish
to delineate the role of the biosensor surface and diffusional limitations on the
binding and dissociation reactions involved.
In the introductory chapter, we have given a background for the need for
biosensors and the different types of immunoassays. Traditional kinetics are
described under the influence of diffusion on antigen-antibody binding
xi
xii Preface
kinetics in biosensors in Chapter 2. Lateral interactions are included in
Chapter 3.
In our opinion, Chapter 4 is one of the most important chapters in the
book as there we first introduce the concept of fractals, fractal kinetics, and
fractal dimensions. We also give a background of the factors that contribute
toward heterogeneity on a biosensor surface and how it can be explained
using fractal kinetics. There are a host of other parameters-such as
analyte/ligand concentration, regeneration conditions, etc.-that affect
biosensor performance characteristics. In Chapter 5, we try to explain the
influence of these parameters on the surface and consequently on the fractal
dimension values.
Havlin (1989) developed an equation for relating the rate of complex
formation on the surface to the existing fractal dimension in electrochemical
reactions. We have extended this idea to relate the binding rate coefficient and
fractal dimension for an analyte-receptor reaction on a biosensor surface. A
detailed explanation of Havlin’s equation and how it can be made amenable to
suit our needs can be found in Chapter 6. Just as the association between the
analyte and the receptor is important, the reverse (dissociation) is equally
important, perhaps more so from the viewpoint of reusability of the biosensor.
Recognizing its importance, we have treated the dissociation separately in
Chapter 7, where we present equations that we feel can adequately describe
and model the dissociation kinetics involved. We have extended Havlin’s
ideas and applied them successfully, with slight modifications and reasonable
justifications to model the dissociation kinetics. We feel that the analysis of
binding and dissociation kinetics is our contribution in the application of
fractal modeling techniques to model analyte-receptor systems.
There is a very slight shift in focus in Chapter 8 as we go back to the
traditional kinetic models described in Chapters 3 and 4 to describe the
problem of nonspecific binding in biosensors and how design considerations
may have to be altered to account for this phenomenon. We also analyze this
problem using fractals in Chapter 9.
In Chapter 10, we analyze examples from literature wherein DNA
hybridization reactions have been studied using biosensors. In Chapter 11,
we look at cell analyte-receptor examples, and in Chapter 12 we present
examples of biomolecular interactions analyzed using the surface plasmon
resonance (SPR) biosensor. The SPR biosensor is finding increasing
application as an analytical technique in industrial and research laboratories.
We have developed expressions for relating the fractal dimensions and
binding rate coefficients, fractal dimensions/binding rate coefficients and
analyte concentration, and so on.
We conclude with what in our opinion is the highlight of this book: a
chapter on the biosensor market economics. What makes this chapter special
Preface xiii
is the effort that has gone into compiling it from hard-to-obtain industry and
market sales figures over the last several years. Although some of the
projection figures may be outdated, the chapter does give the reader a feel for
the costs involved, and the realistic returns on the investment involved, and
the potential for growth and improvement. Just to emphasize the point and to
make it easier to understand, we have presented a 5-year economic analysis of
a leading biosensor company, BIACORE AB.
We have targeted this book for graduate students, senior undergraduate
students, and researchers in academia and industry. The book should be
particularly interesting for researchers in the fields of biophysics, biochemical
engineering, biotechnology, immunology, and applied mathematics. It can
also serve as a handy reference for people directly involved in the design and
manufacture of biosensors. We hope that this book will foster better
interactions, facilitate a better appreciation of all perspectives, and help in
advancing biosensor design and technology.
Ajit Sadana
CONTENTS
Preface xi
1 Introduction
1.1. Background, Definition, and the Need for Biosensors 1
1.2. Assay Formats 10
1.3. Difficulties with Biosensor Applications 12
1.4. Newer Applications for Biosensors 13
1.5. Commercially Available Biosensors 17
1.6. Biomedical Applications 17
1.7. Overview 19
2 Influence of Diffusional Limitations and Reaction Order
On Antigen-Antibody Binding Kinetics
2.1. Introduction 23
2.2. Theory 24
3 Influence of Diffusional Limitations and Lateral Interactions
on Antigen-Antibody Binding Kinetics
3.1. Introduction 45
3.2. Theory 46
3.3. Conclusions 63
vii
viii Contents
4 Fractal Reaction Kinetics
4.1. Introduction 67
4.2. Fractal Kinetics 69
5 Influence of Different Parameters on Fractal Dimension
Values During the Binding Phase
5.1. Introduction 83
5.2. Theory 85
5.3. Results 89
5.4. Summary and Conclusions 122
6 Fractal Dimension and the Binding Rate Coefficient
6.1. Introduction 127
6.2. Theory 130
6.3. Results 133
6.4. Conclusions 183
7 Fractal Dimension and the Dissociation Rate Coefficient
7.1. Introduction 187
7.2. Theory 190
7.3. Results 195
7.4. Conclusions 216
8 Influence of Nonspecific Binding on the Rate and
Amount of Specific Binding: a classical analysis
8.1. Introduction 221
8.2. Theory 230
9 Influence of Nonspecific Binding on the Rate and Amount
of Specific Binding: a fractal analysis
9.1. Introduction 253
9.2. Theory 255
9.3. Results 257
9.4. Other Examples of Interest 265
9.5. Conclusions 269
ix
Contents
10 Fractal Dimension and Hybridization
10.1. Introduction 273
10.2. Theory 27 5
10.3. Results 276
10.4. Conclusions 307
11 Fractal Dimension and Analyte-Receptor Binding in Cells
11.1. Introduction 311
11.2. Theory 313
11.3. Results 315
11.4. Conclusions 34 1
12 Surface Plasmon Resonance Biosensors
12.1. Introduction 345
12.2. Theory 347
12.3. Results 349
12.4. Conclusions 379
13 Economics and Market for Biosensors
13.1. Introduction 385
13.2. Market Size and Economics 386
13.3. Development Cost of a Biosensor 393
13.4. Cost Reduction Methods 395
Index 399
1
CHAPTER
Introduction
1.1. Background, Definition, and the Need for
Biosensors
1.2. Assay Formats
1.3. Difficulties with Biosensor Applications
1.4. Newer Applications for Biosensors
1.5. Commercially Available Biosensors
1.6. Biomedical Applications
1.7. Overview
1.1. BACKGROUND, DEFINITION, AND THE
NEED FOR BIOSENSORS
A biosensor is a device that uses a combination of two steps: a recognition
step and a transducer step. The recognition step involves a biological sensing
element, or receptor, on the surface that can recognize biological or chemical
analytes in solution or in the atmosphere. The receptor may be an antibody,
enzyme, or a cell. This receptor is in close contact with a transducing element
that converts the analyte-receptor reaction into a quantitative electrical or
optical signal. The signal may be transduced by optical, thermal, electrical, or
electronic elements. Lowe (1985) emphasizes that a transducer should be
highly specific for the analyte of interest. Also, it should be able to respond in
the appropriate concentration range and have a moderately fast response time
(1-60 sec). The transducer also should be reliable, able to be miniaturized,
and suitably designed for practical application. Figure 1.1s hows the principle
of operation of a typical biosensor (Byfield and Abuknesha, 1994).
As early as 1985, Lowe (1985) indicated that most of the major
developments in biosensor technology will come from advances in the health
care field. Efficient patient care is based on frequent measurement of many
analytes, such as blood cations, gases, and metabolites. Emphasizing that, for
inpatient and outpatient care, key metabolites need to be monitored on tissue
fluids such as blood, sweat, saliva, and urine, Lowe indicated that implantable
biosensors could, for example, provide real-time data to direct drug release by
1