Fractal Analysis of the Binding and Dissociation Kinetics for Different Analytes on Biosensor Surfaces This page intentionally left blank Fractal Analysis of the Binding and Dissociation Kinetics for Different Analytes on Biosensor Surfaces Ajit Sadana Department of Chemical Engineering, and National Center for Computational Hydroscience and Engineering, University of Mississippi, University, MS, USA AND Neeti Sadana, MD Department of Anesthesiology, University of Miami, Miami, Florida, USA Amsterdam ●Boston ●Heidelberg ●London ●New York ●Oxford Paris ●San Diego ●San Francisco ●Singapore ●Sydney ●Tokyo Elsevier Radarweg 29, PO Box 211, 1000 AE Amsterdam, The Netherlands Linacre House, Jordan Hill, Oxford OX2 8DP, UK First edition 2008 Copyright ©2008 Elsevier B.V. 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Because of rapid advances in the medical sciences, in particular, independent verification of diagnoses and drug dosages should be made Library of Congress Cataloging-in-Publication Data Acatalog record for this book is available from the Library of Congress British Library Cataloguing in Publication Data Acatalogue record for this book is available from the British Library ISBN: 978-0-444-53010-3 For information on all Elsevier publications visit our website at books.elsevier.com Printed and bound in The Netherlands 08 09 10 11 12 10 9 8 7 6 5 4 3 2 1 Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Cost and Implications of Medical Care of Some Common Diseases . . . . . . . . . . . . . . . . 1 2 Modeling and Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 2.2 Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2.2.1 Variable rate coefficient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 2.2.2 Single-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10 2.2.3 Dual-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 2.2.4 Triple-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14 2.2.5 Pfeifer’s fractal binding rate theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 3 BiosensorPerformance Parameters and theirEnhancement . . . . . . . . . . . . . . . . . . . 19 3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19 3.2 Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.2.1 Single-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.2.2 Dual-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23 3.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 51 4 Fractal Analysis of Harmful Bacteria, Toxins, and Pathogen Detection on BiosensorSurfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 4.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 4.2 Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 4.2.1 Single-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 56 4.2.2 Dual-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57 4.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58 4.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 86 5 Fractal Binding and Dissociation Kinetics of Disease-Related Compounds on BiosensorSurfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 5.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89 5.2 Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 5.2.1 Single-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 5.2.2 Dual-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 5.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 5.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 118 v vi Contents 6 Fractal Analysis of Binding and Dissociation of Analytes that Help Control Diseases on BiosensorSurfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 6.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 6.2 Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 6.2.1 Single-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 124 6.2.2 Dual-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125 6.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 126 6.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 147 7 Fractal Analysis of Binding and Dissociation of Small Molecules Involved in Drug Discovery on BiosensorSurfaces . . . . . . . . . . . . . . . . . . . . . . . . . . 151 7.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 7.2 Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152 7.2.1 Single-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 152 7.2.2 Dual-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 153 7.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 154 7.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 181 8 Fractal Binding and Dissociation Kinetics of Prion-Related Interactions on BiosensorSurfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185 8.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185 8.2 Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186 8.2.1 Single-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 186 8.2.2 Dual-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187 8.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 187 8.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 196 9 Fractal Analysis of Binding and Dissociation of DNA–Analyte Interactions on BiosensorSurfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199 9.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199 9.2 Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 9.2.1 Single-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 200 9.2.2 Dual-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201 9.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 202 9.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 225 10 Fractal Analysis of Binding and Dissociation of Protein–Analyte Interactions on BiosensorSurfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229 10.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 229 10.2 Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230 10.2.1 Single-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 230 10.2.2 Dual-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 231 10.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 232 10.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 255 Contents vii 11 Fractal Analysis of Different Compounds Binding and Dissociation Kinetics on BiosensorSurfaces . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259 11.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259 11.2 Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260 11.2.1 Single-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 260 11.2.2 Dual-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 261 11.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 262 11.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 292 12 Fractal Analysis of Binding and Dissociation Kinetics of Environmental Contaminants and Explosives on BiosensorSurfaces . . . . . . . . . . . . . . . . . . . . . . . . 297 12.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 297 12.2 Theory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298 12.2.1 Single-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 298 12.2.2 Dual-fractal analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299 12.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 299 12.4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 312 13 Market Size and Economics forBiosensors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317 13.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 317 13.2 Collaboration between Companies, Universities, and State and Governmental Agencies: Trends in Collaboration . . . . . . . . . . . . . . . . . . . . . . . . . 320 13.3 Factors that Could Help Increase/Decrease Biosensor Markets . . . . . . . . . . . . . . . 322 13.4 Examples of Biosensor Companies, their Product, and their Financial Backers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 324 13.5 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 331 Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 335 This page intentionally left blank Preface Applications for biosensors in diverse areas of application continue to increase. The initial application for biosensors was for the effective management of diabetes mellitus (DM) by the detection of glucose levels in blood. However, since then medical and other applica- tions for biosensors are gradually increasing. The similarities between the detection of harmful pathogens brought into focus by implied and realistic terrorist threats and bio- markers for the early detection of disease is being exploited in the development of biosen- sors for different applications. The present book in the series of books on analyte–receptor interaction kinetics on biosensor surfaces has a co-author (Neeti Sadana, MD) to empha- size the medical applications of biosensors, and to provide a better perspective of their applications. The initial chapter now provides not only a balance for the whole book, but also eases one into what to expect in the following chapters. Fractal mathematics provides a convenient means to provide novel physical insights into the kinetics of analyte–receptor reactions occurring on biosensor surfaces. It is hoped that eventually this will help improve the biosensor performance parameters such as sen- sitivity, selectivity, response time, stability, etc. with the eventual goal of, for example, (a) the early detection of biomarkers for harmful and insidious diseases and (b) providing emergency personnel that extra few minutes to help move large sections of human popu- lation from terrorist threat affected areas. Chapter 1 focuses on the vast medical implications of fractals in modern medical practice. The cost of current health care on society and diseased individuals is examined. Common illnesses such as cardiovascular disease, cancer, and diabetes mellitus are explored to find practical uses for fractal theory. Chapter 2 outlines the basic fractal theory to model the binding and the dissociation (if applicable) kinetics used. Asimple single-fractal model to analyze the kinetics is initially presented. This is then followed by dual- and triple-fractal models to analyze complex binding and dissociation kinetics when a single-fractal analysis did not provide an ade- quate fit. In Chapter 3 different examples are presented wherein the biosensor performance parameters have been enhanced by experimental modification and validated by the fractal theory kinetics presented. This includes enhancement of biosensor sensitivity, immobi- lization, reproducibility, resolution performance, etc. The detection of harmful bacteria, toxins, and pathogens on biosensor surfaces is out- lined in Chapter 4. TV (CNN) news in the United Sates in February 2007 indicated the concerns that consumers expressed over food items available in grocery stores, and the number of illnesses and also deaths resulting from pathogenic bacteria-contaminated food (particularly different types of meat). Suggestions were made to increase the testing for these pathogenic bacteria (such as Salmonella, Listeria monocytogenes, and Escherichia coli) by the governmental agencies responsible. One of the major themes for the book is the application of biosensors for the early detection of insidious diseases, specifically their biomarkers. This has been brought into proper perspective in the first chapter by an expert ix
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