Introduction to Biosensors
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1 Introduction to Biosensors
2
3 Jeong-Yeol Yoon Introduction to Biosensors From Electric Circuits to Immunosensors
4 Jeong-Yeol Yoon Department of Agricultural and Biosystems Engineering Department of Biomedical Engineering BIO5 Institute University of Arizona Tucson, Arizona USA ISBN ISBN (ebook) DOI / Springer New York Heidelberg Dordrecht London Library of Congress Control Number: # Springer Science+Business Media New York 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher s location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (
5 Preface The title of this textbook, Biosensors: From Electric Circuits to Immunosensors, implies that we are going to learn both electric circuitry (in relation to conventional sensors such as temperature sensors) and biosensors (such as antibody-based immunosensors). The idea of putting these two topics together into a single book came from my decision to add biosensor topics to the Sensors and Controls class taught at the University of Arizona. At that time, I realized there was no available textbook that equally addressed these two topics. In typical sensor textbooks, biosensor topics are relatively sparse. In biosensor textbooks, fundamental electric circuitry is rarely addressed. More importantly, none of those textbooks address the necessary link between these two topics. After all, most biosensors require electric circuit components. This textbook is designed not only for college undergraduate students but also for the scientists and engineers working in the sensor or biosensor industries as a hands-on guide. Although this book may seem to be a collection of laboratory procedures (and certainly can be used for a college-level laboratory class), its primary aim is to deliver hands-on guidance and visual demonstrations of biosensor applications. Readers can complete virtual experiments by reading the lab procedures and viewing the photographs taken during the lab exercises. They can also carry out their own experiments by purchasing the necessary equipment and supplies. This book takes a step-by-step approach towards the end result of building an antibody-based immunosensor from scratch. Many people have provided invaluable help in creating this textbook. First of all, I wish to express my deepest appreciation to my wife, Dr. Sunhi Choi (also at University of Arizona), for her support and advice throughout the writing of this textbook. I also wish to thank my former graduate student Dr. Lonnie J. Lucas (at Applied Energetics) for all the time he spent with me in shaping the entire book, in providing numerous ideas and suggestions, and in proofreading the entire draft. This collaboration with Lonnie was one of the most pleasant collaborations in my entire life. Specifically, Chap. 9 was written jointly with Lonnie. I also thank the students enrolled in my Sensors and Controls class in Fall 2009, Fall 2010, and Fall 2011 at the University of Arizona, who have provided corrections and constructive v
6 vi Preface suggestions on the draft lab procedures. The help of my teaching assistants for this class, Zachary S. Dean, C. Christopher Stemple, and Scott V. Angus, is greatly appreciated as well. Specifically, Zach collected many photographs of lab exercises and proofread many parts of the manuscript. Other students and postdocs in my lab have also provided numerous corrections and suggestions. My former and current department heads, Dr. Donald C. Slack and Dr. Mark R. Riley, have also provided support and suggestions for my class. I also thank the late Dr. Kenneth Jordan (University of Arizona), who taught the Sensors and Controls class for many years before me and laid the foundations for the lab procedures described in Chaps. 2 to 6. Finally, support and suggestions from the editorial office at Springer, Alison Waldron and Steven M. Elliot, are greatly appreciated. None of this would have been possible without the contributions of all of my students, coworkers, and collaborators.
7 About the Author Jeong-Yeol Yoon received his B.S., M.S., and Ph.D. degrees in Chemical Engineering from Yonsei University, Seoul (South Korea) in 1992, 1994, and 1999, respectively, under the guidance of Dr. Woo-Sik Kim, in collaboration with Dr. Jung-Hyun Kim, where he worked primarily on polymer colloids. He received his second Ph.D. degree in Biomedical Engineering from the University of California, Los Angeles in 2004, working on lab-on-a-chip and biomaterials, under the guidance of Dr. Robin L. Garrell. He joined the Agricultural & Biosystems Engineering (ABE) faculty in August 2004 and holds joint appointment in the Department of Biomedical Engineering at the University of Arizona. He is also a faculty member in the Biomedical Engineering Graduate Interdisciplinary Program (BME GIDP), Microbiology Graduate Program, and BIO5 Institute at the University of Arizona. Dr. Yoon is currently an Associate Professor and is directing the Biosensors Lab ( He is a member of the Institute of Biological Engineering (IBE), American Society of Agricultural and Biological Engineers (ASABE) and SPIE The International Society for Optics and Photonics. He currently serves as Associate Editor and Editorial Board Members for numerous journals, including Transactions of the ASABE, Biological Engineering Transactions, Journal of Biological Engineering, and Resource Magazine. Dr. Yoon has published ~50 articles in peer-reviewed journals. vii
8
9 Contents 1 Introduction Sensors Transducers Biosensors Bioreceptors Transducers for Biosensors Overview of this Textbook Bibliography Resistors Electric Circuit Current and Voltage Resistance and Ohm s Law Resistors in Series, or Voltage Divider Potentiometer, or Pot Resistors in Parallel, or Current Divider Laboratory: Resistors Reading Resistor Values Breadboards Connecting to a Power Supply Resistance Measurements Task 1: Resistors in series Task 2: Resistors in parallel Task 3: Droop Potentiometer (Pot) Further Study: Thévenin s theorem Bibliography Diodes and Transistors Semiconductors Diodes ix
10 x Contents 3.3 Zener Diode Transistors Laboratory: Diodes and Transistors Operational Amplifier Task 1: LED Task 2: Zener Diode Task 3: Transistor Bibliography Temperature Sensors Thermocouple Thermistor Diode Temperature Sensor Transistor Temperature Sensor Laboratory: Temperature Sensors Task 1: Thermistor Task 2: Zener Diode Temperature Sensor Task 3: Transistor Temperature Sensor Bibliography Wheatstone Bridge Wheatstone Bridge Strain Gauge Cantilever Biosensor Laboratory: Wheatstone Bridge Task 1: Wheatstone Bridge Task 2: Wheatstone Bridge for a Thermistor Task 3: Wheatstone Bridge for a Strain Gauge Bibliography Op-amp Op-amp Basics of Op-amp Voltage Follower or Buffer Op-amp Non-inverting Op-amp Inverting Op-amp Summing Op-amp Differential Op-amp Laboratory: Op-amp Task 1: Non-inverting Op-amp Operation Task 2: Signal Conditioning for Temperature Sensor Bibliography
11 Contents xi 7 Light Sensors Light Photoresistor Photodiode Phototransistor Light Emitting Diode Laser Diode Laboratory: Photodiode Task 1: Photoconductive Operation Task 2: Photovoltaic Operation Bibliography Spectrophotometry and Optical Biosensor Spectrophotometry Miniature Spectrophotometer Optical Glucose Sensor Laboratory: Glucose Sensor Task 1: Glucose Assay Kit with a Spectrophotometer Task 2: Glucose Assay Kit with LED/PD Circuit Further Study: Pulse Oximeter Bibliography Fluorescence and Optical Fiber Fluorescence Fluorescent Dyes Optical Fibers Laboratory: Optical Fiber Spectrometer Reflection Probe SpectraSuite Software Task 1: Fluorescent Lamp Measurement Task 2: Fluorescent Excitation and Emission Measurement Bibliography Electrochemical Sensors Electrolytic and Electrochemical Cells Ion-Selective Electrodes (Potentiometric) ph Electrode (Potentiometric) Electrochemical Glucose Sensor (Amperometric) Conductometric Biosensors Laboratory: ph Meter and Glucose Meter Buffer Task 1: Buffer Preparations and Their ph Measurements
12 xii Contents Task 2: ph Meter Circuit Task 3: Commercial Electrochemical Glucose Sensor Bibliography Piezoelectric Sensors Piezoelectricity Pressure Sensors Crystal Oscillators Quartz Crystal Microbalance Viscoelasticity Consideration in QCM Flow-Cell QCM as Biosensor Laboratory: Quartz Crystal Microbalance Task 1: Quantifying BSA Adsorption on QCM Sensor Bibliography Immunosensors Enzyme-Linked Immunosorbent Assay Antibodies Antibody Fragments and Aptamers Lateral-Flow Assay Optical Immunosensors Surface Plasmon Resonance Immunosensor Electrochemical Immunosensors Impedance Immunosensors: Interdigitated Microelectrode Immunosensor Piezoelectric Immunosensors: QCM Immunosensor Immunosensing Kits Versus Handheld Immunosensors Laboratory: ELISA kit Task 1: Insulin ELISA Kit Task 2: Insulin ELISA Kit with Optical Fiber Spectrometer Task 3: Insulin ELISA Kit with Cell Phone Camera Further Study: DNA Sensors Bibliography Lab-on-a-Chip Biosensors What Is Lab-on-a-Chip How to Make an LOC: Photolithography and Soft Lithography Early LOC: Capillary Electrophoresis LOC for Point-of-Care Testing Use of Optical Fibers in LOC Sample/Reagent Introduction
13 Contents xiii 13.7 Mixing in LOC LOC with Cell Phone Camera Other Applications of LOC Laboratory: Lab-on-a-Chip Task 1: LOC Fabrication Task 2: Mixing Experiment Further Study: Latex Immunoagglutination AssayinLOC Further Study: Polymerase Chain Reaction in LOC Bibliography Index
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