Life Science Automation Fundamentals and Applications -- Contents v -- Preface xv -- Part I Life Science Basis for Automation 1 -- Chapter 1 Introduction to Nucleic Acids and ClinicalLaboratory Testing 3 -- 1.1 Basics of Nucleic Acid Structure 4 -- 1.1.1 General Principles 4 -- 1.1.2 In Vitro Aspects of DNA 5 -- 1.1.3 Unidirectional Flow of Genetic Information: The Central Dogma 9 -- 1.2 Manipulation of DNA Under Testing Conditions 10 -- 1.2.1 Extraction 10 -- 1.2.2 Amplification 10 -- 1.2.3 Detection 13 -- 1.3 Statistics and Test Utilization Used in Medical Decision Making 16 -- 1.3.1 Sensitivity and Specificity 17 -- 1.3.2 Predictive Values 18 -- 1.3.3 Preanalytical Versus Analytical Stages of Testing 19 -- 1.4 Summary 20 -- Reference 21 -- Chapter 2 Basic Analytical Chemistry for Engineers 23 -- 2.1 Introduction 23 -- 2.2 Chromatographic Separation Methods 24 -- 2.2.1 General Principles 24 -- 2.2.2 Gas Chromatographic Methods 25 -- 2.2.3 Liquid Chromatographic Methods 26 -- 2.2.4 Electrophoresis 27 -- 2.3 Bioanalytical Detection Methods 30 -- 2.3.1 Protein Anal 30 -- 2.3.2 DNA and RNA Analysis 36 -- 2.3.3 Enzymatic Analysis 40 -- 2.3.4 Immunological Methods 49 -- 2.4 Physical Detection Methods 52 -- 2.4.1 Atomic Spectroscopy 53 -- 2.4.2 Optical Molecule Spectroscopy 54 -- 2.4.3 Nuclear Magnetic Resonance Spectroscopy 58 -- 2.4.4 Mass Spectrometry 59 -- 2.5 Future Challenges 63 -- References 63 -- Chapter 3 Basic Health Care Delivery for Engineers 67 -- 3.1 Introduction 67 -- 3.2 The Health Care System: A Holistic Perspective 68 -- 3.2.1 The Department of Veterans Affairs 70 -- 3.2.2 The Military Health Services System 70 -- 3.2.3 Indian Health Service 71 -- 3.2.4 Public Health Service 72 -- 3.3 Health Care Subsystems 72 -- 3.4 Evidence-Based Decision Making in Health Care Delivery 74 -- 3.4.1 The Structure of Clinical Decision Making 75.

3.4.2 Automation Applied to Types of Clinical Decision Making 76 -- 3.4.3 Automation Applied to the Clinical Decision Process 78 -- 3.5 Care Providers 80 -- 3.5.1 Health Professionals 80 -- 3.5.2 Organizational Providers 81 -- 3.5.3 Automated Devices: Control and Oversight 83 -- 3.5.4 Value Migration in the Health System 84 -- 3.6 The Mandate for Improved Clinical Outcomes 86 -- 3.7 The Support Function of the Health System 88 -- 3.7.1 Financing the Health Care System 88 -- 3.7.2 Development and Diffusion of Medical Technology 92 -- 3.8 Conclusions 95 -- References 95 -- Part II Engineering Basis for Life Science Automation -- Chapter 4 Principles of Human-Machine Interfacesand Interactions 101 -- 4.1 Introduction 101 -- 4.2 Fundamentals of Human-Machine Interaction 102 -- 4.2.1 Robotics and Machines for Life Science Automation 103 -- 4.2.2 Design of Automation Systems 103 -- 4.2.3 Performance of Human-Machine Systems 106 -- 4.2.4 Human-Machine Teaming 108 -- 4.2.5 Communication 109 -- 4.3 Current Research 110 -- 4.3.1 HMI Interaction Via Haptic Devices 110 -- 4.3.2 Teamwork 112 -- 4.3.3 Robots for Performance 113 -- 4.4 Future Issues 115 -- 4.4.1 Challenges for Applications in Life Science Automation 116 -- 4.4.2 Challenges for Micro- and Nanoscale Applications 116 -- References 120 -- Chapter 5 Fundamentals of Microscopy andMachine Vision 127 -- 5.1 Introduction 127 -- 5.2 Fundamentals of Light Microscopy 129 -- 5.2.1 Basic Structure of Optical Microscopes 129 -- 5.2.2 Contrast Generation in Microscopy 131 -- 5.2.3 Resolution Configuration and Related Performance Metrics 134 -- 5.2.4 Three-Dimensional Microscopy 136 -- 5.2.5 Several Practical Issues in Microscopy 137 -- 5.2.6 Discussion 138 -- 5.3 Fundamentals of Machine Vision 139 -- 5.3.1 Autofocusing 139 -- 5.3.2 Image Alignment 140 -- 5.3.3 Feature Tracking 143.

5.3.4 Image Segmentation and Deformable Region Tracking 146 -- 5.4 A Representative Application 147 -- 5.5 Future Development and Challenges 148 -- Acknowledgments 148 -- References 149 -- Chapter 6 Control Mechanisms for Life Science Automation 153 -- 6.1 Introduction 153 -- 6.1.3 Discrete-Time State-Space Description 155 -- 6.1.4 Characteristics of Continuous Linear Time-Invariant System 156 -- 6.2 Control Mechanisms 158 -- 6.2.1 PID Control 158 -- 6.2.2 Optimal Control 160 -- 6.2.3 Model Predictive Control 165 -- 6.2.4 Adaptive Control 166 -- 6.2.5 Fuzzy-Logic Control 168 -- 6.2.6 Hybrid Control 170 -- 6.3 Applications to Life Science Automation 171 -- 6.3.1 Blood Pressure Control 172 -- 6.3.2 Control Mechanism Design 173 -- 6.3.3 Modeling and Control of an Insulin Delivery System 176 -- 6.3.4 Discussion 194 -- 6.4 Conclusions and Future Challenges 194 -- References 195 -- Robotics for Life Science Automation 197 -- 7.1 Introduction 197 -- 7.2 Cell Manipulation Techniques 197 -- 7.2.1 Optical and Electric Micromanipulation 198 -- 7.2.2 Magnetic Micromanipulation 199 -- 7.2.3 Micromanipulation Using Acoustic Energy 199 -- 7.2.4 MEMS and Mechanical Micromanipulation 200 -- 7.3 Robotics in the Life Science Industry 202 -- 7.3.1 Cell Injection 202 -- 7.3.3 High Throughput Processing of Biological Samples 209 -- 7.3.4 Production of DNA and Protein Microarrays 211 -- 7.4 Discussions 213 -- References 214 -- Part III Device Design, Simulation, andFabrication for Automation -- Chapter 8 Sensors and Actuators for Life Science Automation 221 -- 8.1 Introduction 221 -- 8.2 Sensors 222 -- 8.2.1 Pressure and Volume Sensors for Medical Applications 222 -- 8.2.2 Electrochemical Sensors: pH, CO2, and Dissolved Oxygen 226 -- 8.2.3 Impedimetric Sensors 229 -- 8.2.4 DNA/Antigen-Antibody Sensors (Cantilever Sensors) 234 -- 8.2.5 Electromagnetic Sensors 236.

8.3 Actuators 238 -- 8.3.1 Micronozzles for Reagent Printing 239 -- 8.3.2 Thermal Microactuators 242 -- 8.3.3 Electroactive Polymer Actuators 245 -- 8.4 Future Trends 250 -- Acknowledgments 251 -- References 251 -- Chapter 9 Dynamics Modeling and Analysis of aSwimming Microrobot for Drug Delivery 257 -- 9.1 Introduction 257 -- 9.1.1 Routes of Administration for Drug Delivery 258 -- 9.1.2 Controlled Drug Delivery 259 -- 9.1.3 Swimming Microrobots 260 -- 9.1.4 Propulsion Under Low Re Number Environment 262 -- 9.1.5 Features of the Proposed Swimming Microrobot 262 -- 9.1.6 Implementation Issues 263 -- 9.2 Nomenclature 264 -- 9.3 Dynamics Modeling and Analysis 264 -- 9.3.1 The Governing Equations 264 -- 9.3.2 Tail Bifurcation 265 -- 9.3.3 Before the Bifurcation 265 -- 9.3.4 After the Bifurcation 268 -- 9.4 Performance Analysis 270 -- 9.5 Discussions and Conclusions 274 -- References 275 -- Chapter 10 DNA and Protein Microarray Fabrication Automation 279 -- 10.1 Introduction 279 -- 10.2 Microarray Printing Technologies 282 -- 10.2.1 Contact Printing 282 -- 10.2.2 Self-Sensing Pins 284 -- 10.2.3 Semicontact Printing 288 -- 10.2.4 Inkjet Technology for Fluid Dispensing 289 -- 10.2.5 Bead-Based Microarray 291 -- 10.3 Microarray Fabrication Automation 293 -- 10.4 Examples of Automated Microarray Systems 296 -- 10.4.1 Genomic Solutions OmniGrid 100 296 -- 10.4.2 POSaM Inkjet Microarrayer 296 -- 10.4.3 ACAPELLA Automated Fluid Handling System 297 -- 10.4.4 Agilent's Biological Fluid Dispensing System 297 -- 10.5 Future Trends of Microarray Fabrication 299 -- 10.6 Conclusions 300 -- Acknowledgments 300 -- References 300 -- Appendix 10.A List of Commercial Microarray Technology Companies 302 -- Part IV System Integration -- Chapter 11 Automation of Nucleic Acid Extractionand Real-Time PCR: A New Era forMolecular Diagnostics 305 -- 11.1 Introduction 305.

11.2 Nucleic Acids Extraction Automation 306 -- 11.2.1 Generic Robotic Platforms Which Can Perform Automatic NA Extraction 307 -- 11.2.2 Dedicated Robotic Platforms for Automated NA Extraction 309 -- 11.3 Real-Time PCR Automation 312 -- 11.4 Molecular Diagnostic Labeled Automated Platforms 315 -- 11.5 Conclusions 318 -- Chapter 12 Bio-Instrumentation Automation 319 -- 12.1 Introduction 319 -- 12.1.1 Current Trends in Drug Development 319 -- 12.1.2 High-Throughput Screening Market and Trends 320 -- 12.1.3 High-Content Screening Market and Trends 320 -- 12.1.4 Comparison Between HCS and HTS 321 -- 12.2 Detection Systems for High-Throughput Screening 322 -- 12.2.1 Typical HTS Assays 322 -- 12.2.2 Detection Systems for High-Throughput Screening 323 -- 12.3 Detection Systems for High-Content Screening Measurements 325 -- 12.3.1 Principles of High-Content Screening 325 -- 12.3.2 Typical HCS Assays 327 -- 12.3.3 Detection Systems for High-Content Screening 328 -- 12.4 Automation Systems for Mass Spectrometric Measurement 328 -- 12.4.1 Introduction 328 -- 12.4.2 Preferred Ionization Techniques 328 -- 12.4.3 Throughput Levels 329 -- 12.4.4 Mass Spectrometry Instrumentation 330 -- 12.4.5 Automation of Mass Spectrometry for Bioanalytics 330 -- 12.5 Current Developments in Parallel Chromatography 332 -- 12.5.1 Parallel Chromatography 332 -- 12.5.2 Parallel Capillary Electrophoresis 333 -- 12.6 Other Methods 335 -- 12.6.1 Lab-on-a-Chip Systems 335 -- 12.6.2 Patch Clamp Technologies 338 -- 12.7 Automation Systems 339 -- 12.7.1 Dispensing Systems 341 -- 12.7.2 Transportation Systems 342 -- 12.7.3 Liquid Handling Workstations 342 -- 12.8 Future Challenges 342 -- 12.8.1 Challenges Facing HCS 342 -- 12.8.2 Nanodosing 343 -- 12.8.3 Automation and Miniaturization 343 -- References 344.

Chapter 13 In Situ Imaging and Manipulation inNano Biosystems Using the Atomic Force Microscope 349.