
Life Science Automation Fundamentals and Applications
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- 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
- 13.1 Introduction 349
- 13.1.1 AFM: A Promising Tool for Biological Research 349
- 13.1.2 Functionalization of AFM Probe: Paving a New Avenue 350
- 13.1.3 From Imaging to Manipulation: A Big Leap 350
- 13.2 Reviews of Biomolecular Recognition Using AFM 351
- 13.2.1 Surface Functionalization 351
- 13.2.2 Functionalization of AFM Probe 351
- 13.2.3 Force Interaction Measurement 352
- 13.2.4 Single Receptor Recognition by Force Mapping 353
- 13.2.5 Single Receptor Recognition by Phase Changing 353
- 13.3 Techniques for In Situ Probing Membrane Proteins 354
- 13.3.1 Cell Fixation 354
- 13.4 In Situ Probing Angiotensin II Type 1 Receptor 356
- 13.4.1 Renin-Angiotensin System 356
- 13.4.2 Angiotensin II Type 1 Receptor and Its Antibody 357
- 13.4.3 Living Cell Sample Preparation 359
- 13.4.4 Functionalization of AFM Probe with AT1 Antibody 359
- 13.4.5 Single AT1 Receptor Recognition 361
- 13.5 Single Cell Surgery by AFM 361
- 13.6 Conclusion 364
- References 365
- Chapter 14 Biological Cell and Tissue Manipulation Automation 369
- 14.1 Introduction 369
- 14.2 Biological Cell Manipulation 370
- 14.2.1 Cell Manipulation Using Laser Trapping 370
- 14.2.2 Dielectrophoresis Cell Manipulation 371
- 14.2.3 Magnetic Cell Manipulation 373
- 14.2.4 Microrobotic Cell Manipulation 374
- 14.2.5 Computer Vision Microscopy 376
- 14.2.6 Microrobotic Visual Servo Control 381
- 14.2.7 Microrobots and MEMS/Microfluidic Manipulation Tools 382
- 14.2.8 Manipulation of Cells with Atomic Force Microscopy 384
- 14.3 Tissue Manipulation: Robotic Surgery 384
- 14.4 Future Challenges 387
- References 388
- Chapter 15 A General Robotic Approach forHigh-Throughput Automation in theHandling of Biosamples 395
- 15.1 Introduction 395
- 15.2 The Creation of a Robotic System by Integration 396
- 15.3 Delivery of Microliter Volumes of Biosolutions 398
- 15.3.1 Calibration Approaches 398
- 15.3.2 Experiment Using the Calibration Approach 400
- 15.4 Delivery of Nanovolumes of Viscous Biosamples 401
- 15.4.1 Physical and Theoretical Analysis of the Delivering Process 401
- 15.4.2 Experiment Verification 403
- 15.5 Mathematical Modeling of the Delivery of Viscous Biosamples 404
- 15.5.1 The Modeling Approach 404
- 15.5.2 Verification of the Model 406
- 15.6 Conclusions 408
- References 408
- Chapter 16 Biological Cell Sorting Automation 411
- 16.1 Introduction 411
- 16.2 Conventional Macroscale Cell Separation 413
- 16.3 On-Chip Cell Separation: Principles and Applications 413
- 16.3.1 Miniaturized Fluorescence Activated Cell Sorting ( -FACS) 414
- 16.3.2 Miniaturized Magnetic Activated Cell Sorting ( -MACS) 415
- 16.3.3 Micromachined Thermal Fractional Field Flow ( -TFFF) 417
- 16.3.4 Sedimentation Fractional Field Flow (SdFFF) 417
- 16.3.5 Gravitational Fractional Field Flow (GrFFF) 419
- 16.3.6 Flow Fractional Field Flow (FlFFF) 420
- 16.3.7 Dielectrophoresis Sorting 421
- 16.3.8 Ultrasonic Sorting 425
- 16.4 Design Considerations 427
- 16.5 Future Challenges 428
- Acknowledgments 429
- References 429
- Part V Advanced Life Science Automation
- Chapter 17 Modeling and Control ofElectroporation-Mediated Gene Deliveryfor Gene Therapy 437
- 17.1 Introduction 437
- 17.2 Dynamics Modeling 440
- 17.2.1 Chemical Effect 440
- 17.2.2 Electrical Field Effect 442
- 17.2.3 Mechanical Effect 444
- 17.2.4 Membrane Resealing 446
- 17.2.5 Integrated Chemo-Electro-Mechanical Model 446
- 17.3 Control Strategies 448
- 17.4 Simulation Results 452
- 17.4.1 Simulation Case One 452
- 17.4 2 Simulation Case Two 458
- 17.4.3 Discussion of the Two Case Studies 462
- 17.5 Discussions and Conclusions 465
- References 465
- Chapter 18 Nanotechnology for Advanced Life Science Automation
- 18.1 Introduction 469
- 18.2 Nanoimaging in an Aqueous Environment 471
- 18.3 Nanofabrication 474
- 18.4 Nanorobotic Manipulation 475
- 18.5 NEMS 482
- References 487
- About the Editors 491
- Index 493
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