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1 MEASUREMENT SYSTEMS&Kevin Hugo1

1.1 Studying Biomedical Engineering2

1.1.1 Scales of Biological Organization2

1.1.2 Fields of Biomedical Engineering3

1.1.3 Fields of Biological Science5

1.1.4 Workplace Environments for Biomedical Engineers6

1.2 The Need for Bioinstrumentation6

1.2.1 The Scientific Method6

1.2.2 Clinical diagnoses7

1.2.3 Feedback in Measurement Systems7

1.3 Instrumentation8

1.3.1 Measurands8

1.3.2 Sensors9

1.3.3 System Characteristics11

1.3.4 Outputs14

1.3.5 Panels and Series15

1.4 Errors in Measurements15

1.4.1 Sources of Error15

1.4.2 Accuracy and Precision16

1.4.3 Calibration17

1.5 Statistics18

1.5.1 Distributions18

1.5.2 Statistical Estimations21

1.5.3 Hypothesis Testing22

1.6 Lifelong Learning25

1.7 Problems26

1.8 References27

2 BASIC CONCEPTS OF ELECTRONICS&Hong Cao28

2.1 Electronic Components and Circuit Analysis28

2.1.1 Current28

2.1.2 Voltage and Potential30

2.1.3 Resistors and Ohm’s Law30

2.1.4 Basic Circuit Analysis34

2.1.5 Attenuators38

2.1.6 Common Electrical Instruments40

2.1.7 Capacitors43

2.1.8 Inductors45

2.1.9 First-Order Systems47

2.1.10 Frequency50

2.1.11 Series and Parallel Impedances55

2.1.12 Electrical Safety56

2.2 Amplifiers56

2.2.1 Basic Op Amp57

2.2.2 Ideal Op Amp57

2.2.3 Inverter58

2.2.4 Noninverting Amplifier59

2.2.5 Differential Amplifiers61

2.2.6 Comparators63

2.2.7 Frequency Response64

2.3 Filters65

2.3.1 Input—Output Relationship of Filters66

2.3.2 Low-pass Filter67

2.3.3 High-Pass Filter68

2.3.4 Other Filters69

2.3.5 Timers70

2.4 Analog-to-Digital （ADC） and Digital-to-Analog （DAC） Conversion71

2.4.1 Number Systems72

2.4.2 Digital-to-Analog Converters （DAC）74

2.4.3 Analog-to-Digital Converters （ADC）76

2.5 Digital Signal Processing79

2.5.1 Digital Signals79

2.5.2 Sampling Theorem80

2.6 Microcomputers81

2.6.1 Structure of a Microcomputer81

2.6.2 Microprocessor-Based Systems83

2.7 Software and Programming Languages84

2.7.1 Operating System85

2.7.2 Programming Languages86

2.7.3 Algorithms87

2.7.4 Database systems87

2.8 Display Devices88

2.9 Recording Devices89

2.10 Problems90

2.11 References91

3 ANALYSIS OF MOLECULES IN CLINICAL MEDICINE&Mat Klein91

3.1 Spectrophotometry91

3.1.1 Components91

3.1.2 Theory91

3.1.3 Calibration95

3.1.4 Clinical Laboratory Tests95

3.1.5 Microdialysis95

3.2 Oxygen Saturation96

3.3 Bilirubin97

3.4 Lactate98

3.5 Creatinine98

3.6 Urea99

3.7 Glucose100

3.7.1 Glucose Oxidase Method101

3.7.2 Hexokinase method102

3.8 Amperometric Biosensors for Oxygen and Glucose102

3.8.1 Oxygen （PO2）102

3.8.2 Glucose104

3.9 Ion-selective Electrodes for pH and CO2106

3.10 Flame Photometry108

3.10.1 Lithium109

3.10.2 Sodium and Potassium109

3.11 Mass Spectrometry109

3.11.1 Sample Inlet110

3.11.2 Ion Source110

3.11.3 Mass Analyzer112

3.11.4 Detector113

3.12 Carbon Dioxide Concentration Measurement by Infrared Transmission Spectroscopy113

3.13 Nitrogen by Emission Spectrometry114

3.14 Drugs by Fluorometry and Chromatography115

3.14.1 Fluorometry115

3.14.2 Chromatography117

3.14.3 Gas Chromatography118

3.14.4 Liquid Chromatography121

3.14.5 Ion Exchange Chromatography121

3.15 Electrophoresis122

3.15.1 Components of an Electrophoretic System122

3.15.2 Electrophoretic Mobility124

3.16 DNA Sequencing125

3.17 Problems127

3.18 References128

4 SURFACE CHARACTERIZATION IN BIOMATERIALS AND TISSUE ENGINEERING&Jorge E.Monzon129

4.1 Molecules and Biomaterials129

4.1.1 Integrated Approach130

4.1.2 Types of Biomaterials130

4.1.3 Polymers131

4.2 Molecules and Tissue Engineering134

4.2.1 Tissue Engineering134

4.2.2 Cellular Composites134

4.3 Surface Analysis135

4.3.1 Topography136

4.3.2 Chemical Composition147

4.3.3 Polymer—water Interface158

4.4 Protein Adsorption159

4.4.1 Protein Molecule160

4.4.2 Protein Adsorption Fundamentals161

4.4.3 Protein Adsorption Measurements161

4.5 Molecular Size163

4.6 Problems166

4.7 References167

5 HEMATOLOGY&Susanne Clark Cazzanti170

5.1 Blood Components and Processing170

5.1.1 Components of Blood171

5.1.2 Basic Techniques171

5.1.3 Blood Collection171

5.1.4 Centrifugal Method173

5.2 Red Blood Cells174

5.2.1 Factors Affecting Red Blood Cell Count175

5.2.2 Hematocrit175

5.2.3 Hemoglobin175

5.2.4 Red Blood Cell Indices175

5.2.5 Red Blood Cell Count176

5.2.6 Hemoglobin182

5.2.7 Reticulocyte Count183

5.2.8 Sickle Cell Test184

5.3 White Blood Cells184

5.3.1 Differential White Blood Cell Counts184

5.4 Platelets186

5.4.1 Phase Hemocytometer186

5.5 Complete Blood Count188

5.6 Problems188

5.7 References189

6 CELLULAR MEASUREMENTS IN BIOMATERIALS AND TISSUE ENGINEERING&Jeffrey S.Schowalter190

6.1 Cell Measurement Overview190

6.1.1 What Is a Cell？190

6.1.2 Fixed Versus Live Cells192

6.2 Light Microscopy194

6.2.1 Resolution Versus Magnifiication195

6.2.2 Light Microscope Modes197

6.2.3 Electronic Microscopy202

6.2.4 Cellular Markers203

6.2.5 Confocal Laser Scanning Microscopy207

6.2.6 Two-Photon Excitation Microscopy208

6.2.7 Image Processing209

6.3 Cell Orientation210

6.3.1 Orientation Chamber211

6.3.2 Video enhanced contrast microscopy211

6.4 Cell-rolling Velocity211

6.5 Cell Pore Size Determination213

6.5.1 TEM214

6.5.2 SEM214

6.6 Cell Deformation215

6.6.1 Micropipet Technique215

6.6.2 Optical Trapping215

6.7 Cell Shear Stress216

6.7.1 Cone and Plate216

6.7.2 Fluorescent Ratiometric Imaging217

6.8 Cell Adhesion218

6.8.1 Laser Trap218

6.8.2 Interferometry218

6.8.3 SEM218

6.9 Cell Migration219

6.9.1 4-D Image Processing System219

6.10 Cell Uptake219

6.10.1 Nanovid Microscopy219

6.10.2 Electroporation220

6.11 Cell Protein Secretion220

6.11.1 Atomic Force Microscopy220

6.11.2 Fluorescence Lifetime Imaging220

6.11.3 Fluorescence Recovery after Photobleaching221

6.12 Cell Proliferation222

6.12.1 Radiation Monitoring223

6.12.2 Fluorescence Microscopy223

6.13 Cell Differentiation223

6.13.1 Fluorescence Ratio Imaging224

6.13.2 Cell Sorter224

6.14 Cell Signaling and Regulation225

6.14.1 Fluorescence In-Situ Hybridization （FISH）225

6.14.2 Radioactive Labeling226

6.15 Problems227

6.16 References228

7 NERVOUS SYSTEM&Jang-Zern Tsai228

7.1 Cell Potential229

7.1.1 Resting Potential229

7.1.2 Action Potential229

7.2 Brain，EEG，and Evoked Potentials230

7.2.1 Anatomy and Function of the Brain230

7.2.2 Electroencephalography （EEG）231

7.2.3 Evoked Potentials233

7.3 Brain Imaging：X ray237

7.4 Brain Imaging：CT238

7.5 Brain Imaging：MRI238

7.6 Brain Imaging：Nuclear Imaging239

7.7 Brain Imaging：Single-Photon Emission Computed Tomography （SPECT）241

7.8 Brain Imaging：Positron Emission Tomography （PET）241

7.9 Brain Imaging：Biomagnetism242

7.10 Eye，ERG，EOG，and Visual Field244

7.10.1 Electroretinogram （ERG）244

7.10.2 Electro-Oculogram （EOG）245

7.10.3 Visual Field246

7.10.4 Eye Pressure247

7.10.5 Ophthalmoscopy248

7.11 Ears and Audiometry250

7.11.1 The Ears250

7.11.2 Audiometry251

7.11.3 Otoscopy252

7.12 Muscles252

7.12.1 Muscle Contraction，Length and Force252

7.12.2 Electromyography （EMG）256

7.12.3 Neuromuscular Performance257

7.13 Problems258

7.14 References259

8 HEART AND CIRCULATION&Supan Tungjitkusolmun262

8.1 Cardiac Anatomy and Physiology262

8.1.1 Heart Valves263

8.1.2 Cardiac Cycle265

8.1.3 Cardiac Excitation and Control266

8.2 Cardiac Biopotentials267

8.2.1 Electrodes267

8.2.2 Electrocardiogram267

8.2.3 Electrograms273

8.3 Cardiac Pressures274

8.3.1 Strain Gage274

8.3.2 Catheter275

8.4 Cardiac Output276

8.4.1 Fick Method277

8.4.2 Thermodilution278

8.4.3 Dye Dilution279

8.4.4 Radionuclide Angiography280

8.4.5 Echocardiography280

8.4.6 Magnetic Resonance Imaging （MRI）283

8.5 Cardiac Sounds283

8.5.1 Stethoscopes284

8.5.2 Microphones284

8.6 Myocardial Viability286

8.6.1 Positron Emission Tomography （PET）286

8.6.2 Thallium-201 Imaging288

8.6.3 Myocardial Contrast Echocardiography288

8.7 Circulation288

8.8 Blood Flow289

8.8.1 Dilution290

8.8.2 Electromagnetic Flowmeter290

8.8.3 Ultrasonic Flowmeter292

8.8.4 Laser-Doppler Flowmeter292

8.9 Blood Pressure294

8.9.1 Indirect Measurement295

8.9.2 Direct Measurement297

8.9.3 Arterial tonometry297

8.10 Vessel Distension297

8.10.1 Intravascular Ultrasound298

8.10.2 Angiography298

8.11 Vessel Volume Flow298

8.11.1 Flow Visualization299

8.11.2 Ultrasonic Sonography299

8.11.3 Video Microscopy300

8.12 Problems300

8.13 References301

9 LUNG，KIDNEY，BONE，AND SKIN&Shilpa Sawale303

9.1 Lung304

9.2 Pulmonary Volume304

9.2.1 Measurement of Pulmonary Volume306

9.3 Pulmonary Flow310

9.3.1 Measurement of Pulmonary Flow311

9.4 Pulmonary Diffusion312

9.5 Pulmonary Airway Resistance313

9.6 Kidney313

9.7 Kidney Clearance314

9.7.1 Creatinine314

9.8 Kidney Imaging315

9.8.1 Pyelogram315

9.9 Hemodialysis315

9.10 Peritoneal Dialysis318

9.11 Kidney Function321

9.11.1 Extracellular Water by Impedance321

9.12 Bones and Joints322

9.12.1 Bone Mineral Density322

9.12.2 Stress and Strain323

9.12.3 Strain Gage326

9.12.4 LVDT327

9.12.5 Soft Tissue Strain328

9.12.6 Joint Friction329

9.12.7 Bone Position330

9.12.8 Bone Strain-Related Potentials330

9.13 Skin331

9.13.1 Water Loss331

9.13.2 Color334

9.14 Problems336

9.15 References337

10 BODY TEMPERATURE，HEAT，FAT，AND MOVEMENT&Chao-Min Wu339

10.1 Regulation of Body Temperature340

10.2 Clinical Temperature Measurement342

10.2.1 Surface Temperature Measurement342

10.2.2 Core Temperature Measurement343

10.3 Measurement of Body Heat：Calorimetry348

10.3.1 Direct Calorimetry348

10.3.2 Indirect Calorimetry352

10.4 Measurement of Body Fat361

10.4.1 Direct Measurement of Body Fat362

10.4.2 Indirect Measurement of Body Fat366

10.5 Measurement of Body Movement370

10.5.1 Goniometers and Accelerometers371

10.5.2 Video and Optoelectronic Systems372

10.6 Problems374

10.7 References375

INDEX376