[内容简介]

Enables readers to apply process dynamics and control theory to solve bioprocess and drug delivery problems

The control of biological and drug delivery systems is critical to the health of millions of people worldwide. As a result, researchers in systems biology and drug delivery rely on process dynamics and control theory to build our knowledge of cell behavior and to develop more effective therapeutics, controlled release devices, and drug administration protocols to manage disease.

Written by a leading expert and educator in the field, this text helps readers develop a deep understanding of process dynamics and control theory in order to analyze and solve a broad range of problems in bioprocess and drug delivery systems. For example, readers will learn how stability criteria can be used to gain new insights into the regulation of biological pathways and lung mechanics. They'll also learn how the concept of a time constant is used to capture the dynamics of diffusive processes. Readers will also master such topics as external disturbances, transfer functions, and input/output models with the support of the author's clear explanations, as well as:

• Detailed examples from the biological sciences and novel drug delivery technologies
• 160 end-of-chapter problems with step-by-step solutions
• Demonstrations of how computational software such as MATLAB and Mathematica solve complex drug delivery problems

Control of Biological and Drug-Delivery Systems for Chemical, Biomedical, and Pharmaceutical Engineering is written primarily for undergraduate chemical and biomedical engineering students; however, it is also recommended for students and researchers in pharmaceutical engineering, process control, and systems biology. All readers will gain a new perspective on process dynamics and control theory that will enable them to develop new and better technologies and therapeutics to treat human disease.

[目录]

PREFACE xi

ACKNOWLEDGMENTS xv

1 INTRODUCTION 1

1.1 The Role of Process Dynamics and Control in Branches of Biology 1

1.2 The Role of Process Dynamics and Control in Drug-Delivery Systems 10

1.3 Instrumentation 12

1.4 Summary 18

Problems 18

References 19

2 MATHEMATICAL MODELS 21

2.1 Background 22

2.2 Dynamics of Bioreactors 27

2.3 One- and Two-Compartment Models 34

2.4 Enzyme Kinetics 37

2.5 Summary 39

Problems 39

References 41

3 LINEARIZATION AND DEVIATION VARIABLES 43

3.1 Computer Simulations 43

3.2 Linearization of Systems 44

3.3 Glycolytic Oscillation 55

3.4 Hodgkin–Huxley Model 57

3.5 Summary 60

Problems 61

References 63

4 STABILITY CONSIDERATIONS 65

4.1 Definition of Stability 65

4.2 Steady-State Conditions and Equilibrium Points 79

4.3 Phase-Plane Diagrams 80

4.4 Population Kinetics 80

4.5 Dynamics of Bioreactors 83

4.6 Glycolytic Oscillation 85

4.7 Hodgkin–Huxley Model 87

4.8 Summary 88

Problems 88

References 91

5 LAPLACE TRANSFORMS 93

5.1 Definition of Laplace Transforms 93

5.2 Properties of Laplace Transforms 95

5.3 Laplace Transforms of Functions, Derivatives, and Integrals 96

5.4 Laplace Transforms of Linear Ordinary Differential Equation (ODE) and Partial Differential Equation (PDE) 104

5.5 Continuous Fermentation 108

5.6 Two-Compartment Models 110

5.7 Gene Regulation 111

5.8 Summary 113

Problems 113

Reference 115

6 INVERSE LAPLACE TRANSFORMS 117

6.1 Heaviside Expansions 117

6.2 Residue Theorem 126

6.3 Continuous Fermentation 134

6.4 Degradation of Plasmid DNA 136

6.5 Constant-Rate Intravenous Infusion 138

6.6 Transdermal Drug-Delivery Systems 139

6.7 Summary 146

Problems 146

References 148

7 TRANSFER FUNCTIONS 149

7.1 Input–Output Models 149

7.2 Derivation of Transfer Functions 150

7.3 One- and Two-Compartment Models:

Michaelis–Menten Kinetics 154

7.4 Controlled-Release Systems 157

7.5 Summary 158

Problems 158

8 DYNAMIC BEHAVIORS OF TYPICAL PLANTS 163

8.1 First-, Second- and Higher-Order Systems 163

8.2 Reduced-Order Models 167

8.3 Transcendental Transfer Functions 169

8.4 Time Responses of Systems with Rational Transfer Functions 171

8.5 Time Responses of Systems with Transcendental Transfer Functions 190

8.6 Bone Regeneration 192

8.7 Nitric Oxide Transport to Pulmonary Arterioles 193

8.8 Transdermal Drug Delivery 194

8.9 Summary 194

Problems 195

References 197

9 CLOSED-LOOP RESPONSES WITH P, PI, AND PID CONTROLLERS 199

9.1 Block Diagram of Closed-Loop Systems 200

9.2 Proportional Control 203

9.3 PI Control 204

9.4 PID Control 206

9.5 Total Sugar Concentration in a Glutamic Acid Production 207

9.6 Temperature Control of Fermentations 209

9.7 DO Concentration 213

9.8 Summary 214

Problems 215

References 217

10 FREQUENCY RESPONSE ANALYSIS 219

10.1 Frequency Response for Linear Systems 219

10.2 Bode Diagrams 227

10.3 Nyquist Plots 229

10.4 Transdermal Drug Delivery 232

10.5 Compartmental Models 236

10.6 Summary 239

Problems 239

References 240

11 STABILITY ANALYSIS OF FEEDBACK SYSTEMS 243

11.1 Routh–Hurwitz Stability Criterion 243

11.2 Root Locus Analysis 248

11.3 Bode Stability Criterion 249

11.4 Nyquist Stability Criterion 254

11.5 Cheyne–Stokes Respiration 257

11.6 Regulation of Biological Pathways 262

11.7 Pupillary Light Reflex 264

11.8 Summary 265

Problems 265

References 267

12 DESIGN OF FEEDBACK CONTROLLERS 269

12.1 Tuning Methods for Feedback Controllers 269

12.2 Regulation of Glycemia 279

12.3 Dissolved Oxygen Concentration 282

12.4 Control of Biomass in a Chemostat 284

12.5 Controlled Infusion of Vasoactive Drugs 285

12.6 Bone Regeneration 286

12.7 Fed-Batch Biochemical Processes 288

12.8 Summary 289

Problems 289

References 291

13 FEEDBACK CONTROL OF DEAD-TIME SYSTEMS 293

13.1 Smith Predictor-Based Methods 294

13.2 Control of Biomass 300

13.3 Zymomonas mobilis Fermentation for Ethanol Production 302

13.4 Fed-Batch Cultivation of Acinetobacter calcoaceticus RAG-1 304

13.5 Regulation of Glycemia 304

13.6 Summary 306

Problems 306

References 309

14 CASCADE AND FEEDFORWARD CONTROL STRATEGIES 311

14.1 Cascade Control 311

14.2 Feedforward Control 317

14.3 Insulin Infusion 321

14.4 A Gaze Control System 323

14.5 Control of pH 326

14.6 Summary 330

Problems 331

References 333

15 EFFECTIVE TIME CONSTANT 335

15.1 Linear Second-Order ODEs 335

15.2 Sturm–Liouville (SL) Eigenvalue Problems 337

15.3 Relaxation Time Constant 340

15.4 Implementation in Mathematica® 342

15.5 Controlled-Release Devices 342

15.6 Summary 343

Problems 344

References 345

16 OPTIMUM CONTROL AND DESIGN 347

16.1 Orthogonal Collocation Techniques 348

16.2 Dynamic Programming 350

16.3 Optimal Control of Drug-Delivery Rates 350

16.4 Optimal Design of Controlled-Release Devices 351

16.5 Implementation in Mathematica® 352

16.6 Summary 358

Problems 359

References 360

INDEX 361