An important resource that puts the focus on the chemical engineering aspects of biomedical engineering

In the past 50 years remarkable achievements have been advanced in the fields of biomedical and chemical engineering. With contributions from leading chemical engineers, Biomedical Engineering Challenges reviews the recent research and discovery that sits at the interface of engineering and biology. The authors explore the principles and practices that are applied to the ever-expanding array of such new areas as gene-therapy delivery, biosensor design, and the development of improved therapeutic compounds, imaging agents, and drug delivery vehicles.

Filled with illustrative case studies, this important resource examines such important work as methods of growing human cells and tissues outside the body in order to repair or replace damaged tissues. In addition, the text covers a range of topics including the challenges faced with developing artificial lungs, kidneys, and livers; advances in 3D cell culture systems; and chemical reaction methodologies for biomedical imagining analysis. This vital resource:

• Covers interdisciplinary research at the interface between chemical engineering, biology, and chemistry
• Provides a series of valuable case studies describing current themes in biomedical engineering
• Explores chemical engineering principles such as mass transfer, bioreactor technologies as applied to problems such as cell culture, tissue engineering, and biomedical imaging

Written from the point of view of chemical engineers, this authoritative guide offers a broad-ranging but concise overview of research at the interface of chemical engineering and biology.

Vincenzo Piemonte is Associate Professor at University Campus Biomedico of Rome, Faculty of Engineering, Italy. His research activity is primarily focused on the study of Transport phenomena in the artificial and bioartificial organs; new biotreatment technology platform for the elimination of toxic pollutants from water and soil.

Angelo Basile is Senior Researcher at the Institute on Membrane Technology of the Italian National Research Council (ITM-CNR), Rende, Italy. His research activity is primarily focused on membrane applications in several fields.

Taichi Ito is Associate Professor at the University of Tokyo, School of Medicine and Engineering, Japan. His research activity is primarily focused on the study of biomimetic membranes; anti-peritoneal barrier membranes; hemostats; artificial oxygen carriers; scaffolds for tissue engineering and hydrogels for drug delivery of anti-cancer drugs.

Luigi Marrelli is Full professor of Chemical Reactors and of Applied Thermodynamics at University Campus Biomedico of Rome, Faculty of Engineering, Italy. His main research activity deals with thermodynamics of fluid phase equilibria and with kinetics of chemical and biochemical reactions. Some of the results obtained have been applied in the field of artificial and bio-artificial organs.

List of Contributors xi

Preface xiii

1 Introduction 1
Luigi Marrelli

References 6

2 Artificial Kidney: The New Challenge 9
Pasquale Berloco, Simone Novelli, and Renzo Pretagostini

2.1 Introduction 9

2.2 Kidney Transplantation Statistics 11

2.3 Transplantation Costs 12

2.4 Post-Transplant Costs 12

2.5 Renal Replacement Devices 13

2.6 Implantable Artificial Kidney: Prototype Developments 16

2.7 Kidney Tissue Engineering 17

2.8 Next Steps 20

2.9 Conclusion 21

List of Acronyms 22

References 23

3 Current Status and New Challenges of the Artificial Liver 27
Hiroshi Mizumoto, Nana Shirakigawa, and Hiroyuki Ijima

3.1 Introduction 27

3.2 Non-Biological Artificial Liver 28

3.2.1 Classification and Clinical Study 29

3.2.2 PE and HDF 29

3.2.2.1 High-Volume Therapeutic PE 29

3.2.2.2 High-Flow Dialysate Continuous HDF 29

3.2.2.3 PE with Online HDF 30

3.2.3 Blood Purification with Albumin Dialysis 30

3.2.3.1 Single-Pass Albumin Dialysis 30

3.2.3.2 Molecular Adsorbent Recirculating System 31

3.2.3.3 Fractionated Plasma Separation and Adsorption (Prometheus™) 32

3.2.3.4 Hepa Wash 32

3.2.4 Selective Plasma Filtration Therapy 32

3.2.4.1 Biologic-Detoxifilter/Plasma Filter 32

3.2.4.2 Selective Plasma-Exchange Therapy 32

3.2.4.3 Plasma Filtration with Dialysis 33

3.2.5 Clinical Observations of Various Combinations 33

3.3 Bioartificial Liver 35

3.3.1 Bioartificial Liver Support System 35

3.3.2 Cell Source for BAL 37

3.4 New Stream for Artificial Liver 40

3.4.1 Tissue Engineering for Liver Construction 40

3.4.2 Whole Organ Engineering for the Transplantable Artificial Liver 41

3.5 Conclusion and Future Trends 43

List of Acronyms 44

References 45

4 A Chemical Engineering Perspective on Blood Oxygenators 55
Luisa Di Paola

4.1 Introduction 55

4.2 A Historical Note 57

4.3 Chemical Engineering Principles in Blood Oxygenators 60

4.4 Chemical Engineering Process Analogues of ECMO Systems 65

4.5 New Challenges 67

4.6 Conclusion 69

List of Symbols 69

References 69

5 Model Predictive Control for the Artificial Pancreas 75
M. Capocelli, L. De Santis, A. Maurizi, P. Pozzilli, and Vincenzo Piemonte

5.1 Introduction 75

5.2 Phenomenological Models 78

5.2.1 Background and Two-Compartmental Models 78

5.2.2 Three-Compartment Models 79

5.3 Black-Block Approach 85

5.4 Conclusions 90

Nomenclature 91

References 92

6 Multiscale Synthetic Biology: From Molecules to Ecosystems 97
Luisa Di Paola and Alessandro Giuliani

6.1 Introduction: An Historical-Epistemological Perspective 97

6.2 Applications 99

6.2.1 Protein Synthetic Biology 99

6.2.2 Tissue Engineering and Artificial Organs 108

6.2.3 Biotechnology and Ecology Applications 109

6.3 Conclusions 111

List of Symbols 112

References 112

7 Chemical Reaction Engineering Methodologies for Biomedical Imaging Analysis 119
Masahiro Kawahara

7.1 Introduction 119

7.2 Magnetic Resonance Imaging (MRI) 119

7.2.1 1H-MRI 120

7.2.2 19F-MRI 121

7.2.3 MRI using Magnetization Transfer 122

7.3 Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) 123

7.3.1 PET 123

7.3.2 SPECT 125

7.4 Fluorescence Imaging 126

7.4.1 Fluorescent Proteins 126

7.4.2 Small Organic Fluorophores 128

7.5 Conclusion 131

List of Abbreviations 131

References 132

8 Noninvasive and Label-Free Characterization of Cells for Tissue Engineering Purposes 145
Shunsuke Tomita

8.1 Introduction 145

8.2 Multivariate Analyses 146

8.2.1 Principal Component Analysis (PCA) 147

8.2.2 Linear Discriminant Analysis (LDA) 148

8.2.3 Hierarchical Clustering Analysis (HCA) 148

8.2.4 Other Multivariate Analyses 149

8.3 Vibrational Spectroscopic Features 149

8.3.1 Cell Characterization Based on Whole-Cell Analysis by Raman Spectroscopy 151

8.3.2 Cell Characterization Based on Subcellular Analysis by Raman Spectroscopy 153

8.3.3 Raman-Based Cell Characterization Toward Biomedical Applications 157

8.4 Morphological Features 160

8.4.1 Cell Characterization Based on Unstained Microscopic Images of Single Cells 160

8.4.2 Cell Characterization Based on Unstained Microscopic Images of Cell Populations 162

8.5 Secreted Molecule Features 165

8.5.1 Cell Characterization Based on Response Signatures 165

8.6 Conclusion and Outlook 167

List of Acronyms 168

References 168

9 TMS-EEG: Methods and Challenges in the Analysis of Brain Connectivity 175
Elisa Kallioniemi, Mervi Könönen, and Sara Määttä

9.1 Introduction 175

9.1.1 Transcranial Magnetic Stimulation 175

9.1.2 Electroencephalography 176

9.1.3 Combined TMS and Electroencephalography 178

9.1.4 Data Acquisition 178

9.1.5 Artifacts and Their Prevention 180

9.2 Signal Processing Methods 181

9.2.1 Preprocessing 181

9.2.2 Connectivity Analysis Methods in TMS-EEG 182

9.2.3 Time Domain Methods 183

9.2.4 Frequency Domain Methods 183

9.3 TMS-EEG Applications in Studies of Connectivity 184

9.3.1 General Aspects 184

9.3.2 TMS-Evoked Potentials (TEPs) 185

9.3.3 TMS-Induced Oscillations 186

9.3.4 Clinical Perspectives 187

9.3.4.1 Alzheimer’s Disease 187

9.3.4.2 Schizophrenia 188

9.3.4.3 Disorders of Consciousness 189

9.4 Conclusions and Future Trends 189

List of Acronyms 190

References 190

10 Thermal Treatments of Tumors: Principles and Methods 199
P. Saccomandi, E. Schena, M. Diana, J. Marescaux, and G. Costamagna

10.1 Introduction 199

10.2 Effects of Temperature on Living Tissue 199

10.2.1 Hyperthermal Tissue Destruction 200

10.2.2 Cold Temperature for Tissue Destruction 202

10.3 Physical Principles of Thermal Treatments 203

10.3.1 Hyperthermal Treatments 203

10.3.1.1 High-Intensity Focused Ultrasound Ablation 203

10.3.1.2 Radiofrequency Ablation (RFA) 204

10.3.1.3 Microwave Ablation (MWA) 205

10.3.1.4 Laser Ablation (LA) 206

10.3.2 Cryoablation 207

10.4 Mathematical Modeling of Thermal Therapies 209

10.5 Temperature Monitoring During Thermal Treatments 211

10.5.1 Invasive (Contact) Thermometric Techniques 212

10.5.2 Non-Invasive (Contactless) Thermometric Techniques 215

10.6 Conclusions 218

List of Acronyms 219

List of Symbols 219

References 220

Index 229