Microfluidics and Multi Organs on Chip

✍ Scribed by P. V. Mohanan

• Publisher: Springer Nature
• Year: 2022
• Tongue: English
• Leaves: 712
• Category: Library

✦ Synopsis

This book highlights the application of microfluidics in cell biology research, chemical biology, and drug discovery. It covers the recent breakthroughs and prospects of organ-on-a-chip, human-on-a-chip, multi-organ-on-a-chip for personalized medicine. The book presents the preclinical studies of organs-on-a-chip, concepts of multiple vascularized organ-on-chips, application of organ-on-a-chip in blood-brain barrier model, culture and co-culture of cells on multi-organ-on-chip and parameter measurements in microfluidic devices. It underscores the advantage of microfluidic devices for developing efficient drug carrier particles, cell-free protein synthesis systems, and rapid techniques for direct drug screening. Further, it entails human-on-a-chip for measuring the systemic response as well as immediate effects of an organ reaction on other organs. In summary, this book reviews the development of a microfluidic-based organ-on-a-chip device for the preclinical evaluation, ADME studies of drugs, chemicals, and medical devices. This book is a valuable source for pharma companies, product developers, students, researchers, academicians, and practitioners.

✦ Table of Contents

Contents
About the Editor
1: Historical and Technological Background to Organ on a Chip´ 1.1 Introduction 1.2 Origins of Microchip Technology 1.3 Second Phase of Technology: New Materials and Applications 1.4 Third Phase: Microfluidics and Micropumps 1.5 Fourth Phase: Moving into Cell Culture 1.6 Fifth Phase: Translation to the Market 1.7 Status Report and Remaining Challenges 1.8 Roadmap and Conclusions 1.9 Conclusion References 2: Applications of Microfluidics 2.1 Introduction 2.2 In-Channel Techniques 2.2.1 Continuous-Flow-Based In-Channel Microfluidics 2.2.2 Sorting and Separation 2.2.3 Droplet-Based In-Channel Microfluidics 2.2.3.1 Droplet Fission 2.2.3.2 Droplet Fusion 2.2.3.3 Droplet Sorting 2.2.3.4 Encapsulation in Droplets 2.3 Open-Surface Techniques 2.3.1 Electrowetting-on-Dielectric 2.3.2 Liquid Dielectrophoresis 2.4 Acoustofluidics and Applications 2.4.1 Bulk Acoustic Waves 2.4.2 Surface Acoustic Waves 2.4.3 Oscillating Bubbles/Sharp Edges 2.5 Lab/Organ-on-Chip for Drug Testing Application 2.5.1 Limitations of Traditional Drug Development 2.5.2 Introduction to Organ-on-Chip (OOC) 2.5.3 Organ-on-Chip Technology for Drug Development 2.5.4 Future Scope: Human-on-Chip 2.5.5 Challenges and Perspective 2.6 Biosensing Applications 2.6.1 Antibody-Based Detection 2.6.2 Aptamer-Based Detection 2.6.3 Enzyme-Based Detection 2.6.4 Challenges 2.7 Cell Manipulation 2.7.1 Mechanical Manipulation 2.7.2 Electrical Manipulation 2.7.3 Optical Manipulation 2.7.4 Magnetic Manipulation 2.7.5 Other Manipulation 2.8 Conclusion References 3: Microfluidics-Based Organ-on-a-Chip for Cell Biology Studies 3.1 Introduction 3.2 Organ-on-a-Chip 3.3 Organ-on-a-Chip for Cell Biology and Understanding Disease Progression 3.4 Liver-on-a-Chip for Cell Biology Studies 3.5 Heart-on-a-Chip for Cell Biology Studies 3.6 Intestine-on-a-Chip for Cell Biology Studies 3.7 Lung-on-a-Chip for Cell Biology Studies 3.8 Kidney-on-a-Chip for Cell Biology Studies 3.9 Skin-on-a-Chip for Cell Biology Studies 3.10 Vascularised-Organ-on-a-Chip for Cell Biology Studies 3.11 Fabrication of Microfluidic Devices for Organ-on-a-Chip Experiment 3.12 Conclusion References 4: Microfluidics in Chemical Biology 4.1 Introduction 4.2 Microfluidics in Analytical Chemistry 4.2.1 Microfluidic Devices in Chemical Reactions 4.3 Separation and Purification of Biomolecules 4.3.1 Electrophoresis 4.3.1.1 Microchip Capillary Electrophoresis 4.3.1.2 Microchip Gel Electrophoresis 4.3.2 Chromatography 4.3.2.1 Separation of Nucleic Acids 4.3.2.1.1 Open-Channel Microfluidic Chips 4.3.2.1.2 Pillar Structured Microfluidic Chips 4.3.2.1.3 Resin Incorporated Microfluidic Chips 4.3.2.1.4 Monolith Incorporated Microfluidic Chips 4.3.2.1.5 Nanowires Incorporated Microfluidic Chips 4.3.2.2 Separation of Proteins 4.3.2.2.1 Open-Channel Microfluidic Chips 4.3.2.2.2 Resin Incorporated Microfluidic Chips 4.3.2.2.3 Monoliths Incorporated Microfluidic Chips 4.3.2.2.4 Nanowire 4.3.3 Solid-Phase Extraction 4.3.4 Aqueous Two-Phase System 4.3.5 Bioinspired Biomolecule Purification 4.3.6 Miniaturized Free-Interface Diffusion Devices 4.3.7 Droplet-Based Microfluidics 4.3.8 Engineered Micro-batch Experiments 4.3.9 Determination of the Microfluidic Phase Diagram to Optimize Crystallization Conditions 4.3.10 Kinetics-Based Passive and Active Control 4.3.11 Crystal Harvesting Versus On-Chip X-Ray Diffraction 4.3.12 Challenges 4.4 Microfluidics in Molecular Self-Assembly 4.5 Microfluidics in Chemical Biology: Interesting Applications 4.6 Conclusion References 5: Role of Microfluidics in Drug Delivery 5.1 Introduction 5.2 Design of Various Microfluidic Platforms 5.2.1 Materials 5.2.2 Microfluidic Channel Design and Geometry 5.2.2.1 Chamber-Based Devices 5.2.2.2 Continuous-Flow-Based Devices 5.2.2.2.1 T or Y Junction 5.2.2.2.2 Co-flowing Junction 5.2.2.2.3 Flow Focusing Junction 5.2.2.3 Droplet-Based Devices 5.3 Application of Microfluidics in Various Drug Delivery Systems 5.3.1 Emulsions 5.3.1.1 Issues with the Preparation of Emulsions and Improvement via Microfluidics 5.3.1.2 Usage of Microfluidic Devices for Emulsion Preparation 5.3.1.2.1 Production of Single Emulsions Using Microfluidics 5.3.1.2.1.1 Co-flow Glass Microfluidic Device 5.3.1.2.1.2 Flow-Focusing Glass Microfluidic Device 5.3.1.2.2 Production of Multiple Emulsions Using Microfluidics 5.3.1.2.2.1 Capillary Based Microfluidic Devices 5.3.1.2.2.2 Planar Microfluidic Devices 5.3.1.2.2.3 3D Devices 5.3.1.2.2.4 Multi-compartment Double Emulsions 5.3.1.2.3 Tuning of Microchannels 5.3.2 Protein-Based Nanocarriers 5.3.2.1 Methods for Preparing Protein Nanoparticles Using Microfluidic Devices 5.3.2.1.1 Self-Assembly Method (Self-Agglutination of Proteins) 5.3.2.1.2 Using Y-Shaped Microchannels 5.3.2.2 Recent Applications 5.3.2.3 Liposomes 5.3.2.4 Niosomes 5.3.2.5 Micelles 5.3.3 Polymeric and Hybrid Nanoparticles 5.3.3.1 Polymeric Nanoparticles 5.3.3.2 Polyionic Complex 5.3.3.3 Nanocapsules 5.4 Conclusion References 6: Microfluidics in Drug Delivery 6.1 Introduction 6.2 Conventional Drug Delivery Systems and Their Drawbacks 6.3 What Are Microfluidics 6.4 Properties of Microfluidic Devices Which Affect Drug Delivery Systems 6.4.1 Size 6.4.2 Shape and Structure 6.4.3 Surface Modification 6.4.4 Elasticity 6.5 Fabrication of Nanoparticles Using Microfluidics 6.6 Advantages of Using Microfluidics in Local Drug Delivery 6.7 Microfluidics for Localized Drug Delivery 6.7.1 Skin 6.7.2 Inner Ear 6.7.3 Eye 6.7.4 Brain 6.8 Recent Trends in Microfluidic-Mediated Drug Delivery Systems 6.9 Industrial Applications 6.10 Concluding Remarks 6.11 Future Perspectives References 7: Microfluidic-Based Sensors 7.1 Introduction 7.2 Materials for Microfluidic Sensors 7.3 Fabrication Approaches 7.3.1 Screen Printing 7.3.2 Inkjet Printing 7.3.3 Embossing 7.3.4 Molding 7.3.5 Laminating 7.3.6 Laser Ablation 7.3.7 Photolithography 7.3.8 Soft Lithography 7.3.9 3D Printing 7.4 Microfluidic Sensors 7.4.1 Flow Rate Sensors 7.4.2 Pressure Sensors 7.4.3 Temperature and Acoustic Sensors 7.4.4 Gas Sensors 7.4.5 Microfluidic Biosensors 7.4.5.1 Wearable Microfluidic Biosensors 7.4.5.2 Paper-Based Microfluidic Biosensors 7.4.5.3 Other Substrate-Based Microfluidic Biosensors 7.4.6 Microfluidic Chemical Sensors 7.5 Future Aspects and Conclusion References 8: Background and Organ on a Chip 8.1 Introduction 8.2 Current Cell Culture Devices 8.3 Consideration of Hardware 8.4 Effects of Flow 8.5 Modelling Physiology on Chip 8.5.1 Fluid/Fluid Interface 8.5.2 Modelling 3D Tissue 8.6 Major Blood Vessel Routs in the Body and Mapping to Devices References 9: Culture and Co-culture of Cells for Multi-organ on a Chip 9.1 Introduction 9.2 Why Do We Need Multi-organ Cell Culture? 9.3 Sources of Cells in Multi-organ on a Chip 9.3.1 Cell Lines 9.3.2 Primary Cells 9.3.3 Induced Pluripotent Stem Cells 9.4 Cell Culture Techniques in MOC 9.5 Cell Culture in Multi-organ on a Chip 9.6 Conclusion References 10: Cells and Organs on a Chip in Biomedical Sciences 10.1 Introduction 10.2 Key Components 10.3 Design Concept 10.3.1 Fluid Shear Force 10.3.2 Concentration Gradient 10.3.3 Dynamic Mechanical Stress 10.3.4 Cell Patterning 10.4 Various Types of OOCs 10.4.1 Liver OOC 10.4.2 Lung OOC 10.4.3 Heart OOC 10.4.4 Kidney OOC 10.4.5 Intestine OOC 10.4.6 Brain OOC 10.4.7 Tumours on a Chip 10.4.8 Multi-organs-on-a-Chip 10.5 Applications and Challenges for Large-Scale OOC Implementation 10.6 Conclusion and Future Perspectives References 11: Futuristic Aspects of Human Organ on a Chip 11.1 Introduction 11.2 Platforms 11.2.1 Wells and Flasks 11.2.2 Microfluidics 11.2.3 Insert/Microfluidic Hybrids 11.2.4 Gravity-Driven Flow 11.3 Sensors 11.4 What Has Not Been Achieved in Any Platform Yet in Terms of Physiology? 11.4.1 Fluctuating Nutrients and Hormone Profiles 11.4.2 Vascularisation, Blood and Oxygen Pressure 11.4.3 Immune System 11.5 Cell Sources and Modeling Healthy and Diseased Individuals References 12: Development of Human-on-a-Chip 12.1 Introduction 12.2 Why Do We Need a Human-on-a-Chip System? 12.3 Types of Multiorgan Integration Platforms 12.3.1 Static Microscale Platforms 12.3.2 Single-Pass Microfluidic Platforms 12.3.3 Pump-Driven Recirculating Microfluidic Platforms 12.3.4 Pumpless Recirculating Microfluidic Platforms 12.4 Techniques of Fabrication 12.4.1 3D Bioprinting 12.4.2 Stereolithography 12.4.3 Injection Molding 12.4.4 Soft Lithography 12.5 Pros of Body-on-Chip 12.6 Applications of Organ-on-a-Chip Technologies 12.6.1 Drug Discovery 12.6.2 Cardiovascular Diseases 12.6.3 Antiaging Medicine 12.6.4 Cancer 12.7 Limitations of Organ-on-a-Chip/Body-on-a-Chip 12.8 Conclusion References 13: Multiorgans-on-a-Chip for Personalized Medicine 13.1 Introduction 13.2 Personalized Medicine 13.2.1 Prerequisites of Personalized Medicine 13.2.2 Emerging Technologies in Personalized Medicine 13.3 Organs-on-a-Chip: Addressing Unmet Needs 13.4 Design Concept and Key Components of Organs-on-a-Chip 13.4.1 Design Concept 13.4.2 Key Components 13.5 Organs-on-a-Chip Models 13.5.1 Single Organ-on-a-Chip Systems 13.5.1.1 Brain-on-a-Chip 13.5.2 Lung-on-a-Chip 13.5.3 Heart-on-a-Chip 13.5.4 Spleen-on-a-Chip 13.5.5 Liver-on-a-Chip 13.5.6 Intestine-on-a-Chip 13.5.7 Kidney-on-a-Chip 13.5.8 Female Reproductive Organ-on-a-Chip 13.5.9 Skin-on-a-Chip 13.5.10 Multiorgans-on-a-Chip 13.6 Multiorgans-on-a-Chip in Personalized Medicine 13.6.1 Toxicity Screening 13.6.2 Drug Metabolism 13.6.3 Pharmacokinetics and Pharmacodynamics Studies 13.6.4 Personalized Organs-on-Chips 13.7 Conclusion 13.8 Future Perspective References 14: Development and Application of Microfluidics in Organoid Formation 14.1 Introduction 14.2 Microfluidic Technology Based Organoid Models 14.3 Tools and Techniques for Organoid Cultures 14.3.1 ECM Scaffold Method 14.3.2 Spinning Bioreactor Method 14.3.3 Magnetic Levitation 14.3.4 Bioprinting 14.3.5 3D Cell Culture Techniques and 3D Organoids, Stem Cell 3D Organoids 14.3.5.1 3D Cell Culture Techniques 14.3.5.2 Liquid Overlay 14.3.5.3 Hanging-Drop Method 14.3.5.4 Bioreactor 14.3.5.5 Scaffolds 14.3.5.6 3D Organoids 14.3.5.7 Stem Cell 3D Organoids 14.4 Conclusion References 15: Liver-on-a-Chip 15.1 Introduction 15.1.1 Liver-on-a-Chip Device 15.1.2 Parenchymal and Non-parenchymal Cells 15.1.3 Role of Cells in Drug Liver Metabolism and Toxicity 15.2 In Vitro Chip Models 15.2.1 Major Constituents of Organ-on-a-Chip 15.2.2 Materials for Fabrication of Microfluidic Device 15.2.3 Cells in Liver-on-a-Chip Device 15.2.4 Other Supporting Accessories 15.3 Different Models of Liver-on-a-Chip 15.3.1 Liver-on-a-Chip Based on 2D Planar Culture 15.3.2 Liver-on-a-Chip Based on 3D Spheroids 15.3.3 Liver-on-a-Chip Based on Layer-by-Layer Deposition 15.3.4 Liver-on-a-Chip-Based Microarrays 15.3.5 Microfluidic Hepatic Lobule 15.3.6 Microfluidic Zonation of the Lobule 15.3.7 Microfluidic Hepatic Sinusoid 15.3.8 Liver-on-a-Chip Disease Models 15.3.9 Multi-organ Models 15.3.9.1 Liver-Lung Model 15.3.9.2 Liver-Gut Model 15.3.9.3 Liver-Kidney-Lung Model 15.3.9.4 Liver-Testis Model 15.4 Conclusions References 16: Placenta on Chip: A Modern Approach to Probe Feto-Maternal Interface 16.1 Introduction 16.2 Development and Structure of Human Placenta 16.3 Structure Function Relationship of the Human Placenta in Physiology and Pathophysiology 16.4 Placenta-on-Chip 16.4.1 Models of Placental Barrier 16.4.2 Modifications of the Barrier Design 16.4.3 Applications of the Placenta-on-Chip Devices that Simulate the Barrier Function 16.4.4 Placenta-on-Chip Models of Trophoblasts Migration 16.4.4.1 Devices to Study Trophoblast Migration in Response to Chemical Gradients 16.4.4.2 Design to Simulate Spiral Artery 16.5 Limitation of the Placenta-on-Chip Devices 16.6 Future Direction 16.7 Conclusion References 17: Microfluidic Retina-on-Chip 17.1 Introduction 17.2 Need for RoC Technology 17.2.1 Morphology and Pathophysiology of Retina 17.2.2 Retinal Diseases 17.2.3 Evolution of the RoC Technology 17.3 Applications of RoC 17.3.1 Drug Testing 17.3.2 Analysing Functions of Cells/Tissues 17.3.3 Point Accession Signalling Studies 17.3.4 Development of Disease Models and Tissue Morphogenesis 17.4 Fabrication of Microfluidic RoC Model 17.4.1 Microfabrication Methods to Create RoCs 17.4.2 Characterization and Validation of RoCs 17.5 Case Study of RoC 17.5.1 hIPSC-Derived RO Merging RoC Technology 17.6 Advantages and Limitations of the RoC Technology 17.6.1 Advantages of RoC Technology 17.6.1.1 Accelerating Research 17.6.1.2 Overcoming In Vivo Challenges by Mimicking Its Niche in In Vitro Models 17.6.1.3 Technological advantage 17.6.1.4 Alternative to Animal Models 17.6.2 Limitations of RO and RoC Technology 17.6.2.1 Difficult to Maintain Upon Long-Term Cryopreservation 17.6.2.2 Absence or Patches of the RPE Layer 17.6.2.3 Remodelling Vascularization 17.6.2.4 Heterogeneity of Organoids 17.6.2.5 Time-Consuming Multi-step Fabrication Process 17.6.2.6 Extensive Maturation and Differentiation Time 17.7 Impact of RoC Technology 17.7.1 Social Impact 17.7.2 Industry 17.7.3 Economic Implications 17.8 Future Scope of RoC Technology 17.9 Conclusion References 18: Heart-on-a-Chip 18.1 Introduction 18.2 Need for Heart-on-a-Chip Models 18.3 Physiological Environment and Functions of the Heart 18.4 Cell Biological Requirements of a Heart-on-a-Chip 18.4.1 Requirement of Anisotropy and Mechanical Stimulus 18.4.2 Requirement of Electrical Stimulation 18.4.3 Requirement of Non-myocytic Cells and ECM Interactions 18.4.4 Requirement of High Oxygen Level and Removal of Waste Products from Cells 18.4.5 Attaining Cardiomyocyte Maturity 18.5 Heart-on-a-Chip Technology: Cardiac Cells in a Microfluidic Environment 18.5.1 Design of Heart-on-a-Chip 18.5.2 Simulation Studies for Heart-on-a-Chip 18.6 Fabrication of Heart-on-a-Chip Devices 18.6.1 Fabrication of Microfluidic Channels 18.6.2 Fabrication of Electrodes 18.6.3 Culturing Cardiac Cells 18.7 Characterization of the Heart-on-a-Chip Device 18.8 Sensing 18.8.1 Optical Methods 18.8.1.1 Contractility Measurement 18.8.1.2 Measurement of Action Potential 18.8.2 Electrical Methods 18.8.2.1 Contractility Measurement 18.8.2.2 Measurement of Action Potential 18.9 Applications of Heart-on-a-Chip 18.9.1 Modelling Cardiac Diseases Using Heart-on-a-Chip 18.9.2 Drug Sensitivity Testing 18.9.3 Microfluidics for Heart-on-a-Chip Research 18.10 Challenges and Future Scope References 19: Kidney-on-a-Chip 19.1 Introduction 19.1.1 Kidney: Structure and Function 19.1.2 Kidney Pathology 19.1.3 Issues Allied with the Development of In Vitro Kidney Models 19.1.4 Kidney Models 19.1.4.1 2-D vs. 3-D Systems 19.1.4.2 Cellular Models 19.1.4.3 Kidney-on-a-Chip Models 19.2 Motivation for the Organ on the Chip Technology 19.3 State-of-Art Development of Multiple Kidney Components on a Chip 19.4 Kidney-on-a-Chip Physiology and Pathophysiology Models 19.4.1 Glomerulus-on-a-Chip Model 19.4.2 Proximal Tubular-on-a-Chip 19.4.3 Distal Tubule-/Collecting Duct-on-a-Chip 19.5 Clinical Applications of Kidney on Chip Models 19.6 Challenges Towards the Kidney on the Chip Model 19.7 Future Opportunities 19.8 Conclusions References 20: Lung-on-a-Chip 20.1 Features of Human Lungs 20.2 The Ideal Human Lung Model 20.3 Diseases of the Human Lungs 20.4 Limitations of Current Use of Animal Models for Human Lungs 20.5 Animal Models for Human Lungs 20.6 History of Lung-on-a-Chip 20.7 Important Features for Lung-on-a-Chip 20.8 Current Applications 20.8.1 Lung Injury 20.8.2 Pulmonary Inflammation 20.8.3 COPD and Asthma 20.8.4 Cystic Fibrosis 20.8.5 Pulmonary Fibrosis 20.8.6 Cancer 20.8.7 COVID-19 20.9 Way Forward and Future of Lung-on-a-Chip References 21: Brain-on-a-Chip 21.1 Introduction 21.2 Reconstitution of the Central Nervous System on Chip 21.2.1 Dopaminergic Neuron on Chip 21.2.2 Hippocampal Neuron on Chip 21.2.3 Cholinergic, Gabaergic, Glutaminergic, and Serotoninergic Neuron on Chip 21.2.4 Co-culture Study in Microfluidics Platform 21.3 Reconstitution of the Peripheral Nervous System on Chip 21.3.1 Sensory Neuron on Chip 21.3.2 Motor Neuron on Chip 21.3.2.1 Reconstitution of Motor Neurons, Axonal Outgrowth, and Formation of the Neuromuscular Junction on a Microfluidic Plat... 21.3.2.2 ALS on Chip 21.4 Conclusion References 22: Skin-on-Chip 22.1 Introduction, Need, and Importance 22.1.1 An Alternative to Animal Testing 22.1.2 High-Throughput Screening 22.1.3 Diseased Human Skin Models 22.2 What Is Skin-on-a-Chip (SOC)? 22.2.1 Structure and Function of Skin 22.2.2 Improved Mimicking of Cellular Microenvironment 22.2.3 Evolution of In Vitro Skin Models 22.2.4 Types and Variations in In Vitro Skin Models 22.2.4.1 Reconstructed Human Epidermis (RHE) 22.2.4.2 Full-Thickness Skin Models (FT) 22.2.4.3 Full-Thickness (FT) Skin Models with Additional Cell Types 22.2.4.4 Skin-on-a-Chip (SOC) Models 22.2.5 Minimal Requirements for SOC Modelling 22.3 Components and Development of Skin-on-a-Chip (SOC) Devices 22.3.1 Biomaterials and Scaffolds 22.3.2 Material of Construction for SOC Microfluidic Chips 22.3.3 Skin Cells and Reagents 22.3.4 Microfabrication of SOC Device and Its Functionality 22.3.5 Characterization of 3D Skin Cultures 22.3.5.1 Morphological Characterization 22.3.5.1.1 Cell Viability and Orientation of 3D Skin Cultures 22.3.5.1.1.1 Live and Dead Cell Staining/Cell Viability Studies 22.3.5.1.1.2 Differential Staining Using Cell Tracker Dyes 22.3.5.1.2 Histological and Immunohistochemistry (IHC) Analysis 22.3.5.2 Biophysical Characterization 22.3.5.3 Functional Characterization 22.3.6 Validation Using Skin-Related Pharmaceutical Products and Tests 22.3.7 Disease-Specific Skin Biomarkers as End Points of Skin-on-Chip (SOC) Models 22.4 Application and Implementation of SOC Devices 22.4.1 Drug Testing and Toxicological Studies 22.4.2 Wound Healing 22.4.3 Diagnostics 22.4.4 Inflammation 22.4.5 Skin Ageing 22.4.6 Studying Shear Stress 22.5 Impact, IPR, and Regulations of SOC Technology 22.5.1 Social Impact 22.5.2 Industrial Impact 22.5.3 Economic Impact 22.5.4 Regulations and IPR 22.6 Challenges in SOC Development and Future Perspective 22.6.1 Limitations in SOC Co-culture Architecture 22.6.2 Limitations of PDMS-Based SOCs 22.6.3 Limitation in Throughput of Cell Injection, Perfusion, and Sampling 22.6.4 Lack of Integrated Online Analytics of Biosensors 22.7 Current Status and Future Perspectives on Skin-on-a-Chip (SOC) Technology References 23: Organs-on-a-Chip in Preclinical Studies 23.1 Introduction 23.1.1 History of OoC Research 23.1.2 Design Considerations 23.1.2.1 Flow Parameters 23.1.2.2 Materials for OoC Device Fabrication 23.1.2.3 Recapitulating Cellular and Tissue Architecture 23.1.2.4 Allometry 23.1.2.5 Maintaining Consistent Performance for OoC Devices over Extended Periods of Time 23.2 Disease Modelling on a Chip 23.2.1 Inflammatory Disorders 23.2.2 Cardiovascular Diseases 23.2.2.1 Atherosclerosis 23.2.2.2 Thrombosis 23.2.3 Neurological Diseases 23.2.3.1 Alzheimer´s Disease 23.2.3.2 Parkinson´s Disease 23.2.3.3 Multiple Sclerosis 23.2.4 Cancer 23.3 Pharmacokinetic Pharmacodynamic Analysis Using Organ-on-Chips 23.3.1 Relevant Pharmacokinetic Parameters 23.3.2 Relevant Pharmacodynamic (PD) Parameters 23.3.3 PK-PD Modelling Using Microfluidic Organ-on-Chip Models 23.4 Designing Various Organ Chips 23.4.1 Heart-on-a-Chip 23.4.2 Liver-on-a-Chip 23.4.3 Lung-on-a-Chip 23.4.4 Kidney-on-a-Chip 23.4.4.1 Glomerulus-on-a-Chip 23.4.4.2 Tubule-on-a-Chip 23.4.5 Brain-on-a-Chip 23.5 Challenges and Considerations 23.5.1 Defining Context-of-Use 23.5.2 Understanding Diurnal or Endocrine Fluctuations 23.5.3 Cell Sourcing 23.5.4 Platform Fabrication 23.5.5 Scaling Up the Manufacturing Process 23.5.6 Validating Organs-on-Chip 23.6 Conclusions References 24: Application of Organ-on-Chip in Blood Brain Barrier Model 24.1 Introduction 24.1.1 Organ-on-a-Chip 24.1.2 Background: History, Structure, and Functions of the Blood Brain Barrier (BBB) 24.2 Models for Blood Brain Barrier 24.3 Microfluidics-Based Designing 24.3.1 Principles of Microfluidic Device Design 24.3.1.1 Sandwich Design 24.3.1.2 Parallel Design 24.3.1.3 3D Tubular Structure Design 24.3.1.4 Vasculogenesis Design 24.4 Models for the BBB 24.4.1 In Vivo Models 24.4.2 In Vitro Models 24.4.2.1 Cell Sources for Development of In Vitro Models 24.4.3 In Vitro Model Systems 24.4.3.1 2D Static Model 24.4.3.2 2D Organ-on-a-Chip 24.4.3.3 3D BBB Models 24.5 Importance of Developing In Vitro Models of Human BBB 24.6 In Vivo and In Vitro Models: Alternatives to Animal Use 24.6.1 Brain Tumour Studies 24.6.2 Identification of Neurotoxic Compounds 24.6.3 Deciphering the Link Between Inflammation and Neurodegeneration 24.6.4 Drug Development 24.6.5 Drug Screening and Efficacy Evaluation 24.6.6 Personalized Medicine 24.6.7 Viral Infection Studies 24.7 Regulations Concerning Translational Acceptance of OOC 24.8 Challenges Towards Development of OOCs 24.8.1 Permeability 24.8.2 TEER 24.8.3 Cell Selection and Sourcing 24.9 Future Directions References 25: Multi-Organs-on-a-Chip in Disease Modelling 25.1 Introduction 25.2 Cancer and Cancer Metastasis 25.3 Infectious Diseases 25.4 Conclusions References 26: Prospects of Medical-Device-on-a-Chip 26.1 Introduction 26.2 Development Pathway and Design Considerations for Medical Devices 26.3 Microfluidic Technology for Biomedical Application: Fundamentals 26.4 Actuation Mechanisms for Microfluidic Medical Devices 26.4.1 Mechanical Actuation Mechanisms 26.4.1.1 Piezoelectric 26.4.1.2 Pneumatic/Thermopneumatic 26.4.1.3 Rotary/Centrifugal 26.4.1.4 Shape-Memory Alloys (SMAs) 26.4.1.5 Electromagnetic 26.4.1.6 Electrostatic 26.4.1.7 Acoustic 26.4.2 Non-mechanical Actuation Mechanisms 26.4.2.1 Capillary 26.4.2.2 Electrokinetics 26.4.2.3 Optics 26.4.2.4 Magnetohydrodynamic 26.4.2.5 Microbubbles 26.5 Digital Technologies for Medical Devices 26.6 Medical Devices-on-a-Chip 26.6.1 Drug Discovery 26.6.2 Cellular Analysis and Tissue Engineering 26.6.3 Single-Cell Trapping and Micro-robotic Injection 26.6.4 Stem Cell Analysis 26.6.5 Paper-Based Microfluidic Devices 26.6.6 Viral Detection 26.7 Conclusion and Future Perspectives References 27: Lab-on-a-Chip for Functional Testing for Precision Medicine 27.1 Introduction 27.2 Latest Trends on Organ-on-Chip for Precision Medicine 27.2.1 Gut on-Chip (GOC) 27.2.2 Islet-on-Chip (IOC) 27.3 Trends on Multi-Organ-on-Chip for Precision Medicine 27.4 Latest Trends on Lab-on-Chip for Precision Medicine 27.5 Applications of Lab-on-Chip for Precision Medicine (Fig. 27.3) 27.5.1 Detection of Disease Markers 27.5.2 Detection of Microbial Organisms 27.6 Detection of Biological Molecules and Ions 27.7 Detection of Drugs and Toxic Chemicals 27.8 Other Applications of LOC for Precision Medicine 27.9 Conclusion References 28: Tumour-on-a-Chip: Perfusion Systems to Model the Extracellular Breast Tumour Microenvironment-From Tumour Progression to M... 28.1 Introduction 28.2 Parameters to Be Designed intoTumour-on-a-Chip´ to Reconstitute the Physiological Tumour Microenvironment
28.2.1 Interstitial Fluid Flow, Tumour-Associated Changes in Interstitial Pressure and Compressive Stresses
28.2.2 The Extracellular Matrix and the Key Non-cellular Component of the TME
28.2.3 Cellular Interactions Within the Tumour Microenvironment: Stroma and Vasculature
28.2.4 Endothelial Layer and Cancer Cells Circulation
28.3 Breast Cancer In Vitro Models: Past, Present and Future
28.3.1 Modelling the Primary Site
28.3.2 Breast-to-Bone In Vitro Models
28.4 Conclusions and Future Perspectives
References
29: Building Human In Vitro 3D Models to Replace Animal Studies During Drug Discovery Research: Scientific, Ethical and Regula...
29.1 Introduction
29.2 Why Do Drugs Fail?
29.2.1 Phase I Failures
29.2.2 Phase 2 Failures
29.2.3 Phase 3 Failures
29.2.4 Post-marketing Failures
29.3 Key Takeaways from Failures During Drug Development
29.4 Current Approaches of Predicting Clinical Liabilities During Preclinical Stage
29.5 In Vitro Human Models Available to Date
29.6 What Next in In Vitro Human Model Development?
29.7 Use of In Vitro 3D Human Models: Next Paradigm Shift?
29.8 Learnings from Environmental Toxicology
29.9 Carving Out a Regulatory Path
29.10 Conclusions
References