Smart Organ-on-Chip Devices

Dynamic Microfluidic Systems for Cell Culture

1st Edition - April 25, 2025
Imprint: Academic Press
Editors: Tiago Albertini Balbino, Paulo Bartolo, Letícia Charelli
Language: English
Paperback ISBN:
9 7 8 - 0 - 4 4 3 - 1 3 4 0 3 - 6
eBook ISBN:
9 7 8 - 0 - 4 4 3 - 1 3 4 0 4 - 3

Smart Organ-on-Chip Devices: Dynamic Microfluidic Systems for Cell Culture discusses the concepts to engineer functional stimuli responsive organotypic-on-chip devices and its a… Read more

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Smart Organ-on-Chip Devices: Dynamic Microfluidic Systems for Cell Culture discusses the concepts to engineer functional stimuli responsive organotypic-on-chip devices and its application in several fields, including drug development, disease modeling, personalized medicine, and tissue engineering. Groundbreaking studies are presented throughout the book sections to reinforce the importance of adding more reliable and robust in vitro platforms able to closely emulate the dynamism of human physiology.

The authors present new information regarding in silico studies of cell spheroids within microfluidic devices, as well as step-by-step guidance on key procedures. Written for researchers, practitioners and students using microfluidic devices as platforms, by well-respected scientists from both academia and industry.

Title of Book
Cover image
Title page
Table of Contents
Copyright
Contributors
Preface
Acknowledgments
Introduction
Purpose
Audience
Technological evolution and innovations
Relevance to biomedical research
Content overview
Section 1: Microfluidics and organ-on-chip technologies
Section 2: Stimuli-active organotypic-on-chip devices
Section 3: Microphysiological case studies
Relevance
Section 1. Microfluidics and organ-on-chip technologies
Chapter 1. Organotypic on-chip models: Bridging the gap between traditional in vitro culture and animal testing
1 Introduction
2 The need for alternatives to 2D culture and animal testing
3 Advantages of organotypic on-chip models
3.1 Improved physiological relevance
3.2 Enhanced predictive power
3.3 Ethical and economic benefits
4 Market adoption and strategies
4.1 Bridging academia and industry
4.2 Regulatory support
4.3 Industry partnerships
5 Current applications and innovations
5.1 Disease modeling and drug testing
5.2 Personalized medicine
5.3 Multiorgan systems
5.4 Toxicology testing
5.5 Infectious disease research
5.6 Cancer research
5.7 Artificial intelligence and OoC technologies
6 Conclusion
Chapter 2. Microfabrication processes and engineering aspects for the manufacturing of smart organ-on-chip devices
1 Microengineering technology in smart organs-on-chips
2 Engineering spatial and physical cues of the cellular microenvironment
3 Microfabrication of integrated systemic analysis via biosensors for functional readouts
4 Overview of microfabrication techniques for OoC platforms
4.1 Photolithography: Manufacturing microstructures with light
4.2 Soft lithography: Molding microstructures with elastomeric polymers
4.3 Film deposition: Building functional layers for OoC technologies
4.4 Etching: Precision sculpting to build microfluidic architectures
4.5 Microelectromechanical systems in OoC technologies: Merging mechanics and microfluidics
4.6 3D printing and bioprinting: Revolutionizing the bio-microfabrication
4.7 Hybrid manufacturing processes
5 Future perspective and concluding remarks
Chapter 3. Bioprinted organ-on-a-chip: A strategy to achieve humanized in vitro models
1 Introduction
2 Bioprinting techniques used to fabricate organ-on-chip systems
2.1 Nozzle-based methods for bioprinting
2.2 Light-assisted methods for bioprinting
2.3 Microvalve bioprinting
2.4 Acoustic bioprinting
3 Advantages of integrating 3D bioprinting with microfluidic platforms
3.1 Precision and spatial control
3.2 Enhanced integration with fluidic systems
3.3 Customization and complexity
3.4 Scalability and reproducibility
3.5 Integration of multiple tissue types
3.6 Comparative analysis
4 Applications of bioprinted organ-on-chip systems
4.1 Gut–brain axis models
4.2 Cardiovascular models
4.3 Liver models
4.4 Cancer models
5 Challenges and future directions
5.1 Technical challenges
5.2 Biological challenges
5.3 Standardization and reproducibility
6 Conclusion
Chapter 4. Disease modeling and developmental biology through microfluidic channels
1 Microfluidic approaches for disease modeling
2 Modern developmental biology via microfluidics
3 Microenvironmental precision: Modeling gradient flows in microfluidic systems
4 Microfluidic approaches for disease model applications
4.1 Toward a reliable heart-beating study model
4.2 Ophthalmic disease models
4.3 Brain-on-chip: In vitro systems for neurological disease modeling
4.4 Gastrointestinal mimetics for digesting-on-chip devices
4.5 Cutaneous conditions via microfluidics
5 Studying mechanical forces and spatial constraints of diseases
6 Insights into the microenvironmental influence on development
Chapter 5. Artificial intelligence–assisted organ-on-chip systems
1 Introduction
2 Adaptation of AI to OOC devices: Design parameters
2.1 A computer vision example
3 Paradigm shift with AI-integrated organs-on-chip models
4 Conclusion
Section 2. Stimuli-active organotypic-on-chip devices
Chapter 6. Mechanically active organotypic-on-chip devices for dynamic cell culture
1 Mechanotransduction in organotypic-on-chip models
2 Simulating dynamic mechanical environments: Compression and stretch in organs-on-chip
3 Integration of mucosal tissues and vasculature in dynamic OoC models
4 Advances in 3D-bioprinting for mechanically active organotypic models
5 Material innovations for enhanced mechanical functionality in organ-on-chip devices
6 Multianalyte monitoring of mechanically induced cellular responses
7 Challenges and future directions in mechanically active organotypic models
Chapter 7. Sensors within microfluidic chips: Optofluidics to explore in vitro organoid behavior
1 Toward automated in situ analysis: Leveraging optofluidic sensors
1.1 Integrating optofluidic sensors with minimal intrusion
1.2 Achieving high precision in sensor data acquisition
1.3 Automated sensor data analysis for real-time monitoring
2 Unveiling the organoid microenvironment: Optofluidic sensors for extracellular parameters (e.g., pH, O2, temperature)
2.1 Oxygen gradient mapping in microfluidic organoid models
2.2 Temperature control and monitoring for optimized organoid growth
3 Decoding organoid function: Monitoring soluble protein biomarkers with optofluidics
3.1 Integrating ELISA-based sensors for protein biomarker detection
Chapter 8. Photothermal and magnetic cell stimuli caused by nanoparticles inside organ-on-chip platforms
1 Brief introduction about nanopharmaceuticals and “smart” nanoparticles
2 Types of active stimuli caused by nanoparticles to generate hyperthermia in dynamic cell culture
3 How does magnetic hyperthermia work?
4 How photothermal stimuli work
5 How can these stimuli be used for cellular therapy
Section 3. Microphysiological case studies
Chapter 9. Brain-on-chip microplatforms for precision medicine, disease modeling, and developmental biology
1 Introduction
2 Biomaterials and nonmicrofluidic 3D models
3 Brain-on-chip platforms
4 Applications
4.1 Brain physiology
4.2 Injury
4.3 Blood–brain barrier
4.4 Disease modeling
5 Challenges and future directions
5.1 Physiology
5.2 Electrophysiology monitoring and biosensing
5.3 Multi-organ-on-chip and personalized medicine
5.4 Standardization
6 Conclusion
Chapter 10. Dynamic microphysiological systems to access sickle cell disease—A case study for disease modeling
1 Introduction
2 Computational modeling of hemodynamics in sickle cell disease
3 Changes in mechanical properties of red blood cells in sickle cell disease
4 Patient-specific modeling of vascular pathologies in SCD
5 Microfluidic platforms for modeling sickle cell disease: Challenges and innovations
6 Oxygen gradient control in microfluidic devices for SCD research
7 Advances in microfabrication techniques for SCD organ-on-chip models
8 Application of microfluidic-based SCD models in drug testing and personalized medicine
Chapter 11. Microtechnologies and mathematical modeling in signaling cascades multiorgan microphysiological systems
1 Importance of understanding the cellular signaling cascade and disease associated signaling
2 Types of cellular signaling: Autocrine, paracrine, and endocrine signaling
3 Role of gap junctions and ion channels in signaling
4 Membrane receptors of the tyrosine kinase and G protein-coupled receptor types
5 Intracellular and nuclear receptors in gene regulation
6 Mathematical modeling of fluid behavior in microphysiological systems
7 Exploring the fluid dynamics in continuous-flow microfluidics
8 Dynamic in vitro platforms and fluid-flow behavior in microenvironments
9 The future of modeling and simulation in organs-on-chip platforms
Chapter 12. Heart-on-a-chip: Towards a reliable model for cardiac physiopathological and pharmacological research
1 Introduction
2 Heart MPS features
3 Cardiac organoids
3.1 The cardiovascular system
3.2 Cardiac muscle biology
3.3 Spheroidal versus customized engineered cardiac tissue
4 HOC system applicability
4.1 HOC systems for physiological investigation
4.2 HOC systems for pathophysiological investigation
4.3 HOC systems for pharmacological assessment
5 Conclusion
Chapter 13. Remaining challenges: Are we close to a physiologically representative in vitro model for clinical deployment?
1 Introduction
2 Scalability and maturation of tissue models
3 Complexity and reproducibility
4 Regulatory and validation hurdles
5 Throughput and data integration
6 Addressing the challenges
7 Conclusion
Index

Tiago Albertini Balbino

Tiago Albertini Balbino, PhD, is a professor at the Alberto Luiz Coimbra Institute for Graduate Studies and Research in Engineering (COPPE) at the Federal University of Rio de Janeiro (UFRJ), Brazil. He coordinates the Graduate Program in Nanotechnology Engineering, which is housed at Latin America’s largest center for research and education in engineering. Professor Balbino is a chemical engineer with a PhD and master’s in chemical engineering from the UNICAMP (São Paulo, Brazil). His doctoral research focused on developing microfluidic processes for creating nanostructured systems used in vaccines and other nanomedicines, a focus he expanded during his internship at the National Institute of Standards and Technology (NIST) in the United States, where he worked on microfabrication techniques for biomedical applications. He later pursued a postdoctoral fellowship at the Department of Mechanical Engineering at PUC-Rio, advancing his expertise in microfluidic chip design. Currently, his work centers on designing innovative microfluidic chips to address challenges in nanotechnology engineering. He is also actively involved in advancing organ-on-chip technologies, with applications in drug development, disease modeling, and tissue engineering. His work bridges engineering and biomedical science, contributing to cutting-edge research that aims to transform healthcare and train the next generation of scientists and engineers.T

Affiliations and expertise

Professor, Alberto Luiz Coimbra Institute, Federal University of Rio de Janeiro, Brazil

Paulo Bartolo

Paulo Bartolo is Professor of Advanced Manufacturing at the School of Mechanical and Aerospace Engineering (MAE), Nanyang Technological University (NTU), Executive Director of the Singapore Centre for 3D Printing (SC3DP), and Programme Director of the National Additive Manufacturing Innovation Cluster (NAMIC) hub at NTU. He is Fellow of CIRP (International Academy for Production Engineering), Honorary/Visiting Professor at several Universities in China, Europe and North America and Advisor of several Funding Agencies and Research Institutes across the world.

He authored/co-authored more than 700 publications in journal papers, book chapters and conference proceedings, co-edited 23 books and holds 16 patents in the fields of additive manufacturing, biomanufacturing and tissue engineering. Throughout his career he received several awards and public recognitions including the Gold Medal of Merit of the Portuguese Communities from the Portuguese Government, Professor Honoris Causa from the Polytechnic University of Leiria, the Kobayahi Award for his contributions in the field of biomanufacturing, commendations and public recognitions from the Portuguese Government and the Polytechnic University of Leiria published in the Portuguese Government’s Law Journal and the Medal of Merit from the city of Leiria among others. Paulo Bartolo is among the Top 2% Scientists Worldwide.

Affiliations and expertise

Executive Director, Singapore Centre for 3D Printing, Nanyang Technological University, Singapore; Professor, School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore

Letícia Charelli

Ms. Letícia Charelli has a BSc and an MSc in Biotechnology with emphasis on biofabrication, 3D cell culture, and microfluidics. She is currently working with industry players to optimize protocols for regenerative medicine, drug development, and disease modeling. Letícia uses her extensive knowledge to translate the research data from the bench to the bedside as a functional product. Her expertise in microfluidics (e.g., organ-on-chip platforms) have resulted in several international articles, partnership with industries as well as lecturing for undergraduate, graduate, and professionals of several fields.

Affiliations and expertise

Researcher, Universidade Federal do Rio de Janeiro, Brazil

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Smart Organ-on-Chip Devices

Dynamic Microfluidic Systems for Cell Culture

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Paulo Bartolo

Letícia Charelli

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