Preface: Microfluidics in Biotechnology
Contents
Microfluidics in Biotechnology: Overview and Status Quo
1 Introduction
1.1 Biotechnology
1.2 Microfluidics
1.3 The Vision of a Microfluidic Lab-on-a-Chipยดยด
2 Microfluidics in Biotechnology
2.1 History and Milestones
2.2 Application Areas
3 Analytics and Screening
4 Cell Cultivation and Processing
4.1 Single-Cell Analysis andOmicsยดยด
4.2 Chances and Challenges
5 Conclusion
References
A Primer on Microfluidics: From Basic Principles to Microfabrication
1 Introduction
2 Microfluidic Fundamentals
2.1 Flow Behavior at Small Scales
2.2 Surface Effects
2.3 Diffusion and Mixing
2.4 Transport of Suspended Particles
3 Microfluidic Fabrication Techniques
3.1 Clean-Room Microfabrication
3.2 Photolithography
3.3 Deposition Techniques
3.4 Etching Techniques
3.5 Bonding Techniques
3.6 Soft Lithography
3.7 Maskless Micro- and Nanofabrication
4 Conclusion
References
Emerging Technologies and Materials for High-Resolution 3D Printing of Microfluidic Chips
1 Introduction
2 Emerging Technologies
2.1 Stereolithography
2.1.1 Challenge 1: Z-Overcuring - Polymerizing Resin in the Embedded Channel
2.1.2 Challenge 2: Non-cured Resin Inside the Embedded Channel
2.1.3 Challenge 3: High Resolution at High Lateral Sizes
2.2 Upcoming Trends in Optical 3D Printing
2.3 2-Photon Polymerization
2.4 Upcoming Trends in 2-Photon Polymerization
3 Emerging Materials
3.1 Noncytotoxic Polymers
3.2 Transparent Glass
3.3 Polydimethylsiloxane
3.4 Polymethylmethacrylate
4 Outlook
References
Microbioreactors for Process Development and Cell-Based Screening Studies
1 Microbioreactors for Cell Cultivation
2 Homogenization of Microbioreactors
2.1 Mixing via Stirring
2.2 Pumping
2.3 Pneumatic Gassing
2.4 Orbital Shaking
2.5 Mixing of Droplet Microbioreactors
3 Application of Microbioreactors
3.1 Microbioreactors for Process Development and Scale-Up
3.1.1 Microtiter Plate-Based Microbioreactors
3.1.2 Microbioreactors with Rotating Mixers
3.1.3 Microbioreactors Without Movable Mixing Elements
3.1.4 Challenges in Upscaling of Processes Evaluated in Microbioreactors
3.1.5 Scaling Parameters
3.2 Droplet Bioreactors as Analytical Screening Tool
4 Conclusions and Future Perspectives
References
Microfluidic Devices as Process Development Tools for Cellular Therapy Manufacturing
1 Challenges of Cellular Therapy Manufacturing and Advantages of Microfluidics
2 Microfluidic Devices for Cell Processing Unit Operations
2.1 Cell Isolation and Separation
2.2 T Cell Activation
2.3 Gene Delivery
2.4 Cell Expansion
2.5 Stem Cell Differentiation
3 Summary and Perspective
References
Droplet Microfluidics for Microbial Biotechnology
1 Introduction
2 Droplet Microfluidics for Microbial Cultivation
3 Detecting Microbial Activity in Droplet Microfluidics
4 Droplet Cultivations of Rare Microbes and to Search for New Antimicrobials
5 Ultrahigh-Throughput Enzyme Activity Screening and Selection
6 Conclusions
References
Microfluidic Single-Cell Analytics
1 Introduction
2 Growth Analysis of Single Cells
2.1 Cell Counting, Morphometrics, and Segmentation
2.2 Mass Imaging
2.3 Picobalances
3 Substrate Uptake
3.1 Fluorescence Analysis
3.2 Mass Spectrometry
3.3 Inferring Kinetic Constants of Substrate Uptake
4 Product Formation
4.1 Fluorescence Analysis
4.2 Mass Spectrometry
5 Gene Expression, Protein Synthesis, and Regulation
6 Analytical Pitfalls in Microfluidic Single-Cell Analysis
7 Conclusion
References
Analytics in Microfluidic Systems
1 Introduction
2 Theory of Analytical Methods
2.1 Electrophoresis
2.2 Dielectrophoresis
2.3 Electric Impedance Analysis
3 Applications of Analytical Methods
3.1 Electrophoretic Analysis
3.2 Dielectrophoretic Analysis
3.3 Electric Impedance Analysis
4 Conclusion
References
Biocatalysis in Continuous-Flow Microfluidic Reactors
1 Biocatalysis and Continuous-Flow Microreactors
1.1 Biocatalysis Goes with the Flow
1.2 New Demands of Biocatalysis for Reactor Engineering
1.3 Scope of this Book Chapter
2 Biocatalytic Microfluidic Reactors with Free Enzymes
2.1 Modern Biocatalysis with Free Enzymes and Emerging Demands: The Context of Microfluidic Technology
2.2 Biocatalysis in Monophasic Aqueous Medium
2.2.1 Compartmentalization of Complex Reactions in Microfluidic Devices
2.2.2 Advanced Monitoring in Continuous Reactors
2.3 Biocatalysis in Multiphasic Medium
2.3.1 Biocatalysis with Free Enzymes in Liquid-Liquid Flow
2.3.2 Biocatalysis with Free Enzymes in Gas-Liquid Flow
3 Biocatalytic Microfluidic Reactors with Immobilized Enzymes
3.1 Enzyme Immobilization and Conventional Continuous Reactors: The Need for New Technologies
3.1.1 Enzyme Immobilization and Continuous Reactors
3.1.2 Format of Conventional Continuous Reactors with Immobilized Enzymes
3.1.3 Conventional Continuous Reactors: Limitations and Need for New Technologies
3.2 Modern Heterogeneous Biocatalysis and Emerging Demands: The Context of Microfluidic Technology
3.3 Immobilized Enzymes in Microfluidic Reactors: Challenges and Practical Implementation
3.3.1 Enzyme Immobilization into Microfluidic Reactors
3.3.2 High Quality Enzyme Immobilization in Microfluidic Reactors
3.3.3 Enzyme Immobilization in High Quantity in Microfluidic Reactors
4 Exploitation of Microfluidic Enzyme-Immobilized Reactors
4.1 Promises and Advantages of Microfluidics in Enzyme-Immobilized Reactors
4.2 Intensification of Solid-Liquid Reactions in Microfluidic Reactors
4.2.1 Miniaturization in Flow Wall-Coated Reactors and Fast Reactions
4.2.2 Miniaturization in Flow and Reaction Intensification
4.3 Intensification of Solid-Fluid-Fluid Reactions in Microfluidic Reactors
4.3.1 Liquid-Liquid Reactions with Immobilized Enzymes in Flow
4.3.2 Gas-Liquid Reactions with Immobilized Enzyme in Microfluidic Reactions
4.4 Assembly of Enzyme-Immobilized Cascades
4.5 Generation of Novel Process Windows
4.6 Scale-Up and Scale-Down Impact on Productivity and Space-Time Yield
5 Conclusions
References
Lab-on-a-Chip Devices for Point-of-Care Medical Diagnostics
1 Introduction
2 From Paper-Based Assays to Microfluidic Chips
3 Magnetic-Assisted Platforms
4 Centrifugal Microfluidic Platforms
5 Smartphone-Based Detection
6 Conclusions and Outlook
References
Microfluidics for Environmental Applications
1 Introduction
2 Applications of Microfluidics in Environmental Science and Engineering
2.1 Microfluidics Used for Contaminant Analysis
2.1.1 Heavy Metal Ion Analysis
2.1.2 Organic Compound Analysis
2.1.3 Nitrate and Ammonia Analysis
2.2 Microfluidics Used for Microorganism Detection
2.2.1 Virus Detection
2.2.2 Bacteria Detection
2.2.3 Protozoa Detection
2.3 Microfluidics Used as Research Platforms
2.3.1 Mechanisms of Bacteria Electron Transfer
2.3.2 Biofilm Formation
2.3.3 Antibiotic Resistance Gene Transfer
2.3.4 Electroporation
2.3.5 On-Chip Toxicity Test
3 Perspectives on Microfluidicsยด Applications in Environmental Science and Engineering
References
Microfluidic Systems for Antimicrobial Susceptibility Testing
1 Introduction
2 Antimicrobial Susceptibility Testing (AST)
3 Microfluidic AST
3.1 Optical Detection
3.1.1 Single-Cell Imaging
3.1.2 Time-Lapse Microscopy
3.1.3 Interferometry
3.1.4 Fluorescence Imaging
3.1.5 Relative Optical Density
3.2 Electrical Detection
3.2.1 Measuring the Electrical Resistance Change
3.2.2 Electrochemical Detection
3.3 Biochemical Detection
3.4 Mechanical Detection
4 Conclusion
References
Organ-on-a-Chip
1 Introduction
1.1 A Global Health Challenge
1.2 What Is an Organ-on-a-Chip?
2 Multi-organ-Chips and Humans-on-a-Chip
2.1 Potentials of the Platform
2.2 Design Considerations and Challenges
2.2.1 Required Functions
2.2.2 Materials
2.2.3 Design Principles and Scaling Rules
2.2.4 Cell Sources
2.2.5 Medium
2.2.6 Sensory Systems (Instrumentation)
2.3 Generated Multi-organ Platforms
2.4 Commercialization
2.5 Ongoing Research
3 Conclusion and Outlook
References
Emerging Biosensor Trends in Organ-on-a-Chip
1 Introduction
2 Bipolar and Tetrapolar Electrode Approaches for Transepithelial and Endothelial Resistance (TEER) Measurements at Human In V...
3 Bipolar and Tetrapolar Impedance Spectroscopy Approaches for Integrity Monitoring of Human In Vitro Organ and Barrier Models
4 Monitoring of Organ Function Using Electrochemical Analysis Techniques: Straight Through the Heart
5 Monitoring Organ/Tissue Metabolism Using Electrochemical Analysis Techniques
6 Monitoring of Organ Metabolism and Architecture Using Optical Sensors
7 Conclusion
References
Microfluidics in Biotechnology: Quo Vadis
1 Introduction
2 Main Fields of Microfluidics in Biotechnology and Their Realized Potential
3 Challenges and Solutions for Microfluidic Proof-of-Concept Systems in Biotechnology
3.1 Design and Fabrication
3.2 Handling
3.3 Standardization
4 Emerging LOCs: From the Lab to the Chip
4.1 Directed Evolution and Adapted Laboratory Evolution
4.2 ``CRISPR-on-a-Chipยดยด (COC)
4.3 Organisms-on-a-Chip
5 Future LOC Technologies: From Lab Applications to Point-of-Use Solutions
5.1 Advanced Microfluidic Technologies
5.2 Advanced Miniaturized Analytics
5.3 Digitalization: Machine Learning, Neuronal Networks, and Artificial Intelligence
6 Integrated Point-of-Use Devices for Monitoring, Understanding, and Controlling Bioprocesses
7 Concluding Remarks
References