Advanced Microfluidics Based Point-of-Care Diagnostics: A Bridge Between Microfluidics and Biomedical Applications

Cover
Half Title
Title Page
Copyright Page
Table of Contents
Editor Biographies
List of Contributors
Chapter 1 The Basic Concept for Microfluidics-Based Devices
	List of Abbreviations
	1.1 What is Microfluidics?
		1.1.1 Evolution of Microfluidics
		1.1.2 Importance of Microfluidics
		1.1.3 Applications of Microfluidics
	1.2 Scaling Laws and Governing Equations
		1.2.1 Correlation of Physical Quantities with Length Scale in Microfluidics
		1.2.2 Scaling of Dimensionless Numbers in Microfluidics with Length Scale (L)
			1.2.2.1 Reynolds Number
			1.2.2.2 Knudsen Number
			1.2.2.3 Weber Number
			1.2.2.4 Froude Number
			1.2.2.5 Capillary Number
			1.2.2.6 Péclet Number
	1.3 Types of Fluid
	1.4 Types of Fluid Flow
	1.5 Role of Mechanical Parameters in the Fluid Flow
		1.5.1 Shear
		1.5.2 Viscosity
			1.5.2.1 Absolute Viscosity
			1.5.2.2 Kinematic Viscosity
		1.5.3 Surface Tension
	1.6 Interface, Surface Tension, and Capillary Action
		1.6.1 Laplace’s Law
		1.6.2 Measurement of Surface Tension
		1.6.3 Parameters Affecting Surface Tension
			1.6.3.1 Temperature
			1.6.3.2 Chemical Addition
			1.6.3.3 Oxidation
		1.6.4 Contact Angle, Drop Thickness, and Wettability
			1.6.4.1 Thermodynamics and Force Balance
		1.6.5 Nature-Inspired Phenomenon
			1.6.5.1 Young’s Model
			1.6.5.2 Wenzel’s Model
			1.6.5.3 Cassie–Baxter model
	1.7 Newton’s Second Law vs the Navier–Stokes Equation
	1.8 Mixing Inside a Microchannel
		1.8.1 Mechanism of Mixing in Macroscale and Microscale
			1.8.1.1 Macromixing
			1.8.1.2 Mesomixing
			1.8.1.3 Micromixing
		1.8.2 Types of Mixing: Passive and Active Mixing
		1.8.3 Brownian Motion, Taylor Dispersion, and Chaotic Advection
			1.8.3.1 Brownian Motion or Diffusive Transport
			1.8.3.2 Taylor Dispersion
			1.8.3.3 Chaotic Advection
		1.8.4 Diffusion: Molecular Diffusion, Eddy Diffusion, and Bulk Diffusion
			1.8.4.1 Molecular Diffusion
			1.8.4.2 Eddy Diffusion
			1.8.4.3 Bulk Diffusion
		1.8.5 Role of Channel Architecture and Physical Forces
			1.8.5.1 Split and Recombine
			1.8.5.2 Ridges, Grooves, or Slanted walls
			1.8.5.3 Multiphase Mixing
			1.8.5.4 Microstirrers
			1.8.5.5 Acoustic Mixing
	1.9 Summary of Materials and Fabrication Techniques for Microfluidics Devices
	1.10 Conclusion
	References
Chapter 2 Role of Microfluidics-Based Point-of-Care Testing (POCT) for Clinical Applications
	2.1 Introduction
	2.2 Impact of Microfluidic-Based POCT in Resource-Limited Settings
	2.3 Clinical Applications Using Microfluidics-Based Devices for POCT
		2.3.1 Glucose Monitoring for Diagnosis of Diabetes
		2.3.2 Cardiac Disease-Associated Marker Detection
		2.3.3 Infectious Diseases
		2.3.4 COVID-19 POC Diagnostics
		2.3.5 Tuberculosis (TB) POC Diagnostics
		2.3.6 Human Immunodeficiency Virus (HIV) POC Diagnostics
		2.3.7 Malaria POC Diagnostics
		2.3.8 Sepsis POC Diagnostics
		2.3.9 Other Infectious Diseases (SARS, Dengue, Tuberculosis) POC Diagnostics
		2.3.10 Cholesterol Monitoring
		2.3.11 Pregnancy and Infertility Testing
		2.3.12 Hematological and Blood Gas Testing
		2.3.13 Other POCT Devices
	2.4 Limitations of Conventional POC Diagnostic
	2.5 Current Trends, Future Prospects, and Concluding Remarks
	Acknowledgments
	References
Chapter 3 Microfluidic Paper-Based Analytical Devices for Glucose Detection
	List of Abbreviations
	3.1 Paper-Based Microfluidic Devices: An Introduction
	3.2 Fabrication Methods
		3.2.1 Lithography
			3.2.1.1 Basic Principle
		3.2.2 Wax Printing
			3.2.2.1 Basic Principle
		3.2.3 Inkjet Printing
			3.2.3.1 Basic Principle
			3.2.3.2 Continuous Inkjet (CIJ) Printing
			3.2.3.3 Drop-On-Demand (DOD) Inkjet Printing
		3.2.4 Role of Semiconductor Oxides for the Fabrication of Microchannels
		3.2.5 Other Methodologies
			3.2.5.1 Plasma Treatment
			3.2.5.2 Spray Drying
			3.2.5.3 3D Printing
	3.3 Surface Modification and Characterization
		3.3.1 Surface Functionalization
			3.3.1.1 Sol–Gel Coatings Method
			3.3.1.2 Modification Using Surfactant
			3.3.1.3 Grafting Polymer Method
			3.3.1.4 Surface-Initiated Atom Transfer Radical Polymerization (SI-ATRP)
		3.3.2 Characterization
			3.3.2.1 Drop Shape Analysis (DSA)
			3.3.2.2 Scanning Electron Microscopy (SEM)
			3.3.2.3 Energy Dispersive X-Ray (EDX) Microanalysis
	3.4 Methods for the Detection of Glucose
		3.4.1 Electrochemical Method
			3.4.1.1 Electro-Chemiluminescence (ECL) Detection
			3.4.1.2 Chemiluminescence (CL) Detection
		3.4.2 Enzymatic Determination (Colorimetric Method)
			3.4.2.1 Alternative Color Indicators for Glucose μPADs
			3.4.2.2 Fluorescence
	3.5 Color Calibration Techniques, Tools, and Methods Adopted
	3.6 Conclusion
	References
Chapter 4 Microfluidics-Based Point-of-Care Diagnostic Devices
	4.1 Introduction
	4.2 Point-of-Care: The Current Scenario
	4.3 Components of a Generalized Microfluidic System for POC Applications
		4.3.1 Flow Pumping and Control
		4.3.2 Sample Preparation and Processing
		4.3.3 Target Detection and Analysis
	4.4 Low-Cost Paper-Based Devices
		4.4.1 Blood Diagnostics
		4.4.2 The Road Ahead for Paper-Based Diagnostics
	4.5 Commercialization of POC Devices
	4.6 Outlook and Future Perspectives
	References
Chapter 5 Microfluidics Device for Isolation of Circulating Tumor Cells in Blood
	5.1 Introduction
	5.2 Metastasis and Importance of CTC Isolation
	5.3 Principles of CTC Isolation from Blood
		5.3.1 Passive Techniques
		5.3.2 Active Techniques
		5.3.3 Combined Techniques
	5.4 Commercialization of Microfluidics Devices for CTC Isolation
	5.5 Summary and Outlook
	References
Chapter 6 3D-Printed Microfluidic Device with Integrated Biosensors for Biomedical Applications
	6.1 Introduction
		6.1.1 History of Microfluidics
	6.2 3D Printing
		6.2.1 Working of 3D Printer
		6.2.2 3D-Printing Techniques
			6.2.2.1 Role of 3D Printing in the Fabrication of Microfluidics Devices
	6.3 3D Technologies
		6.3.1 Stereolithography (SLA)
		6.3.2 Digital Light Processing (DLP)
		6.3.3 Fused Deposition Modeling (FDM)
		6.3.4 Laminated Object Manufacturing (LOM)
		6.3.5 Selective Laser Sintering (SLS)
		6.3.6 Selective Laser Melting (SLM)
		6.3.7 Direct Laser Writing (DLW)
		6.3.8 PolyJet Process
		6.3.9 Multi Jet Fusion (MJF)
	6.4 Advantageous Features of 3D-Printed Microfluidics Devices
	6.5 Biosensor
	6.6 How 3D-Printed Microfluidics Devices Integrate with Biosensors
	6.7 Conclusion
	References
Chapter 7 Integrated Biosensors for Rapid and Point-of-Care Biomedical Diagnosis
	7.1 Introduction
	7.2 Types of Integrated Biosensor
		7.2.1 Biosensors Categorized Based on the Type of Biological Recognition Element and Immobilization Technique
			7.2.1.1 Enzyme-Modified Biosensor
			7.2.1.2 Antibody-Modified Biosensor
			7.2.1.3 Aptamer-Modified Biosensor
		7.2.2 Different Biosensors Based on the Type of Transducer
			7.2.2.1 Electrochemical-Modified Biosensor
			7.2.2.2 Optical-Modified Biosensors
			7.2.2.3 Colorimetric Biosensors
			7.2.2.4 Mass Biosensors
			7.2.2.5 Magnetic Biosensors
	7.3 Various Integrated Biosensors for PoC Biomedical Diagnosis
		7.3.1 Biosensors for POC Diagnosis of Cancer
		7.3.2 Biosensors for POC Diagnosis of Diabetes
		7.3.3 Biosensors for POC Diagnosis of Infectious Diseases
		7.3.4 Biosensors for PoC Diagnosis of Malaria
		7.3.5 Biosensors for PoC Diagnosis of Human Immunodeficiency Virus (HIV)
		7.3.6 Biosensors for POC Diagnosis of Bilharzia
	7.4 Conclusion
	References
Chapter 8 Paper-Based Microfluidics Devices with Integrated Nanostructured Materials for Glucose Detection
	8.1 Introduction
		8.1.1 Microfluidics Paper-Based Analytical Devices (μPADs)
		8.1.2 Glucose Detection Techniques
	8.2 Nanostructured Electrode-Integrated μPADs for Glucose Detection
		8.2.1 Carbon Nanomaterials
			8.2.1.1 Carbon Nanotubes
			8.2.1.2 Carbon Ink
			8.2.1.3 Graphene
			8.2.1.4 Graphite Ink
			8.2.1.5 Graphite Pencil
		8.2.2 Metal Electrodes (Au, Pt)
		8.2.3 Nanowires (ZnO)
		8.2.4 Nanoparticles (NPs)
		8.2.5 Quantum Dots
	8.3 Conclusion and Future Aspects
	References
Chapter 9 Microfluidics Devices as Miniaturized Analytical Modules for Cancer Diagnosis
	9.1 Introduction
	9.2 Microfluidics Approaches for Cancer Detection
		9.2.1 Cell-Affinity MicroChromatography (CAMC)
		9.2.2 Immunomagnetic Separation (IMS)
		9.2.3 Size-Based Cancer Cell Detection and Separation
		9.2.4 On-Chip Dielectrophoresis (DEP)
	9.3 Outlook for Microfluidics Approaches for Cancer Detection
	Acknowledgments
	References
Chapter 10 Analytical Devices with Instrument-Free Detection Based on Paper Microfluidics
	10.1 Introduction: Background
	10.2 Colorimetric Measurement via Transportable Small Devices
		10.2.1 Combination of Additional Cover Boxes with/without Light Sources
		10.2.2 Design of Paper Devices with Pattern Recognition
		10.2.3 Design of Paper Devices with Color Rescaling
		10.2.4 Development of Software/Applications
	10.3 Colorimetric Detection and Quantification via an Instrument-Free Readout
		10.3.1 Distance-Based Method
		10.3.2 Time-Based Method
		10.3.3 Counting-Based Method
		10.3.4 Text-Based Method
	10.4 Conclusions
	References
Chapter 11 Micromixers and Microvalves for Point-of-Care Diagnosis and Lab-on-a-Chip Applications
	11.1 Micromixers for Lab-on-a-Chip Applications
		11.1.1 Principle of Micromixing
		11.1.2 Mixing Efficiency in Microchannels
		11.1.3 Classification of Micromixers
			11.1.3.1 Active Micromixers
			11.1.3.2 Passive Micromixers
		11.1.4 Applications of Micromixers
	11.2 Microvalves for Lab-on-a-Chip Applications
		11.2.1 Principle of Microvalves
		11.2.2 Classification of Microvalves
			11.2.2.1 Active Microvalves
			11.2.2.2 Passive Microvalves
		11.2.3 Applications of Microvalves
	11.3 Conclusion
	References
Chapter 12 Microfluidic Contact Lenses for Ocular Diagnostics
	12.1 Introduction
	12.2 Significance of Microfluidic Contact Lenses for Ocular Diagnostics
	12.3 Five Methods of Manufacturing Microfluidic Contact Lenses
		12.3.1 Thermoforming
		12.3.2 Microlithography
	12.4 Microfluidic Contact Lenses for Intraocular Pressure (IOP) Sensing
		12.4.1 Microfluidic IOP Sensors
	12.5 Microfluidic Contact Lenses for Glucose Sensing
		12.5.1 Microfluidic Contact Lens Sensors for Multiple Targets
	12.6 Microfluidic Contact Lenses for pH Sensing
	12.7 Microfluidic Contact Lenses for Protein Sensing
	12.8 Microfluidic Contact Lenses for Nitrite Ion Sensing
	12.9 Microfluidic Contact Lens Sensor for Corneal Temperature Sensing
	12.10 Conclusion and Future Prospects
	Acknowledgements
	References
Chapter 13 Microfluidic Platforms for Wound Healing Analysis
	13.1 Introduction
	13.2 Wound Fluid Analysis – Challenges and Key Considerations
	13.3 Microfluidics-Based Diagnostic Devices
	13.4 Cost-Effective Paper-Based Microfluidics: New Tools for Point-of-Care Diagnostics
	13.5 Parameters Assessed to Determine Wound Healing
		13.5.1 Microbial Load and Activity
		13.5.2 Enzymes and Their Substrates
		13.5.3 Immunohistochemical Markers
		13.5.4 Nitric Oxide
		13.5.5 Nutritional Factors
		13.5.6 pH of Wound Fluid
		13.5.7 Reactive Oxygen Species
		13.5.8 Temperature
		13.5.9 Transepidermal Water Loss
		13.5.10 C-Reactive Protein
		13.5.11 Interleukin-6
		13.5.12 Uric Acid
		13.5.13 Glucose
	13.6 Future Perspectives
	13.7 Conclusion
	References
Chapter 14 Chromatographic Separation and Visual Detection on Wicking Microfluidics Devices
	14.1 Introduction
	14.2 Overview
	14.3 Fabrication
		14.3.1 Plasma Treatment and Dot Counting
		14.3.2 Chemical Vapor-Phase Deposition (CVD) Technique
		14.3.3 Wax Patterning and Plotting
		14.3.4 Photolithography
		14.3.5 Laser Patterning Treatment
		14.3.6 Plotting, Cutter, and Shaper
	14.4 Applications
		14.4.1 Detection of Heavy Metal
			14.4.1.1 Copper
			14.4.1.2 Nickel, Chromium, and Mercury
			14.4.1.3 Detection of Arsenic
		14.4.2 Detection of Glucose
		14.4.3 Detection of Horseradish Peroxidase
		14.4.4 Immunoassay
		14.4.5 Detection of Hematocrit of Whole Blood
		14.4.6 Detection of Sickle Cell Disease
		14.4.7 Detection of Nitrite Ion and Uric Acid
		14.4.8 Detection of Endocrine Disruptors
		14.4.9 Detection of Hydrogen Peroxide
		14.4.10 Detection of Protein, Ketone Bodies, and Nitrite
	14.5 Conclusion
	References
Chapter 15 Microfluidic Electrochemical Sensor System for Simultaneous Multi Biomarker Analyses
	15.1 Introduction
	15.2 Platforms for Microfluidic Electrochemical Sensor Systems and Applications
	15.3 Non-Paper-Based Devices
		15.3.1 Cancer
		15.3.2 Cardiac Disease and Hypertension
		15.3.3 Virus, DNA/RNA Sequences and Others
	15.4 Paper-Based Devices
		15.4.1 Hydrophobic Barrier Fabrication
		15.4.2 Electrode Fabrication
	15.5 Multiplexed Detection of Biomarkers in µPEDs
		15.5.1 Cancer
		15.5.2 Clinical Biomarkers
	15.6 Conclusion and Future Scope
	Acknowledgment
	References
Chapter 16 Commercialization of Microfluidic Point-of-Care Diagnostic Devices
	16.1 Introduction
	16.2 Fabrication of Microfluidic Device
	16.3 Future Development of Microfluidics-Based Devices
	16.4 Pathway to Commercialization
	16.5 Microfluidics Device Market
	16.6 Microfluidics-Based Point-of-Care Diagnostics
	16.7 Microfluidics Device Market, Company Profiles
	16.8 Overcoming Challenges to Commercialization
	16.9 Concluding Remarks and Future Perspectives
	Acknowledgments
	References
Index