Centrifugal Microfluidics for Nanobiotechnology

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Publication Date 2024/02/28
Pages/Weight/Size 188*257*20mm
ISBN 9788963564517
Categories 대학교재 > 자연과학 계열
Description
Since the inception of lab-on-a-chip (LOC) and micro-total-analysis-systems (μTAS) concepts, a diverse array of microsystems founded on microfluidics has been introduced. Among these, centrifugal microfluidics emerges as particularly noteworthy, showcasing several distinctive advantages over alternative forms. Its most pronounced merit lies in its divergence from the necessity for intricate tubes or pumps in controlling solution flow, a departure from the complexities inherent in other microfluidic devices. This characteristic streamlines device design and fabrication, thereby amplifying data reproducibility through the elimination of manual interventions.

For several years, my research has focused on microdevices for genetic diagnostics grounded in various driving forces such as electrokinetic and hydrodynamic forces. The challenges encountered in establishing consistent conditions for the same chip, stemming from complications in creating tube connection part on a chip, managing multiple tubes for sample in-and-out, and addressing irregular pump operations, have prompted a search for more efficient solutions. In this context, centrifugal microfluidics has proven invaluable, effortlessly executing fundamental unit operations such as volume splitting, solution merging, passive valving, and flow switching solely through rotational force and direction. This capability, coupled with straightforward microfluidic design and surface treatment, underscores the practicality of centrifugal microfluidics.

Within our specialized genetic diagnostics research lab, centrifugal microfluidics was initially introduced for genomic extraction in 2008. Subsequent developments encompassed various forms of genetic diagnostic centrifugal microfluidics, including polymerase chain reaction, isothermal amplification, a lateral flow strip assay, and a solution-loading cartridge facilitating the entire process from sample loading to diagnosis. Additionally, our lab has expanded its focus to high-throughput immuno-diagnostics and nanoparticle synthesis using centrifugal microfluidics, culminating in a high-throughput concept capable of concurrently processing up to 40 samples in a single device, offering a distinct advantage over other microfluidic forms.

Collating our laboratory's published papers, I organized them into ten chapters. The central theme of this book revolves around two primary applications of centrifugal microfluidic technologies: genetic analysis and nanoparticle synthesis. These sections distinguish themselves through their depth and detail, providing a comprehensive examination of the processes from both theoretical and practical perspectives. Each chapter intricately dissects device design, operational principles, and the unparalleled efficiency of centrifugal microfluidics in molecular diagnostics and nanoparticle synthesis.

It is my hope that this work stimulates contemplation among readers regarding the potential impacts of these technologies across various sectors, particularly in the field of nanobiotechnology. With its resonance within both the scientific community and industry practitioners, the book can offer insights into how centrifugal microfluidics is shaping the future of rapid and accurate biomedical diagnostics, contributing significantly to global health strategies, as well as exploring novel smart nanomaterials for the future.
Contents
Preface 1
Acknowledgements 3
Chapter 1. Centrifugal Microfluidic Device for Sample Pretreatment 8
1. Background 8
2. Chip Design 9
2.1. A low-throughput centrifugal microfluidic chip for sample pretreatment 10
2.2. A high-throughput centrifugal microfluidic chip for sample pretreatment 13
3. Chip fabrication 14
4. Chip operation 16
4.1. Principle of a centrifugal microfluidics 16
4.2. Operation of a low-throughput centrifugal microfluidic chip for sample pretreatment 17
4.3. Operation of a high-throughput centrifugal microfluidic chip for sample pretreatment 19
5. Performance of nucleic acid extraction 22
5.1. RNA extraction on a low-throughput centrifugal microfluidic chip 22
5.2. DNA extraction on a high-throughput centrifugal microfluidic chip 24
6. Conclusion 26
References 27

Chapter 2. Centrifugal Microfluidic Device for Polymerase Chain Reaction 30
1. Background 30
2. Centrifugal PCR chip 32
2.1. Material for a microfluidic chip 32
2.2. Chip design 33
2.3. Chip fabrication 34
3. Centrifugal PCR system 35
3.1. Rotational motor 35
3.2. Heater 36
3.3. Fluorescence detection 38
4. Chip operation 39
5. Performance of PCR on a centrifugal microdevice 40
6. Conclusion 43
References 43
Chapter 3. Centrifugal Microfluidic Device for Isothermal Amplification 45
1. Background 45
1.1. A LAMP reaction 46
1.2. An RCA reaction 46
1.3. An RPA reaction 47
2. Centrifugal chip for isothermal amplification 48
2.1. Chip design for LAMP 48
2.2. Chip design for RCA 49
2.3. Chip design for RPA 50
3. Chip fabrication process 52
4. Chip operation 55
5. Performance of isothermal amplification on a centrifugal microdevice 60
6. Conclusion 66
References 67

Chapter 4. Colorimetric Loop-mediated Isothermal Amplification Reaction on a Centrifugal Microfluidic Device 71
1. Background 71
1.1. Colorimetric assay for genetic analysis 71
1.2. Colorimetric PCR and colorimetric LAMP 72
1.3. Principle of EBT-based colorimetric detection 74
2. Centrifugal microdevice for colorimetric LAMP reactions 75
2.1. Chip design 75
2.2. Chip fabrication 78
3. Chip operation 79
4. Application for food-borne pathogen detection 83
4.1. Monoplex detection of pathogen 83
4.2. Multiplex detection of pathogen 85
4.3. Limit-of-detection test 88
5. Conclusion 90
References 90

Chapter 5. Lateral Flow Strip Assay-Incorporated Centrifugal Microfluidic Device for Genetic Analysis 93
1. Background 93
1.1. Lateral flow strip assay 93
1.2. Principle of amplicon detection on a lateral flow strip 95
2. Lateral flow assay-incorporated centrifugal microfluidic chip 97
2.1. Design of a LAMP-lateral flow strip chip 97
2.2. Design of a sample pretreatment-LAMP-lateral flow strip chip 99
2.3. Chip fabrication 100
3. Chip operation 102
4. Application of pathogen detection 104
4.1. Virus detection on a LAMP-lateral flow strip chip 105
4.2. Bacterial detection on a sample pretreatment-LAMP-lateral flow strip chip 108
5. Conclusion 111
References 112

Chapter 6. Combination of a Solution-loading Cartridge with a Centrifugal Microfluidic Device 115
1. Background 115
2. Chip design 117
2.1. Design and fabrication of a solution-loading cartridge 117
2.2. Design and fabrication of an integrated centrifugal microdevice 121
3. Development of a portable genetic analyzer 125
4. Chip operation 129
5. Application of multiplex pathogen detection 132
6. Conclusion 142
References 143

Chapter 7. Centrifugal Microfluidic Device for High-throughput Genetic Analysis 147
1. Background 147
2. Centrifugal microfluidic chip for HTP genetic analysis 148
2.1. Overall design of a centrifugal HTP microfluidic chip 148
2.2. A single unit-centrifugal microfluidics chip with multiple reaction chambers 150
2.3. A centrifugal HTP microfluidics chip with 10 units for COVID-19 diagnostics 151
2.4. A centrifugal HTP microfluidics chip with 30 units for COVID-19 diagnostics 154
3. Fabrication of a centrifugal HTP chip 155
4. Construction of a portable HTP genetic analyzer 157
5. Chip operation 159
6. Application of pathogen detection 163
6.1. A single unit-centrifugal microfluidics chip with multiple reaction chambers 163
6.2. A centrifugal HTP microfluidics chip with 10 units for COVID-19 diagnostics 164
6.3. A centrifugal HTP microfluidics chip with 30 units for COVID-19 diagnostics 166
7. Conclusion 169
References 170

Chapter 8. Centrifugal Microfluidic Device for High-throughput Enzyme-linked Immunosorbent Assay 173
1. Background 173
2. Design of a centrifugal ELISA HTP chip 175
3. Immobilization of antibody on a microfluidic device 177
4. Fabrication of a centrifugal ELISA HTP chip 178
5. Construction of a portable HTP genetic analyzer 179
6. Chip operation 181
7. Application of COVID-19 detection 183
8. Conclusion 186
References 187

Chapter 9. Centrifugal Microfluidic Device for High-throughput Nanoparticle Synthesis 189
1. Background 189
1.1. Limitations of traditional nanoparticle synthetic approaches 189
1.2. Microfluidics based nanoparticle synthesis 190
1.3. High-throughput nanoparticle synthesis on a microfluidic device 191
2. Design of a centrifugal HTP chip for nanoparticle synthesis 192
2.1. A zigzag aliquot structure for efficient and rapid solution loading 193
2.2. Regulating the release of the solution through centrifugal force 194
2.3. Design for a 30-unit centrifugal HTP chip 195
2.4. Design for a 60-unit centrifugal HTP chip 196
2.5. Design for a 60-unit centrifugal HTP chip with a serially diluting structure 197
3. Fabrication of a centrifugal HTP chip for nanoparticle synthesis 199
4. Chip operation 200
5. Application of nanoparticle synthesis 203
5.1. Quantum dots 203
5.2. Gold nanoparticles 206
5.3. Bimetallic catalysts 210
6. Conclusion 211
References 212

Chapter 10. Automatic Centrifugal Microfluidic Device 216
1. Background 216
1.1. Automation 217
1.2. Robot Arm 218
2. Design of components 219
2.1. A robotic solution pipetting device 219
2.2. A solution loading cartridge 221
2.3. Design and fabrication of a centrifugal microfluidic disc 223
3. Integration of a robotic solution pipetting device with a centrifugal chip 224
4. Construction of a portable genetic analyzer 225
5. Chip operation 227
6. Respiratory infectious virus detection from nasopharyngeal swab samples 228
7. Conclusion 232
References 233

Author 235
Author
서태석
Dr. Tae Seok Seo is a Professor of Chemical Engineering at Kyung Hee University, South Korea. He earned his bachelor's degree from Seoul National University, Korea (1996), and his master's degree from KAIST, Korea (1998). He completed his doctoral degree at Columbia University, USA (2004), where he developed a next-generation sequencing technology. Subsequently, he moved to UC Berkeley, USA as a post-doctoral researcher (2007) and contributed to point-of-care genetic analysis projects based on the lab-on-a-chip technique.

Dr. Seo held a faculty position at KAIST from 2007 and has been at Kyung Hee University since 2016. Well-regarded for his research in microfluidics, molecular diagnostics, biosensors, flow chemistry, and nanobiotechnology, Prof. Tae Seok Seo has authored over 150 scientific papers and holds more than 60 patents, in addition to facilitating 8 technology transfers to venture companies. His notable recognitions include Excellent Result 100 in National Research, KAIST Technology Innovation Award, and the Best Industrial Technical Minister Award, etc. He lives in Suwon with his wife and four children. He enjoys golfing, meditating, and participating in Catholic religious activities.
Dr. Tae Seok Seo is a Professor of Chemical Engineering at Kyung Hee University, South Korea. He earned his bachelor's degree from Seoul National University, Korea (1996), and his master's degree from KAIST, Korea (1998). He completed his doctoral degree at Columbia University, USA (2004), where he developed a next-generation sequencing technology. Subsequently, he moved to UC Berkeley, USA as a post-doctoral researcher (2007) and contributed to point-of-care genetic analysis projects based on the lab-on-a-chip technique.

Dr. Seo held a faculty position at KAIST from 2007 and has been at Kyung Hee University since 2016. Well-regarded for his research in microfluidics, molecular diagnostics, biosensors, flow chemistry, and nanobiotechnology, Prof. Tae Seok Seo has authored over 150 scientific papers and holds more than 60 patents, in addition to facilitating 8 technology transfers to venture companies. His notable recognitions include Excellent Result 100 in National Research, KAIST Technology Innovation Award, and the Best Industrial Technical Minister Award, etc. He lives in Suwon with his wife and four children. He enjoys golfing, meditating, and participating in Catholic religious activities.