Droplet-based Microfluidic Chip Design for High Throughput Screening Applications

Droplet-based Microfluidic Chip Design for High Throughput Screening Applications
Title Droplet-based Microfluidic Chip Design for High Throughput Screening Applications PDF eBook
Author Xiaoming Chen
Publisher
Pages 262
Release 2015
Genre Drops
ISBN

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Droplet-based microfluidics has been considered as a prospective tool for high throughput screening analysis, which is highly demanded in a wide range of areas including but not limited to life science research, drug discovery, material synthesis and environmental monitoring. Low sample consumption, reduced reaction time, high throughput manipulation, fast mixing, and prevention of cross contamination at channel walls are just some of the benefits of droplet-based microfluidics. Although extensive research efforts have been reported in the study of droplet-based microfluidics over the past decades, it has yet to be widely commercialized. One of the challenges that limit droplet microfluidic chips from being commercialized is the difficulty in integrating multiple functions robustly without increasing the device footprint. Major functionalities of interest include generating droplets with controlled volume and frequency, and precisely controlling and manipulating each individual droplet such as sorting, detecting, merging, splitting, pairing, mixing, trapping, releasing, long term and short term storing, etc. Since many of these functionalities rely on the accuracy of droplet generation which is the first step, it is crucial to investigate the droplet formation process and understand how to design microfluidic structures to manipulate each individual droplet effectively. To this end, this thesis started with a fundamental study of droplet generation in a flow focusing geometry based on extensive experimental data, from which a physical model was developed to describe droplet formation processes, then move on to study droplet generation in a geometry with two junctions in series, with the goal of improving single encapsulation (one particle per droplet) efficiency. Later, droplet merging towards whole genome amplification and drug screening applications was investigated, and finally a microfluidic chip integrated with multiple functionalities was developed, and its robustness was validated. The first project studied the fundamental principles of liquid-liquid droplet generation in a flow focusing device. This work presents a 3D physical model with less fitting parameters than existing ones. The model describes droplet formation process in flow focusing devices operating in the squeezing regime, where droplet size is usually larger than the channel width, and was developed based on a systematic and extensive experimental study. In particular, it incorporates an accurate geometric description of the 3D droplet shape during the formation process, an estimation of the time period for the formation cycle based on the conservation of mass, and a semi-analytical model predicting the pressure drop over the 3D corner gutter between the droplet curvature and channel walls, which allows droplet size, spacing and formation frequency to be determined accurately. The model takes into account change in channel geometry (height to width ratio), viscosity contrast, flow rate ratio and capillary number with a wide variety. In the second project, liquid-liquid droplet generation in a flow focusing device with two junctions in series was investigated using experimental approach. Extra emphasis was placed on the device's ability to encapsulate single cell and particle. . This study employs glycerol solutions with different concentrations as the dispersed phase, which tends to form stratified flow at the first junction due to viscosity contrast. The stratified flow proceeds to form droplets in oil stream at the second junction. To obtain a comprehensive understanding of the droplet formation dynamics involving stratified flow, five different scenarios were considered. These include a single stream of 10%glycerol aqueous solution, a single stream of 80%glycerol aqueous solution, as well as the simultaneous flow of multiple streams of the above mentioned solution. Droplet size and formation period for these cases were compared and analyzed considering the same geometric and flow conditions. It is found that stratified flow structure strongly influences droplet formation dynamics such as droplet size and formation frequency and the scenario with 80%glyc surrounded by 10%glyc in the first junction generates the largest droplet size. Each structure finds its own applications. For the purpose of single encapsulation, the scenario with 80%glyc surrounded by 10%glyc in the first junction is most suitable because the high viscosity of 80%glyc allows particles to be focused into a thin stream and spaced out before entering droplets. On the other hand, the scenario with two fluids side by side in the first junction generates droplets with high monodispersity for a larger range of flow ratios, which is useful for high throughput reactions involving different reagents. After understanding the fundamentals of the droplet generation process, several designs for practical use were proposed to generate or manipulate droplets. These designs include: i) a flow focusing device that improve droplet size uniformity through changing junction angle; ii) a system for droplet generation on demand, which is essential to controlling droplets of specific reagents; iii) a geometry for generating droplet pairs with uniform droplet sizes and controlled droplet spacing , and to study the interaction between two nearby droplets; iv) a simple droplet merging chamber for controlled reagent volume; and v) a droplet trapping and releasing on demand system for drug screening. The final part of this thesis presents a complex microfluidic system that integrates multiple functionalities, including droplet generation, pairing, trapping, merging, mixing, and releasing. The criterion of this design was analyzed and verified by experiments. This design does not require any synchronization of droplet frequency, spacing or velocity, which makes the microfluidic chip work robustly, and is controlled entirely by liquid flow eliminating the needs for electrodes, magnets or any other moving parts. This design can be applied to many chemical or biological reactions, such as drug screening, chemical synthesis, and cell culture, etc.

Droplet Microfluidics

Droplet Microfluidics
Title Droplet Microfluidics PDF eBook
Author Abraham Lee
Publisher Royal Society of Chemistry
Pages 315
Release 2020-11-27
Genre Science
ISBN 1788017692

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Edited by two leaders, this book has drawn together expertise from around the globe to form a unified, cohesive resource for the droplet microfluidics community. Starting with the basic theory of droplet microfluidics before introducing its use as a tool, the reader is treated to chapters on important techniques, including robust passive and active droplet manipulations and applications such as single cell analysis, which is key for drug discovery. This book is a go-to resource for the community yearning to adopt and promote droplet microfluidics into different applications.

Microfluidics and Lab-on-a-Chip

Microfluidics and Lab-on-a-Chip
Title Microfluidics and Lab-on-a-Chip PDF eBook
Author Andreas Manz
Publisher Royal Society of Chemistry
Pages 307
Release 2020-09-24
Genre Science
ISBN 1782628339

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Responding to the need for an affordable, easy-to-read textbook that introduces microfluidics to undergraduate and postgraduate students, this concise book will provide a broad overview of the important theoretical and practical aspects of microfluidics and lab-on-a-chip, as well as its applications.

Miniaturization of High Throughput Screening in Microfluidics Based on Plugs and SlipChip

Miniaturization of High Throughput Screening in Microfluidics Based on Plugs and SlipChip
Title Miniaturization of High Throughput Screening in Microfluidics Based on Plugs and SlipChip PDF eBook
Author Liang Li
Publisher
Pages 262
Release 2010
Genre
ISBN 9781109689891

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This dissertation describes the development of microfluidic systems based on plugs and SlipChip, for applications in high throughput screening. The advancement of high throughput screening and assays benefits from miniaturization of fluid handling. Robotic systems automate the process of pipette-dispensing solutions into well plates and run on a much smaller scale, but these systems are expensive and inherit some intrinsic problems from dispensing solutions into open wells. Microfluidics handles small amounts (nanoliters to femtoliters) of fluids in enclosed chambers or channels; consequently, it overcomes the intrinsic problems in robotic systems. Among microfluidics-based systems, valve-based microfluidics, compact-disc (CD)-based microfluidics, and droplet (plug)-based microfluidics are applicable to high throughput screening and assays. Valve-based and CD-based microfluidics performs thousands of nanoliter experiments in parallel, but the devices are complicated to manufacture and require expensive instrumentation to operate. Droplet (plug)-based microfluidics drives fluids by pumps and droplets form spontaneously, therefore it is less complicated. This thesis will discuss the development and improvement of methods using plug-based microfluidics to perform high throughput screening. It will also describe the development of the SlipChip, a new technology that accurately manipulates nanoliter fluids without any instruments.

Digital Microfluidic Biochips

Digital Microfluidic Biochips
Title Digital Microfluidic Biochips PDF eBook
Author Krishnendu Chakrabarty
Publisher CRC Press
Pages 228
Release 2018-10-03
Genre Technology & Engineering
ISBN 1420008307

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Digital Microfluidic Biochips focuses on the automated design and production of microfluidic-based biochips for large-scale bioassays and safety-critical applications. Bridging areas of electronic design automation with microfluidic biochip research, the authors present a system-level design automation framework that addresses key issues in the design, analysis, and testing of digital microfluidic biochips. The book describes a new generation of microfluidic biochips with more complex designs that offer dynamic reconfigurability, system scalability, system integration, and defect tolerance. Part I describes a unified design methodology that targets design optimization under resource constraints. Part II investigates cost-effective testing techniques for digital microfluidic biochips that include test resource optimization and fault detection while running normal bioassays. Part III focuses on different reconfiguration-based defect tolerance techniques designed to increase the yield and dependability of digital microfluidic biochips. Expanding upon results from ongoing research on CAD for biochips at Duke University, this book presents new design methodologies that address some of the limitations in current full-custom design techniques. Digital Microfluidic Biochips is an essential resource for achieving the integration of microfluidic components in the next generation of system-on-chip and system-in-package designs.

Droplet and Digital Microfluidics

Droplet and Digital Microfluidics
Title Droplet and Digital Microfluidics PDF eBook
Author Sanket Goel
Publisher Elsevier
Pages 276
Release 2024-03-11
Genre Technology & Engineering
ISBN 0443154171

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Droplet and Digital Microfluidics: Ideation to Implementation is a detailed introduction to the dynamics of droplet and digital microfluidics, also featuring coverage of new methods and applications. The explosion of applications of microelectromechanical systems (MEMS) in recent years has driven demand for expertise and innovation in fluid flow in the microchannels they contain. In this book, detailed descriptions of methods for biological and chemical applications of microfluidics are provided, along with supporting foundational knowledge. In addition, the principles of droplet and digital microfluidics are explained, along with their different applications and governing physics. New additions to the technological knowledgebase that enable advances in droplet and digital microfluidics include machine learning and exciting future avenues for research. - Provides step-by-step fabrication, testing, and characterization instructions in each chapter to support implementation - Includes explanations of applications and methods in biological and chemical settings - Describes the path to automation of digital and droplet microfluidic platforms

Microfluidics

Microfluidics
Title Microfluidics PDF eBook
Author Fouad Sabry
Publisher One Billion Knowledgeable
Pages 477
Release 2022-01-16
Genre Technology & Engineering
ISBN

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What Is Microfluidics Microfluidics refers to the behavior, precise control, and manipulation of fluids that are geometrically constrained to a small scale at which surface forces dominate volumetric forces. It is a multidisciplinary field that involves engineering, physics, chemistry, biochemistry, nanotechnology, and biotechnology. It has practical applications in the design of systems that process low volumes of fluids to achieve multiplexing, automation, and high-throughput screening. Microfluidics emerged in the beginning of the 1980s and is used in the development of inkjet printheads, DNA chips, lab-on-a-chip technology, micro-propulsion, and micro-thermal technologies. How You Will Benefit (I) Insights, and validations about the following topics: Chapter 1: Microfluidics Chapter 2: Droplet-based microfluidics Chapter 3: Digital microfluidics Chapter 4: Paper-based microfluidics Chapter 5: Microfluidic cell culture Chapter 6: Electroosmotic pump Chapter 7: Materials science (II) Answering the public top questions about microfluidics. (III) Real world examples for the usage of microfluidics in many fields. (IV) 17 appendices to explain, briefly, 266 emerging technologies in each industry to have 360-degree full understanding of microfluidics' technologies. Who This Book Is For Professionals, undergraduate and graduate students, enthusiasts, hobbyists, and those who want to go beyond basic knowledge or information for any kind of microfluidics.