Finger Powered Digital Microfluidics For Micro Droplet Manipulation

Microfluidic devices that do not require bulky peripheral hardware, such as pumps and external battery/power supplies, are a suitable technology for portable applications in resource-constrained settings, such as point-of-care (POC) diagnosis in developed countries, environmental monitoring, and on-site forensic analysis, etc. The existing portable microfluidic devices are mostly based on microchannel structures, in which the pre-defined channels limit their functional flexibility, rendering them difficult to scale up. Digital microfluidics, on the other hand, can tackle this problem since they deal with discrete droplets individually and can therefore provide more on-demand flexibility and versatility. Most digital microfluidic devices, however, require external electric power sources. We first propose finger-powered digital microfluidic (F-DMF) based on electrowetting on dielectric (EWOD). Instead of requiring an external power supply, our F-DMF uses piezoelectric elements to convert the mechanical energy produced by human fingers into electric voltage pulses for droplet manipulation. The voltage outputs of piezoelectric element mounted in cantilever beam configuration are studied theoretically and experimentally. Using this energy conversion scheme, the basic modes of droplet operations, such as droplet transport, splitting, and merging on EWOD devices are confirmed. The key assay steps involved in glucose detection and immunoassay are also successfully performed using F-DMF-EWOD. Exploiting the same energy conversion scheme, F-DMF based on the electrophoretic transport of discrete droplets (EPD), which has the potential to overcome pinning and surface contamination often encountered in EWOD, is then presented. Successful EPD actuation, however, requires the piezoelectric elements to provide both sufficient charge and voltage pulse duration. These requirements are quantified using numerical models to predict the electrical charges induced on the droplets and the subsequent electrophoretic forces. The transport and merging of aqueous droplets as well as direct manipulation of body fluids is experimentally demonstrated using F-EPD-DMF. Further, a mechanical system and an efficient pin-assignment scheme are explored to facilitate the practical implementation of pre-programmed and functional actuation of droplets in the EPD-based system. For the second part of this thesis, one practical issue in digital microfluidics biochip (DMFB) design is discussed: the droplet routing problem, which largely decides the performance and correctness of the system. The problem is formulated to a multi-agent path finding problem (MAPF) and an approximate algorithm based on Independent Detection (ID) is applied to solve the problem. The modified ID algorithm shows promising performance on selected benchmark problems with medium number of droplets ( 12). Overall, it achieves better timing result (~15% reduction) and total routing length (~50% reduction) with no compromise in fault tolerance (indicated by the total number of used cells), when compared with the previous best known results.

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

After spending over 12 years developing new microsystems for biotechnology – especially concerned with the microfluidic aspects of these devices – Jean Berthier is considered a leading authority in the field. Now, following the success of his book, Microfluidics for Biotechnology, Dr. Berthier returns to explain how new miniaturization techniques have dramatically expanded the area of microfluidic applications and microsystems into microdrops and digital microfluidics. Engineers interested in designing more versatile microsystems and students who seek to learn the fundamentals of microfluidics will all appreciate the wide-range of information found within Microdrops and Digital Microfluidics. The most recent developments in digital microfluidics are described in clear detail, with a specific focus on the computational, theoretical and experimental study of microdrops. Over 500 equations and more than 400 illustrations Authoritative reporting on the latest changes in microfluidic science, where microscopic liquid volumes are handled as "microdrops" and separately from "nanodrops" A methodical examination of how liquid microdrops behave in the complex geometries of modern miniaturized systems and interact with different morphological (micro-fabricated, textured) solid substrates A thorough explanation of how capillary forces act on liquid interfaces in contact with micro-fabricated surfaces Analysis of how droplets can be manipulated, handled, or transported using electric fields (electrowetting), acoustic actuation (surface acoustic waves), or by a carrier liquid (microflow) A fresh perspective on the future of microfluidics

The combination of microfabrication and microfluidics has enabled a variety of opportunities in making new tools for biological and diagnostic applications. For example, microdroplets-based systems have attracted lots of attentions in recent years due to potential advantages in controlled environments with fast reaction time, high-throughput and low noises. This work presents a number of advanced microfluidic systems in process, control and manipulation of microdroplets, including finger-powered pumps to generate microdroplets, continuous-flow rupture reactors for the rupture and content retrieval of microdroplets, and magnetic microcapsules for drug delivery applications. Prototype `finger-powered' pumping systems have been designed and constructed and integrated with passive fluidic diodes to pump microfluidics, including the formation of microdroplets. No electrical power is needed for pumping by using a human finger as the actuation force to generate pressure heads. Both multilayer soft lithography and injection molding processes have been successfully utilized to make the pumping systems. Experimental results revealed that the pressure head generated from a human finger could be tuned based on the geometric characteristics of the system, with a maximum observed pressure of 7.6±0.1 kPa. In addition to the delivery of multiple, distinct fluids into microfluidic channels, the finger-powered pumping system is also employed to achieve rapid formation of both water-in-oil droplets (106.9±4.3 [mu]m in diameter) and oil-in-water droplets (75.3±12.6 [mu]m in diameter), as well as the encapsulation of endothelial cells in microdroplets without using any external or electrical controllers. To advance the technology of microdroplets in microfluidic systems, the technique to rupture microdroplets via the continuous-flow micropost array railing systems has been developed. The key step is to transport water-in-oil microdroplets with surfactant into the pure oil microchannel to wash away the surfactant and allow the washed microdroplets to transport to the next water microchannel and rupture at the oil-water interface boundary. Microdroplets-based nanoparticle synthesis systems have been fabricated to demonstrate synthesis and retrieval of iron oxide nanoparticles without the need of an external centrifuge machine. In a second demonstration, a rapid solution alteration system for the bead-in-droplet microreactors has been demonstrated via the continuous flow micropost array railing technique. The prototype system has accomplished: (i) the retrieval of microbeads in water-in-oil droplets by the 'rupture' of the droplets, (ii) transfer of the released microbeads into a second solution, and (iii) the formation of new water-in-oil droplets containing the original microbeads and a different, second droplet solution. In these experiments, a total of four different microdroplets generation systems have been fabricated and different designs and operation conditions result in different sizes of microdroplets, including 41.1 [mu]m for the basic microdroplets rupture demonstration, 67.5 [mu]m for nanoparticle synthesis experiments, 61.1 [mu]m in the original solution, and 38.6 [mu]m for the new solution in the bead-in- droplets alternation experiments. In the last example, a new class of magnetic microcapsules with aqueous core and polymer shell containing magnetic nanoparticles has been demonstrated for possible drug delivery applications. The combination of multi-layer flow-focusing methodology and an optofluidic polymerization process is employed to form double emulsions of water-in-photocurable polymer microdroplets. A subsequently polymerization process cure the magnetic polymer shells and encapsulates drug materials in the core. Experimentally, remote manipulations of the magnetic microcapsules by applying an external magnetic field have been achieved. As such, the proposed microcapsules have the potential to overcome a number of hurdles associated with current state-of-art technologies: (1) magnetic shells can be guided by DC magnetic field for location control; (2) magnetic particles can be heated by AC magnetic field to break or change the porosity of the shells for active drug release control; and (3) encapsulated microdroplets can prevent the possible degradation and contamination of the drug materials during the transportation processes.

Microdroplet technology has recently emerged to provide new and diverse applications via microfluidic functionality, especially in various areas of biology and chemistry. This book, then, gives an overview of the principle components and wide-ranging applications for state-of-the-art of droplet-based microfluidics. Chapter authors are internationally-leading researchers from chemistry, biology, physics and engineering that present various key aspects of micrdroplet technology -- fundamental flow physics, methodology and components for flow control, applications in biology and chemistry, and a discussion of future perspectives. This book acts as a reference for academics, post-graduate students, and researcher wishing to deepen their understand of microfluidics and introduce optimal design and operation of new droplet-based microfluidic devices for more comprehensive analyte assessments.

Droplet microfluidics offers tremendous potential as an enabling technology for high-throughput screening. It promises to yield novel techniques for personalised medicine, drug discovery, disease diagnosis, establishing chemical libraries, and the discovery of new materials. Despite the enormous potential to contribute to a broad range of applications, the expected adoption has not yet been seen, partly due to the interdisciplinary nature and the fact that, up until now, information has been scattered across the literature. This book goes a long way to addressing these issues. 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 will be 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 and will interest researchers and practitioners working across chemistry, biology, physics, materials science, micro- and nano-technology, and engineering.

Microfluidics is a broad research field that encompasses applications for the medical, chemical, industrial and environment industries by leveraging the ability to control and manipulate micro-scale volumes of fluids. Most applications involve some sort of sensing capability for the presence of specific biological, chemical, or mineral compounds which has been termed Lab-on-a-chip(LOC). This refers to the miniaturization of standard laboratory analysis systems on to a single device to allow for faster yield times, reduced reagent and sample use and overall reduced costs. There are currently two primary fluid handling methods used involving fixed-channel, continuous flow or discrete droplet manipulation. Fixed-channel microfluidic devices have been proven to be reliable for several LOC applications, however, there is no ability to reconfigure or repurpose a device without a complete redesign and fabrication. The second handling method, known as digital microfluidics, uses electrical stimuli to move and manipulate individual droplets over an array of electrodes. By using this method, reconfigurability can be realized simply by changing a sequence of droplet(s) movements and therefore, a single platform can be used for a multitude of LOC applications without a complete device redesign. To further the overall capabilities of a digital microfluidic platform, the ability to control and hold some fluidic shape without an applied voltage adds not only bistability to the system, but can be advantageous for reduced energy consumption, extra functionalities and improved fluidic control. This also allows for simple displays applications to be realized. Presented in this dissertation is a cross-platform digital microfluidic device developed for both LOC and simple displays applications which utilizes an electrowetting grid array and Laplace barriers for bistability. Materials improvements, electrical control methods and the ability to perform all necessary tasks for both types of applications were developed and will be demonstrated throughout.

Droplet microfluidics has dramatically developed in the past decade and has been established as a microfluidic technology that can translate into commercial products. Its rapid development and adoption have relied not only on an efficient stabilizing system (oil and surfactant), but also on a library of modules that can manipulate droplets at a high-throughput. Droplet microfluidics is a vibrant field that keeps evolving, with advances that span technology development and applications. Recent examples include innovative methods to generate droplets, to perform single-cell encapsulation, magnetic extraction, or sorting at an even higher throughput. The trend consists of improving parameters such as robustness, throughput, or ease of use. These developments rely on a firm understanding of the physics and chemistry involved in hydrodynamic flow at a small scale. Finally, droplet microfluidics has played a pivotal role in biological applications, such as single-cell genomics or high-throughput microbial screening, and chemical applications. This Special Issue will showcase all aspects of the exciting field of droplet microfluidics, including, but not limited to, technology development, applications, and open-source systems.

Manipulation of microparticles by droplets is a very useful and important technique for many microfluidics applications. Due to the large specific surface necessary for chemical binding and easy recovery from a dispersion, utilization of nanospheres or microspheres has become more and more popular for different medical, biological, and optical applications. The goal of this research is to understand the mechanism for the manipulation of microparticles by droplets. Dissipative particle dynamics (DPD), which is extensively used to model mesoscale flow phenomena, is applied as the numerical tool for this study. A model for solid microparticles is designed to study the interactions among microparticles, liquid droplets, and solid substrates. A spherical shell is used to represent the microparticle, and the shell surface is packed by dense enough beads to avoid undesired penetration of liquid beads into solid microparticles, conserving the momentum automatically. After that, the interaction between a rigid microparticle and a solid substrate is modeled based on contact mechanics, including adhesion forces, normal forces, and friction forces. After the model for microparticles is built, a baseline case simulating the pickup and transport of a hydrophobic microparticle by a droplet is demonstrated and compared with experimental observations. Then, the flow structures within a droplet containing a hydrophobic microparticle are revealed. With this developed numerical tool, parametric studies are conducted to investigate the effect on the manipulation processes (including pickup, transport, and drop off) of a microparticle by droplet sizes, wetting properties of microparticles, and particle-substrate friction coefficients. The increase of droplet size can speed up the transport of microparticles. However, the increase of particle-substrate friction coefficients can lead to drop-off of a hydrophobic microparticle. The mechanism for the drop-off, or delivery, is analyzed by checking the development of the friction force and driving force on the microparticle during the transport process. The critical velocity, defined as the instantaneous velocity of the microparticle right before the occurrence of delivery, is measured, and it is found that the critical velocity is about same for different sizes of droplets. Based on the numerical results, two different designs, namely passive delivery and active delivery, have been demonstrated to be capable of controlling the location for the delivery of single hydrophobic microparticle without any trap design or external field forces. These numerical results provide a fundamental understanding of interactions among the microparticle, the droplet and the substrate to facilitate the optimal experimental design of digital microfluidic system utilizing microparticles.

With the development of lithography techniques, microfluidic systems have drastically evolved in the past decades. Digital microfluidics (DMF), which enables discrete droplet actuation without any carrying liquid as opposed to the continuous-fluid-based microfluidics, emerged as the candidate for the next generation of lab-on-a-chip systems. The DMF has been applied to a wide variety of fields including electrochemical and biomedical assays, drug delivery, and point-of-care diagnosis of diseases. Most of the DMF devices are made with photolithography which requires complicated processes, sophisticated equipment, and cleanroom setting. Based on the fabrication technology being used, these DMF manipulate droplets in a planar format that limits the increase of chip density. The objective of this study is to introduce additive manufacturing (AM) into the fabrication process of DMF to design and build a 3D-structured DMF platform for droplet actuation between different planes. The creation of additively manufactured DMF is demonstrated by fabricating a planar DMF device with ion-selective sensing functions. Following that, the design of vertical DMF electrodes overcomes the barrier for droplets to move between different actuation components, and the application of AM helps to construct free-standing xylem DMF to drive the droplet upward. To form a functional system, the horizontal and xylem DMF are integrated so that a three-dimensional (3D) droplet manipulation is demonstrated. The integrated system performs a droplet actuation speed of 1 mm/s from horizontal to vertical with various droplet sizes. It is highly expected that the 3D-structured DMF open new possibilities for the design of DMF devices that can be used in many practical applications.