Microfabricated integrated circuits revolutionized computation by vastly reducing the space, labor, and time required for calculations. Microfluidic systems hold similar promise for the large-scale automation of chemistry and biology, suggesting the possibility of numerous experiments performed rapidly and in parallel, while consuming little reagent. While it is too early to tell whether such a vision will be realized, significant progress has been achieved, and various applications of significant scientific and practical interest have been developed. Here a review of the physics of small volumes (nanoliters) of fluids is presented, as parametrized by a series of dimensionless numbers expressing the relative importance of various physical phenomena. Specifically, this review explores the Reynolds number Re, addressing inertial effects; the Peclet number Pe, which concerns convective and diffusive transport; the capillary number Ca expressing the importance of interfacial tension; the Deborah, Weissenberg, and elasticity numbers De, Wi, and El, describing elastic effects due to deformable microstructural elements like polymers; the Grashof and Rayleigh numbers Gr and Ra, describing density-driven flows; and the Knudsen number, describing the importance of noncontinuum molecular effects. Furthermore, the long-range nature of viscous flows and the small device dimensions inherent in microfluidics mean that the influence of boundaries is typically significant. A variety of strategies have been developed to manipulate fluids by exploiting boundary effects; among these are electrokinetic effects, acoustic streaming, and fluid-structure interactions. The goal is to describe the physics behind the rich variety of fluid phenomena occurring on the nanoliter scale using simple scaling arguments, with the hopes of developing an intuitive sense for this occasionally counterintuitive world.

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Microfluidics: Fluid physics at the nanoliter scale

Microfluidic devices for manipulating fluids are widespread and finding uses in many scientific and industrial contexts. Their design often requires unusual geometries and the interplay of multiple physical effects such as pressure gradients, electrokinetics, and capillarity. These circumstances lead to interesting variants of well-studied fluid dynamical problems and some new fluid responses. We provide an overview of flows in microdevices with focus on electrokinetics, mixing and dispersion, and multiphase flows. We highlight topics important for the description of the fluid dynamics: driving forces, geometry, and the chemical characteristics of surfaces.

Engineering flows in small devices

基礎講座 電気泳動(Electrophoresis)

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

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Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America

Electrowetting has become one of the most widely used tools for manipulating tiny amounts of liquids on surfaces. Applications range from 'lab-on-a-chip' devices to adjustable lenses and new kinds of electronic displays. In the present article, we review the recent progress in this rapidly growing field including both fundamental and applied aspects. We compare the various approaches used to derive the basic electrowetting equation, which has been shown to be very reliable as long as the applied voltage is not too high. We discuss in detail the origin of the electrostatic forces that induce both contact angle reduction and the motion of entire droplets. We examine the limitations of the electrowetting equation and present a variety of recent extensions to the theory that account for distortions of the liquid surface due to local electric fields, for the finite penetration depth of electric fields into the liquid, as well as for finite conductivity effects in the presence of AC voltage. The most prominent failure of the electrowetting equation, namely the saturation of the contact angle at high voltage, is discussed in a separate section. Recent work in this direction indicates that a variety of distinct physical effects?rather than a unique one?are responsible for the saturation phenomenon, depending on experimental details. In the presence of suitable electrode patterns or topographic structures on the substrate surface, variations of the contact angle can give rise not only to continuous changes of the droplet shape, but also to discontinuous morphological transitions between distinct liquid morphologies. The dynamics of electrowetting are discussed briefly. Finally, we give an overview of recent work aimed at commercial applications, in particular in the fields of adjustable lenses, display technology, fibre optics, and biotechnology-related microfluidic devices.

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Electrowetting: from basics to applications

A microactuator for rapid manipulation of discrete microdroplets is presented. Microactuation is accomplished by direct electrical control of the surface tension through two sets of opposing planar electrodes fabricated on glass. A prototype device consisting of a linear array of seven electrodes at 1.5 mm pitch was fabricated and tested. Droplets (0.7–1.0 μl) of 100 mM KCl solution were successfully transferred between adjacent electrodes at voltages of 40–80 V. Repeatable transport of droplets at electrode switching rates of up to 20 Hz and average velocities of 30 mm/s have been demonstrated. This speed represents a nearly 100-fold increase over previously demonstrated electrical methods for the transport of droplets on solid surfaces.

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Electrowetting-based actuation of liquid droplets for microfluidic applications

The serviceability of microfluidics-based instrumentation including ‘lab-on-a-chip’ systems critically depends on control of fluid motion. We are reporting here an alternative approach to microfluidics based upon the micromanipulation of discrete droplets of aqueous electrolyte by electrowetting. Using a simple open structure, consisting of two sets of opposing planar electrodes fabricated on glass substrates, positional and formational control of microdroplets ranging in size from several nanoliters to several microliters has been demonstrated at voltages between 15–100 V. Since there are no permanent channels or structures between the plates, the system is highly flexible and reconfigurable. Droplet transport is rapid and efficient with average velocities exceeding 10 cm s−1 having been observed. The dependence of the velocity on voltage is roughly independent of the droplet size within certain limits, thus the smallest droplets studied (∼3
nl) could be transported over 1000 times their length per second. Formation, mixing, and splitting of microdroplets was also demonstrated using the same microactuator structures. Thus, electrowetting provides a means to achieve high levels of functional integration and flexibility for microfluidic systems.

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Electrowetting-based actuation of droplets for integrated microfluidics

Point of care testing is playing an increasingly important role in improving the clinical outcome in health care management. The salient features of a point of care device are rapid results, integrated sample preparation and processing, small sample volumes, portability, multifunctionality and low cost. In this paper, we demonstrate some of these salient features utilizing an electrowetting-based Digital Microfluidic platform. We demonstrate the performance of magnetic bead-based immunoassays (cardiac troponin I) on a digital microfluidic cartridge in less than 8 minutes using whole blood samples. Using the same microfluidic cartridge, a 40-cycle real-time polymerase chain reaction was performed within 12 minutes by shuttling a droplet between two thermal zones. We further demonstrate, on the same cartridge, the capability to perform sample preparation for bacterial infectious disease pathogen, methicillin-resistant Staphylococcus aureus and for human genomic DNA using magnetic beads. In addition to rapid results and integrated sample preparation, electrowetting-based digital microfluidic instruments are highly portable because fluid pumping is performed electronically. All the digital microfluidic chips presented here were fabricated on printed circuit boards utilizing mass production techniques that keep the cost of the chip low. Due to the modularity and scalability afforded by digital microfluidics, multifunctional testing capability, such as combinations within and between immunoassays, DNA amplification, and enzymatic assays, can be brought to the point of care at a relatively low cost because a single chip can be configured in software for different assays required along the path of care.

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Development of a digital microfluidic platform for point of care testing

Mixing of analytes and reagents is a critical step in realizing a lab-on-a-chip. However, mixing of liquids is very difficult in continuous flow microfluidics due to laminar flow conditions. An alternative mixing strategy is presented based on the discretization of liquids into droplets and further manipulation of those droplets by electrowetting. The interfacial tensions of the droplets are controlled with the application of voltage. The droplets act as virtual mixing chambers, and mixing occurs by transporting the droplet across an electrode array. We also present an improved method for visualization of mixing where the top and side views of mixing are simultaneously observed. Microliters of liquid droplets are mixed in less than five seconds, which is an order of magnitude improvement in reported mixing times of droplets. Flow reversibility hinders the process of mixing during linear droplet motion. This mixing process is not physically confined and can be dynamically reconfigured to any location on the chip to improve the throughput of the lab-on-a-chip.

Electrowetting-based droplet mixers for microfluidic systems

Digital-microfluidic lab-on-a chip (LoC) technology offers a platform for developing diagnostic applications with the advantages of portability, sample and reagent volume reduction, faster analysis, increased automation, low power consumption, compatibility with mass manufacturing, and high throughput. In addition to diagnostics, digital microfluidics is finding use in airborne chemical detection, DNA sequencing by synthesis, and tissue engineering. In this article, we review efforts to develop various LoC applications using electrowetting-based digital microfluidics. We describe these applications, their implementation, and associated design issues.

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Michael G. Pollack

Papers

Electrowetting-based actuation of liquid droplets for microfluidic applications

Electrowetting-based actuation of droplets for integrated microfluidics

Development of a digital microfluidic platform for point of care testing

Electrowetting-based droplet mixers for microfluidic systems

Chemical and Biological Applications of Digital-Microfluidic Devices