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 digital microfluidic platform for performing heterogeneous sandwich immunoassays based on efficient handling of magnetic beads is presented in this paper. This approach is based on manipulation of discrete droplets of samples and reagents using electrowetting without the need for channels where the droplets are free to move laterally. Droplet-based manipulation of magnetic beads therefore does not suffer from clogging of channels. Immunoassays on a digital microfluidic platform require the following basic operations: bead attraction, bead washing, bead retention, and bead resuspension. Several parameters such as magnetic field strength, pull force, position, and buffer composition were studied for effective bead operations. Dilution-based washing of magnetic beads was demonstrated by immobilizing the magnetic beads using a permanent magnet and splitting the excess supernatant using electrowetting. Almost 100% bead retention was achieved after 7776-fold dilution-based washing of the supernatant. Efficient resuspension of magnetic beads was achieved by transporting a droplet with magnetic beads across five electrodes on the platform and exploiting the flow patterns within the droplet to resuspend the beads. All the magnetic-bead droplet operations were integrated together to generate standard curves for sandwich heterogeneous immunoassays on human insulin and interleukin-6 (IL-6) with a total time to result of 7 min for each assay.

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Heterogeneous immunoassays using magnetic beads on a digital microfluidic platform

This paper details the development of a digital microfluidic platform for multiplexed real-time polymerase chain reactions (PCR). Liquid samples in discrete droplet format are programmably manipulated upon an electrode array by the use of electrowetting. Rapid PCR thermocycling is performed in a closed-loop flow-through format where for each cycle the reaction droplets are cyclically transported between different temperature zones within an oil-filled cartridge. The cartridge is fabricated using low-cost printed-circuit-board technology and is intended to be a single-use disposable device. The PCR system exhibited remarkable amplification efficiency of 94.7%. To test its potential application in infectious diseases, this novel PCR system reliably detected diagnostic DNA levels of methicillin-resistant Staphylococcus aureus (MRSA), Mycoplasma pneumoniae, and Candida albicans. Amplification of genomic DNA samples was consistently repeatable across multiple PCR loops both within and between cartridges. In ad...

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Multiplexed Real-Time Polymerase Chain Reaction on a Digital Microfluidic Platform

An apparatus is provided for manipulating droplets The apparatus is a single-sided electrode design in which all conductive elements are contained on one surface on which droplets are manipulated An additional surface can be provided parallel with the first surface for the purpose of containing the droplets to be manipulated Droplets are manipulated by performing electrowetting-based techniques in which electrodes contained on or embedded in the first surface are sequentially energized and de-energized in a controlled manner The apparatus enables a number of droplet manipulation processes, including merging and mixing two droplets together, splitting a droplet into two or more droplets, sampling a continuous liquid flow by forming from the flow individually controllable droplets, and iterative binary or digital mixing of droplets to obtain a desired mixing ratio

Apparatus for manipulating droplets by electrowetting-based techniques

In this work, a method is presented for controlling on-chip droplet dispensing by electro-wetting actuation in conjunction with capacitance feedback. The method exploits the built-in capacitance of an electro-wetting device to meter the droplet volume and control the dispensing process. A self-contained system is built to provide continuous-flow loading, capacitance measurement, and electro-wetting chip control. Automated droplet generation at rates up to 120 droplets/min is demonstrated for droplets of 0.1 M KCl aqueous solution dispensed onto 1 mm pitch buried electrodes and a 500 μm channel gap. The reproducibility of the droplet volumes is tested against dispensing parameters including production rate, fluid viscosity, channel aspect ratio, dispensing needle position and dispensing volume. The overall reproducibility is ±5% for production rates varying from 8 to 45 droplets/min and ±6% for fluidic viscosity ranging from 1 to 58 Cst, which implies the application of the method to wide ranges of solutions and pressures. Feedback metering compares well with droplet dispensing without capacitance feedback, which gives a reproducibility of ±13% for on-chip dispensing from a reservoir and ±12% for constant pressure-assisted dispensing.

Automated on-chip droplet dispensing with volume control by electro-wetting actuation and capacitance metering

A model is formulated to describe the dynamics of electro-wetting-induced transport of liquid droplets. The velocity of droplet transport as a function of actuation voltage is derived. The operating parameters include the viscosity of the droplet and the medium through which it actuates, contact-line friction, system geometry, and surface tension. Numerical coefficients are extracted from experimental data to represent the effect of operating parameters on electro-wetting dynamics. The power dissipation of droplet transport is analyzed which reveals the key limiting factors for device operation as well the effect of scaling on device power requirements. # 2002 Published by Elsevier Science B.V.

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Michael G. Pollack

Papers

Heterogeneous immunoassays using magnetic beads on a digital microfluidic platform

Multiplexed Real-Time Polymerase Chain Reaction on a Digital Microfluidic Platform

Apparatus for manipulating droplets by electrowetting-based techniques

Automated on-chip droplet dispensing with volume control by electro-wetting actuation and capacitance metering

Dynamics of electro-wetting droplet transport