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

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

This review reports the progress on the recent development of micromixers. The review first presents the different micromixer types and designs. Micromixers in this review are categorized as passive micromixers and active micromixers. Due to the simple fabrication technology and the easy implementation in a complex microfluidic system, passive micromixers will be the focus of this review. Next, the review discusses the operation points of the micromixers based on characteristic dimensionless numbers such as Reynolds number Re, Peclet number Pe, and in dynamic cases the Strouhal number St. The fabrication technologies for different mixer types are also analysed. Quantification techniques for evaluation of the performance of micromixers are discussed. Finally, the review addresses typical applications of micromixers.

https://iopscience.iop.org/article/10.1088/0960-1317/15/2/R01/pdf

Micromixers?a review

This critical review summarizes developments in microfluidic platforms that enable the miniaturization, integration, automation and parallelization of (bio-)chemical assays (see S. Haeberle and R. Zengerle, Lab Chip, 2007, 7, 1094–1110, for an earlier review). In contrast to isolated application-specific solutions, a microfluidic platform provides a set of fluidic unit operations, which are designed for easy combination within a well-defined fabrication technology. This allows the easy, fast, and cost-efficient implementation of different application-specific (bio-)chemical processes. In our review we focus on recent developments from the last decade (2000s). We start with a brief introduction into technical advances, major market segments and promising applications. We continue with a detailed characterization of different microfluidic platforms, comprising a short definition, the functional principle, microfluidic unit operations, application examples as well as strengths and limitations of every platform. The microfluidic platforms in focus are lateral flow tests, linear actuated devices, pressure driven laminar flow, microfluidic large scale integration, segmented flow microfluidics, centrifugal microfluidics, electrokinetics, electrowetting, surface acoustic waves, and dedicated systems for massively parallel analysis. This review concludes with the attempt to provide a selection scheme for microfluidic platforms which is based on their characteristics according to key requirements of different applications and market segments. Applied selection criteria comprise portability, costs of instrument and disposability, sample throughput, number of parameters per sample, reagent consumption, precision, diversity of microfluidic unit operations and the flexibility in programming different liquid handling protocols (295 references).

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Microfluidic lab-on-a-chip platforms: requirements, characteristics and applications

http://hg272.persiangig.com/che/Most%20Populare%20Papers/Micromixers%E2%80%94a%20review%20on%20passive%20and%20active%20mixing%20principles.pdf

Micromixers—a review on passive and active mixing principles

The mixing of analytes and reagents for a biological or chemical lab-on-a-chip is an important, yet difficult, microfluidic operation. As volumes approach the sub-nanoliter regime, the mixing of liquids is hindered by laminar flow conditions. An electrowetting-based linear-array droplet mixer has previously been reported. However, fixed geometric parameters and the presence of flow reversibility have prevented even faster droplet mixing times. In this paper, we study the effects of varying droplet aspect ratios (height ∶ diameter) on linear-array droplet mixers, and propose mixing strategies applicable for both high and low aspect ratio systems. An optimal aspect ratio for four electrode linear-array mixing was found to be 0.4, with a mixing time of 4.6 seconds. Mixing times were further reduced at this ratio to less than three seconds using a two-dimensional array mixer, which eliminates the effects of flow reversibility. For lower aspect ratio (≤0.2) systems, we present a split-and-merge mixer that takes advantage of the ability to perform droplet splitting at these ratios, resulting in a mixing time of less than two seconds.

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Rapid droplet mixers for digital microfluidic systems.

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

MALDI-MS (matrix-assisted laser desorption/ionization mass spectrometry) is one of the most commonly used techniques for protein analysis. In conventional systems sample preparation is typically done in well-plates and transferred onto a MALDI target by robotic systems, which are complex, huge, expensive and slow. In this paper, we present a droplet-based microfluidic interface to transfer protein samples from a well-plate format onto a MALDI target for MS analysis. The droplets are actuated using the electrowetting phenomenon, and are immersed in silicone oil which prevents non-specific adsorption and enables the manipulation of high concentrations of proteins. Droplet transport and droplet formation were evaluated as a function of protein concentration using bovine serum albumin (BSA) as a test system. Droplet transport was possible for BSA concentrations up to 10mg/mL which is three orders of magnitude higher than previously reported results on handling proteins by electrowetting. Droplet formation from on-chip reservoirs, using only electrowetting forces and no external pressure assistance, was possible up to concentrations of 0.01mg/mL. An interface between a well-plate format and the electrowetting chip, and a scheme to passively stamp droplets onto a target substrate was then designed and tested by stamping BSA solutions. In two separate experiments 3.6fmoles and 16fmoles of BSA were stamped onto a glass slide using 0.001mg/mL and 0.01mg/mL samples respectively. A protein mixture with known constituents (ABI 4700 proteomics analyzer calibration solution) was stamped onto a MALDI plate and the individual proteins were correctly identified in the mass spectrum obtained using MALDI-TOF MS. The preliminary results establish the feasibility of using an electrowetting-based microfluidic system to handle proteins especially for protein stamping applications. The proposed system has a small footprint, is easy to control, and is very fast compared to conventional robotic systems. In addition, there are no moving parts and the associated mechanical reliability issues. Future work involves scaling to a larger number of samples and integration of sample preparation steps on-chip.

/pdf/protein-stamping-for-maldi-mass-spectrometry-using-an-rx11w2elqu.pdf

Protein stamping for maldi mass spectrometry using an electrowetting-based microfluidic platform

Matrix protein gene expression in intervertebral disc cells subjected to altered osmolarity.

Thermal management has emerged as a critical issue in the design of integrated circuits (ICs). As feature sizes decrease and package densities increase, current package-level cooling techniques will soon become inadequate. While a number of MEMS-based cooling solutions have been proposed to address cooling at the IC level, many are not equipped to address the problem of real-time active and "smart" cooling, where hotter thermal regions (i.e., hot areas) are detected and subsequently cooled at an increased rate. We describe an alternative cooling method, on a platform we call "digital microfluidics", where nanoliter-sized discrete liquid droplets immersed in oil are manipulated. Cooling droplets are actuated independently in user-defined patterns over an array of electrodes by electrowetting, eliminating the need for external pumps. This paper presents the effects of temperature-dependent system parameters on droplet transport in this digital

/pdf/thermal-effects-on-droplet-transport-in-digital-4i8tgnx1xt.pdf

Phil Paik

Papers

Rapid droplet mixers for digital microfluidic systems.

Electrowetting-based droplet mixers for microfluidic systems

Protein stamping for maldi mass spectrometry using an electrowetting-based microfluidic platform

Matrix protein gene expression in intervertebral disc cells subjected to altered osmolarity.

Thermal effects on droplet transport in digital microfluidics with applications to chip cooling