Rapid droplet mixers for digital microfluidic systems.
TL;DR: This paper studies the effects of varying droplet aspect ratios on linear-array droplet mixers, and proposes mixing strategies applicable for both high and low aspect ratio systems, and presents a split-and-merge mixer that takes advantage of the ability to perform droplet splitting at these ratios.
Abstract: 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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TL;DR: In this paper, the authors 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.
Abstract: 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.
1,962 citations
Cites background from "Rapid droplet mixers for digital mi..."
...The small droplets can be merged and mixed to induce chemical reactions [109-111]....
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TL;DR: In this paper, the authors report the progress on the recent development of micromixers and present different types and designs of active and passive MCMs, as well as the operation points of the MCMs.
Abstract: 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.
1,651 citations
TL;DR: This critical review summarizes developments in microfluidic platforms that enable the miniaturization, integration, automation and parallelization of (bio-)chemical assays and attempts to provide a selection scheme based on key requirements of different applications and market segments.
Abstract: 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).
1,536 citations
TL;DR: A review on microstructured mixer devices and their mixing principles concerning miscible liquids (and gases) is given in this article, supplemented by the description of typical mixing element designs, methods for mixing characterisation, and application fields.
Abstract: A review on microstructured mixer devices and their mixing principles concerning miscible liquids (and gases) is given. This is supplemented by the description of typical mixing element designs, methods for mixing characterisation, and application fields. The mixing principles applied can be divided in two classes relying either on the pumping energy or provision of other external energy to achieve mixing, termed passive and active mixing, respectively. As far as passive mixing is concerned, devices and techniques such as Y- and T-type flow-, multi-laminating-, split-and-recombine-, chaotic-, jet colliding-, recirculation flow-mixers and others are discussed. Active mixing can be accomplished by time-pulsing flow owing to a periodical change of pumping energy or electrical fields, acoustic fluid shaking, ultrasound, electrowetting-based droplet shaking, microstirrers, and others.
1,354 citations
Cites background from "Rapid droplet mixers for digital mi..."
...Droplets can be moved via electrowetting which is the change of surface energies by applying electric fields (Palk et al., 2003)....
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...If mixing is achieved by droplet movement only, this is passive mixing owing to convections (Palk et al., 2003)....
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..., 2001), periodic variation of flow rate (Glasgow and Aubry, 2003; Niu and Lee, 2003; Qian and Bau, 2002), electrowetting-induced merging of droplets (Palk et al., 2003), piezoelectric vibrating membranes (Woias et al....
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...A voltage of 50V was applied (Palk et al., 2003)....
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...It is described above that by electrowetting droplets can be merged and passive mixing takes place (Palk et al., 2003)....
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TL;DR: This work presents an alternative paradigm--a fully integrated and reconfigurable droplet-based "digital" microfluidic lab-on-a-chip for clinical diagnostics on human physiological fluids, and demonstrates reliable and repeatable high-speed transport of microdroplets.
Abstract: Clinical diagnostics is one of the most promising applications for microfluidic lab-on-a-chip systems, especially in a point-of-care setting. Conventional microfluidic devices are usually based on continuous-flow in microchannels, and offer little flexibility in terms of reconfigurability and scalability. Handling of real physiological samples has also been a major challenge in these devices. We present an alternative paradigm—a fully integrated and reconfigurable droplet-based “digital” microfluidic lab-on-a-chip for clinical diagnostics on human physiological fluids. The microdroplets, which act as solution-phase reaction chambers, are manipulated using the electrowetting effect. Reliable and repeatable high-speed transport of microdroplets of human whole blood, serum, plasma, urine, saliva, sweat and tear, is demonstrated to establish the basic compatibility of these physiological fluids with the electrowetting platform. We further performed a colorimetric enzymatic glucose assay on serum, plasma, urine, and saliva, to show the feasibility of performing bioassays on real samples in our system. The concentrations obtained compare well with those obtained using a reference method, except for urine, where there is a significant difference due to interference by uric acid. A lab-on-a-chip architecture, integrating previously developed digital microfluidic components, is proposed for integrated and automated analysis of multiple analytes on a monolithic device. The lab-on-a-chip integrates sample injection, on-chip reservoirs, droplet formation structures, fluidic pathways, mixing areas and optical detection sites, on the same substrate. The pipelined operation of two glucose assays is shown on a prototype digital microfluidic lab-on-chip, as a proof-of-concept.
1,124 citations
References
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TL;DR: In this paper, the authors report the completion of four fundamental fluidic operations considered essential to build digital microfluidic circuits, which can be used for lab-on-a-chip or micro total analysis system (/spl mu/TAS): 1) creating, 2) transporting, 3) cutting, and 4) merging liquid droplets, all by electrowetting.
Abstract: Reports the completion of four fundamental fluidic operations considered essential to build digital microfluidic circuits, which can be used for lab-on-a-chip or micro total analysis system (/spl mu/TAS): 1) creating, 2) transporting, 3) cutting, and 4) merging liquid droplets, all by electrowetting, i.e., controlling the wetting property of the surface through electric potential. The surface used in this report is, more specifically, an electrode covered with dielectrics, hence, called electrowetting-on-dielectric (EWOD). All the fluidic movement is confined between two plates, which we call parallel-plate channel, rather than through closed channels or on open surfaces. While transporting and merging droplets are easily verified, we discover that there exists a design criterion for a given set of materials beyond which the droplet simply cannot be cut by EWOD mechanism. The condition for successful cutting is theoretically analyzed by examining the channel gap, the droplet size and the degree of contact angle change by electrowetting on dielectric (EWOD). A series of experiments is run and verifies the criterion.
1,522 citations
TL;DR: A device was developed that uses microfabricated fluidic channels, heaters, temperature sensors, and fluorescence detectors to analyze nanoliter-size DNA samples to facilitate the use of DNA analysis in applications such as rapid medical diagnostics and point-of-use agricultural testing.
Abstract: A device was developed that uses microfabricated fluidic channels, heaters, temperature sensors, and fluorescence detectors to analyze nanoliter-size DNA samples. The device is capable of measuring aqueous reagent and DNA-containing solutions, mixing the solutions together, amplifying or digesting the DNA to form discrete products, and separating and detecting those products. No external lenses, heaters, or mechanical pumps are necessary for complete sample processing and analysis. Because all of the components are made using conventional photolithographic production techniques, they operate as a single closed system. The components have the potential for assembly into complex, low-power, integrated analysis systems at low unit cost. The availability of portable, reliable instruments may facilitate the use of DNA analysis in applications such as rapid medical diagnostics and point-of-use agricultural testing.
1,486 citations
TL;DR: In this article, a microactuator for rapid manipulation of discrete microdroplets is presented, which is accomplished by direct electrical control of the surface tension through two sets of opposing planar electrodes fabricated on glass.
Abstract: 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.
1,471 citations
TL;DR: In this paper, an alternative approach to microfluidics based upon the micromanipulation of discrete droplets of aqueous electrolyte by electrowetting is reported.
Abstract: 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.
1,078 citations
01 Jan 2002
TL;DR: Electrowetting and electrowetting-on-dielectric (EWOD) as discussed by the authors can control the wettability of liquids on solid surfaces using electric potential, which can be applied to microfluidic devices.
Abstract: This paper deals with electrowetting (EW) and electrowetting-on-dielectric (EWOD) principles applied to microfluidic devices. EW and EWOD are principles that can control wettability of liquids on solid surfaces using electric potential. While EW is controlling wettability of a certain electrolyte on a metal electrode by varying electric energy across the electrical double layer (EDL), EWOD applies to virtually any aqueous liquid by varying electric energy across the thin dielectric film between the liquid and conducting substrate. These driving mechanisms have many advantages. By electrically changing the wettability of each of the electrode patterns on a surface, a liquid on these electrodes can be shaped and driven along the active electrodes, making microfluidics extremely simple both for device fabrication and operation. It is also worth noting that, driven by surface tension, the mechanism becomes more effective as the size of the device becomes smaller. This paper describes fundamental concepts and the proof-of-concept experiments, modeling and design, microfabrication processes, and initial testing results for the microfluidic devices based on the EW and EWOD principles.
643 citations