Electrowetting-based droplet mixers for microfluidic systems
TL;DR: In this paper, an alternative mixing strategy is presented based on the discretization of liquids into droplets and further manipulation of those droplets by electrowetting, where interfacial tensions of the droplets are controlled with the application of voltage.
Abstract: 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.
TL;DR: 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 as mentioned in this paper.
Abstract: 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.
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.
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).
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.
TL;DR: To understand the opportunities and limitations of EWD microfluidics, this paper looks at the development of lab-on-chip applications in a hierarchical approach.
Abstract: The suitability of electrowetting-on-dielectric (EWD) microfluidics for true lab-on-a-chip applications is discussed. The wide diversity in biomedical applications can be parsed into manageable components and assembled into architecture that requires the advantages of being programmable, reconfigurable, and reusable. This capability opens the possibility of handling all of the protocols that a given laboratory application or a class of applications would require. And, it provides a path toward realizing the true lab-on-a-chip. However, this capability can only be realized with a complete set of elemental fluidic components that support all of the required fluidic operations. Architectural choices are described along with the realization of various biomedical fluidic functions implemented in on-chip electrowetting operations. The current status of this EWD toolkit is discussed. However, the question remains: which applications can be performed on a digital microfluidic platform? And, are there other advantages offered by electrowetting technology, such as the programming of different fluidic functions on a common platform (reconfigurability)? To understand the opportunities and limitations of EWD microfluidics, this paper looks at the development of lab-on-chip applications in a hierarchical approach. Diverse applications in biotechnology, for example, will serve as the basis for the requirements for electrowetting devices. These applications drive a set of biomedical fluidic functions required to perform an application, such as cell lysing, molecular separation, or analysis. In turn, each fluidic function encompasses a set of elemental operations, such as transport, mixing, or dispensing. These elemental operations are performed on an elemental set of components, such as electrode arrays, separation columns, or reservoirs. Examples of the incorporation of these principles in complex biomedical applications are described.
TL;DR: This work presents a passive method for mixing streams of steady pressure-driven flows in microchannels at low Reynolds number, and uses bas-relief structures on the floor of the channel that are easily fabricated with commonly used methods of planar lithography.
Abstract: It is difficult to mix solutions in microchannels. Under typical operating conditions, flows in these channels are laminar—the spontaneous fluctuations of velocity that tend to homogenize fluids in turbulent flows are absent, and molecular diffusion across the channels is slow. We present a passive method for mixing streams of steady pressure-driven flows in microchannels at low Reynolds number. Using this method, the length of the channel required for mixing grows only logarithmically with the Pe «clet number, and hydrodynamic dispersion along the channel is reduced relative to that in a simple, smooth channel. This method uses bas-relief structures on the floor of the channel that are easily fabricated with commonly used methods of planar lithography.
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.
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.
TL;DR: A three-dimensional serpentine microchannel design with a "C shaped" repeating unit is presented in this paper as a means of implementing chaotic advection to passively enhance fluid mixing.
Abstract: A three-dimensional serpentine microchannel design with a "C shaped" repeating unit is presented in this paper as a means of implementing chaotic advection to passively enhance fluid mixing. The device is fabricated in a silicon wafer using a double-sided KOH wet-etching technique to realize a three-dimensional channel geometry. Experiments using phenolphthalein and sodium hydroxide solutions demonstrate the ability of flow in this channel to mix faster and more uniformly than either pure molecular diffusion or flow in a "square-wave" channel for Reynolds numbers from 6 to 70. The mixing capability of the channel increases with increasing Reynolds number. At least 98% of the maximum intensity of reacted phenolphthalein is observed in the channel after five mixing segments for Reynolds numbers greater than 25. At a Reynolds number of 70, the serpentine channel produces 16 times more reacted phenolphthalein than a straight channel and 1.6 times more than the square-wave channel. Mixing rates in the serpentine channel at the higher Reynolds numbers are consistent with the occurrence of chaotic advection. Visualization of the interface formed in the channel between streams of water and ethyl alcohol indicates that the mixing is due to both diffusion and fluid stirring.
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.