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Proceedings ArticleDOI

Electrowetting-based on-chip sample processing for integrated microfluidics

08 Dec 2003-
TL;DR: In this article, results and data are reported on key aspects of sample processing protocols performed on-chip in a digital microfluidic lab on-a-chip (LABON-A-chip).
Abstract: In this work, results and data are reported on key aspects of sample processing protocols performed on-chip in a digital microfluidic lab-on-a-chip We report the results of experiments on aspects of sample processing, including on-chip preconcentration and dilution, on-chip sample injection or dispensing, and sample mixing It is shown that high speed transport and mixing of analytes and reagents can be performed using biological solutions without system contamination
Citations
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Journal ArticleDOI
Richard B. Fair1
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.

1,094 citations


Cites background or methods from "Electrowetting-based on-chip sample..."

  • ...This result demonstrated that strand separation in a 1 ll droplet sample can be performed in 3 s rather than 45 s required in conventional systems (Pollack et al. 2003; Fair et al. 2003)....

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  • ...2006), much less work has been reported on electrowetting or electrostatic-based PCR devices (Tokoro et al. 2002; Pollack et al. 2003; Fair et al. 2003)....

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  • ...In EWD devices droplet-based dilution has been investigated using a binary interpolating mixing algorithm and architecture (Ren et al. 2003a, b; Fair et al. 2003; Griffith et al. 2006)....

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  • ...…PCR have been reported on continuous-flow microfluidic chips (Lagally et al. 2000; Schneegass et al. 2001; Cady et al. 2004; Ottesen et al. 2006), much less work has been reported on electrowetting or electrostatic-based PCR devices (Tokoro et al. 2002; Pollack et al. 2003; Fair et al. 2003)....

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  • ...40 indicate that there was no substantial crosscontamination between the droplets (Fair et al. 2003)....

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Patent
10 Nov 2009
TL;DR: In this article, a method of splitting a droplet is provided, the method including providing a droplets microactuator including a single droplet including one or more beads and immobilizing at least one of the beads.
Abstract: The present invention relates to droplet-based surface modification and washing. According to one embodiment, a method of splitting a droplet is provided, the method including providing a droplet microactuator including a droplet including one or more beads and immobilizing at least one of the one or more beads. The method further includes conducting one or more droplet operations to divide the droplet to yield a set of droplets including a droplet including the one or more immobilized beads and a droplet substantially lacking the one or more immobilized beads.

177 citations

Journal ArticleDOI
TL;DR: This work proposes a system design methodology that attempts to apply classical high-level synthesis techniques to the design of digital microfluidic biochips and develops an optimal scheduling strategy based on integer linear programming and two heuristic techniques that scale well for large problem instances.
Abstract: Microfluidic biochips offer a promising platform for massively parallel DNA analysis, automated drug discovery, and real-time biomolecular recognition. Current techniques for full-custom design of droplet-based “digital” biochips do not scale well for concurrent assays and for next-generation system-on-chip (SOC) designs that are expected to include microfluidic components. We propose a system design methodology that attempts to apply classical high-level synthesis techniques to the design of digital microfluidic biochips. We focus here on the problem of scheduling bioassay functions under resource constraints. We first develop an optimal scheduling strategy based on integer linear programming. However, because the scheduling problem is NP-complete, we also develop two heuristic techniques that scale well for large problem instances. A clinical diagnostic procedure, namely multiplexed in-vitro diagnostics on human physiological fluids, is first used to illustrate and evaluate the proposed method. Next, the synthesis approach is applied to a protein assay, which serves as a more complex bioassay application. The proposed synthesis approach is expected to reduce human effort and design cycle time, and it will facilitate the integration of microfluidic components with microelectronic components in next-generation SOCs.

172 citations


Cites methods from "Electrowetting-based on-chip sample..."

  • ...The basic operations for protein as­say have been implemented on a digital micro.uidic biochip [Srinivasan et al. 2004-2] [Fair et al. 2003]....

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  • ...This on-chip dilution is performed using multiple hierarchies of binary mixing/splitting phases, referred to as the interpolating serial dilution method [Fair et al. 2003]....

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  • ...This on-chip dilution is performed using multiple hierar­chies of binary mixing/splitting phases, referred to as the interpolating serial dilution method [Fair et al. 2003]....

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Patent
30 Jan 2006
TL;DR: The use of soldermask as an electrode insulator for droplet manipulation as well as techniques for adapting other traditional PCB layers and materials for droplets-based microfluidics are also disclosed in this article.
Abstract: Apparatuses and methods for manipulating droplets on a printed circuit board (PCB) are disclosed. Droplets are actuated upon a printed circuit board substrate surface by the application of electrical potentials to electrodes defined on the PCB. The use of soldermask as an electrode insulator for droplet manipulation as well techniques for adapting other traditional PCB layers and materials for droplet-based microfluidics are also disclosed.

166 citations

Journal ArticleDOI
TL;DR: A polynomial-time algorithm for coordinating droplet movement under such hardware limitations is developed and described, and a layout-based system that can be rapidly reconfigured for new biochemical analyses is introduced.
Abstract: This paper describes a computational approach to designing a digital microfluidic system (DMFS) that can be rapidly reconfigured for new biochemical analyses. Such a “lab-on-a-chip” system for biochemical analysis, based on electrowetting or dielectrophoresis, must coordinate the motions of discrete droplets or biological cells using a planar array of electrodes. The authors have earlier introduced a layout-based system and demonstrated its flexibility through simulation, including the system's ability to perform multiple assays simultaneously. Since array-layout design and droplet-routing strategies are closely related in such a DMFS, their goal is to provide designers with algorithms that enable rapid simulation and control of these DMFS devices. In this paper, the effects of variations in the basic array-layout design, droplet-routing control algorithms, and droplet spacing on system performance are characterized. DMFS arrays with hardware limited row-column addressing are considered, and a polynomial-time algorithm for coordinating droplet movement under such hardware limitations is developed. To demonstrate the capabilities of our system, we describe example scenarios, including dilution control and minimalist layouts, in which our system can be successfully applied.

164 citations


Cites methods from "Electrowetting-based on-chip sample..."

  • ...[14] describe an interpolating serial dilution scheme....

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  • ...[14] describe experiments on injection, dispensing, dilution, and mixing of samples in an electrowetting DMFS....

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References
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Journal ArticleDOI
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


"Electrowetting-based on-chip sample..." refers background or methods in this paper

  • ...[ 6 ], forms the basis of the work reported here....

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  • ...A number of methods for manipulating microdroplets have been proposed including dielectrophoresis [1], structured surfaces [2], thermocapillary [3,4], electrostatic [5, 6 ], electrochemical [7] and photochemical effects [8]....

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Journal ArticleDOI
02 Jun 2000-Science
TL;DR: The light-driven motion of a fluid substance in a surface-modified glass tube suggests potential applicability to microscale chemical process systems.
Abstract: The macroscopic motion of liquids on a flat solid surface was manipulated reversibly by photoirradiation of a photoisomerizable monolayer covering the surface. When a liquid droplet several millimeters in diameter was placed on a substrate surface modified with a calix[4]resorcinarene derivative having photochromic azobenzene units, asymmetrical photoirradiation caused a gradient in surface free energy due to the photoisomerization of surface azobenzenes, leading to the directional motion of the droplet. The direction and velocity of the motion were tunable by varying the direction and steepness of the gradient in light intensity. The light-driven motion of a fluid substance in a surface-modified glass tube suggests potential applicability to microscale chemical process systems.

1,352 citations


"Electrowetting-based on-chip sample..." refers methods in this paper

  • ...A number of methods for manipulating microdroplets have been proposed including dielectrophoresis [1], structured surfaces [2], thermocapillary [3,4], electrostatic [5,6], electrochemical [7] and photochemical effects [ 8 ]....

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Journal ArticleDOI
01 Jan 1999-Science
TL;DR: Electrochemical methods were combined with redox-active surfactants to actively control the motions and positions of aqueous and organic liquids on millimeter and smaller scales to guide droplets of organic liquids through simple fluidic networks.
Abstract: Electrochemical methods were combined with redox-active surfactants to actively control the motions and positions of aqueous and organic liquids on millimeter and smaller scales. Surfactant species generated at one electrode and consumed at another were used to manipulate the magnitude and direction of spatial gradients in surface tension and guide droplets of organic liquids through simple fluidic networks. Solid microparticles could be transported across unconfined surfaces. Electrochemical control of the position of surface-active species within aqueous films of liquid supported on homogeneous surfaces was used to direct these films into periodic arrays of droplets with deterministic shapes and sizes.

448 citations


"Electrowetting-based on-chip sample..." refers methods in this paper

  • ...A number of methods for manipulating microdroplets have been proposed including dielectrophoresis [1], structured surfaces [2], thermocapillary [3,4], electrostatic [5,6], electrochemical [ 7 ] and photochemical effects [8]....

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Journal ArticleDOI
TL;DR: In this article, the authors demonstrate a new class of high-speed DEP actuators, including wallless flowstructures, siphons, and nanodroplet dispensers that operate with water.
Abstract: Water, like any polarizable medium, responds to a nonuniform electric field by collecting preferentially in regions of maximum field intensity. This manifestation of dielectrophoresis(DEP) makes possible a variety of microelectromechanicalliquid actuation schemes. In particular, we demonstrate a new class of high-speed DEP actuators, including “wall-less” flowstructures, siphons, and nanodroplet dispensers that operate with water. Liquid in these microfluidic devices rests on a thin, insulating, polyimide layer that covers the coplanar electrodes. Microliter volumes of water, deposited on these substrates from a micropipette, are manipulated, transported, and subdivided into droplets as small as ∼7 nl by sequences of voltage application and appropriate changes of electrode connections. The finite conductivity of the water and the capacitance of the dielectric layer covering the electrodes necessitate use of rf voltage above ∼60 kHz. A simple RC circuit model explains this frequency-dependent behavior. DEP actuation of small water volumes is very fast. We observe droplet formation in less than 0.1 s and transient, voltage-driven movement of water fingers at speeds exceeding 5 cm/s. Such speed suggests that actuation can be accomplished using preprogrammed, short applications of the rf voltage to minimize Joule heating.

443 citations

Journal ArticleDOI
Masao Washizu1
05 Oct 1997
TL;DR: In this paper, a device for the electrostatic actuation of liquid droplets on a solid surface is developed, where arrays of electrodes are micro-fabricated on a substrate, which is covered by a hydrophobic layer.
Abstract: A device for the electrostatic actuation of liquid droplets on a solid surface is developed. Arrays of electrodes are micro-fabricated on a substrate, which is covered by a hydrophobic layer. Wafer droplets, typically /spl mu/l in volume, takes a spherical shape on the surface, and are actuated dielectrophoretically by switching the voltage applied to the electrode array. Transportation of droplets, deflecting a droplet in either of the bifurcating paths, and the mixing of two droplets by collision are experimentally demonstrated. The device can be used for a micro chemical reactor where transport, sorting and mixing of reagents constitute basic unit-operations.

398 citations


"Electrowetting-based on-chip sample..." refers methods in this paper

  • ...A number of methods for manipulating microdroplets have been proposed including dielectrophoresis [1], structured surfaces [2], thermocapillary [3,4], electrostatic [ 5 ,6], electrochemical [7] and photochemical effects [8]....

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