Achromatic doublet electrowetting prism array for beam steering device in foveated display.

A foveated display is a technology that can solve the problem of insufficient angular resolution (relative to the human eye) for near-eye display. In a high-resolution foveated display, a beam steering element is required to track the human gaze. An electrowetting prism array is a transmissive non-mechanical beam steering device, that allows a light and compact optical system to be configured and a large aperture possible. However, the view is obstructed by the sidewall of the prism array. When the size of the cell prism is 7mm, the prism array has an 87% fill-factor. To push the fill-factor to 100%, the cell prisms were magnified using a lens array. Image processing was performed such that the image produced by the lens array was identical to the original. Beam steering by refraction is accompanied by chromatic dispersion, which causes chromatic aberration, making colors appear blurry. The refractive index condition to reduce chromatic dispersion was obtained using the doublet structure of the electrowetting prism. The chromatic dispersion was reduced by 70% on average.

Melt Electrowritten In Vitro Radial Device to Study Cell Growth and Migration.

The development of in vitro assays for 3D microenvironments is essential for understanding cell migration processes. A 3D-printed in vitro competitive radial device is developed to identify preferred Matrigel concentration for glioblastoma migration. Melt electrowriting (MEW) is used to fabricate the structural device with defined and intricate radial structures that are filled with Matrigel. Controlling the printing path is necessary to account for the distance lag in the molten jet, the applied electric field, and the continuous direct-writing nature of MEW. Circular printing below a diameter threshold results in substantial inward tilting of the MEW fiber wall. An eight-chamber radial device with a diameter of 9.4 mm is printed. Four different concentrations of Matrigel are dispensed into the radial chambers. Glioblastoma cells are seeded into the center and grow into all chambers within 8 days. The cell spreading area demonstrates that 6 and 8 mg mL-1 of Matrigel are preferred over 2 and 4 mg mL-1 . Furthermore, topographical cues via the MEW fiber wall are observed to promote migration even further away from the cell seeding depot. Previous studies implement MEW to fabricate cell invasive scaffolds whereas here it is applied to 3D-print in vitro tools to study cell migration.

PortaDrop: A portable digital microfluidic platform providing versatile opportunities for Lab-On-A-Chip applications.

Electrowetting-on-dielectric is a decent technique to manipulate discrete volumes of liquid in form of droplets. In the last decade, electrowetting-on-dielectric systems, also called digital microfluidic systems, became more frequently used for a variety of applications because of their high flexibility and reconfigurability. Thus, one design can be adapted to different assays by only reprogramming. However, this flexibility can only be useful if the entire system is portable and easy to use. This paper presents the development of a portable, stand-alone digital microfluidic system based on a Linux-based operating system running on a Raspberry Pi, which is unique. We present "PortaDrop" exhibiting the following key features: (1) an "all-in-one box" approach, (2) a user-friendly, self-explaining graphical user interface and easy handling, (3) the ability of integrated electrochemical measurements, (4) the ease to implement additional lab equipment via Universal Serial Bus and the General Purpose Interface Bus as well as (5) a standardized experiment documentation. We propose that PortaDrop can be used to carry out experiments in different applications, where small sample volumes in the nanoliter to picoliter range need to be handled an analyzed automatically. As a first application, we present a protocol, where a droplet is consequently exchanged by droplets of another medium using passive dispensing. The exchange is monitored by electrical impedance spectroscopy. It is the first time, the media exchange caused by passive dispensing is characterized by electrochemical impedance spectroscopy. Summarizing, PortaDrop allows easy combination of fluid handling by means of electrowetting and additional sensing.

Electrowetting-based Digital Microfluidics Platform for Automated Enzyme-linked Immunosorbent Assay.

Electrowetting is the effect by which the contact angle of a droplet exposed to a surface charge is modified. Electrowetting-on-dielectric (EWOD) exploits the dielectric properties of thin insulator films to enhance the charge density and hence boost the electrowetting effect. The presence of charges results in an electrically induced spreading of the droplet which permits purposeful manipulation across a hydrophobic surface. Here, we demonstrate EWOD-based protocol for sample processing and detection of four categories of antigens, using an automated surface actuation platform, via two variations of an Enzyme-Linked Immunosorbent Assay (ELISA) methods. The ELISA is performed on magnetic beads with immobilized primary antibodies which can be selected to target a specific antigen. An antibody conjugated to HRP binds to the antigen and is mixed with H2O2/Luminol for quantification of the captured pathogens. Assay completion times of between 6 and 10 min were achieved, whilst minuscule volumes of reagents were utilized.

Liquid Combination with High Refractive Index Contrast and Fast Scanning Speeds for Electrowetting Adaptive Optics.

Electrowetting adaptive optical devices are versatile, with applications ranging from microscopy to remote sensing. The choice of liquids in these devices governs its tuning range, temporal response, and wavelength of operation. We characterized a liquid system, consisting of 1-phenyl-1-cyclohexene and deionized water, using both lens and prism devices. The liquids have a large contact angle tuning range, from 173 to 60°. Measured maximum scanning angle was realized at ±13.7° in a two-electrode prism, with simulation predictions of ±18.2°. The liquid's switching time to reach 90° contact angle from rest, in a 4 mm diameter device, was measured at 100 ms. Steady-state scanning with a two-electrode prism showed linear and consistent scan angles of ±4.8° for a 20 V differential between the two electrodes, whereas beam scanning using the liquid system achieved ±1.74° at 500 Hz for a voltage differential of 80 V.

Digital microfluidics comes of age: high-throughput screening to bedside diagnostic testing for genetic disorders in newborns.

INTRODUCTION: Digital microfluidics (DMF) is an emerging technology with the appropriate metrics for application to newborn and high-risk screening for inherited metabolic disease and other conditions that benefit from early treatment. Areas covered: This review traces the development of electrowetting-based DMF technology toward the fulfillment of its promise to provide an inexpensive platform to conduct enzymatic assays and targeted biomarker assays at the bedside. The high-throughput DMF platform, referred to as SEEKER®, was recently authorized by the United States Food and Drug Administration to screen newborns for four lysosomal storage disorders (LSDs) and is deployed in newborn screening programs in the United States. The development of reagents and methods for LSD screening and results from screening centers are reviewed. Preliminary results from a more compact DMF device, to perform disease-specific test panels from small volumes of blood, are also reviewed. Literature for this review was sourced using principal author and subject searches in PubMed. Expert commentary: Newborn screening is a vital and highly successful public health program. DMF technology adds value to the current testing platforms that will benefit apparently healthy newborns with underlying genetic disorders and infants at-risk for conditions that present with symptoms in the newborn period.

Self-Powered Microfluidic Transport System Based on Triboelectric Nanogenerator and Electrowetting Technique.

Electrowetting technique is an actuation method for manipulating position and velocity of fluids in the microchannels. By combining electrowetting technique and a freestanding mode triboelectric nanogenerator (TENG), we have designed a self-powered microfluidic transport system. In this system, a mini vehicle is fabricated by using four droplets to carry a pallet (6 mm × 8 mm), and it can transport some tiny object on the track electrodes under the drive of TENG. The motion of TENG can provide both driving power and control signal for the mini vehicle. The maximum load for this mini vehicle is 500 mg, and its highest controllable velocity can reach 1 m/s. Freestanding TENG has shown excellent capability to manipulate microfluid. Under the drive of TENG, the minimum volume of the droplet can reach 70-80 nL, while the tiny droplet can freely move on both horizontal and vertical planes. Finally, another strategy for delivering nanoparticles to the designated position has also been demonstrated. This proposed self-powered transport technique may have great applications in the field of microsolid/liquid manipulators, drug delivery systems, microrobotics, and human-machine interactions.

A 3D microblade structure for precise and parallel droplet splitting on digital microfluidic chips.

Existing digital microfluidic (DMF) chips exploit the electrowetting on dielectric (EWOD) force to perform droplet splitting. However, the current splitting methods are not flexible and the volume of the droplets suffers from a large variation. Herein, we propose a DMF chip featuring a 3D microblade structure to enhance the droplet-splitting performance. By exploiting the EWOD force for shaping and manipulating the mother droplet, we obtain an average dividing error of <2% in the volume of the daughter droplets for a number of fluids such as deionized water, DNA solutions and DNA-protein mixtures. Customized droplet splitting ratios of up to 20 : 80 are achieved by positioning the blade at the appropriate position. Additionally, by fabricating multiple 3D microblades on one electrode, two to five uniform daughter droplets can be generated simultaneously. Finally, by taking synthetic DNA targets and their corresponding molecular beacon probes as a model system, multiple potential pathogens that cause sepsis are detected rapidly on the 3D-blade-equipped DMF chip, rendering it as a promising tool for parallel diagnosis of diseases.

Two-phase microfluidic flow modeling in an electrowetting display microwell.

Digital microfluidics provides precise control of a single microdroplet, producing more opportunities for bio-molecule studies, chemical reaction and optofluidics applications. By manipulating the surface of droplets, light can be focused, scattered, or reflected toward different positions. We build a model of electro-responsive optical microfluidic system, operated based on the electrowetting mechanism, which can split or push droplets moving within a microwell. The initial close state and operated open state in a single microwell displays the color of a dye oil droplet and the substrate, respectively, represented as the dark and bright pixel in the display board. Our results indicate that the microdroplets interface could be successfully deformed and moved towards different directions within a short period of time.

Fertilization of Mouse Gametes in Vitro Using a Digital Microfluidic System.

We demonstrated in vitro fertilization (IVF) using a digital microfluidic (DMF) system, so-called electrowetting on dielectric (EWOD). The DMF device was proved to be biocompatible and the DMF manipulation of a droplet was harmless to the embryos. This DMF platform was then used for the fertilization of mouse gametes in vitro and for embryo dynamic culture based on a dispersed droplet form. Development of the embryos was instantaneously recorded by a time-lapse microscope in an incubator. Our results indicated that increasing the number of sperms for IVF would raise the rate of fertilization. However, the excess of sperms in the 10 µL culture medium would more easily make the embryo dead during cell culture. Dynamic culture powered with EWOD can manipulate a single droplet containing mouse embryos and culture to the eight-cell stage. The fertilization rate of IVF demonstrated by DMF system was 34.8%, and about 25% inseminated embryos dynamically cultured on a DMF chip developed into an eight-cell stage. The results indicate that the DMF system has the potential for application in assisted reproductive technology.

Digital Microfluidic Dynamic Culture of Mammalian Embryos on an Electrowetting on Dielectric (EWOD) Chip.

Current human fertilization in vitro (IVF) bypasses the female oviduct and manually inseminates, fertilizes and cultivates embryos in a static microdrop containing appropriate chemical compounds. A microfluidic microchannel system for IVF is considered to provide an improved in-vivo-mimicking environment to enhance the development in a culture system for an embryo before implantation. We demonstrate a novel digitalized microfluidic device powered with electrowetting on a dielectric (EWOD) to culture an embryo in vitro in a single droplet in a microfluidic environment to mimic the environment in vivo for development of the embryo and to culture the embryos with good development and live births. Our results show that the dynamic culture powered with EWOD can manipulate a single droplet containing one mouse embryo and culture to the blastocyst stage. The rate of embryo cleavage to a hatching blastocyst with a dynamic culture is significantly greater than that with a traditional static culture (p<0.05). The EWOD chip enhances the culture of mouse embryos in a dynamic environment. To test the reproductive outcome of the embryos collected from an EWOD chip as a culture system, we transferred embryos to pseudo-pregnant female mice and produced live births. These results demonstrate that an EWOD-based microfluidic device is capable of culturing mammalian embryos in a microfluidic biological manner, presaging future clinical application.

Nanophotonic implementation of optoelectrowetting for microdroplet actuation.

The development and ultimate operation of a nanocomposite high-aspect-ratio photoinjection (HARP) device is presented in this work. The device makes use of a nanocomposite material as the optically active layer and the device achieves a large optical penetration depth with a high aspect ratio which provides a strong actuation force far away from the point of photoinjection. The nanocomposite material can be continuously illuminated and the position of the microdroplets can, therefore, be controlled to diffraction limited resolution. The nanocomposite HARP device shows great potential for future on-chip applications.

A Low-Cost and High-Resolution Droplet Position Detector for an Intelligent Electrowetting on Dielectric Device.

A low-cost and high-resolution capacitive-to-digital converter integrated circuit is used for droplet position detection in a digital microfluidic system. A field-programmable gate array FPGA is used as the integrated logic hub of the system for a highly reliable and efficient control of the circuit. A fast-fabricating PCB (printed circuit board) substrate microfluidic system is proposed. Smaller actuation threshold voltages than those previously reported are obtained. Droplets (3 µL) are actuated by using a 200 V, 500 Hz modulating pulsed voltage. Droplet positions can be detected and displayed on a PC-based 3D animation in real time. The actuators and the capacitance sensing circuits are implemented on one PCB to reduce the size of the system. With the capacitive droplet position detection system, the PCB-based electrowetting on dielectric device (EWOD) reported in this work has promise in automating immunohistochemistry experiments.

Detaching droplets in immiscible fluids from a solid substrate with the help of electrowetting.

The detachment (or removal) of droplets from a solid surface is an indispensable process in numerous practical applications which utilize digital microfluidics, including cell-based assay, chip cooling, and particle sampling. When a droplet that is fully stretched by impacting or electrowetting is released, the conversion of stored surface energy to kinetic energy can lead to the departure of the droplet from a solid surface. Here we firstly detach sessile droplets in immiscible fluids from a hydrophobic surface by electrowetting. The physical conditions for droplet detachment depend on droplet volume, viscosity of ambient fluid, and applied voltage. Their critical conditions are determined by exploring the retracting dynamics for a wide range of driving voltages and physical properties of fluids. The relationships between physical parameters and dynamic characteristics of retracting and jumping droplets, such as contact time and jumping height, are also established. The threshold voltage for droplet detachment in oil with high viscosity is largely reduced (~70%) by electrowetting actuations with a square pulse. To examine the applicability of three-dimensional digital microfluidic (3D-DMF) platforms to biological applications such as cell culture and cell-based assays, we demonstrate the detachment of droplets containing a mixture of human umbilical vein endothelial cells (HUVECs) and collagen (concentration of 4 × 10(4) cells mL(-1)) in silicone oil with a viscosity of 0.65 cSt. Furthermore, to complement the technical limitations due to the use of a needle electrode and to demonstrate the applicability of the 3D-DMF platform with patterned electrodes to chemical analysis and synthesis, we examine the transport, merging, mixing, and detachment of droplets with different pH values on the platform. Finally, by using DC and AC electrowetting actuations, we demonstrate the detachment of oil droplets with a very low contact angle (<~13°) in water on a hydrophobic surface.

Electrocapillarity of an electrolyte solution in a nanoslit with overlapped electric double layer: continuum approach.

A nanoslit is a long narrow opening between two parallel plates that are nanometers apart from each other. When an electrolyte solution is present inside a nanoslit, an overlapped electrical double layer (EDL) is formed and there exist distributions of the osmotic pressure and the Maxwell stress across the nanoslit. It is well known that the total normal stress (osmotic pressure contribution + Maxwell stress contribution) in the direction normal to the nanoslit surface is uniform and the value is the same as the osmotic pressure at the centerline. On the other hand, it is not well known that the total normal stress in the direction parallel to the slit surface is not uniform. When there is an electrolyte-gas interface inside a nanoslit, this total normal stress in the direction parallel to the slit surface generates the electrocapillarity effect. In the present work, the electromechanical approach is adopted to estimate the electrocapillarity effect in terms of the slit surface potential (or the surface charge density), the gap size, and the bulk ion concentrations. In order to handle the problem analyically, it is assumed that the nanoslit problem is in the continuum range and the interface is initially flat. The deformation of the interface due to the nonuniform total normal stress along the interface is also obtained by using the first order perturbation method. The significance of the present work can be manifested by the fact that external voltage is frequently used in nanoscaled systems and the electrocapillarity effect should be considered in addition to the intrinsic capillarity due to surface tension.

Electrowetting-on-dielectrics for manipulation of oil drops and gas bubbles in aqueous-shell compound drops.

We present the manipulation of oil, organic and gaseous chemicals by electrowetting-on-dielectric (EWOD) technology using aqueous-shell compound drops. We demonstrate that the transport and coalescence of viscous oil drops, the reaction of bromine with styrene in benzene solution, and the reaction of red blood cells with carbon monoxide bubbles can be accomplished using this method.

An EWOD-based microfluidic chip for single-cell isolation, mRNA purification and subsequent multiplex qPCR.

Single cell analysis circumvents the need to average data from large populations by observing each cell individually, thus enabling the analysis of cell-to-cell variability. The ability to work on this scale presents many new opportunities for the life sciences and biomedical applications. Microfluidics has become a tool of choice for such studies and electrowetting on dielectric (EWOD) technology is well adapted for samples with reduced size and biological studies at the single cell level. In the present manuscript, for the first time, we present an integrated and automated system based on EWOD that can process the complete workflow on a single device, from the isolation of a single cell to mRNA purification and gene expression analysis.

Active digital microfluidic paper chips with inkjet-printed patterned electrodes.

Active, paper-based, microfluidic chips driven by electrowetting are fabricated and demonstrated for reagent transport and mixing. Instead of using the passive capillary force on the pulp to actuate a flow of a liquid, a group of digital drops are transported along programmed trajectories above the electrodes printed on low-cost paper, which should allow point-of-care production and diagnostic activities in the future.

Design and analysis of a low actuation voltage electrowetting-on-dielectric microvalve for drug delivery applications.

This paper presents a low actuation voltage microvalve with optimized insulating layers that manipulates a conducting ferro-fluid droplet by the principle of electrowetting-on-dielectric (EWOD). The proposed EWOD microvalve contains an array of chromium (Cr) electrodes on the soda-lime glass substrate, covered by both dielectric and hydrophobic layers. Various dielectric layers including Su-8 2002, Polyvinylidenefluoride (PVDF) and Cyanoethyl pullulan (CEP), and thin (50 nm) hydrophobic Teflon and Cytonix are used to analyze the EWOD microvalves at different voltages. The Finite Element Method (FEM) based software, Coventorware is used to carry out the simulation analysis. It is observed that the EWOD microvalve having a CEP dielectric layer with dielectric constant of about 20 and thickness of 1 µm, and a Cytonix hydrophobic layer with thickness of 50 nm operated the conducting ferro-fluid droplet at the actuation voltage as low as 7.8 V.

An inkjet-printed electrowetting valve for paper-fluidic sensors.

Paper-fluidic devices have become an emerging trend for micro total analysis systems (microTAS) in the bioengineering field due to their ability to maintain the rapid, sensitive and specific attributes of microfluidic devices. Subsequently, paper-fluidic devices are also more portable, have a lower production cost and are easier to use. However, one of the obstacles in developing paper fluidic devices is the limited ability to control the rate of fluid flow during an assay. In our project, we use electrowetting on dielectrics where a dielectric, which is normally hydrophobic, is polarized and becomes hydrophilic. We have fabricated paper-fluidic devices by inkjet printing and spraying conductive hydrophobic electrodes/valves in conjunction with conductive hydrophilic electrodes which are able to stop the fluid front of phosphate buffered saline (PBS). The hydrophobic valves were then actuated by an applied potential which altered the fluorinated monolayer on the electrode. As the applied potential between the electrodes was increased, the amount of time for the fluid front to pass the valve decreased because the monolayer was altered faster. However, we did not observe significant differences in time as we increased the distance between the electrodes. The valves were also incorporated in a lateral flow assay where the device was used to detect Saccharomyces cerevisiae rRNA sequences. With the ability to control the fluid flow in a paper-fluidic device, more complex and intricate assays can be developed, which not only can be applied in the biomedical, food and environmental fields, but also can be used in low resource settings for the detection of diseases.