Digital Microfluidic System Research Articles

Dynamics of Electrowetting Droplet Motion in Digital Microfluidics Systems: From Dynamic Saturation to Device Physics

A quantitative description of the dynamics of droplet motion has been a long-standing concern in electrowetting research. Although many static and dynamic models focusing on droplet motion induced by electrowetting-on-dielectric (EWOD) already exist, some dynamic features do not fit these models well, especially the dynamic saturation phenomenon. In this paper, a dynamic saturation model of droplet motion on the single-plate EWOD device is presented. The phenomenon that droplet velocity is limited by a dynamic saturation effect is precisely predicted. Based on this model, the relationship between droplet motion and device physics is extensively discussed. The static saturation phenomenon is treated with a double-layer capacitance electric model, and it is demonstrated as one critical factor determining the dynamics of droplet motion. This work presents the relationship between dynamics of electrowetting induced droplet motion and device physics including device structure, surface material and interface electronics, which helps to better understand electrowetting induced droplet motions and physics of digital microfluidics systems.

A dielectrophoretic-gravity driven particle focusing technique for digital microfluidic systems

In the present study, a particle focusing technique functioning based on the cumulative effects of gravity and negative dielectrophoresis (nDEP) is developed for digital microfluidic (DMF) systems. This technique works using the conventional electrodes used for droplet manipulation without a need for geometrical modification. Particle manipulation is performed by applying an AC voltage to the electrode above which there is the droplet containing the non-buoyant particles. The particles sediment due to the difference between the gravitational and the vertical component of the nDEP forces, while the horizontal component of the nDEP force concentrates them on the center of the electrode. Therefore, the magnitude of the voltage must be kept within an effective range to have simultaneous effects of sedimentation (dominated by gravity) and concentration (due to the horizontal component of the nDEP force). The physics of the phenomenon is explained using simulation. The effects of the magnitude of the applied voltage, the particle size and density, and the electrode size on the focusing behavior of the particles are studied. Finally, a potential application of the present technique is illustrated for particle concentration in DMF.

Fabrication of digital microfluidic devices on flexible paper-based and rigid substrates via screen printing

In this work, a new fabrication method is presented for digital microfluidic (DMF) devices in which the electrodes are generated using the screen printing technique. This method is applicable to both rigid and flexible substrates. The proposed screen printing approach, as a batch printing technique, is advantageous to the widely reported DMF fabrication methods in terms of fabrication time, cost and capability of mass production. Screen printing provides an effective means for printing different types of conductive materials on a variety of substrates. Specifically, screen printing of conductive silver and carbon based inks is performed on paper, glass and wax paper. As a result, the fabricated DMF devices are characterized by being flexible, disposable and incinerable. Hence, the main advantage of screen printing carbon based inks on paper substrates is more pronounced for point-of-care applications that require a large number of low cost DMF chips, and laboratory setups that lack sophisticated microfabrication facilities. The resolution of the printed DMF electrodes generated by this technique is examined for proof of concept using manual screen printing, but higher resolution screens and automated machines are available off-the-shelf, if needed. Another contribution of this research is the improved actuation techniques that facilitate droplet transport in electrode configurations with relatively large electrode spacing to alleviate the disadvantage of lower resolution screens. Thus, we were able to reduce the cost of fabrication significantly without compromising the DMF performance. The paper-based devices have already shown to be effective in continuous microfluidics domain, so the investigation of their applicability in DMF systems is worthwhile. With this in mind, successful integration of a paper-based microchannel with paper-based digital microfluidic chip is demonstrated in this work.

Automation Highlights from the Literature

Automation Highlights from the Literature

The spontaneous motion of a slug of miscible liquids in a capillary tube

This contribution explores a droplet actuation mechanism which involves mixing slugs of two different liquids in a glass capillary. The resulting contrast in surface tension which arises provides the necessary propulsive power for the droplet. The conceptual idea is demonstrated for an ethanol-water system. The droplet is observed to rapidly reach a peak velocity which then gradually decreases with time as the two miscible liquids mix. A model is proposed based on Newton's second law which is able to capture the main observed flow phenomena and explain the driving and dissipative mechanisms simultaneously at play in the droplet. This passive actuation mechanism could prove an attractive alternative in digital microfluidics systems for which bulky pumping systems are often required.

Improving the dielectric properties of an electrowetting-on-dielectric microfluidic device with a low-pressure chemical vapor deposited Si3N4 dielectric layer.

Dielectric breakdown is a common problem in a digital microfluidic system, which limits its application in chemical or biomedical applications. We propose a new fabrication of an electrowetting-on-dielectric (EWOD) device using Si3N4 deposited by low-pressure chemical vapor deposition (LPCVD) as a dielectric layer. This material exhibits a greater relative permittivity, purity, uniformity, and biocompatibility than polymeric films. These properties also increase the breakdown voltage of a dielectric layer and increase the stability of an EWOD system when applied in biomedical research. Medium droplets with mouse embryos were manipulated in this manner. The electrical properties of the Si3N4 dielectric layer-breakdown voltage, refractive index, relative permittivity, and variation of contact angle with input voltage-were investigated and compared with a traditional Si3N4 dielectric layer deposited as a plasma-enhanced chemical vapor deposition to confirm the potential of LPCVD Si3N4 applied as the dielectric layer of an EWOD digital microfluidic system.

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.

Gravity-driven hydrodynamic particle separation in digital microfluidic systems

In the present study, the electrode configuration and actuation scheme are designed in a fashion to implement a gravity-based hydrodynamic particle separation method on digital microfluidic systems.

Correlation of Heat Transfers Mechanism(s) and Time Constant Equilibrium on Digital Rayleigh-SAW Microfluidic System

The goal of this work is to determine the heat transfer mechanisms for digital microfluidic device through the correlation of Rayleigh-SAW streaming and thermal effect, two concomitant phenomena. Péclet number for heat transfer PeTH, which depends on the internal streaming velocity within the droplet, has been used to determine the preponderant transfer mechanism(s). In this sense, determination of flow velocity by Particle Image Velocimetry method and IR measurements, have been necessary. The substrate used was LiNbO3 128Y-X to generate pure Rayleigh SAW. Typically, streaming velocity can reach 40mm.s-1 for 10μl water droplet and PIDT=0.63W, corresponding to PeTH>>1. Forced convection is the predominant mechanism within the water droplet, so the thermodynamic equilibrium is achieved quickly compared to conductive time scale. When the liquid viscosity increases, the streaming is less intensive because of viscous friction and the time constant to reach equilibrium can increase drastically.

Compound droplet manipulations on fiber arrays.

Recent works demonstrated that fiber arrays may constitute new means of designing open digital microfluidic systems. Various processes, such as droplet motion, fragmentation, trapping, release, mixing and encapsulation, may be achieved on fiber arrays. However, handling a large number of tiny droplets resulting from the mixing of several liquid components is required for developing microreactors, smart sensors or microemulsifying drugs. Here, we show that the manipulation of tiny droplets onto fiber networks allows for creating compound droplets with a high complexity level. Moreover, this cost-effective and adjustable method may also be implemented with optical fibers in order to develop fluorescence-based biosensor.

Chemical reaction and mixing inside a coalesced droplet after a head-on collision

We investigated the phenomena of a chemical reaction inside a coalesced droplet after a direct (head-on) collision. A droplet containing an alkaline solution collided with a droplet containing a pH indicator on a surface with a wettability gradient. We used a high-speed camera to observe the color-changing reaction inside the coalesced droplet. Compared with a traditional dye-mixing test, the chemical reaction inside the coalesced droplet facilitated the mixing of two counter-reactive fluids and was more than 100 times as efficient as for unreactive fluids mixing inside the coalesced droplet. Instead of mere mixing, a chemical reaction inside a coalesced droplet is valuable for applications in a digital microfluidic open system. In droplet coalescence, the characteristics of the fluids and the ratio of volumes of two droplets caused a varied profile of the droplet coalescence, especially the neck curvature that affects the shape of the material interface between the two droplets at an initial phase. We observed the evolution of the chemical reaction with a varying radius of neck curvature inside the coalesced droplet. For the case of a small radius of neck curvature, the small interfacial area between two reactive fluids accumulated an intense heat of reaction and induced a rapid growth of the fingers. For the case of a large radius of neck curvature, the growth of fingers was slight and the interface was uniform across the large interfacial area. Our work illustrates a correlation between the rate of chemical reaction and the profile of a coalesced droplet, which is a significant reference in droplet-based microfluidic systems for biochemical applications.

Island-ground single-plate electro-wetting on dielectric device for digital microfluidic systems

In this paper, we present a single-plate electro-wetting on dielectric (SEWOD) device by integrating an island-ground electrode (IG), which is surrounded by the driving electrodes and looks like an island. Both experiments and theoretical analysis have been conducted to investigate the performance of the IG-SEWOD device. The driving voltage of a fabricated IG-SEWOD has been measured to be 15 V, which is half of that of a floating SEWOD. The digital dynamic properties of the EWOD device are greatly enhanced due to the “double locking” effect and rapid residual charges elimination provided by the IG. The proposed EWOD device shows great potential in constructing advanced microfluidics platforms for bio-chemical detection and disease diagnosis.

Hepatic organoids for microfluidic drug screening.

We introduce the microfluidic organoids for drug screening (MODS) platform, a digital microfluidic system that is capable of generating arrays of individually addressable, free-floating, three-dimensional hydrogel-based microtissues (or 'organoids'). Here, we focused on liver organoids, driven by the need for early-stage screening methods for hepatotoxicity that enable a "fail early, fail cheaply" strategy in drug discovery. We demonstrate that arrays of hepatic organoids can be formed from co-cultures of HepG2 and NIH-3T3 cells embedded in hydrogel matrices. The organoids exhibit fibroblast-dependent contractile behaviour, and their albumin secretion profiles and cytochrome P450 3A4 activities are better mimics of in vivo liver tissue than comparable two-dimensional cell culture systems. As proof of principle for screening, MODS was used to generate and analyze the effects of a dilution series of acetaminophen on apoptosis and necrosis. With further development, we propose that the MODS platform may be a cost-effective tool in a "fail early, fail cheaply" paradigm of drug development.

Optimal Test Droplets Dispensing for Parallel Testing for Digital Microfluidic Biochip

Digital microfluidic systems (DMFS) are an emerging class of lab-on-chip systems. They become widespread in safety-critical biomedical applications, and dependability is a critical performance parameter for them. For most parallel test schemes, the test droplets are preloaded into their test region before the start of testing, and the time needed for transferring the test droplets to their corresponding test region that called the dispensing time may be very long. To reduce dispensing time, an optimal test droplets dispensing for parallel testing is proposed in the paper. The problem that we address here is to minimize the system testing time by optimally assigning test droplets dispending to the test sources. Even though the decision version of the problem is shown to be NP-complete, it can be solved exactly for practical instances using integer linear programming (ILP). The experimental results show the effective of the proposed test scheme.

Analysis on the go: quantitation of drugs of abuse in dried urine with digital microfluidics and miniature mass spectrometry.

We report the development of a method coupling microfluidics and a miniature mass spectrometer, applied to quantitation of drugs of abuse in urine. A custom digital microfluidic system was designed to deliver droplets of solvent to dried urine samples and then transport extracted analytes to an array of nanoelectrospray emitters for analysis. Tandem mass spectrometry (MS/MS) detection was performed using a fully autonomous 25 kg instrument. Using the new method, cocaine, benzoylecgonine, and codeine can be quantified from four samples in less than 15 min from (dried) sample to analysis. The figures of merit for the new method suggest that it is suitable for on-site screening; for example, the limit of quantitation (LOQ) for cocaine is 40 ng/mL, which is compatible with the performance criteria for laboratory analyses established by the United Nations Office on Drugs and Crime. More importantly, the LOQ of the new method is superior to the 300 ng/mL cutoff values used by the only other portable analysis systems we are aware of (relying on immunoassays). This work serves as a proof-of-concept for integration of microfluidics with miniature mass spectrometry. The system is attractive for the quantitation of drugs of abuse from urine and, more generally, may be useful for a wide range of applications that would benefit from portable, quantitative, on-site analysis.

Amorphous silicon photosensors for on-chip detection in digital microfluidic system

In this paper we present the integration, on a single glass substrate, of amorphous silicon photodiodes with an electrowetting-on-dielectric (EWOD) system as a technological demonstrator for achieving a compact, stand alone Lab-on-Chip (LoC) system. The EWOD system comprises a thin film of indium tin oxide (ITO) acting as actuation electrodes and a 1μm-thick polydimethylsiloxane (PDMS) layer acting as both insulation and hydrophobic layer. The a-Si:H photosensors are ITO/p-type/intrinsic/n-type/metal stacked structures, aligned with the transparent EWOD electrodes, to detect optical signals generated inside (or modulated by) the liquid droplets handled by the digital microfluidic system.The fabrication process has been designed and performed taking into account the compatibility of all the technological steps of the photosensor and EWOD structures fabrication. The successful integration has been demonstrated checking the correct geometry of EWOD electrodes and measuring the optoelectronic performances of the a-Si:H photosensors at the end of the system fabrication. The correct operation and potentiality of the presented device has been assessed monitoring a photodiode current when a water droplet is moved forward and backward over the EWOD electrodes aligned with the photosensors.

Capacitively catenary feedback control for open-type digital microfluidics

With the rapid development and technical support by microelectromechanical systems, a lab-on-a-chip or micrototal analysis system has been widely developed for medical tests due to its low cost, simple, disposable, and less contamination. Comparing to the continuous microfluidics system, a digital microfluidics system has the advantages of being without micropump and easily driven using the alternative change of hydrophilic and hydrophobic properties. A feedback control system is proposed for driving digital microfluidics by using capacitive catenary as a sensor. In the proposed system, the moving droplet can be real-time positioned and controlled to overcome the imperfection of fabricated devices and the environmental disturbance. Furthermore, with the compensation of adjusting the amount of applied voltage online, the droplets can run smoothly toward the desired position in the chip through the feedback control. As a result, the proposed system is capable of moving droplets with higher speed, compared to most of the existing system, and improves the reliability of handling microfluidics. The chip for microfluidics operation has been successfully fabricated. With the self-designed circuit and LabVIEW interface, the experiments for operating microdroplets in an open channel are conducted to verify the performances of proposed devices.

NMR-DMF: a modular nuclear magnetic resonance-digital microfluidics system for biological assays.

We present a modular nuclear magnetic resonance-digital microfluidics (NMR-DMF) system as a portable diagnostic platform for miniaturized biological assays. With increasing number of combinations between designed probes and a specific target, NMR has become an accurate and rapid assay tool, which is capable of detecting particular kinds of proteins, DNAs, bacteria and cells with a customized probe quantitatively. Traditional sample operation (e.g., manipulation and mixing) relied heavily on human efforts. We herein propose a modular NMR-DMF system to allow the electronic automation of multi-step reaction-screening protocols. A figure-8 shaped coil is proposed to enlarge the usable inner space of a portable magnet by 4.16 times, generating a radio frequency (RF) excitation field in the planar direction. By electronically managing the electro-wetting-on-dielectric (EWOD) effects over an electrode array, preloaded droplets with the inclusion of biological constituents and targets can be programmed to mix and be guided to the detection site (3.5 × 3.5 mm(2)) for high-sensitivity NMR screening (static B field: 0.46 T, RF field: 1.43 mT per ampere), with the result (voltage signal) displayed in real-time. To show the system's utility, automated real-time identification of 100 pM of avidin in a 14 μL droplet was achieved. The system shows promise as a robust and portable diagnostic device for a wide variety of biological analyses and screening applications.

A droplet-based screen for wavelength-dependent lipid production in algae

We report a digital microfluidic system designed for droplet-based long-term culture and analysis of algae. The system includes unique innovations relative to standard devices including an active reservoir structure to maintain homogeneous cell density, a customized device layout capable of controlling a wide range of different droplet volumes, vertical interconnects to collect spent reagents, detection zones compatible with parallel-scale optical measurements using a standard multiwell plate reader, and optimized features for droplet dispensing in parallel. The method allows for automated, multiplexed analysis with significant reductions in human intervention, representing a decrease from 600 pipette steps (for a conventional screen in multiwell plates) to fewer than 20 (for the new microfluidic technique). The system was applied to screen conditions favourable for lipid generation in the widely used algal model for biofuel production, Cyclotella cryptica. A dependence on illumination wavelength was observed, with the best conditions (representing a four-fold increase relative to control) comprising an alternation between yellow (∼580 nm) and blue (∼450 nm) illumination wavelengths. These effects were observed for both micro- and macro-scale cultures, and are consistent with a putative mechanism involving photooxidative stress. We propose that the microfluidic system described here is an attractive new screening tool with potential advantages for applications in renewable energy, biotechnology, materials science, and beyond.

Real-Time Error Recovery in Cyberphysical Digital-Microfluidic Biochips Using a Compact Dictionary

A cyberphysical digital microfluidics system is an emerging technology that enables the integration of fluid-handling operations, reaction-outcome detection, and automated error recovery on a biochip. Cyberphysical biochip systems studied thus far suffer from a significant increase in reaction time for error recovery. We present a hardware-assisted method that can be implemented in real-time on a field-programmable gate array (FPGA). In order to store the error dictionary in the limited memory available in the FPGA, we utilize and adapt two data compaction techniques from the literature. We use four laboratorial protocols to demonstrate that, compared to software-based methods, the proposed dictionary-based error-recovery method has low response time, and requires a simple experimental setup, and only a small amount of memory.