Electrical actuation of dielectric droplets by negative liquid dielectrophoresis

This paper presents an electrical actuation scheme of dielectric droplet by negative liquid dielectrophoresis. A general model of lumped parameter electromechanics for evaluating the electromechanical force acting on the droplets is established. The model reveals the influence of actuation voltage, device geometry, and dielectric parameter on the actuation force for both conductive and dielectric medium. Using this model, we compare the actuation forces for four liquid combinations in the parallel-plate geometry and predict the low voltage actuation of dielectric droplets by negative dielectrophoresis. Parallel experimental results demonstrate such electric actuation of dielectric droplets, including droplet transport, splitting, merging, and dispending. All these dielectric droplet manipulations are achieved at voltages < 100 V_rms. The frequency dependence of droplet actuation velocity in aqueous solution is discussed and the existence of surfactant molecules is believed to play an important role by realigning with the AC electric field. Finally, we present coplanar manipulation of oil and water droplets and formation of oil-in-water emulsion droplet by applying the same low voltage.     

Spontaneous generation of emulsion droplets by autonomous fluid-pumping using the gas permeability of poly(dimethylsiloxane) (PDMS)

Conventional droplet-based microfluidic systems require expensive, bulky external apparatuses, such as electric power supplies and pressure-driven pumps for fluid transportation. This study demonstrates an alternative way to produce emulsion droplets by autonomous fluid-handling based on the gas permeability of poly(dimethylsiloxane) (PDMS). Furthermore, basic concepts of fluid-handling are expanded to control the direction of the microfluid in the microfluidic device. The alternative pumping energy resulting from the high gas permeability of PDMS is used to generate water-in-oil (W/O) emulsions, which require no additional structures apart from microchannels. We can produce emulsion droplets by simple loading of the oil and aqueous solutions into the inlet reservoirs. During the operation of the microfluidic device, changes in droplet size, volumetric flow rate, and droplet generation frequency were quantitatively analyzed. As a result, we found that changes in the wetting properties of the microchannel greatly influence the volumetric flow rate and droplet generation frequency. This alternative microfluidic approach for preparing emulsion droplets in a simple and efficient manner is designed to improve the availability of emulsion droplets for point of care bioanalytical applications, in situ synthesis of materials, and on-site sample preparation tools.     

微流控芯片液滴生成与检测技术研究进展

微流控芯片液滴技术是一种操控微小体积液体的新技术,既可实现高通量微观样本的生成及控制,也可进行独立液滴的操作。分散的微液滴单元可作为理想的微反应器,在生物医药中的药物筛选、材料筛选和高附加值微颗粒材料合成领域展现出巨大的应用潜力。液滴微流控芯片是利用流体剪切力的改变,使互不相溶的两相流体在其界面处生成稳定、有序的液滴,目前微液滴的生成方法主要有水动力法、气动法、光控法和电动法等。基于液滴的微流控系统越来越多地被应用于执行复杂的多重反应、测量和分析,可以进行超小体积和超高吞吐量的化学和生物实验。对液滴微流控系统而言,液滴的速度、大小和内容物含量会影响最终的检验结果,因此对液滴形成速率和液滴的内容物含量的实时检测至关重要,目前最常用的液滴检测方法有光学检测技术与电学传感检测技术。对两相流液滴生成机理以及现有液滴生成技术开展了讨论分析,同时对液滴检测技术进行了评述。     

Droplet-based microscale colorimetric biosensor for multiplexed DNA analysis via a graphene nanoprobe

The development of simple and inexpensive DNA detection strategy is very significant for droplet-based microfluidic system. Here, a droplet-based biosensor for multiplexed DNA analysis is developed with a common imaging device by using fluorescence-based colorimetric method and a graphene nanoprobe. With the aid of droplet manipulation technique, droplet size adjustment, droplet fusion and droplet trap are realized accurately and precisely. Due to the high quenching efficiency of graphene oxide (GO), in the absence of target DNAs, the droplet containing two single-stranded DNA probes and GO shows dark color, in which the DNA probes are labeled carboxy fluorescein (FAM) and 6-carboxy-X-rhodamine (ROX), respectively. The droplet changes from dark to bright color when the DNA probes form double helix with the specific target DNAs leading to the dyes far away from GO. This colorimetric droplet biosensor exhibits a quantitative capability for simultaneous detection of two different target DNAs with the detection limits of 9.46 and 9.67 × 10⁻⁸ M, respectively. It is also demonstrated that this biosensor platform can become a promising detection tool in high throughput applications with low consumption of reagents. Moreover, the incorporation of graphene nanoprobe and droplet technique can drive the biosensor field one more step to some extent.     

Dynamically controlled dielectrophoresis using resonant tuning

Electrically polarizable micro- and nanoparticles and droplets can be trapped using the gradient electric field of electrodes. But the spatial profile of the resultant dielectrophoretic force is fixed once the electrode structure is defined. To change the force profile, entire complex lab-on-a-chip systems must be re-fabricated with modified electrode structures. To overcome this problem, we propose an approach for the dynamic control of the spatial profile of the dielectrophoretic force by interfacing the trap electrodes with a resistor and an inductor to form a resonant resistor–inductor–capacitor (RLC) circuit. Using a dielectrophoretically trapped water droplet suspended in silicone oil, we show that the resonator amplitude, detuning, and linewidth can be continuously varied by changing the supply voltage, supply frequency, and the circuit resistance to obtain the desired trap depth, range, and stiffness. We show that by proper tuning of the resonator, the trap range can be extended without increasing the supply voltage, thus preventing sensitive samples from exposure to high electric fields at the stable trapping position. Such unprecedented dynamic control of dielectrophoretic forces opens avenues for the tunable active manipulation of sensitive biological and biochemical specimen in droplet microfluidic devices used for single-cell and biochemical reaction analysis.     

Controlled generation of droplets using an electric field in a flow-focusing paper-based device

Droplet-based microfluidics is a modular platform in high-throughput single-cell and small sample analyses. However, this droplet microfluidic system was widely fabricated using soft lithography or glass capillaries, which is expensive and technically demanding for various applications, limiting use in resource-poor settings. Besides, the variation in droplet size is also restricted due to the limitations on the operating forces that the paper-based platform is able to withstand. Herein, we develop a fully integrated paper-based droplet microfluidic platform for conducting droplet generation and cell encapsulation in independent aqueous droplets dispersed in a carrier oil by incorporating electric fields. Through imposing an electric field, the droplet size would decrease with increasing the electric field and smaller droplets can be produced at high applied voltage. The droplet diameter can be adjusted by the ratio of inner and outer flow velocities as well as the applied electric field. We also demonstrated the proof of concept encapsulation application of our paper device by encapsulating yeast cells under an electric field. Using a simple wax printing method, carbon electrodes can be integrated on the paper. The integrated paper-based microfluidic platform can be fabricated easily and conducted outside of centralized laboratories. This microfluidic system shows great potential in drug and cell investigations by encapsulating cells in resource-limited environments.     

Characterization of electrode alignment for optimal droplet charging and actuation in droplet‐based microfluidic system

The actuation method using electric force as a driving force is utilized widely in droplet‐based microfluidic systems. In this work, the effects of charging electrode alignment on direct charging of a droplet on electrified electrodes and a subsequent electrophoretic control of the droplet are investigated. The charging characteristics of a droplet according to different electrode alignments are quantitatively examined through experiments and systematic numerical simulations with varying distances and angles between the two electrodes. The droplet charge acquired from the electrified electrode is directly proportional to the distance and barely affected by the angle between the two electrodes. This implies that the primary consideration of electrode alignment in microfluidic devices is the distance between electrodes and the insignificant effect of angle provides a great degree of freedom in designing such devices. Not only the droplet charge acquired from the electrode but also the force exerted on the droplet is analyzed. Finally, the implications and design guidance for microfluidic systems are discussed with an electrophoresis of a charged droplet method‐based digital microfluidic device.     

Droplet-based microfluidics for dose–response assay of enzyme inhibitors by electrochemical method

A simple but robust droplet-based microfluidic system was developed for dose–response enzyme inhibition assay by combining concentration gradient generation method with electrochemical detection method. A slotted-vials array and a tapered tip capillary were used for reagents introduction and concentration gradient generation, and a polydimethylsiloxane (PDMS) microfluidic chip integrated with microelectrodes was used for droplet generation and electrochemical detection. Effects of oil flow rate and surfactant on electrochemical sensing were investigated. This system was validated by measuring dose–response curves of three types of acetylcholinesterase (AChE) inhibitors, including carbamate pesticide, organophosphorus pesticide, and therapeutic drugs regulating Alzheimer's disease. Carbaryl, chlorpyrifos, and tacrine were used as model analytes, respectively, and their IC₅₀ (half maximal inhibitory concentration) values were determined. A whole enzyme inhibition assay was completed in 6 min, and the total consumption of reagents was less than 5 μL. This microfluidic system is applicable to many biochemical reactions, such as drug screening and kinetic studies, as long as one of the reactants or products is electrochemically active.     

Quantitative analysis of the three-dimensional trap stiffness of a dielectrophoretic corral trap

Dielectrophoresis is a robust approach for the manipulation and separation of (bio)particles using microfluidic platforms. We developed a dielectrophoretic corral trap in a microfluidic device that utilizes negative dielectrophoresis to capture single spherical polystyrene particles. Circular-shaped micron-size traps were employed inside the device and the three-dimensional trap stiffness (restoring trapping force from equilibrium trapping location) was analyzed using 4.42 μm particles and 1 MHz of an alternating electric field from 6 V_P-P to 10 V_P-P. The trap stiffness increased exponentially in the x- and y-direction, and linearly in the z-direction. Image analysis of the trapped particle movements revealed that the trap stiffness is increased 608.4, 539.3, and 79.7% by increasing the voltage from 6 V_P-P to 10 V_P-P in the x-, y-, and z-direction, respectively. The trap stiffness calculated from a finite element simulation of the device confirmed the experimental results. This analysis provides important insights to predict the trapping location, strength of the trapping, and optimum geometry for single particle trapping and its applications such as single-molecule analysis and drug discovery.     

Reduction in microparticle adsorption using a lateral interconnection method in a PDMS‐based microfluidic device

Microparticle adsorption on microchannel walls occurs frequently due to nonspecific interactions, decreasing operational performance in pressure‐driven microfluidic systems. However, it is essential for delicate manipulation of microparticles or cells to maintain smooth fluid traffic. Here, we report a novel microparticle injection technique, which prevents particle loss, assisted by sample injection along the direction of fluid flow. Sample fluids, including microparticles, mammalian (U937), and green algae (Chlorella vulgaris) cells, were injected directly via a through hole drilled in the lateral direction, resulting in a significant reduction in microparticle attachment. For digital microfluidic application, the proposed regime achieved a twofold enhancement of single‐cell encapsulation compared to the conventional encapsulation rate, based on a Poisson distribution, by reducing the number of empty droplets. This novel interconnection method can be straightforwardly integrated as a microparticle or cell injection component in integrated microfluidic systems.     

Measurement of microchannel fluidic resistance with a standard voltage meter

A simplified method for measuring the fluidic resistance (R_fluidic) of microfluidic channels is presented, in which the electrical resistance (R_elec) of a channel filled with a conductivity standard solution can be measured and directly correlated to R_fluidic using a simple equation. Although a slight correction factor could be applied in this system to improve accuracy, results showed that a standard voltage meter could be used without calibration to determine R_fluidic to within 12% error. Results accurate to within 2% were obtained when a geometric correction factor was applied using these particular channels. When compared to standard flow rate measurements, such as meniscus tracking in outlet tubing, this approach provided a more straightforward alternative and resulted in lower measurement error. The method was validated using 9 different fluidic resistance values (from ∼40 to 600 kPa s mm⁻³) and over 30 separately fabricated microfluidic devices. Furthermore, since the method is analogous to resistance measurements with a voltage meter in electrical circuits, dynamic R_fluidic measurements were possible in more complex microfluidic designs. Microchannel R_elec was shown to dynamically mimic pressure waveforms applied to a membrane in a variable microfluidic resistor. The variable resistor was then used to dynamically control aqueous-in-oil droplet sizes and spacing, providing a unique and convenient control system for droplet-generating devices. This conductivity-based method for fluidic resistance measurement is thus a useful tool for static or real-time characterization of microfluidic systems.     

Dielectrophoretic deformation of breast cancer cells for lab on a chip applications

This paper presents the development and experimental analysis of a curved microelectrode platform for the DEP deformation of breast cancer cells (MDA‐MB‐231). The platform is composed of arrays of curved DEP microelectrodes which are patterned onto a glass slide and samples containing MDA‐MB‐231 cells are pipetted onto the platform's surface. Finite element method is utilised to characterise the electric field gradient and DEP field. The performance of the system is assessed with MDA‐MB‐231 cells in a low conductivity 1% DMEM suspending medium. We applied sinusoidal wave AC potential at peak to peak voltages of 2, 5, and 10 V_pp at both 10 kHz and 50 MHz. We observed cell blebbing and cell shrinkage and analyzed the percentage of shrinkage of the cells. The experiments demonstrated higher percentage of cell shrinkage when cells are exposed to higher frequency and peak to peak voltage electric field.     

Experimental study of dielectrophoresis and liquid dielectrophoresis mechanisms for particle capture in a droplet

This work presents a microfluidic system that can transport, concentrate, and capture particles in a controllable droplet. Dielectrophoresis (DEP), a phenomenon in which a force is exerted on a dielectric particle when it is subjected to a non-uniform electric field, is used to manipulate particles. Liquid dielectrophoresis (LDEP), a phenomenon in which a liquid moves toward regions of high electric field strength under a non-uniform electric field, is used to manipulate the fluid. In this study, a mechanism of droplet creation presented in a previous work that uses DEP and LDEP is improved. A driving electrode with a DEP gap is used to prevent beads from getting stuck at the interface between air and liquid, which is actuated with an AC signal of 200 V(pp) at a frequency of 100 kHz. DEP theory is used to calculate the DEP force in the liquid, and LDEP theory is used to analyze the influence of the DEP gap. The increment of the actuation voltage due to the electrode with a DEP gap is calculated. A set of microwell electrodes is used to capture a bead using DEP force, which is actuated with an AC signal of 20 V(pp) at a frequency of 5 MHz. A simulation is carried out to investigate the dimensions of the DEP gap and microwell electrodes. Experiments are performed to demonstrate the creation of a 100-nL droplet and the capture of individual 10-μm polystyrene latex beads in the droplet.     

Insulator‐based dielectrophoresis combined with the isomotive AC electric field and applied to single cell analysis

We developed an insulator‐based dielectrophoretic (iDEP) creek‐gap device that enables the isomotive movement of cells and that is suitable for determining their DEP properties. In the iDEP creek‐gap device, a pair of planar insulators forming a single fan‐shaped channel allows the induction of the isomotive iDEP force on cells. Hence, the cells’ behavior is characterized by straight motion at constant velocity in the longitudinal direction of the channel. Operation of the device was demonstrated using human breast epithelial cells (MCF10A) by applying an AC voltage of V_pp = 34 V peak‐to‐peak and frequencies of 200 kHz and 50 MHz to the device. Subsequently, the magnitude of DEP forces and the real part of the ClausiusMossotti (CM) factor, Re(β), were deduced from the measured cell velocity. The values of Re(β) were 0.14 ± 0.01 for the frequency of 200 kHz and ?0.12 ± 0.01 for 50 MHz. These results demonstrated that the DEP properties of the cells could be extracted over a wide field frequency range. Therefore, the proposed iDEP creek‐gap device was found to be applicable to cell analysis.     

Modeling of droplet traffic in interconnected microfluidic ladder devices

The problem of controlling the droplet motion in multiphase flows on the microscale has gained increasing attention because the droplet-based microfluidic devices provide great potentials for chemical and biological applications. It is critical to understand the relevant physics on droplet hydrodynamics and thus control the generation, motion, splitting, and coalescence of droplets in complex microfluidic networks. Numerical simulations using the volume of fluid algorithm are conducted to investigate the time-dependent dynamics of droplets in gas-liquid multiphase devices. An analytical model based on the electronic-hydraulic analogy is developed to describe the hydrodynamic behavior of the droplets in interconnected microfluidic ladder devices. It is found that the pressure drop caused by the droplets plays a critical role in the droplet synchronization. A fitted formula for pressure drops in the presence of surfactant is achieved by using numerical simulations. Both the numerical and the theoretical results agree well with the corresponding experimental results.     

Effects of viscosity on droplet formation and mixing in microfluidic channels

This paper characterizes the conditions required to form nanoliter-sized droplets (plugs) of viscous aqueous reagents in flows of immiscible carrier fluid within microfluidic channels. For both non-viscous (viscosity of 2.0 mPa s) and viscous (viscosity of 18 mPa s) aqueous solutions, plugs formed reliably in a flow of water-immiscible carrier fluid for Capillary number less than 0.01, although plugs were able to form at higher Capillary numbers at lower ratios of the aqueous phase flow rate to the flow rate of the carrier fluid (in all the experiments performed, the Reynolds number was less than 1). The paper also shows that combining viscous and non-viscous reagents can enhance mixing in droplets moving through straight microchannels by providing a nearly ideal initial distribution of reagents within each droplet. The study should facilitate the use of this droplet-based microfluidic platform for investigation of protein crystallization, kinetics, and assays.     

Magnetic digital microfluidics on a bioinspired surface for point‐of‐care diagnostics of infectious disease

Magnetic digital microfluidics uses magnetic force to manipulate droplets on a Teflon‐coated substrate through the added magnetic particles. To achieve a wide range of droplet manipulation, hydrophilic patterns, known as surface energy traps, are introduced onto the Teflon‐coated hydrophobic substrate. However, the Teflon‐coated substrate is difficult to modify because it is nonwettable, and existing techniques for patterning surface energy traps have many limitations. Inspired by the mussel adhesion mechanism, we use polydopamine, a bioinspired substance that adheres strongly to almost any materials, to pattern surface energy traps on the Teflon‐coated substrate with a great ease. We have optimized the polydopamine coating protocol and characterized the surface properties of the polydopamine surface energy traps. Droplet operations including particle extraction, liquid dispensing, liquid shaping, and cross‐platform transfer have been demonstrated on the polydopamine surface energy trap‐enabled magnetic digital microfluidic platform in both single‐plate and two‐plate configurations. Furthermore, the detection of hepatitis B surface antigen using ELISA has been demonstrated on the new magnetic dgitial microfluidic platform. This new bioinspired magnetic digital microfluidic platform is easy to fabricate and operate, showing a great potential for point‐of‐care applications.     

流动聚焦型微流控体系中的液滴的图案化排列和转变模式

流体在微流通道中形成剪切流场（低雷诺数）．不同于宏观体系,由于剪切力和表面张力的竞争作用,产生的液滴在微尺度下的微流通道中形成特殊的排列现象---周期性类似“晶格”排列现象．设计了新型流动聚焦型微流控芯片,分析研究在微流体系中液滴周期性图案化排列和转变机理性,液滴排列模式受两方面因素影响：水油两相的流速比值和微通道尺寸．当微通道宽度为250或300 μm时,液滴形成单层分散,双层和单层挤压排列．当微通道宽度为350 μm 时,液滴会形成单层分散到三层排列到双层挤压最后到单层挤压排列．当出口通道宽度增加到400 μm时,甚至出现了液滴四层排列的现象．同时研究了各个液滴排列模式的“转变点”.     

A Flexible Composite Mechanical Energy Harvester from a Ferroelectric Organoamino Phosphonium Salt

A new binary organic salt diphenyl diisopropylamino phosphonium hexaflurophosphate (DPDP?PF₆) was shown to exhibit a good ferroelectric response and employed for mechanical energy harvesting application. The phosphonium salt crystallizes in the monoclinic noncentrosymmetric space group Cc and exhibits an H‐bonded 1D chain structure due to N?H???F interactions. Ferroelectric measurements on the single crystals of DPDP?PF₆ gave a well‐saturated rectangular hysteresis loop with a remnant (P_r) polarization value of 6 μC cm^?2. Further, composite devices based on polydimethylsiloxane (PDMS) films for various weight percentages (3, 5, 7, 10 and 20 wt %) of DPDP?PF₆ were prepared and examined for power generation by using an impact test setup. A maximum output peak‐to‐peak voltage (V_PP) of 8.5 V and an output peak‐to‐peak current (I_PP) of 0.5 μA was obtained for the non‐poled composite film with 10 wt % of DPDP?PF₆. These results show the efficacy of organic ferroelectric substances as potential micropower generators.     

Formation of Concentrated Nanoemulsions by Extreme Shear

Abstract

We have systematically investigated the production of “nanoemulsions,” droplets of one liquid phase in another immiscible liquid phase that have diameters less than 100 nm. Our approach relies on a combination of extreme shear due to multipass, high‐pressure microfluidic injection and systematic control of the emulsion's composition. By repeatedly shearing a silicone oil‐in‐water emulsion in an inhomogeneous extensional shear flow, the multipass approach enables us to reduce the droplet polydispersity and average radius. Using dynamic light scattering, we study the changes in the average radius, ?a?, as a function of the number of passes, driving injection pressure (i.e., shear rate), droplet volume fraction, surfactant concentration, and droplet oil viscosity. The smallest nanoemulsion that we obtain has ?a?=18 nm. At large droplet volume fractions φ≥0.65, we observe phase inversion, rather than a reduction in the droplet size. This provides evidence that droplet coalescence can occur during extreme shear, even when a significant excess of a strongly stabilizing surfactant is present.