Likai Hou

Electrocoalescence of paired droplets encapsulated in double-emulsion drops

We utilize an ac electric field to trigger the on-demand fusion of two aqueous cores inside water-in-oil-in-water (W/O/W) double-emulsion drops. We attribute the coalescence phenomenon to field-induced structural polarization and breakdown of the stress balance at interfaces. This method provides not only accurate control over the reaction time of coalescence but also protection of the reaction from cross contamination.

In-plane microvortices micromixer-based AC electrothermal for testing drug induced death of tumor cells

Herein, we first describe a perfusion chip integrated with an AC electrothermal (ACET) micromixer to supply a uniform drug concentration to tumor cells. The in-plane fluid microvortices for mixing were generated by six pairs of reconstructed novel ACET asymmetric electrodes. To enhance the mixing efficiency, the novel ACET electrodes with rotating angles of 0°, 30°, and 60° were investigated. The asymmetric electrodes with a rotating angle of 60° exhibited the highest mixing efficiency by both simulated and experimental results. The length of the mixing area is 7 mm, and the mixing efficiency is 89.12% (approximate complete mixing) at a voltage of 3 V and a frequency of 500 kHz. The applicability of our micromixer with electrodes rotating at 60° was demonstrated by the drug (tamoxifen) test of human breast cancer cells (MCF-7) for five days, which implies that our ACET in-plane microvortices micromixer has great potential for the application of drug induced rapid death of tumor cells and mixing of biomaterials in organs-on-a-chip systems.

A dual-core double emulsion platform for osmolarity-controlled microreactor triggered by coalescence of encapsulated droplets

Droplet-based microfluidics has provided a means to generate multi-core double emulsions, which are versatile platforms for microreactors in materials science, synthetic biology, and chemical engineering. To provide new opportunities for double emulsion platforms, here, we report a glass capillary microfluidic approach to first fabricate osmolarity-responsive Water-in-Oil-in-Water (W/O/W) double emulsion containing two different inner droplets/cores and to then trigger the coalescence between the encapsulated droplets precisely. To achieve this, we independently control the swelling speed and size of each droplet in the dual-core double emulsion by controlling the osmotic pressure between the inner droplets and the collection solutions. When the inner two droplets in one W/O/W double emulsion swell to the same size and reach the instability of the oil film interface between the inner droplets, core-coalescence happens and this coalescence process can be controlled precisely. This microfluidic methodology enables the generation of highly monodisperse dual-core double emulsions and the osmolarity-controlled swelling behavior provides new stimuli to trigger the coalescence between the encapsulated droplets. Such swelling-caused core-coalescence behavior in dual-core double emulsion establishes a novel microreactor for nanoliter-scale reactions, which can protect reaction materials and products from being contaminated or released.

Flexible particle flow-focusing in microchannel driven by droplet-directed induced-charge electroosmosis

We report herein a novel microfluidic particle concentrator that utilizes constriction microchannels to enhance the flow‐focusing performance of induced‐charge electroosmosis (ICEO), where viscous hemi‐spherical oil droplets are embedded within the mainchannel to form deformable converging‐diverging constriction structures. The constriction region between symmetric oil droplets partially coated on the electrode strips can improve the focusing performance by inducing a granular wake flow area at the diverging channel, which makes almost all of the scattered sample particles trapped within a narrow stream on the floating electrode. Another asymmetric droplet pair arranged near the outlets can further direct the trajectory of focused particle stream to one specified outlet port depending on the symmetry breaking in the shape of opposing phase interfaces. By fully exploiting rectification properties of induced‐charge electrokinetic phenomena at immiscible water/oil interfaces of tunable geometry, the expected function of continuous and switchable flow‐focusing is demonstrated by preconcentrating both inorganic silica particles and biological yeast cells. Physical mechanisms responsible for particle focusing and locus deflection in the droplet‐assisted concentrentor are analyzed in detail, and simulation results are in good accordance with experimental observations. Our work provides new routes to construct flexible electrokinetic framework for preprocessing on‐chip biological samples before performing subsequent analysis.

Continuously Electrotriggered Core Coalescence of Double-Emulsion Drops for Microreactions

Microfluidically generated double emulsions are promising templates for microreactions, which protect the reaction from external disturbance and enable in vitro analyses with large-scale samples. Controlled combination of their inner droplets in a continuous manner is an essential requirement toward truly applications. Here, we first generate dual-cored double-emulsion drops with different inner encapsulants using a capillary microfluidic device; next, we transfer the emulsion drops into another electrode-integrated polydimethylsiloxane microfluidic device and utilize external AC electric field to continuously trigger the coalescence of inner cores inside these emulsion drops in continuous flow. Hundreds of thousands of monodisperse microreactions with nanoliter-scale reagents can be conducted using this approach. The performance of core coalescence is investigated as a function of flow rate, applied electrical signal, and core conductivity. The coalescence efficiency can reach up to 95%. We demonstrate the utility of this technology for accommodating microreactions by analyzing an enzyme catalyzed reaction and by fabricating cell-laden hydrogel particles. The presented method can be readily used for the controlled triggering of microreactions with high flexibility for a wide range of applications, especially for continuous chemical or cell assays.

Sequential Coalescence Enabled Two-Step Microreactions in Triple-Core Double-Emulsion Droplets Triggered by an Electric Field

Advances in microfluidic emulsification have enabled the generation of exquisite multiple-core droplets, which are promising structures to accommodate microreactions. An essential requirement for conducting reactions is the sequential coalescence of the multiple cores encapsulated within these droplets, therefore, mixing the reagents together in a controlled sequence. Here, a microfluidic approach is reported for the conduction of two-step microreactions by electrically fusing three cores inside double-emulsion droplets. Using a microcapillary glass device, monodisperse water-in-oil-in-water droplets are fabricated with three compartmented reagents encapsulated inside. An AC electric field is then applied through a polydimethylsiloxane chip to trigger the sequential mixing of the reagents, where the precise sequence is guaranteed by the discrepancy of the volume or conductivity of the inner cores. A two-step reaction in each droplet is ensured by two times of core coalescence, which totally takes 20-40 s depending on varying conditions. The optimal parameters of the AC signal for the sequential fusion of the inner droplets are identified. Moreover, the capability of this technique is demonstrated by conducting an enzyme-catalyzed reaction used for glucose detection with the double-emulsion droplets. This technique should benefit a wide range of applications that require multistep reactions in micrometer scale.

Effects of Chip Geometries on Dielectrophoresis and Electrorotation Investigation

The electric fields employed for such work are generated using chips, such as planar linear interdigitated arrays or two parallel arrays. However, chip geometries usually affect the investigation of dielectrophoresis (DEP) and electrorotation (ER) significantly, and even may misdirect the theoretical prediction. In order to understand the electrodes geometries effect and provide a suitable range of parameters, three-dimensional simulations for the DEP and ER characterizations on the quadrupolar hyperbolical electrodes are carried out. Influences of the electrodes gaps, cell height, work region, energized voltage and frequencies for the DEP and ER manipulations are analyzed, and the analysis results show that the gaps of the electrodes and the cell height have enormous effects, but the work region is not so important. Moreover, depending on the theoretical analysis, ER experiments for polystyrene microspheres with the diameter of 20 μm are carried out on two kinds of chips. The experimental results show that the microspheres rotate in the counter-field direction and the maximum rotation speed appears in the megahertz range. In addition, the experimental results are compared with the simulation results, showing that the three-dimensional simulations considering the chip geometries are more accurate than the two-dimensional predictions. This paper provides a new understanding for the theoretical predictions of DEP and ER manipulations, which decreases the difference of the theoretical and experimental results significantly, and will be significant for the lab chip research.

A simple microfluidic method for one-step encapsulation of reagents with varying concentrations in double emulsion drops for nanoliter-scale reactions and analyses

This work reports a simple microfluidic method for one-step encapsulation of two reagents with varying concentrations in water-in-oil-in-water (W/O/W) double-emulsion drops. This method not only enables nanoliter-scale reactions and analyses under a series of controlled concentrations of two reagents without stopping the experiments or changing solutions, but also protects the reactions from external disturbance for an extended amount of time by the core–shell structure. To achieve this, a capillary device embedded with a theta-shaped tube is fabricated to produce monodisperse emulsion drops, in which the concentrations of the reagents encapsulated are varied by tuning the flow rates in the two individual channels of the theta tube. The relative volume ratio of the encapsulated reagents can reach up to 1 : 20. In addition, microcapsules converted from emulsion drops have excellent long-term robustness. As a proof of concept, we conduct two frequently used reactions at the nanoliter scale with varying concentrations: acid–base reaction and enzyme-catalyzed redox reaction for glucose detection.

High-Throughput Separation, Trapping, and Manipulation of Single Cells and Particles by Combined Dielectrophoresis at a Bipolar Electrode Array

Microfluidic systems have been developed widely in scaled-down processes of laboratory techniques, but they are usually limited in achieving stand-alone functionalities. It is highly desirable to exploit an integrated microfluidic device with multiple capabilities such as cell separation, single-cell trapping, and cell manipulation. Herein, we reported a microfluidic platform integrated with actuation electrodes, for separating cells and microbeads, and bipolar electrodes, for trapping, rotating, and propelling single cells and microbeads. The separation of cells and microbeads can be first achieved by deflective dielectrophoresis (DEP) barriers. Trapping experiments with yeast cells and polystyrene (PS) microbeads suspended in aqueous solutions with different conductivities were then conducted, showing that both cells and particles can be trapped at the center of wireless electrodes by negative DEP force. Upon application of a rotating electric field, yeast cells exhibit translational movement along the electrode edges, and self-rotation is seen at an array of bipolar electrodes when electrorotational torque and traveling wave DEP force are applied on the cells. The current approach allows us to switch the propulsion and rotation direction of cells by varying the frequency of the applied electric field. Beyond the achievements of single-cell manipulation, this system permits effective control of several particles or cells simultaneously. The integration of parallel sorting and single trapping stages within a microfluidic chip enables the prospect of high-throughput cell separation, single trapping, and large-scale cell locomotion and rotation in a noninvasive and disposable format, showing great potential in single-cell analysis, targeted drug delivery, and surgery.

Flexible continuous particle-beam switching via external-field-reconfigurable asymmetric induced-charge electroosmosis

Continuous sample switching is an essential process for developing an integrated platform incorporating multiple functionality with applications typically ranging from chemical to biological assays. Herein we propose a unique method of external-field-reconfigurable symmetry breaking in induced-charge electroosmosis above a simple planar bipolar electrode for continuous particle beam switching. In the proposed system, the spatial symmetry of a nonlinear electroosmotic vortex flow can be artificially reordered to achieve an asymmetric electrically floating-electrode polarization by regulating the configurations of the external ac signals, thus contributing to flexible particle beam switching. This switching system comprises an upstream flow-focusing region where particles are prefocused into a beam on the bipolar electrode by transversal electroconvective mass transfer, and a deflecting region in which the resulting particle beam is deflected to generate a steerable lateral displacement to enter the desired region via the action of an asymmetric polarization-induced reshapable electroosmotic flow stagnation line in a controllable background field gradient. A lateral particle displacement on the order of hundreds of micrometers can be achieved in a deterministic manner by varying the voltage, frequency, and inlet flow rate, thereby enabling multichannel particle switching. Furthermore, the versatility of the switching mechanism is extended by successfully accomplishing fluorescent nanoparticle beam switching, yeast cell switching, five-outlet particle switching, and simultaneous switching of two particle types. The proposed switching approach provides a promising technique for flexible electrokinetic sample preconcentration prior to any subsequent analysis and can be conveniently integrated with other micro/nanofluidic components into a complete functional on-chip platform owing to its simple electrode structure.