Optical separation of droplets on a microfluidic platform

This paper describes the optical separation of microdroplets according to their refractive indices. The behavior of the droplets was characterized in terms of the optical force and the hydrodynamic effects present upon illumination of the droplets in a direction normal to the flow direction in a rectangular microfluidic channel. The optical forces acting on the droplets and the resultant droplet trajectories were analyzed and compared with the numerically predicted values. The relationship between the drag force and optical force was examined to understand the system performance properties in the context of screening applications involving the removal of unwanted droplets. Two species of droplets were compared for their photophoretic displacements by varying the illumination intensity. Because the optical forces exerted on the droplets were functions of the refractive indices and sizes of the droplets, a variety of chemical species could be separated simultaneously.     

A microfluidic platform for formation of double-emulsion droplets

A new method for actively controlling the number of internal droplets of water-in-oil-in-water (W/O/W) double-emulsion droplets was demonstrated. A new microfluidic platform for double-emulsion applications has been developed, which integrates T-junction channels, moving-wall structures, and a flow-focusing structure. Inner water-in-oil (W/O) single-emulsion droplets were first formed at a major T-junction. Then the droplets were sub-divided into smaller uniform droplets by passing through a series of secondary T-junctions (branches). The moving-wall structures beside the secondary T-junctions were used to control the number of the sub-divided droplets by selectively blocking the branches. Finally, double-emulsion droplets were formed by using a flow-focusing structure downstream. Experimental data demonstrate that the inner and outer droplets have narrow size distributions with coefficient of variation (CV) of less than 3.5% and 5.7%, respectively. Double-emulsion droplets with 1, 2, 3, and up to 10 inner droplets have been successfully formed using this approach. The size of the inner droplets and outer droplets could be also fine-tuned with this device. The development of this new platform was promising for drug delivery applications involving double emulsions.     

Integration of impedance spectroscopy sensors in a digital microfluidic platform

Digital microfluidics combines the advantages of a low consumption of reagents with a high flexibility of processing fluid samples. For applications in life sciences not only the processing but also the characterization of fluids is crucial. In this contribution, a microfluidic platform, combining the actuation principle of electrowetting on dielectrics for droplet manipulations and the sensor principle of impedance spectroscopy for the characterization of the fluid composition and condition, is presented. The fabrication process of the microfluidic platform comprises physical vapor deposition and structuring of the metal electrodes onto a substrate, the deposition of a dielectric isolator and a hydrophobic top coating. The key advantage of this microfluidic chip is the common electric nature of the sensor and the actuation principle. This allows for fabricating digital microfluidic devices with a minimal number of process steps. Multiple measurements on fluids of different composition (including rigid particles) and of different conditions (temperature, sedimentation) were performed and process parameters were monitored online. These sample applications demonstrate the versatile applications of this combined technology.     

Microfluidic sorting of droplets by size

Droplet sorting by size was achieved in microfluidic channels through controlling the bifurcating junction geometry and the flow rates of the daughter channels. The sorting designs separated droplets with a radius difference of as little as 4 μm. The developed droplet channel design can be potentially used in combination with other particle sorting system to improve the sorting efficiency without the control of electrodes or fluidic valves.     

Reliable addition of reagents into microfluidic droplets

This article reports a design that reliably adds reagents into droplets by exploiting the physics of fluid flow at a T-junction in the microchannel. An expanded section right after the T-junction enhances merging of a stream with a droplet, eliminates the drawbacks such as extra droplet formation and long mixing time. The expanded section reduces the pressure buildup at the T-junction and minimizes the tendency to form extra droplets; plays the role in creating low Laplace pressure jump across the interface of the droplet forming from the T-junction which reduces the probability of forming extra droplet in the merging process; provides space for droplet coalescence if there is an extra droplet due to droplet break-up before merging. In this design, after merging, the reactants are in axial arrangement inside the droplets which lead to faster mixing. Reliable addition of reagent to the droplets happens for the combination of flow rates in a broad range from 25 to 250 μl/h, for both DI water (Q _DI) and fluorescent (Q _fluo) streams.     

Creating, transporting, cutting, and merging liquid droplets by electrowetting-based actuation for digital microfluidic circuits

Reports the completion of four fundamental fluidic operations considered essential to build digital microfluidic circuits, which can be used for lab-on-a-chip or micro total analysis system (/spl mu/TAS): 1) creating, 2) transporting, 3) cutting, and 4) merging liquid droplets, all by electrowetting, i.e., controlling the wetting property of the surface through electric potential. The surface used in this report is, more specifically, an electrode covered with dielectrics, hence, called electrowetting-on-dielectric (EWOD). All the fluidic movement is confined between two plates, which we call parallel-plate channel, rather than through closed channels or on open surfaces. While transporting and merging droplets are easily verified, we discover that there exists a design criterion for a given set of materials beyond which the droplet simply cannot be cut by EWOD mechanism. The condition for successful cutting is theoretically analyzed by examining the channel gap, the droplet size and the degree of contact angle change by electrowetting on dielectric (EWOD). A series of experiments is run and verifies the criterion.     

Aliquoting on the centrifugal microfluidic platform based on centrifugo-pneumatic valves

We present a new method for aliquoting liquids on the centrifugal microfluidic platform. Aliquoting is an essential unit operation to perform multiple parallel assays (“geometric multiplexing”) from one individual sample, such as genotyping by real-time polymerase chain reactions (PCR), or homogeneous immunoassay panels. Our method is a two-stage process with an initial metering phase and a subsequent transport phase initiated by switching a centrifugo-pneumatic valve. The method enables aliquoting liquids into completely separated reaction cavities. It includes precise metering that is independent on the volume of pre-stored reagents in the receiving cavities. It further excludes any cross-contamination between the receiving cavities. We characterized the performance for prototypes fabricated by three different technologies: micro-milling, thermoforming of foils, and injection molding. An initial volume of ~90 μl was split into 8 aliquots of 10 μl volume each plus a waste reservoir on a thermoformed foil disk resulting in a coefficient of variation (CV) of the metered volumes of 3.6%. A similar volume of ~105 μl was split into 16 aliquots of 6 μl volume each on micro-milled and injection-molded disks and the corresponding CVs were 2.8 and 2.2%, respectively. Thus, the compatibility of the novel aliquoting structure to the aforementioned prototyping and production technologies is demonstrated. Additionally, the important question of achievable volume precision of the aliquoting structure with respect to the production tolerances inherent to each of these production technologies is addressed experimentally and theoretically. The new method is amenable to low cost mass production, since it does not require any post-replication surface modifications like hydrophobic patches.     

Continuous-flow ferrohydrodynamic sorting of particles and cells in microfluidic devices

A new sorting scheme based on ferrofluid hydrodynamics (ferrohydrodynamics) was used to separate mixtures of particles and live cells simultaneously. Two species of cells, including Escherichia coli and Saccharomyces cerevisiae, as well as fluorescent polystyrene microparticles were studied for their sorting throughput and efficiency. Ferrofluids are stable magnetic nanoparticles suspensions. Under external magnetic field gradients, magnetic buoyancy forces exerted on particles and cells lead to size-dependent deflections from their laminar flow paths and result in spatial separation. We report the design, modeling, fabrication and characterization of the sorting device. This scheme is simple, low-cost and label-free compared to other existing techniques.     

Utilizing a high fundamental frequency quartz crystal resonator as a biosensor in a digital microfluidic platform

We demonstrate the operation of a digital microfluidic lab-on-a-chip system utilizing Electro Wetting on Dielectrics (EWOD) as the actuation principle and a High Fundamental Frequency (HFF; 50?MHz) quartz crystal microbalance (QCM) resonator as a mass-sensitive sensor. In a first experiment we have tested the reversible formation of a phosphor-lipid monolayer of phospholipid vesicles out of an aqueous buffer suspension onto a bio-functionalized integrated QCM sensor. A binding of bio-molecules results in an altered mass load of the resonant sensor and a shift of the resonance frequency can be measured. In the second part of the experiment, the formation of a protein multilayer composed of the biomolecule streptavidin and biotinylated immunoglobulin G was monitored. Additionally, the macroscopic contact angle was optically measured in order to verify the bio-specific binding and to test the implications onto the balance of the surface tensions. Using these sample applications, we were able to demonstrate and to verify the feasibility of integrating a mass-sensitive QCM sensor into a digital microfluidic chip.     

Particle separation and sorting in microfluidic devices: a review

Separation and sorting of micron-sized particles has great importance in diagnostics, chemical and biological analyses, food and chemical processing and environmental assessment. By employing the unique characteristics of microscale flow phenomena, various techniques have been established for fast and accurate separation and sorting of microparticles in a continuous manner. The advancements in microfluidics enable sorting technologies that combine the benefits of continuous operation with small-sized scale suitable for manipulation and probing of individual particles or cells. Microfluidic sorting platforms require smaller sample volume, which has several benefits in terms of reduced cost of reagents, analysis time and less invasiveness to patients for sample extraction. Additionally, smaller size of device together with lower fabrication cost allows massive parallelization, which makes high-throughput sorting possible. Both passive and active separation and sorting techniques have been reported in literature. Passive techniques utilize the interaction between particles, flow field and the channel structure and do not require external fields. On the other hand, active techniques make use of external fields in various forms but offer better performance. This paper provides an extensive review of various passive and active separation techniques including basic theories and experimental details. The working principles are explained in detail, and performances of the devices are discussed.     

基于微流控芯片的癌细胞分选仪硬件系统设计

设计了基于微流控芯片的癌细胞分选仪的硬件系统。系统采用光电倍增管(PMT)采集微流控芯片沟道内流动细胞的荧光信号,通过设计的微弱电流信号采集电路进行光电倍增管输出信号的处理,完成对细胞微弱荧光信号的检测。此外,设计了0~1 200 V范围幅值与脉宽可调的高压脉冲源,可产生随机高压脉冲用于癌细胞的分选。整个系统实现了微流控芯片上癌细胞检测、计数以及分选的结合。     

Electric field driven addressing of ATPS droplets in microfluidic chips

The possibility of controlled droplet motion (droplet addressing) mediated by DC electric field in aqueous two-phase systems (ATPS) is here reported for the first time. Three ATPS of polyethylene glycol (PEG)/salt type, namely PEG/phosphate, PEG/sulphate, and PEG/carbonate, were selected for this study. We observed fast motion of salty droplets dispersed in PEG continuous phase induced by electric field of relative low strength. Hence, three fluidic systems with separated electrode chambers for the evaluation of electrophoretic mobilities and for addressing experiments were fabricated. Electrophoretic mobilities of salty droplets always exceeded the value of \(1\times 10^{-7}\, \hbox {m}^2\hbox {V}^{-1}\hbox {s}^{-1}\), which is about by one magnitude higher value than those typically measured in water–oil droplet systems. The electrophoretic mobilities in systems with free surface are the same or even smaller than in closed microfluidic structures, which is accounted mainly to the fact that a significant part of salty droplets is exposed to air and does not contribute to droplet forcing. Series of addressing and merging experiments in a microfluidic chip shows that DC electric field can be used as a powerful tool for smart manipulation of droplets in microfluidic systems with PEG/salt ATPS.     

Production of uniform droplets using membrane, microchannel and microfluidic emulsification devices

This review provides an overview of major microengineering emulsification techniques for production of monodispersed droplets. The main emphasis has been put on membrane emulsification using Shirasu Porous Glass and microsieve membrane, microchannel emulsification using grooved-type and straight-through microchannel plates, microfluidic junctions and flow focusing microfluidic devices. Microfabrication methods for production of planar and 3D poly(dimethylsiloxane) devices, glass capillary microfluidic devices and single-crystal silicon microchannel array devices have been described including soft lithography, glass capillary pulling and microforging, hot embossing, anisotropic wet etching and deep reactive ion etching. In addition, fabrication methods for SPG and microseive membranes have been outlined, such as spinodal decomposition, reactive ion etching and ultraviolet LIGA (Lithography, Electroplating, and Moulding) process. The most widespread application of micromachined emulsification devices is in the synthesis of monodispersed particles and vesicles, such as polymeric particles, microgels, solid lipid particles, Janus particles, and functional vesicles (liposomes, polymersomes and colloidosomes). Glass capillary microfluidic devices are very suitable for production of core/shell drops of controllable shell thickness and multiple emulsions containing a controlled number of inner droplets and/or inner droplets of two or more distinct phases. Microchannel emulsification is a very promising technique for production of monodispersed droplets with droplet throughputs of up to 100?l?h^?1.     

基于FPGA和线阵CCD的色选实验平台研究

提出了一种基于FPGA和线阵CCD的色选实验平台．利用线阵CCD对下落的大米进行在线动态扫描,通过FPGA对采集到的大米图像信息进行分析和处理,识别出异色米粒,并通过分离装置剔除不合格大米。详细介绍了硬件平台的设计以及采用的色选算法,该研究对高性能大米色选机的研制具有重要的参考价值。     

Surfactant-induced retardation in lateral migration of droplets in a microfluidic confinement

The present study deals with the effect of surfactants on the cross-stream migration of droplets in a confined fluidic environment, both experimentally and theoretically. Presence of an imposed flow induces droplet deformation and disturbs the equilibrium that results in subsequent surfactant redistribution along the interface. This further creates a gradient in surface tension, thus generating a Marangoni stress that significantly alters the droplet dynamics. On subsequent experimental investigation, it is found that presence of surfactants reduces the cross-stream migration velocity of the droplet. High-speed photography is utilized to visualize the transport of droplets in a microfluidic channel. It is shown that the channel confinement significantly enhances the surfactant-induced retardation of the droplet. In addition, a larger surfactant concentration is found to induce a greater reduction in cross-stream migration velocity of the droplet, the effect of which is reduced when the initial transverse position of the droplet is shifted closer to the channel centerline. To support our experimental results, an asymptotic approach is adopted to solve the flow field in the presence of bulk-insoluble surfactants and under the assumption of small shape deformation. A good match between our theoretical prediction and the experimental results is obtained. The present analysis provides us with a wide scope of application towards various droplet-based microfluidic as well as medical diagnostic devices where manipulation of droplet trajectory is a major issue.     

Design,simulation and experiment of electroosmotic microfluidic chip for cell sorting

A microfluidic cell sorting chip has been developed using micromachining technology, where electroosmotic flow (EOF) is exploited to drive and switch cells. For this electroosmotically driven system, it is found that the effect of induced hydrostatic pressure caused by unequal levels in solution reservoirs is not negligible. In this work, the numerical simulation of EOF and opposing pressure induced flow in microchannels is presented and the velocity profiles in the microchannels are measured experimentally using microparticle imaging velocimetry (PIV) system. The result shows that the final resulting velocity is the superposition of the two flows. A total volume of 0.305 μl is transported in the 50 μm microchannel and the back flow occurs after 240 s transportation. The task of sorting cells is realized at the switching structure by adjusting the electric fields in the microchannels. The performance of the cell sorting chip is optimized by investigating the effect of different switching structures. A Y-junction switching structure with 90° switching angle is highly recommended with simulated leakage distance of 53 μm and switching time of 8 ms.     

数字微流控生化芯片多液滴稀释方法的研究

生化试验中如何将样品试剂配备过程转化成有效的数字生化芯片实现的协议,并给出相应的操作过程中的稀释/混合操作优化算法非常关键,是样品试剂配备过程的一个挑战。为减少操作步骤和节省药品,提出针对数字微流控生物芯片多液滴混合器稀释/混合操作优化算法,该算法允许多个液体参与混合分离操作,可以在误差允许范围内利用片上多液滴混合器用较少的操作步骤获得目标浓度的液滴。相对传统的两液滴混合方法,减少了稀疏/混合的步骤和稀释/混合时间,同时减少中间废弃液滴的数目。实验结果也表明可以在允许的误差范围内高效地进行混合/分离操作,获得目标浓度的液滴。     

Thermal actuation and confinement of water droplets on paper-based digital microfluidics devices

In this paper, the thermocapillary actuation is implemented to manipulate and confine the fluid droplets in a paper-based digital microfluidics (PB-DMF) device. The main advantage of using the thermocapillary actuation over the traditional electrowetting-on-dielectric actuation in the DMF devices is its ability to work with lower operating DC voltages. The proposed device is fabricated by the low-cost screen printing method using very low-cost materials. In order to overcome the weak controllability of the device over the droplets, a new thermal confinement technique is proposed which simply embedded in the device electrode pattern. A new thermally actuated valve is also designed to work based on thermocapillary actuation for switching on or off the droplets. The fabricated DMF device and the thermal valve are both combined with a microfluidics paper-based analytical device to form a hybrid paper chip in which the droplets are driven by both channel-based and droplet-based devices. The device operation is tested by using a biochemical glucose colorimetric detection assay.