Microchannel geometry design for rapid and uniform reagent distribution

Rapid and uniform reagent distribution is critical to the performance of a high-throughput microfluidic system, and its geometric design of the microchannels dominates the accuracy and distribution uniformity of the daughter droplets. This research’s purpose is to optimize the geometry of the T-junction to achieve a uniform distribution of two daughter droplets from a single liquid droplet. Models of gas–liquid flow were realized in the transient numerical simulations to investigate the geometry-dependent pressure distributions and the flowing velocities inside the droplet during the splitting process that leads to an improved design of the T-junction that can increase the stability of the droplet splitting process. To validate that increasing the stability of the splitting process can help improve the distribution uniformity of the daughter droplets, microfluidic devices were manufactured on poly(methyl methacrylate) substrates with micromilling and thermal bonding for experiments. In the multiple experiments, 2 μl of reagent was loaded into the microfluidic device and a uniform pneumatic pressure was applied to push the droplet into the T-junction for splitting. The experimental results, after statistical analysis, show that the improved T-junction can achieve better distribution uniformity of the daughter droplets with a higher reliability and a less reagent loss during the splitting process.     

Exploitation of a microfluidic device capable of generating size-tunable droplets for gene delivery

This study presents a new microfluidic chip that generates micro-scale emulsion droplets for gene delivery applications. Compared with conventional methods of droplet formation, the proposed chip can create uniform droplets (size variation <7.1%) and hence enhance the efficiency of the subsequent gene delivery. A new microfluidic chip was developed in this study, which used a new design with a pneumatic membrane chamber integrated into a T-junction microchannel. Traditionally, the size of droplets was controlled by the flow rate ratio of the continuous and disperse phase flows, which can be controlled by syringe pumps. In this study, a pneumatic chamber near the intersection of the T-junction channel was designed to locally change the flow velocity and the shear force. When the upper air chamber was filled with compressed air, the membrane was deflected and then the droplet size could be fine-tuned accordingly. Experimental data showed that using the new design, the higher the air pressure applied to the active tunable membrane, the smaller the droplet size. Finally, droplets were used as carriers for DNA to be transfected into the Cos-7 cells. It was also experimentally found that the size of the emulsion droplets plays an important role on the efficiency of the gene delivery. The preliminary results of this paper have been presented at the 2007 IEEE International Conference of Nano/Molecular Medicine and Engineering (IEEE NANOMED 2007), Macau, China, 6–9 August, 2007.     

Fiber Bragg grating sensor for two-phase flow in microchannels

A new non-intrusive measurement technique for two-phase flow in microchannels is presented. The development of an evanescent field-based optical fiber Bragg grating (FBG) sensor is described, and experiments coupled with flow visualization demonstrating the performance of this sensor are presented. Two adjacent 1-mm FBGs in etched D-shaped fiber are embedded into the surface of a PDMS microchannel. Experiments are conducted in both droplet and slug flow regimes and high-speed digital video is captured synchronously with the sensor data. The FBGs exhibit an on?Coff type response to the passage droplets which is shown to correlate precisely with the passage of the liquid phase. This correlation enables the measurement of droplet average velocity and size using only the sensor data. In addition to the use of both FBG signals for the purpose of measuring droplet speed and size, it is shown that for droplets larger than the FBG length, a single FBG can be used to estimate the convection velocity and size of fast moving droplets. This sensing method is potentially useful for monitoring two-phase flow in fuel cells and microfluidic applications such as micro-heat exchangers and lab-on-a-chip systems.     

Meter-scale large-area capacitive pressure sensors with fabric with stripe electrodes of conductive polymer-coated fibers

We developed meter-scale large-area capacitive fabric pressure sensors for floor sensors to monitor human position. In the fabric pressure sensor, two fabrics with stripe electrodes of conductive polymer-coated fibers woven into them were stacked vertically, and the capacitance changes between the top and bottom stripe electrodes were measured when pressure was applied. By using the die-coating of a conductive polymer and weaving the resultant fibers with meter-scale automatic looming machines, the 1 m × 1 m area with stripe electrodes at a 20 cm pitch was constructed. The pressure sensitivity, which depends on the number of the sensor fibers forming the stripe electrodes, was characterized and optimized to increase output capacitance change. The stripe electrodes with five sensor fibers were found to exhibit a capacitance change of 1.37 pF when pushed with the average foot pressure (i.e., 2.6 N/cm²), which is large enough to detect with conventional capacitance measurement circuits. Finally, pressure sensing with our woven pressure sensor fabric is demonstrated. Our meter-scale pressure sensor fabric technology will be used for bed and floor sensors for monitoring old people in nursing homes and hospitals.     

Thin-film electrode based droplet detection for microfluidic systems

We report on a droplet-producing microfluidic system with electrical impedance-based detection. The microfluidic devices are made of polydimethylsiloxane (PDMS) and glass with thin film electrodes connected to an impedance-monitoring circuit. Immiscible fluids containing the hydrophobic and hydrophilic phases are injected with syringe pumps and spontaneously break into water-in-oil droplet trains. When a droplet passes between a pair of electrodes in a medium having different electrical conductivity, the resulting impedance change signals the presence of the particle for closed-loop feedback during processing. The circuit produces a digital pulse for input into a computer control system. The droplet detector allows estimation of a droplet's arrival time at the microfluidic chip outlet for dispensing applications. Droplet detection is required in applications that count, sort, and direct microfluidic droplets. Because of their low cost and simplicity, microelectrode-based droplet detection techniques should find applications in digital microfluidics and in three-dimensional printing technology for rapid prototyping and biotechnology.     

Rapid label-free DNA analysis in picoliter microfluidic droplets using FRET probes

We report a novel microfluidic system that is capable of rapidly detecting DNA and its mutants in microfluidic droplets, in addition to elucidating the dynamic hybridization process. This microfluidic picoliter droplet analysis system is able to overcome the limitations of conventional analytical techniques that utilize immobilized sensing probes on a substrate. Molecular beacon (MB), a fluorescence resonance energy transfer (FRET) molecule, was used as the DNA sensing probe in picoliter droplets. The MB-DNA duplex formation process was analyzed by the change in FRET signal, which was acquired by the time-resolved method: converting distance traveled to hybridization time. This technique demonstrates the ability to detect presence of target nucleic acids within few seconds, multiplex DNA samples in microdroplet, and distinguish single nucleotide polymorphisms. It is promising for analyzing biomolecules or reactions, such as mRNA, cells, enzymatic activity, and protein folding whose analysis requires rapid mixing and small volume.     

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.     

A facile on-demand droplet microfluidic system for lab-on-a-chip applications

We present a facile microfluidic droplet-on-demand (DOD) system in which a pulsed pressure generated by a high-speed solenoid valve is used to control the formation and movement of water-in-oil emulsion droplets in a T-junction microchannel. We investigated the working principle of the DOD system and established a scaling model for the droplet volume in terms of the amplitude and duration of the pulse and the hydraulic resistance of the injection channel. The droplet formation was characterized in three designs at various pressure pulses. The experimental results support our scaling model very well. In the DOD system we developed, nanoliter-volume droplets with a throughput of a few droplets per second were on-demand generated. Moreover, we examined the applicable scope of the DOD system. As examples of practical applications of the DOD system, we demonstrated a digital display module to show droplets formed at a prescribed time and a droplet array with a concentration gradient to show droplets formed with a precise volume. We expect our work can provide design guidelines for a robust DOD system and improve the capabilities of droplet-based microfluidics in ‘lab-on-a-chip’ systems.     

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.     

Generation of droplets in the T-junction with a constriction microchannel

Droplet microfluidics plays an essential role in science and technology with various applications such as chemical engineering, environment, energy and other fields. T-junction with a constriction microchannel is designed for the controlled production of monodisperse microdroplets, which could produce droplets with the same size under a lower flow resistance. The influence of the microchannel structure, operating conditions, and physical properties on the dispersion rules is systematically investigated by combinations of micro-particle image velocimetry (Micro-PIV), high-speed camera and numerical simulation. Compared to the traditional T-junction channel, the T-junction with a constriction microchannel can generate smaller droplets whose size conforms to the size prediction formula of the traditional T-junction channel. It is found that the velocity vector of the T-junction with a constriction microchannel is faster than that in the T-junction channel at each stage of droplet generation. The droplet size is mainly based on the Ca number, the flow rate ratio and viscosity ratio of the continuous phases in our channel, and the range of the index of Ca with the droplet size is found. The constriction width has a significant influence on the dispersion rule, as there is a decreasing tendency for the droplet size with reducing constriction width.     

An end-effector based imaging proximity sensor

A two-dimensional array of small capacitive sensors detects the distance between each sensor tip and the target object. When touching the surface or operating at close distance, an image of the surface contour is obtained. Each capacitive sensor consists of a thin short lead (line capacitance) embedded in a hard ceramic substrate. The sensor array is rugged and can, due to its small size, be configured to almost any desired shape in order to examine even hard-to-reach surfaces. An electronic circuit converts the capacitance variations into voltage signals. The sensing process is controlled by a microcomputer, which addresses the sensors in serial order through a multiplexer, samples the data and linearizes them according to the calibration curve. When compared to resistive touch sensors, the capacitive sensing method offers potentially higher package density and image resolution; another advantage is the capability to detect the presence of objects while approaching, before physical contact is made. A proximity sensor array mounted on a robot end effector can determine geometrical parameters such as edges of surfaces, hole center locations, and the end effector pose (angle of alignment between end effector and target surface).     

Y- and T-junction microfluidic devices: effect of fluids and interface properties and operating conditions

Water-in-oil emulsions were produced in microchannels with Y- and T-junction geometries by individual droplet generation. For each microchannel configuration, the effect of the fluids and interface properties as well as of the process conditions was evaluated. The size of the droplets depended mainly on the relative velocity between continuous and dispersed phases and the relative fluid viscosity between phases. Those variables were related to the shear stress between the phases, which caused the droplet detachment. In addition, the interfacial forces played a minor role in Y-junction, and they had no effect in the droplets formation in T-junction microchannels. In Y-junction, a large variation in the droplet size was observed, depending on the system composition and the operating conditions. At low relative velocity and fluid viscosity, no droplets were generated. In contrast, the process in T-junction resulted in a lower variation of droplets size and the droplets were formed even at less favorable conditions. Such results indicate that the knowledge of the mechanism of droplets generation in each microchannel geometry makes it possible to choose the appropriate configuration according to the type of fluid, and the operating conditions can be adjusted to obtain the desired final emulsion.     

Driving and sorting of the fluorescent droplets on digital microfluidic platform

In this paper, we present a digital microfluidic droplet sorting platform to achieve automated droplet sorting based on fluorescent detection. We design and fabricate a kind of digital microfluidic chip for manipulating nano-liter-sized liquid droplets, and the chip is integrated with a fluorescence-initiated feedback system for real-time sorting control. The driving and sorting characteristics of fluorescent droplets encapsulating fluorescent-labeled particles are studied on this platform. The droplets dispensed from on-chip reservoir electrode are transported to a fluorescence detection site and sorted according to their fluorescence signals. The fluorescent droplets and non-fluorescent droplets are successfully separated and the number of fluorescent particles inside each droplet is quantified by its fluorescent intensity. We realize droplet sorting at 20 Hz and obtain a linear relationship between the fluorescent particle concentrations and the fluorescence signals. This work is easily adapted for sorting out fluorescent-labeled microparticles, cells and bacteria and thus has the potential of quantifying catalytic or regulatory bio-activities.     

Design of a flow-controlled asymmetric droplet splitter using computational fluid dynamics

In this work the design of a segmented flow microfluidic device is presented that allows droplet splitting ratios from 1:1 up to 20:1. This ratio can be dynamically changed on chip by altering an additional oil flow. The design was fabricated in PDMS chips using the standard SU-8 mold technique and does not require any valves, membranes, optics or electronics. To avoid a trial and error approach, fabricating and testing several designs, a computational fluid dynamics model was developed and validated for droplet formation and splitting. The model was used to choose between several variations of the splitting T-junction with the extra oil inlet, as well to predict the additional flow rate needed to split the droplets in various ratios. Experimental and simulated results were in line, suggesting the model’s suitability to optimize future designs and concepts. The resulting asymmetric droplet splitter design opens possibilities for controlled sampling and improved magnetic separation in bio-assay applications.     

基于AD7745的数字式油品检测传感器设计

植物油掺伪后难以检测,根据不同油品具有不同介电常数的特性,设计了通过电容值进行检测的数字式油品传感器,建立了传感器等效电路,分析了传感器结构对电容检测的影响。传感器为插杆状结构,平板电容极板为敏感元件,检测时不同油品介质引起的电容量变化经AD7745转换成相应的数字量通过I2C串行总线口输出。实验结果表明:数字式油品传感器能够对掺伪3%以上的植物油进行快速有效鉴别,重复性优于0.2%。     

Engineering droplet navigation through tertiary-junction microchannels

We present an experimental and in silico investigation of path selection by a single droplet inside a tertiary-junction microchannel using oil-in-water as a model system. The droplet was generated at a T-junction inside a microfluidic chip, and its flow behavior as a function of droplet size, streamline position, viscosity, and Reynolds number (Re) of the continuous phase was studied downstream at a tertiary junction having perpendicular channels of uniform square cross section and internal fluidic resistance proportional to their lengths. Numerical studies were performed using the multicomponent lattice Boltzmann method. Both the experimental and numerical results showed good agreement and suggested that at higher Re equal to 3, the flow was dominated by inertial forces resulting in the droplets choosing a path based on their center position in the flow streamline. At lower Re of 0.3, the streamline-assisted path selection became viscous force-assisted above a critical droplet size. As the Re was further reduced to 0.03, or when the viscosity of the dispersed phase was increased, the critical droplet size for transition also decreased. This multivariate approach can in future be used to engineer sorting of cells, e.g., circulating tumor cells (CTCs) allowing early-stage detection of life-threatening diseases.     

电容式传感器探测电极设计

为提高电容式传感器的探测灵敏度,对传感器的探测电极进行了设计,当两电极面积之和为一定值,且与目标等距离接近时,为获得最大的电容变化,应使两电极的表面积尽量相等,同时,进行了具有隔离极的探测电极结构设计,经实验证明:当满足隔离极宽度大于2倍探测极宽度时,该结构的探测电极能够显著提高电容式传感器的探测灵敏度,从而提高电容引信的探测距离.     

Global network design for robust operation of microfluidic droplet generators with pressure-driven flow

This study investigates the influence of both local generator design and global network architecture in improving the stability and operational performance of microfluidic droplet generators. We identify naturally occurring short-term and long-term oscillations that are related to changes in the flow of the two phases. Short-term oscillations are related to the creation of each droplet and are quantified by tracking droplet speed in the network. Long-term oscillations are caused by dynamic feedback associated with the periodic change in the hydrodynamic resistance of the network as droplets enter and exit the system. Our analysis identifies that these long-term oscillations are best quantified by measuring changes in droplet spacing rather than the conventional method of using droplet size. Furthermore, we find that these long-term oscillations have a periodicity that matches the residence time of droplets within the network. In combination with experiments, a simple compact model is developed to study these oscillations and guide the network design of droplet generators. As part of this analysis a set of design rules is developed to help improve overall generator performance using pressure-driven flow.     

Generating gas/liquid/liquid three-phase microdispersed systems in double T-junctions microfluidic device

This article describes the generation of microdispersed bubbles and droplets in a double T-junctions microfluidic device to form immiscible gas/liquid/liquid three-phase flowing systems. Segmented gas plugs are controllably prepared in water at the first T-junction to form gas/liquid two-phase fluid with the perpendicular flow cutting method. Then using this two-phase fluid as the cross-shearing fluid for the oil phase at the second T-junction, the gas/liquid/liquid three-phase flowing systems are prepared. Interestingly, it is found that the break-up of the oil droplets is mainly dominated by the cutting effect of the gas/liquid interface or the pressure drop across the emerging droplet, but independent with the viscous shearing effect of the continuous phase, even at the capillary number (Ca = u _wμ_w/γ_ow) higher than 0.01. The size laws and the distributions of the bubbles and droplets are investigated carefully, and a mathematical model has been developed to relating the operating conditions with the dispersed sizes.     

A printed circuit board capacitive sensor for air bubble inside fluidic flow detection

This paper presents a three-electrode capacitive fluidic sensor for detecting an air bubble inside a fluidic channel such as blood vessels, oil or medical liquid channels. The capacitor is designed and fabricated based on a printed circuit board (PCB). The electrodes are fabricated by using copper via structure through top to bottom surface of the PCB. A plastic pipe is layout through the capacitive sensor and perpendicular to the PCB surface. Capacitance of sensor changes when an air bubble inside fluidic flow cross the sensor. The capacitance change can be monitored by using a differential capacitive amplifier, a lock-in amplifier, filter and an NI acquisition card. Signal is processed and calculated on a computer. Air bubble inside the liquid flow are detected by monitor the unbalance signal between the three electrode potential voltages. Output voltage depends on the volume of the air bubble due to dielectric change between capacitor’s electrodes. Output voltage is up to 53 mV when an 2.28 mm³ air bubble crosses the sensing channel. Air bubble velocity can be estimated based on the output pulse signal. This proposed fluidic sensor can be used for void fraction detection in medical devices and systems; fluidic characterization; and water–gas, oil–water and oil–water–gas multiphase flows in petroleum technology. That structure also can apply to the micro-size for detecting in microfluidic to monitor and control changes in microfluidic channels.