Droplet-based Microfluidic Devices Research Articles

A journey of trains of droplets in droplet-based microfluidic devices.

In this paper, we propose a microfluidic platform toseparate magnetic particles with a constant volumetric flow condition. In order to realize this architecture, three main functions for a droplet manipulation based system are integrated into a single device: synchronization of droplets by matching a location of droplets; lateral electro-coalescence; and magnetic particle manipulation. For an optimized condition of this device, a droplet generation was controlled by varying a droplet size at a fixed flow rate ratio 0.86. The electro-coalescence efficiency and maximum throughput are investigated at a given flow rate condition.

Simple and inexpensive microfluidic devices for the generation of monodisperse multiple emulsions

Droplet-based microfluidic devices have become a preferred versatile platform for various fields in physics, chemistry and biology. Polydimethylsiloxane soft lithography, the mainstay for fabricating microfluidic devices, usually requires the usage of expensive apparatus and a complex manufacturing procedure. Here, we report the design and fabrication of simple and inexpensive microfluidic devices based on microscope glass slides and pulled glass capillaries, for generating monodisperse multiple emulsions. The advantages of our method lie in a simple manufacturing procedure, inexpensive processing equipment and flexibility in the surface modification of the designed microfluidic devices. Different types of devices have been designed and tested and the experimental results demonstrated their robustness for preparing monodisperse single, double, triple and multi-component emulsions.

Micro-optical lens array for fluorescence detection in droplet-based microfluidics

We demonstrate the design and integration of droplet-based microfluidic devices with microoptical element arrays for enhanced detection of fluorescent signals. We show that the integration of microlenses and mirror surfaces in these devices results in an 8-fold increase in the fluorescence signal and in improved spatial resolution. Using an array of microlenses, massively parallel detection of droplets containing fluorescent dyes was achieved, leading to detection throughputs of about 2000 droplets per second and per lens, parallelized over 625 measurement points.

Characterization of Nontoxic Liquid-Metal Alloy Galinstan for Applications in Microdevices

We have obtained interfacial properties of Galinstan, a nontoxic liquid-metal alloy, to help replace mercury in miniature devices. To prevent formation of an oxide skin that severely hinders the fluidic behavior of small Galinstan droplets and leads to inaccurate property data, we performed our experiments in a nitrogen-filled glove box. It was found that only if never exposed to oxygen levels above 1 part per million (ppm) would Galinstan droplets behave like a liquid. Two key properties were then investigated: contact angles and surface tension. Advancing and receding contact angles of Galinstan were measured from sessile droplets on various materials: for example, 146.8 and 121.5, respectively, on glass. Surface tension was measured by the pendant-drop method to be 534.6 10.7 mN/m. All the measurements were done in nitrogen at 28 with oxygen and moisture levels below 0.5 ppm. To help design droplet-based microfluidic devices, we tested the response of Galinstan to electrowetting-on-dielectric actuation.

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.

Teaching Single-Cell Digital Analysis Using Droplet-Based Microfluidics

Microfluidics allows the manipulation of small quantities of reagents in a high-throughput manner and is therefore highly amenable to single cell characterization and more generally to digital analysis, with applications in fields as varied as genomics, diagnostics, directed evolution, and drug screening. The growing place of microfluidics in biology laboratories encouraged us to develop a teaching method where advanced undergraduate or first-year graduate-level students are taught to fabricate droplet-based microfluidic devices, characterize them, and finally use them to perform a digital analysis of bacterial samples based on a phenotypic marker.

Peptide nucleic acid molecular beacons for the detection of PCR amplicons in droplet-based microfluidic devices

The use of droplet-based microfluidics and peptide nucleic acid molecular beacons for the detection of polymerase chain reaction (PCR)-amplified DNA sequences within nanoliter-sized droplets is described in this work. The nanomolar-attomolar detection capabilities of the method were preliminarily tested by targeting two different single-stranded DNA sequences from the genetically modified Roundup Ready soybean and the Olea europaea genomes and detecting the fluorescence generated by peptide nucleic acid molecular beacons with fluorescence microscopy. Furthermore, the detection of 10 nM solutions of PCR amplicon of DNA extracted from leaves of O. europaea L. encapsulated in nanoliter-sized droplets was performed to demonstrate that peptide nucleic acid molecular beacons can discriminate O. europaea L. cultivar species carrying different single-nucleotide polymorphisms.

Measuring rapid kinetics by a potentiometric method in droplet-based microfluidic devices

Droplets containing RNA and Mg(2+) were generated in microfluidic channels. By integrating a group of pneumatic valves and phase separation channels in the microfluidic system, the rapid RNA-Mg(2+) binding kinetics was studied by measuring the Mg(2+) ion concentration using an ion-selective electrode.

Inititiation, Flow Rate, and Routing of Capillary-Driven Flow of Liquid Moving through Microchannels on a Slipchip

This study is devoted to controlling the initiation and flow rate of spontaneous liquid-liquid flow passing through microfluidic channels in response to capillary action on a non-wetting droplet. Aqueous droplets were generated on a hydrophobic SlipChip in a shallow channel, and then a stepwise change in capillary force was induced by connecting the shallow channel to a deeper channel filled with immiscible oil. A model to predict the rate of spontaneous flow was developed based on the balance of net capillary pressure with viscous flow resistance; the inputs to the model were the liquid-liquid surface tension, advancing and receding contact angles at the three-phase aqueous-oil-surface interface, and the geometry of the device. The effects of contact angle hysteresis, presence or absence of a lubricating oil layer, and adsorption of surfactants at liquid-liquid or liquid-solid interfaces were quantified. Two different regimes of flow were studied. Faster (mm/s) flow rates were obtained when oil being displaced by the aqueous could escape through connected channels, and slower (μm/s) flow rates were obtained when displaced oil could escaped only through a μm-scale gap between the plates of the SlipChip (“dead-end flow”). Both diluted salt solutions and complex biological media such as human blood plasma were found to flow using this approach, and we anticipate it being useful in the future for control of flow in microfluidic designs that do not require external power, valves, or pumps. Approaches based on initiation of spontaneous flow would be useful for design and operation of the SlipChip platform as well as for other droplet-based and plug-based microfluidic devices.

Fabrication of Advanced Particles and Particle‐Based Materials Assisted by Droplet‐Based Microfluidics

Recent advances in the fabrication of complex particles and particle-based materials assisted by droplet-based microfluidics are reviewed. Monodisperse particles with expected internal structures, morphologies, and sizes in the range of nanometers to hundreds of micrometers have received a good deal of attention in recent years. Due to the capability of generating monodisperse emulsions and of executing precise control and operations on the suspended droplets inside the microchannels, droplet-based microfluidic devices have become powerful tools for fabricating complex particles with desired properties. Emulsions and multiple-emulsions generated in the microfluidic devices can be composed of a variety of materials including aqueous solutions, gels, polymers and solutions containing functional nanoparticles. They are ideal microreactors or fine templates for synthesizing advanced particles, such as polymer particles, microcapsules, nanocrystals, and photonic crystal clusters or beads by further chemical or physical operations. These particles are promising materials that may be applicable for many fields, such as photonic materials, drug delivery systems, and bio-analysis. From simple to complex, from spherical to nonspherical, from polymerization and reaction crystallization to self-assembly, this review aims to help readers be aware of the many aspects of this field.

A microfluidic device for self-synchronised production of droplets

The primary requirement for a mixing operation in droplet-based microfluidic devices is an accurate pairing of droplets of reaction fluids over an extended period of time. In this paper, a novel device for self-synchronous production of droplets has been demonstrated. The device uses a change in impedance across a pair of electrodes introduced due to the passage of a pre-formed droplet to generate a second droplet at a second pair of electrodes. The device was characterised using image analysis. Droplets with a volume of ~23.5 ± 3.1 nl (i.e.~93% of the volume of pre-formed droplets) were produced on applying a voltage of 500 V. The synchronisation efficiency of the device was 83%. As the device enables self-synchronised production of droplets, it has a potential to increase the reliability and robustness of mixing operations in droplet-based microfluidic devices.

Droplet formation via flow-through microdevices in Raman and surface enhanced Raman spectroscopy—concepts and applications

This review outlines concepts and applications of droplet formation via flow-through microdevices in Raman and surface enhanced Raman spectroscopy (SERS) as well as the advantages of the approach. Even though the droplet-based flow-through technique is utilized in various fields, the review focuses on implementing droplet-based fluidic systems in Raman and SERS as these highly specific detection methods are of major interest in the field of analytics. With the combination of Raman or SERS with droplet-based fluidics, it is expected to achieve novel opportunities for analytics. Besides the approach of using droplet-based microfluidic devices as a detection platform, the unique properties of flow-through systems for the formation of droplets are capitalized to produce SERS active substrates and to accomplish uniform sample preparation. Within this contribution, previous reported applications on droplet-based flow-through Raman and SERS approaches and the additional benefit with regard to the importance in the field of analytics are considered.

Thermoset polyester droplet-based microfluidic devices for high frequency generation

The vast majority of droplet-based microfluidic devices are made from polydimethylsiloxane (PDMS). Unfortunately PDMS is not suitable for high frequency droplet generation at high operating pressure due to its low shear modulus. In this paper, we report the fabrication and testing of microfluidic devices using thermoset polyester (TPE). The optical characteristics of the fabricated devices were assessed and substrate resistance to pressure also investigated. TPE devices bonded using an O(2) plasma treated PET substrate at 76 °C were shown to function efficiently at pressures up to 18 MPa. TPE material retains many of the attractive features of PDMS such as ease of fabrication but significantly, has superior mechanical properties. The improved resistance of TPE to high pressures enabled investigation of high frequency droplet generation as a function of a wide range of flow-rates with three different oils as continuous phase.

Advanced microfluidic droplet manipulation based on piezoelectric actuation

As droplet-based microfluidic devices evolve, the demand for simple-to-fabricate droplet manipulation modules increases. Of these modules, droplet sorting has drawn much attention due to its ability not only to enrich, but also to selectively isolate droplet subpopulations of interest. In this paper, we present an innovative piezoelectric-driven droplet sorter that is simple to fabricate, reproducible and robust, which provides extensive control over spatio-temporal droplet pattern. This degree of control is demonstrated by sorting droplets of alternating volumes and by grouping defined number of droplets into traveling clusters. The ability to automatically sort droplets is demonstrated by computerized detection and sorting of droplets based on their color. The sorter performance was investigated and found to work on a wide range of sorting parameters. The sorter is created by a single step fabrication process and does not rely on complex electronics or optics. These advantages simplify the adoption of droplet-based microfluidic technology by the scientific community and provide an ideal platform for single cell assays.

Synthesis of crystals and particles by crystallization and polymerization in droplet-based microfluidic devices

The recent advances in crystallization and polymerization assisted by droplet-based microfluidics to synthesize micro-particles and micro-crystals are reviewed in this paper. Droplet-based microfluidic devices are powerful tools to execute some precise controls and operations on the flow inside microchannels by adjusting fluid dynamics parameters to produce monodisperse emulsions or multiple-emulsions of various materials. Major features of this technique are producing particles of monodispersity to control the shape of particles in a new level, and to generate droplets of diverse materials including aqueous solutions, gels and polymers. Numerous microfluidic devices have been employed to generate monodisperse droplets of range from nm to μm, such as T junctions, flow-focusing devices and co-flow or cross-flow capillaries. These discrete, independently controllable droplets are ideal microreactors to be manipulated in the channels to synthesize the nanocrystals, protein crystals, polymer particles and microcapsules. The generated monodisperse particles or crystals are to meet different technical demands in many fields, such as crystal engineering, encapsulation and drug delivery systems. Microfluidic devices are promising tools in the synthesis of micron polymer particles that have diverse applications such as the photonic materials, ion-exchange and chromatography columns, and field-responsive rheological fluids. Processes assisted by microfluidic devices are able to produce the polymer particles (including Janus particles) with precise control over their sizes, size distribution, morphology and compositions. The technology of micro-fluidics has also been employed to generate core-shell microcapsules and solid microgels with precise controlled sizes and inner structures. The chosen “smart” materials are sensitive to an external stimulus such as the change of the pH, electric field and temperature. These complex particles are also able to be functionalized by encapsulating nanoparticles of special functions and by attaching some special groups like targeting ligands. The nucleation kinetics of some crystals like KNO3 was investigated in different microfluidic devices. Because of the elimination of the interactions among crystallites in bulk systems, using independent droplets may help to measure the nucleation rate more accurately. In structural biology, the droplets produced in microfluidic devices provide ideal platforms for protein crystallization on the nanoliter scale. Therefore, they become one of the promising tools to screen the optimal conditions of protein crystallization.

Measuring Rapid Enzymatic Kinetics by Electrochemical Method in Droplet-Based Microfluidic Devices with Pneumatic Valves

This paper describes a droplet-based microfluidic chip with pneumatic valves for measuring millisecond enzyme kinetics using amperometric detection method. Aqueous streams containing reactants were injected to an oil flow to form droplets, and each droplet represented one microreactor. Pneumatic valves were used to control the moving distance and in turn the reaction time of the droplets. The reaction time was also fine-tuned by varying the flow rate of the droplets in microchannels. A complete Michaelis-Menten kinetics of catalase was successfully measured by amperometric method in a single-run experiment, and the total consumption of reagents was less than 50 microL. In the current experiment, the best time resolution was about 0.05 s, and the reaction time measured was from 0.05 to 25 s. This microfluidic system is applicable to many biochemical reactions, as long as one of the reactants or products is electrochemically active. With appropriate quenching method at the outlet, various detection methods can be integrated into the microfluidic system, further extending the application of the combination of pneumatic valves and droplets in microchannels.

On-chip micromanipulation and assembly of colloidal particles by electric fields

We overview the ways in which electric fields can be used for on-chip manipulation and assembly of colloidal particles. Particles suspended in water readily respond to alternating (AC) or direct current (DC) electric fields. Charged particles in DC fields are moved towards oppositely charged electrodes by electrophoresis. Dielectrophoresis, particle mobility in AC fields, allows precise manipulation of particles through a range of parameters including field strength and frequency and electrode geometry. Simultaneously, DC or AC electrokinetics may drive liquid flows inside the experimental cells, which also leads to transport and redistribution of the suspended particles. Examples of dielectrophoretic manipulation and assembly of nanoparticles and microparticles by planar on-chip electrodes are presented. The structures assembled include conductive microwires from metallic nanoparticles and switchable two-dimensional crystals from polymer microspheres. We also discuss how dielectrophoresis and AC electrokinetics can be used in droplet-based microfluidic chips, biosensors, and devices for collection of particles from diluted suspensions.