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.     

Electroporation of cells in microfluidic devices: a review

In recent years, several publications on microfluidic devices have focused on the process of electroporation, which results in the poration of the biological cell membrane. The devices involved are designed for cell analysis, transfection or pasteurization. The high electric field strengths needed are induced by placing the electrodes in close proximity or by creating a constriction between the electrodes, which focuses the electric field. Detection is usually achieved through fluorescent labeling or by measuring impedance. So far, most of these devices have only concerned themselves solely with the electroporation process, but integration with separation and detection processes is expected in the near future. In particular, single-cell content analysis is expected to add further value to the concept of the microfluidic chip. Furthermore, if advanced pulse schemes are employed, such microdevices can also enhance research into intracellular electroporation.     

Toward low-voltage dielectrophoresis-based microfluidic systems: A review

Dielectrophoretically driven microfluidic devices have demonstrated great applicability in biomedical engineering, diagnostic medicine, and biological research. One of the potential fields of application for this technology is in point-of-care (POC) devices, ideally allowing for portable, fully integrated, easy to use, low-cost diagnostic platforms. Two main approaches exist to induce dielectrophoresis (DEP) on suspended particles, that is, electrode-based DEP and insulator-based DEP, each featuring different advantages and disadvantages. However, a shared concern lies in the input voltage used to generate the electric field necessary for DEP to take place. Therefore, input voltage can determine portability of a microfluidic device. This review outlines the recent advances in reducing stimulation voltage requirements in DEP-driven microfluidics.     

Organs on microfluidic chips: A mini review

Microfluidic technology provides opportunities to create in vitro models with physiological microenvironment for cell study. Introducing the identified key aspects, including tissue-tissue interfaces, spatiotemporal chemical gradients, and dynamic mechanical forces, of living organs into the microfluidic system, “organs-on-chips” display an unprecedented application potential in a lot of biological fields such as fundamental physiological and pathophysiological research, drug efficacy and toxicity testing, and clinical diagnosis. Here, we review the recent development of organs-on-chips and briefly discuss their future challenges.     

Recent research advances of the biomimetic tumor microenvironment and regulatory factors on microfluidic devices: A systematic review

Tumor microenvironment is a multicomponent system consisting of tumor cells, noncancer cells, extracellular matrix, and signaling molecules, which hosts tumor cells with integrated biophysical and biochemical elements. Because of its critical involvement in tumor genesis, invasion, metastasis, and resistance, the tumor microenvironment is emerging as a hot topic of tumor biology and a prospective therapeutic target. Unfortunately, the complex of microenvironment modeling in vitro is technically challenging and does not effectively generalize the local tumor tissue milieu. Recently, significant advances in microfluidic technologies have provided us with an approach to imitate physiological systems that can be utilized to mimic the characterization of tumor responses with pathophysiological relevance in vitro. In this review, we highlight the recent progress and innovations in microfluidic technology that facilitates the tumor microenvironment study. We also discuss the progress and future perspective of microfluidic bionic approaches with high efficiency for the study of tumor microenvironment and the challenges encountered in cancer research, drug discovery, and personalized therapy.     

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.     

Characterizing the impact of thermal gels on isotachophoresis in microfluidic devices

Thermally reversible Pluronic gels have been employed as separation matrices in microfluidic devices in the analysis of biological macromolecules. The phase of these gels can be tuned between liquid and solid states using temperature to vary fluidic resistance and alter peak resolution. Although separations in thermal gels have been characterized, their effect on isotachophoresis has not. This study used fluorescein as a model analyte to evaluate isotachophoretic preconcentration as a function of thermal polymer concentration and temperature. Results demonstrated that increasing polymer concentration in microfluidic channels increased the apparent analyte concentration. A critical minimum of 10% (w/v) Pluronic was required to achieve efficient preconcentration with maximum focusing occurring in 20 and 25% polymer gels. Temperature of the thermal gel also impacted analyte focusing. Most efficient focusing was achieved at 25°C with diminishing analyte accumulation at higher and lower temperatures. Under optimal conditions, isotachophoretic preconcentration increased an additional threefold simply by including thermal gels in the system. This approach can be readily implemented in other applications to increase detection sensitivity and measure low-concentration analytes within simple microfluidic devices.     

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.     

Numerical modeling of surface reaction kinetics in electrokinetically actuated microfluidic devices

We outline a comprehensive numerical procedure for modeling of species transport and surface reaction kinetics in electrokinetically actuated microfluidic devices of rectangular cross section. Our results confirm the findings of previous simplified approaches that a concentration wave is created for sufficiently long microreactors. An analytical solution, developed for the wave propagation speed, shows that, when normalizing with the fluid mean velocity, it becomes a function of three parameters comprising the channel aspect ratio, the relative adsorption capacity, and the kinetic equilibrium constant. Our studies also reveal that the reactor geometry idealized as a slit, instead of a rectangular shape, gives rise to the underestimation of the saturation time. The extent of this underestimation increases by increasing the Damkohler number or decreasing the dimensionless Debye–Hückel parameter. Moreover, increasing the values of the Damkohler number, the dimensionless Debye–Hückel parameter, the relative adsorption capacity, and the velocity scale ratio results in lower saturation times.     

A review on continuous-flow microfluidic PCR in droplets: Advances,challenges and future

Significant advances have been made in developing microfluidic polymerase chain reaction (PCR) devices in the last two decades. More recently, microfluidic microdroplet technology has been exploited to perform PCR in droplets because of its unique features. For example, it can prevent crossover contamination and PCR inhibition, is suitable for single-cell and single-molecule analyses, and has the potential for system integration and automation. This review will therefore focus on recent developments on droplet-based continuous-flow microfluidic PCR, and the major research challenges. This paper will also discuss a new way of on-chip flow control and a rational design simulation tool, which are required to underpin fully integrated and automated droplet-based microfluidic systems. We will conclude with a scientific speculation of future autonomous scientific discoveries enabled by microfluidic microdroplet technologies.     

Phase-changing sacrificial layers in microfluidic devices: adding another dimension to separations

The use of polymers in microchip fabrication affords new opportunities for the development of powerful, miniaturized separation techniques. One method in particular, the use of phase-changing sacrificial layers, allows for simplified designs and many additional features to the now standard fabrication of microchips. With the possibility of adding a third dimension to the design of separation devices, various means of enhancing analysis now become possible. The application of phase-changing sacrificial layers in microchip analysis systems is discussed, both in terms of current uses and future possibilities. Figure Phase-changing sacrificial materials enable multilayer microfluidic device layouts     

Experimental study and numerical estimation of current changes in electroosmotically pumped microfluidic devices

Electroosmotic flow (EOF) was investigated in microfabricated fluidic devices using the current monitoring technique. Current changes ranging from 50 to 130 pA/s were detected. These observations indicate that in microfluidic devices with small reservoir volumes, electrolysis of water influences the fluid transport, giving rise to changes in pH and increase in concentration of ionic species in the fluidic system. As a result of the electrolysis and associated increment in ion concentration, the thickness of the Debye layer and surface potential vary, affecting the overall migration behavior of the solution. The magnitude of EOF and the electrophoretic properties of molecules can no longer be treated as constant/invariant. These temporal anomalies are undesirable during analytical separations and in fluid control applications. A numerical analysis of the impact of the continuous ionic strength increase on the EOF dynamics is presented using well-established conduction and EOF theories. The numerical results are found to be in good agreement with the observed current changes. These results indicate that to improve assay reproducibility, monitoring the electric current is an effective tool to determine whether electrolytic reactions are taking place. Our work also serves to test the numerical accuracy of EOF theories and models.     

Comprehensive model of electromigrative transport in microfluidic paper based analytical devices

A complete mathematical model for electromigration in paper-based analytical devices is derived, based on differential equations describing the motion of fluids by pressure sources and EOF, the transport of charged chemical species, and the electric potential distribution. The porous medium created by the cellulose fibers is considered like a network of tortuous capillaries and represented by macroscopic parameters following an effective medium approach. The equations are obtained starting from their open-channel counterparts, applying scaling laws and, where necessary, including additional terms. With this approach, effective parameters are derived, describing diffusion, mobility, and conductivity for porous media. While the foundations of these phenomena can be found in previous reports, here, all the contributions are analyzed systematically and provided in a comprehensive way. Moreover, a novel electrophoretically driven dispersive transport mechanism in porous materials is proposed. Results of the numerical implementation of the mathematical model are compared with experimental data, showing good agreement and supporting the validity of the proposed model. Finally, the model succeeds in simulating a challenging case of free-flow electrophoresis in paper, involving capillary flow and electrophoretic transport developed in a 2D geometry.     

Role of streaming potential on pulsating mass flow rate control in combined electroosmotic and pressure-driven microfluidic devices

In the present study, we investigate the implications of streaming potential on the mass flow rate control in a microfluidic device actuated by the combined application of a pulsating pressure gradient and a pulsating, externally applied, electric field. We demonstrate that the temporal dynamics due to streaming potential effects may lead to interesting non-trivial aspects of the resultant transport characteristics. Our results highlight the importance of an adequate accounting of the streaming potential effects for temporally tunable mass flow rate control strategies, which may act as a useful design artifice to augment mass flow rates in practical scenarios.