Preparation of monodispersed oil-in-water emulsions through semi-metal microfluidic EDGE systems

EDGE (Edge-based Droplet GEneration) emulsification systems with the ability to produce multiple droplets simultaneously from a single nozzle, were used for the preparation of monodispersed oil-in-water emulsions. The devices (with plateau height of 1 µm) were coated with metals (Cu, CuNi and CuNi/Cu) and had different surface roughness and wettability properties. This influenced the emulsification behavior significantly. The large surface roughness of the CuNi/Cu coated system resulted in stronger non-uniform filling of the plateau as compared to the smoother surfaces of Cu and less rough CuNi, and less droplet formation points in the CuNi/Cu coated system relative to the Cu and CuNi systems. The less hydrophilic CuNi surface, however, provided wider pressure stability than the more hydrophilic Cu and CuNi/Cu surface. A narrower pressure stability (Cu surface) and lower number of droplet formation points (CuNi/Cu surface) resulted in lower overall droplet formation frequency when compared with CuNi system. All metal coated EDGE systems reliably produced monodispersed droplets (with sizes being 6 times the plateau height), similar to the silicon-based EDGE systems having much smoother surfaces. The pressure stability for CuNi coated surfaces was wider, while the droplet formation frequency was comparable to that with the silicon system. This indicated that the use of metal is not a limitation in these systems as initially expected, but may be used for more robust and productive emulsification systems, which lend themselves well for scale-out to practical productivity rates.     

Physical sensors for water-in-oil emulsions

For many applications, the detection of water content in an oily base liquid is of crucial importance. Typical examples are automotive oils, e.g. engine and transmission oils, where water content in the order of a few percent needs to be detected. In this contribution, we analyze the suitability of permittivity and viscosity sensors for this application. It turns out, that permittivity sensors yield a clear indication of the water content in the oil being moreover to first order independent of the exact permittivity of the contaminating water. On the other hand, the output of microacoustic viscosity sensors, in contrast to conventional rotational rheometers, is hardly influenced by the water content as long as the droplet size is larger than the penetration depth of the evanescent microacoustic wave. Thus, they can be used for continued monitoring of the base oil’s viscosity even in case of an apparent water contamination.     

Developing heatable microfluidic chip to generate gelatin emulsions and microcapsules

The heatable microfluidic chip developed herein successfully integrates a microheater and flow-focusing device to generate uniform-sized gelatin emulsions under various flow rate ratios (sample phase/oil phase, Q _s/Q _o) and driven voltages. The gelatin emulsions can be applied to encapsulate vitamin C for drug release. Our goal is to create the thermal conditions for thermo-sensitive hydrogel materials in the microfluidic chip and generate continuous and uniform emulsions under any external environment. The gelatin emulsion sizes have a coefficient of variation of <5 % and can be precisely controlled by altering the flow rate ratio (Q _s/Q _o) and driven voltage. The gelatin emulsion diameters range from 45 to 120 μm. Moreover, various sizes of these gelatin microcapsules containing vitamin C were used for drug release. The developed microfluidic chip has the advantages of a heatable platform in the fluid device, active control over the emulsion diameter, the generation of uniform-sized emulsions, and simplicity. This new approach for gelatin microcapsules will provide many potential applications in drug delivery and pharmaceuticals.     

Production of monodisperse water-in-oil emulsions consisting of highly uniform droplets using asymmetric straight-through microchannel arrays

This paper reports the production of monodisperse water-in-oil (W/O) emulsions using new microchannel emulsification (MCE) devices, asymmetric straight-through MC arrays that were hydrophobically modified. The silicon asymmetric straight-through MC arrays consisted of numerous pairs of microslots and circular microholes whose cross-sectional sizes were 10 μm. This paper primarily focused on investigating the effect of the osmotic pressure of a dispersed phase (Π_d) on MCE. This paper also investigated the effects of the type of continuous-phase oils and the dispersed-phase flux (J _d) on MCE. The dispersed phases were Milli-Q water and Milli-Q water solutions containing sodium chloride. The continuous phases were decane (as control), hexane, medium chain triacylglyceride (MCT), and refined soybean oil (RSO) solutions containing tetraglycerin monolaurate condensed ricinoleic acid ester (TGCR) as a surfactant. At Π_d of exceeding threshold, highly uniform aqueous droplets with coefficients of variation of less than 3% were stably generated via hydrophobic asymmetric straight-through MCs. Monodisperse W/O emulsions with average droplet diameters between 32 and 45 μm were produced using the alkane–oil and triglyceride–oil solutions as the continuous phase. This work also demonstrated that the hydrophobic asymmetric straight-through MC array had remarkable ability to produce highly uniform aqueous droplets at very high J _d of up to 1,200 L m⁻² h⁻¹.     

Electrokinetic mixing in microfluidic systems

The applications of electrokinetics in the development of microfluidic devices have been widely attractive in the past decade. Electrokinetic devices generally require no external mechanical moving parts and can be made portable by replacing the power supply by small battery. Therefore, electrokinetic-based microfluidic systems can serve as a viable tool in creating a lab-on-a-chip (LOC) or micro-total analysis system (μTAS) for use in biological and chemical assays. Mixing of analytes and reagents is a critical step in realizing lab-on-a-chip. This step is difficult due to the low Reynolds numbers flows in microscale devices. Hence, various schemes to enhance micro-mixing have been proposed in the past years. This review reports recent developments in the micro-mixing schemes based on DC and AC electrokinetics, including electrowetting-on-dielectric (EWOD), dielectrophoresis (DEP), and electroosmosis (EO). These electrokinetic-based mixing approaches are generally categorized as either active or passive in nature. Active mixers either use time-dependent (AC or DC field switching) or time-independent (DC field) external electric fields to achieve mixing, while passive mixers achieve mixing in DC fields simply by virtue of their geometric topology and surface properties, or electrokinetic instability flows. Typically, chaotic mixing can be achieved in some ways and is helpful to mixing under large Péclet number regimes. The overview given in this article provides a potential user or researcher of electrokinetic-based technology to select the most favorable mixing scheme for applications in the field of micro-total analysis systems.     

Ion bridges in microfluidic systems

Recently many microfluidic systems are increasingly equipped with functional units for ionic controls for various applications. In this review article, we define an ion bridge as a structure that controls current or distribution of ions in a microfluidic system, and summarize the ion bridges in the literature in terms of characteristics, fabrication methods, advantages and disadvantages. The ion bridges play two basic roles, namely to ensure electrical contact in a microfluidic network and mechanically separate a liquid phase from another. More interestingly, the charged surfaces of ion bridges, which can be chemically modified, create new characteristics such as permselectivity and concentration polarization. Asymmetric ion transport as well as ionic conductivity through the ion bridges suggests a variety of applications including sample preconcentration, electroosmotic pump, electrospray ionization, electrically driven valve and many others. This review categorizes the ion bridges into several classes and describes the structures, materials, fundamental functions and applications. In Perspectives, new opportunities of microfluidics and nanofluidics provided by the ion bridges are discussed.     

Simulation of advanced microfluidic systems with dissipative particle dynamics

Computational Fluid Dynamics (CFD) is widely and successfully used in standard design processes for microfluidic μTAS devices. But for an increasing number of advanced applications involving the dynamics of small groups of beads, blood cells or biopolymers in microcapillaries or sorting devices, novel simulation techniques are called for. Representing moving rigid or flexible extended dispersed objects poses serious difficulties for traditional CFD schemes. Meshless, particle-based simulation approaches, such as Dissipative Particle Dynamics (DPD) are suited for addressing these complicated flow problems with sufficient numerical efficiency. Objects can conveniently be represented as compound objects embedded seamlessly within an explicit model for the solvent. However, the application of DPD and related methods to realistic problems, in particular the design of microfluidics systems, is not well developed in general. With this work, we demonstrate how the method appears when used in practice, in the process of designing and simulating a specific microfluidic device, a microfluidic chamber representing a prototypical bead-based immunoassay developed in our laboratory (Glatzel et al. 2006a, b; Riegger et al. 2006). Thomas Steiner: born Glatzel.     

EWOD microfluidic systems for biomedical applications

As the technology advances, a growing number of biomedical microelectromechanical systems (bio-MEMS) research involves development of lab-on-a-chip devices and micrototal analysis systems. For example, a portable instrument capable of biomedical analyses (e.g., blood sample analysis) and immediate recording, whether the patients are in the hospital or home, would be a considerable benefit to human health with an excellent commercial viability. Digital microfluidic (DMF) system based on the electrowetting-on-dielectric (EWOD) mechanism is an especially promising candidate for such point-of-care systems. The EWOD-based DMF system processes droplets in a thin space or on an open surface, unlike the usual microfluidic systems that process liquids by pumping them in microchannels. Droplets can be generated and manipulated on EWOD chip only with electric signals without the use of pumps or valves, simplifying the chip fabrication and the system construction. Microfluidic operations by EWOD actuation feature precise droplet actuation, less contamination risk, reduced reagents volume, better reagents mixing efficiency, shorter reaction time, and flexibility for integration with other elements. In addition, the simplicity and portability make the EWOD-based DMF system widely popular in biomedical or chemical fields as a powerful sample preparation platform. Many chemical and biomedical researches, such as DNA assays, proteomics, cell assays, and immunoassays, have been reported using the technology. In this paper, we have reviewed the recent developments and studies of EWOD-based DMF systems for biomedical applications published mostly during the last 5 years.     

A microvalve for hybrid microfluidic systems

A hybrid valve for lab on chip applications is presented. The valve is assembled by bonding poly (methyl methacrylate), PMMA, and silicon-based elastomers. The process used to promote the hybrid bonding includes the deposition of an organosilane (TMSPM) on the thermoplastic polymer, PMMA to interface PMMA and elastomers. For this study, a membrane in ELASTOSIL^? is bonded in correspondence of the end of two microfluidic channels of a fabricated PMMA microfluidic chip. Prior the bonding, a plasma etching process has been used to remove the TMSPM in a confined circular area. This process made possible to bond selectively the edge of a membrane leaving free to move its central part. Actuating the membrane with an external positive pressure or vacuum is possible, respectively, to obstruct or to connect the microfluidic channels. The microvalve may be simply integrated in microfluidic devices and permits the control of microvolumes of fluid in processes such as transport, separation, and mixing. The deposition of the TMSPM, the bonding of the valve and its actuation has been characterized and tested. The flow rate control of liquids through the valve has been characterized. The results have been discussed and commented. The valve can stand up to 14 psi without showing leakages.     

Using an electro-spraying microfluidic chip to produce uniform emulsions under a direct-current electric field

An electro-spraying microfluidic chip was integrated with a parallel electrode and flow-focusing device to successfully generate uniform emulsions with an electric field. This approach utilizes a high electric field driven by a direct-current voltage to form a stable Taylor cone in the flow-focusing position. The Taylor cone can then generate stable and uniform emulsions that are less than 5?μm in diameter. The emulsion size is controlled by the surfactant concentration, the ratio of the water and oil phase flow rates and the strength of the electric field. When the strength of the electric field increases at a high surfactant concentration and low ratio of flow rates, the Taylor angle decreases, which causes the emulsion size to decrease. In this study, the water emulsion diameter ranged from 1 to 98?μm, and the poly(lactic-co-glycolic acid) (PLGA) emulsion size ranged from 7 to 70?μm. The microfluidic chip developed in this work has the advantages of actively controlling the emulsion size and generating uniform emulsions (the relative standard deviation was less than 10%) and represents a new emulsion generation process.     

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.     

Electroosmotic pumps and their applications in microfluidic systems

Electroosmotic pumping is receiving increasing attention in recent years owing to the rapid development in micro total analytical systems. Compared with other micropumps, electroosmotic pumps (EOPs) offer a number of advantages such as creation of constant pulse-free flows and elimination of moving parts. The flow rates and pumping pressures of EOPs matches well with micro analysis systems. The common materials and fabrication technologies make it readily integrateable with lab-on-a-chip devices. This paper reviews the recent progress on EOP fabrications and applications in order to promote the awareness of EOPs to researchers interested in using micro- and nano-fluidic devices. The pros and cons of EOPs are also discussed, which helps these researchers in designing and constructing their micro platforms.     

Self-priming of liquids in capillary autonomous microfluidic systems

We present a numerical approach to the capillary rise dynamics in microfluidic channels of complex 3D geometries. In order to optimize the delivery of specific biological fluids to target regions in microfluidic capillary autonomous systems (CAS), we analyze self-priming of liquid water into a microfluidic device consisting of a microfluidic channel that feeds a rectangular microfluidic cavity trough an appropriately designed micro-chamber. The target performance criteria in our optimization are (1) fast and complete wetting of the cavity bottom while (2) minimizing the probability of trapping air bubble in the device. The numerical model is based on the lattice Boltzmann method (LBM) and a three-dimensional single-component multiple-phase (SCMP) scheme. By using a parallel implementation of this algorithm, we investigate the physical processes related to the invasion of the liquid–gas interfaces in rectangular cavities at different liquid–solid contact angle and shapes of the transition micro-chamber. The numerical results has successfully captured important qualitative and some key quantitative effects of the liquid–solid contact angle, the roughness of the cavity edges, the depth of the holes and shape of the micro-chambers. Moreover, we present and validate experimentally simple geometrical optimizations of the microfluidic device that ensure the complete filling the microfluidic cavity with liquid. Critical parameters related to the overall priming time of the device are presented as well.     

Replication and bonding techniques for integrated microfluidic systems

From the technical and economic points of view, systems integration, and packaging represent a crucial step in the production of microsystems. Compared to purely silicon- or glass-based systems, the variety of materials and geometries available for purely polymer microfluidic systems is much larger, due to the outstanding material properties. Moreover, polymers may be shaped and joined by comparably simple methods. Examples are polymer microreplication as well as various bonding methods. With them, complete polymer microsystems can be integrated. In addition, a number of established, compatible processes are available for the integration of functional elements that may also be made of other materials.     

Behavior of capillary valves in centrifugal microfluidic devices prepared by three-dimensional printing

This paper details the behavior of capillary valves in centrifugal microfluidic devices prepared by three-dimensional (3D), or solid-object, printing. Microfluidic structures containing valve channels with different widths, heights, and radial distances from the center of rotation were studied and compared with extant capillary valve theories. Due to the printing process, the produced valve channels possessed a ridged or “scalloped” pattern. Hence, actual channel widths at the widest and narrowest points of the ridged pattern were determined, and used in comparisons between theoretical and empirical values. In addition, variations in contact angle resulting from the ridged pattern were measured and employed in theoretical calculations. For 1-mm high valve channels, the critical angular frequency (rpm) required to overcome capillary valve pressure was found to be independent of width. However, as the height of the valve channel was reduced, the critical rpm was found to become progressively more width-dependent increasing more rapidly for narrower channels. Both of these observations point to a role for feature sharpness, as well as the geometry of the valve channel opening, in valve behavior. Otherwise, valves followed a predictable trend of increasing critical rpm with decreased valve height and decreased radial distance from the rotation center. Using these results as a guide, then, it is possible to prepare centrifugal microfluidic devices by 3D printing with operability comparable to devices prepared by other microfabrication techniques.     

Electrokinetically controlled concentration gradients in micro-chambers in microfluidic systems

Concentration gradient in a chamber appended to a microchannel is important to cell-movement control and to the concentration-gradient based assays on Lab-on-a-Chip devises. In this paper, the effects on the concentration field of the asymmetrical injection, the Peclet number, the mobility ratio of electrophoresis to electroosmosis, the chamber’s downstream position, and the chamber’s geometry parameters are investigated. The most sensitive parameter is the asymmetrical injection, which can increase the concentration gradient twice as large as that in the symmetrical injection. Additionally, use of heterogeneous surface patches is a very effective way to enhance the concentration gradient generated in the chamber. Furthermore, the influence of a fixed cell-sized particle on the concentration gradient in the chamber and around the particle is examined as an example. The existence of the particle decreases the concentration difference between the front and the back of the particle. Finally, experimental visualization of the concentration fields was conducted, and good agreements were found between the numerical simulation results and the experimental results of the concentration fields generated in a micro-chamber with/without a particle and with/without a heterogeneous patch.     

压力传感技术在微流控系统中的研究进展

回顾了压力传感在微流控系统中的应用研究进展。在对微流控系统中使用传感技术必要性分析的基础上,详细阐述了微流控系统中的两大压力传感技术,电学式压力传感与光学式压力传感的研究现状,剖析总结了微流控系统中的压力传感技术存在的问题,并对未来的发展趋势进行了展望。