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.     

A microfluidic platform for electrical detection of DNA hybridization

Current methods used for detection of DNA hybridization involve the use of DNA microarrays which require overnight incubation times along with bulky and expensive fluorescent scanners. Here, we demonstrate electrical detection of DNA hybridization in an oligonucleotide functionalized microfluidic channel. We use microchannels functionalized with DNA probes integrated with electrodes for measuring conductance across the channel. As beads conjugated with the target DNA passing through the channel are captured on the surface, we are able to electrically detect changes in resistance due to bead capture. Our assay can be completed in less than an hour using less than a microliter of reagent, and has the potential for extensive multiplexing. Such a device can be useful as a handheld platform in a clinical setting where one would need to rapidly genotype a small number of genes rapidly.     

A novel integrated microfluidic platform to perform fluorescence in situ hybridization for chromosomal analysis

The fluorescence in situ hybridization (FISH) technique has been commonly employed to detect the chromosomal abnormalities. However, applications of this technique are limited due to its lengthy process and labor-intensive sample preparation. In this study, a novel integrated microfluidic chip capable of performing the entire FISH protocol automatically was reported. This novel technique can achieve several advantages, including reduce the consumption of bio-samples and reagents, automation and rapid analysis compared to the conventional method. In this study, several functional microfluidic devices were integrated on a single chip to perform automatic FISH on the microfluidic platform. Experimental data demonstrated that the developed microfluidic system successfully provided superior performance for probing the chromosomal abnormality of cells. Furthermore, the novel microfluidic system performed the entire process automatically within 3 h, where the conventional method required 10 h to perform the entire protocol manually. This data indicated superior performance of the novel method. Our findings conclude that the novel integrated FISH protocol is more convenient to perform large quantities of samples, which can be used in clinical trials.     

Capillarity in microfluidic channels with hydrophilic and hydrophobic walls

The authors investigate the spontaneous filling of microchannels with mixed hydrophilic and hydrophobic walls. We show that in these channels, unlike that case when all the walls are either hydrophilic or hydrophobic, the local distribution of capillary drive can make partial filling of the channel the most favorable filling type. A strategy for finding the most favorable filling type is presented and tested against capillary filling experiments made on oxygen plasma treated SU-8 microchannels. Good agreement is found between the theory and the experiments.     

A microfluidic platform with integrated flow sensing for focal chemical stimulation of cells and tissue

A microfluidic platform for precise biochemical control of the extracellular microenvironment was developed. A chemical interface was established with cells or tissues through the precise and focal delivery of soluble chemical agents through a pore addressed by a polymer microchannel. Thermal flow sensors were integrated along the length of the microchannel and monitored internal flow rate. Sensor performance was characterized in anticipation of future studies with real-time feedback control of focal delivery. The microfluidic system was characterized by determining the fluid delivery rates through the pores and concentration profiles of agents delivered. Finally, focal delivery to rat retinal tissue was demonstrated.     

A 3D printed centrifugal microfluidic platform for automated colorimetric urinalysis

Colorimetric urinalysis is a commonly performed test for rapid and low-cost diagnosis. Conventional colorimetric urinalysis is manually conducted using dipsticks and suffers from difficulties in control of sample distribution and color interpretation. This paper reports a microfluidic platform for conducting automated colorimetric urinalysis. Centrifugal microfluidic technology was used for regulating the distribution of urine sample in designed volume and time sequence. The prototype of the microfluidic chip was fabricated using 3D printing technology. To test the feasibility of the prototype system, commercial urinalysis strips were integrated with the microfluidic system for detecting glucose, specific gravity, PH, and protein from simulated urine sample. The color change of the strips was recorded using a smartphone and analyzed to quantify the interested parameters. The H (hue), S (saturation) and V (value) coordinates of the HSV color space were extracted and related to the change of the four parameters. The intensity change of V channel showed good representation of the change of glucose concentration and specific gravity. The intensity change of S channel decreased as the increase of PH and protein concentration. The proposed Lab-on-CD platform has potential for automating colorimetric urinalysis to reduce the user errors, thus to made the testing results conducted by non-professionals more reliable.

     

Ferromagnetic nano model study for the peristaltic flow in a plumb duct with permeable walls

Microsystem Technologies - The purpose of the present enquiry is to analyse the mechanics of an incompressible fluid, with water as base fluid, through a radially symmetric plumb duct with...     

A suction-type, pneumatic microfluidic device for liquid transport and mixing

This study presents a new suction-type, pneumatically driven microfluidic device for liquid delivery and mixing. The three major components, including two symmetrical, normally closed micro-valves and a sample transport/mixing unit, are integrated in this device. Liquid samples can be transported by the suction-type sample transport/mixing unit, which comprised a circular air chamber and a fluidic reservoir. Experimental results show that volume flow rates ranging from 50 to 300 μl/min can be precisely controlled during the sample transportation processes. Moreover, the transport/mixing unit can also be used as a micro-mixer to generate efficient mixing between two reaction chambers by regulating the time-phased deformation of the polydimethylsiloxane (PDMS) membranes. A mixing efficiency as high as 98.4% can be achieved within 5 s utilizing this prototype pneumatic microfluidic device. Consequently, the development of this new suction-type, pneumatic microfluidic device can be a promising tool for further biological applications and for chemical analysis when integrated into a micro-total analysis system (μ-TAS) device.     

A generic model for diffusive dynamics of the substrate and fluorescein tagged enzyme in microfluidic platform

Microsystem Technologies - The aim of this study was to develop a model that describes enzymatic conversion in a microfluidic system along with convective and diffusive transport of...     

A post-bonding-free fabrication of integrated microfluidic devices for mass spectrometry applications

This paper presents a novel process for fabricating integrated microfluidic devices with embedded electrodes which utilizes low-cost UV curable resins. Commercial UV glue is sandwiched between two substrates and is used for both the structural material and the bonding adhesive. During the exposure procedure, the pattern of micro-fluidic channels is defined using a standard lithography process while the two substrates are bonded. The un-cured UV glue is then removed by vacuum suction to form the sealed microfluidic channel. With this simple approach, conventional high-temperature bonding processes can be excluded in the fabrication of sealed microfluidic structures such that the developed method is highly advantageous for fabricating microchip devices with embedded electrodes. The overall time required to fabricate the sealed microchip device is less than 10 min since no time-consuming etching and bonding process is necessary. An innovative micro-reactor integrated with an in-channel micro-plasma generator for real-time chemical reaction analysis is fabricated using the developed process. On-line mass-spectrum (MS) detection of an esterification reaction is successfully demonstrated, which results in a fast, label-free, preparation-free analysis of chemical samples. The developed process can thus show its potential for rapid and low-cost microdevice manufacturing.     

A novel three-dimensional microfluidic platform for on chip multicellular tumor spheroid formation and culture

The formation of three-dimensional (3D) multicellular cell spheroids such as microspheres and embryoid bodies has recently gained much attention as a useful cell culture technique, but few studies have investigated the suitability of glass for spheroids formation and culture. In this work, we present a novel three-dimensional microfluidic device made of poly(dimethylsiloxane) (PDMS) and glass for the easy and rapid synthesis and culture of tumor spheroid. The cell culture unit is composed of an array of microwells on the bottom of a glass plate, bigger microwells and elastomeric microchannels on the top of a PDMS plate. Cell suspension can be easily introduced into the cell culture unit and exchange with the external liquid environment by the microfluidic channels. A single tumor spheroid can be formed and cultured in each glass cell culture chamber, the surface of which was modified with poly(vinyl alcohol) to render it to be resistant to cell adhesion. As the cell culture medium could be replaced, spheroids of the human breast cancer (MCF-7) cells were cultured on the chip for 3 days, reaching the diameters of about 150 μm. Furthermore, the MCF-7 cells were successfully cultured on the chip in 2D and 3D culture modes. Results have shown that glass is well suitable for multicellular tumor spheroids culture. The established platform provides a convenient and rapid method for tumor spheroid culture, which is also adaptable for anticancer drug screening and fundamental biomedical research in cell biology.     

An integrated genetic analysis microfluidic platform with valves and a PCR chip reusability method to avoid contamination

Clinical diagnostics and genomic research often require performing numerous genetic tests. While microfluidic devices provide a low-cost alternative to such demands, integrated microfluidic devices are fabricated using expensive technology not always affordable for single use. However, carryover cross-contamination (CXC) concerns (i.e. either false positive or false negative PCR data) in PCR chips prevent reuse, defying much of the advantages of miniaturized systems developed using expensive MEMS processing. In this work, we present an integrated and reusable PCR–CE glass microfluidic chip capable of multi-chamber PCR and sequential CE, with emphasis on a unique chip reusability approach to avoid CXC. For reliable PCR, the surface of the chamber is re-configured from its virgin hydrophilic (CA < 20°) to hydrophobic (CA > 110°) by silanization. To then extend this silanization method as a chip reusability technique, the silanization coating is ‘stripped and re-silanized’ (SRS) to create a fresh coating prior to each successive PCR run. Experimental confirmation of the effectiveness of SRS method in avoiding the CXC is demonstrated using plasmid DNA and HIV-1 infected DNA samples. We also present passive plug microvalves incorporated in the chip to enable fluid/vapor retention during the PCR and controlled fluid flow from the PCR chamber to the CE section for further analysis.     

A droplet-based microfluidic platform for rapid immobilization of quantum dots on individual magnetic microbeads

Quantum dots (QDs) provide opportunities for the development of bioassays, biosensors, and drug delivery strategies. Decoration of the surface of QDs offers unique functions such as resistance to non-specific adsorption, selective binding to target molecules, and cellular uptake. The quality of decoration has substantial impact on the functionality of modified QDs. Single-phase microfluidic devices have been demonstrated for decorating QDs with biological molecules. The device substrate can serve as a solid-phase reaction platform, with a limitation being difficulty in the realization of reproducible decoration at high density of coverage of QDs. Magnetic beads (MBs) have been explored as an alternative form of solid-phase reaction platform for decorating QDs. As one example, controlled decoration to achieve unusually high density can be realized by first coating MBs with QDs, followed by the addition of molecules such as DNA oligonucleotides. Uniformity and high density of coatings on QDs have been obtained using MBs for solid-phase reactions in bulk solution, with the further advantage that the MBs offer simplification of procedural steps such as purification. This study explores the use of a droplet microfluidic platform to achieve solid-phase decoration of MBs with QDs, offering control of local reaction conditions beyond that available in bulk solution reactions. A microchannel network with a two-junction in-series configuration was designed and optimized to co-encapsulate one single 1 µm MB and many QDs into individual droplets. The microdroplet became the reaction vessel, and enhanced conjugation through the confined environment and fast mixing. A high density of QDs was coated onto the surface of single MB even when using a low concentration of QDs. This approach quickly produced decorated MBs, and significantly reduced QD waste, ameliorating the need to remove excess QDs. The methodology offers a degree of precision to control conjugation processes that cannot be attained in bulk synthesis methods. The proposed droplet microfluidic design can be widely adopted for nanomaterial synthesis using solid-phase assays.     

A novel integrated microfluidic platform based on micro-magnetic sensor for magnetic bead manipulation and detection

We present a novel integrated microfluidic platform based on micro-magnetic sensor for manipulating and detecting magnetic beads (MB). A micro-spiral planar coil in MB manipulating system microfabricated by micro-electro-mechanical system technology is implemented to manipulate MB, and a giant magnetoimpedance (GMI) based micro-magnetic sensor is employed to detect the trapped MB. In our work, MB can be efficiently trapped by trapping force generated from micro-coil in microchannel. Next, trapped MB are detected by the changing ratio of impedance, as well as the variation of resistance and reactance in GMI sensor for trapped MB induce weak stray magnetic field under the magnetization by external magnetic field. The maximum difference of GMI ratio between with beads condition and without beads condition is 4.0% at the optimum driving frequency of 20 MHz under the external magnetic field of 15 Oe, and resistance ratio varies more significantly than reactance ratio. In comparison with traditional MB detecting methods by GMI sensor, the integrated microfluidic platform based on GMI sensor can not only manipulate and detect MB signal sensitively, but also enhance detection efficiency and decrease the experiment errors. Furthermore, this platform avoids contamination from the solutions in chemically reactive layers and reduces assay time in future biomarker detection. In our work, the microfluidic platform based on GMI sensor has potential applications in biomarker detection via MB manipulation and detection.     

Modelling of interfacial mass transfer in microfluidic solvent extraction: part II. Heterogeneous transport with chemical reaction

The use of a microfluidic device in determining the extraction kinetics of Co^II ions by di-(2-ethylhexyl) phosphoric acid (DEHPA) was demonstrated. Experimental data obtained using a Y-Y-shaped microchannel were modelled using a finite volume method. The contributions of diffusion and reaction transport resistances to the overall rate of mass transfer were obtained. A diffusion-controlled transfer assumption could not account for the experimental data, confirming that transport occurs under a mixed reaction–diffusion resistance regime. The reaction rate constant was determined to be $(2.4 \pm 0.6) \times 10^{-10}$  m/s, in good agreement with corresponding Lewis cell measurements from the literature.     

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.     

Modelling of interfacial mass transfer in microfluidic solvent extraction: part I. Heterogenous transport

An investigation of molecular diffusion of solutes across water/oil interfaces in a Y-Y-shaped microchannel with an integrated guide structure is presented. Finite volume numerical simulations were compared with experimental literature data. Analytical approaches including an infinite composite medium model, phase-specific mass transfer coefficient models, and a static transfer cell model were also assessed. An increase in accuracy for the mass transfer coefficient models was achieved by using local coefficients as opposed to length-averaged expressions. The static transfer cell model was shown to improve when based on the interfacial contact time, as opposed to the organic phase residence time. The results presented in this work have immediate application to the determination of kinetic rate constants in reactive mass transfer systems, as considered in Part II of this study (Ciceri et al. Microfluid Nanofluid, 2012).     

A versatile technology platform for microfluidic handling systems,part II: channel design and technology

Microfluidic devices often require channels of a specific size and shape. These devices are then made in a fabrication process that is often specialized to produce only those (and very similar) channels. As a result, devices requiring channels of different size and shape cannot easily be integrated on the same chip. This paper presents a method to fabricate microfluidic channels in a wide range of shape and size on the same chip by using a slit pattern through which the channels are etched. The fabrication process to fabricate these channels is discussed in detail, and an empirical model is presented to find the optimal slit pattern for a required size and shape. This part of the paper focusses on the channel design and fabrication. Details on the whole fabrication process and optional functionalization of the channels are presented in part I of this paper.