Microfluidics analysis of nanoparticle mixing in a microchannel system

The microfluidics of controlled nanodrug delivery to living cells in a representative, partially heated microchannel was analyzed, using a validated computer model. The objective was to achieve uniform nanoparticle exit concentrations at a minimum microchannel length with the aid of simple static mixers, e.g., a multi-baffle-slit or perforated injection micro-mixer. A variable wall heat flux, which influences the local nanofluid properties and carrier-fluid velocities, was added to ensure that mixture delivery to the living cells occurred at the required (body) temperature of 37°C. The results show that both the baffle-slit micro-mixer and the perforated injection micro-mixer aid in decreasing the microchannel length while achieving uniform nanoparticle exit concentrations. The injection micro-mixer not only decreases best the system’s dimension, but also reduces the system power requirement. The baffle-slit micro-mixer also decreases the microchannel length; however, it may add to the power requirement. The imposed wall heat flux aids in enhanced nanoparticle and base-fluid mixing as well.     

Extraction of genomic DNA and detection of single nucleotide polymorphism genotyping utilizing an integrated magnetic bead-based microfluidic platform

This study presents a new magnetic bead-based microfluidic platform, which integrates three major modules for rapid leukocytes purification, genomic DNA (gDNA) extraction and fast analysis of genetic gene. By utilizing microfluidic technologies and magnetic beads conjugated with CD_15/45 antibodies, leukocytes in a human whole blood sample can be first purified and concentrated, followed by extraction of gDNA utilizing surface-charge switchable, DNA-specific, magnetic beads in the lysis solution. Then, specific genes associated with genetic diseases can be amplified by an on-chip polymerase chain reaction (PCR) process automatically. The whole pretreatment process including the leukocytes purification and gDNA extraction can be performed in an automatic fashion with the incorporation of the built bio-separators consisting of microcoils array within less than 20 min. The detection of single nucleotide polymorphism (SNP) genotyping of methylenetetra-hydrofolate reductase (MTHFR) C677T region associated with an increased risk of genetic diseases was further performed to demonstrate the capability of the proposed system. The extracted gDNA can be transported into a micro PCR chamber for on-chip fast nucleic acid amplification of detection genes with minimum human intervention. Hence, the developed system may provide a powerful automated platform for pretreatment of human leukocytes, gDNA extraction and fast analysis of genetic gene.     

Maskless writing of microfluidics: Rapid prototyping of 3D microfluidics using scratch on a polymer substrate

We present a new rapid prototyping method designed for simple fabrication of 3D microfluidics using a maskless direct writing technique on polymer substrates. The entire process is enabled by a commercial cutter plotter with 10 μm resolution precision and high speed. A CAD design of top and bottom microstructures is directly written on a polymer substrate using a cutter plotter after setting up the suitable force. The smallest channel width of 20 μm was obtained with the minimum force and 100 μm from the maximum. Also the written depth increased linearly with force from 30 to 130 μm. Several 3D microfluidic devices are demonstrated using a maskless writing technique. The entire fabrication process from CAD layout to a final 3D device can be completed in 30 min outside the clean room facilities.     

Development of high throughput microfluidic cell culture chip for perfusion 3-dimensional cell culture-based chemosensitivity assay

This study reports a microfluidic cell culture chip encompassing 36 microbioreactors for high throughput perfusion 3-dimensional (3D) cell culture-based chemosensitivity assays. Its advantages include the capability for multiplexed medium delivery, and the function for both efficient and high throughput micro-scale 3D culture construct preparation and loading. The results showed that the proposed medium pumping mechanism was able to provide a uniform pumping rates ranging from 1.2 to 3.9 μl h⁻¹. In addition, the simple cell/hydrogel loading scheme has been proven to be able to carry out 3D cell culture construct preparation and loading precisely and efficiently. Furthermore, a chemosensitivity assay was successfully demonstrated using the proposed cell culture chip. The results obtained were also compared with the same evaluation based on a conventional 2D monolayer cell culture. It can be concluded that the choice of cell culture format can result in different chemosensitivity evaluation results. Overall, because of the nature of miniaturized perfusion 3D cell culture, the cell culture chip not only can provide stable, well-defined and more biologically relevant culture environments, but it also features low consumption of research resources. All these traits are found particularly useful for high-precision and high-throughput 3D cell culture-based assays.     

An integrated microfluidic system for fast, automatic detection of C-reactive protein

C-reactive protein (CRP) is a well-known inflammation marker in human beings. This study reports a new microfluidic system for fast, automatic detection of CRP. It contains pneumatic micropumps, a vortex-type micromixer, a pneumatic micro-injector and several microvalves to automatically perform the entire protocol for CRP detection. This includes sample/reagent transportation, incubation between the target CRP and a CRP-specific aptamer, washing processes, and the chemiluminescence development process. In addition, the chemiluminescence signal is measured by using a custom-made optical system which consists of a photomultiplier tube, a portable air compressor and eight electronic magnet valves to quantify the concentration of CRP. When compared to previous works, not only can this new microfluidic system automatically perform the entire process via a new integrated micro-injector and new micropumps, but a new CRP-specific DNA aptamer with a higher affinity and specificity is also used for CRP measurement. Experimental data show that the developed system can automatically complete the entire protocol within 30 min with a detection limit of 0.0125 mg/L, which is superior to previous published results. Moreover, this study also measures CRP concentration from clinical samples to verify the performance of the developed microfluidic system. The results indicate that the measured CRP concentrations from human serums are consistent with those using a benchtop system. The developed system can also detect CRP concentrations from human whole blood without any external sample pretreatment process. This microfluidic system may be promising for point-of-care applications for CRP detection in the future.     

Suitable properties of ink to create inkjet-printed surface-directed microchannels that utilize the pinning effect of a triple line on a rough surface

If microfluidic devices can be directly produced using printing techniques, the combination of microfluidics and printing techniques for other applications, such as printed electronics, will make all-printed highly-functionalized microfluidic devices possible. Therefore, we have made efforts to develop a technique for producing microfluidic devices using an inkjet printer. The microchannels that could be created using this technique were a kind of surface-directed channels that utilize the pinning effect of a triple line on a rough surface. In this study, we focused on what were the required properties of the printer ink during the wetting and drying processes of the ink. As a result, one of the properties required during the wetting process was that the advancing contact angle of the ink should be smaller than a certain value, which depended on the average volume of the ink drops ejected from the printhead and the number of drops per unit area. The receding contact angle should be smaller than about one third of each advancing angle. In addition, during the drying process, a small amount of surfactant added to the ink played a critical role in order to leave a continuous stain of the ink. As an application of this inkjet-printed channel, we also created a device for mixing aqueous solutions.     

Droplet creation using liquid dielectrophoresis

Dielectrophoresis (DEP) is defined as polarizable particles moving into regions of higher electric field intensity. In liquid DEP (LDEP), a dielectric liquid tends to flow toward regions of high electric field intensity under a non-uniform electric field. This work presents a theoretical model of LDEP based on parallel electrodes. The LDEP force is derived using the lump parameter electromechanical method. The relationship between the minimum actuation voltage and the electrode width is investigated experimentally and theoretically. We also propose a method for creating a 20 nl droplet of deionized water using LDEP. The creation of a water droplet containing 15 μm polystyrene beads is placed at the desired location from a continuous flow driven by LDEP using the developed method.     

Simulations of extensional flow in microrheometric devices

We present a detailed numerical study of the flow of a Newtonian fluid through microrheometric devices featuring a sudden contraction–expansion. This flow configuration is typically used to generate extensional deformations and high strain rates. The excess pressure drop resulting from the converging and diverging flow is an important dynamic measure to quantify if the device is intended to be used as a microfluidic extensional rheometer. To explore this idea, we examine the effect of the contraction length, aspect ratio and Reynolds number on the flow kinematics and resulting pressure field. Analysis of the computed velocity and pressure fields show that, for typical experimental conditions used in microfluidic devices, the steady flow is highly three-dimensional with open spiraling vortical structures in the stagnant corner regions. The numerical simulations of the local kinematics and global pressure drop are in good agreement with experimental results. The device aspect ratio is shown to have a strong impact on the flow and consequently on the excess pressure drop, which is quantified in terms of the dimensionless Couette and Bagley correction factors. We suggest an approach for calculating the Bagley correction which may be especially appropriate for planar microchannels. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Electrospinning hollow and core/sheath nanofibers using hydrodynamic fluid focusing

Hollow poly (vinylpyrrolidone) (PVP) + TiO₂ and polypyrrole (core)/PVP (sheath) nanofibers were successfully electrospun using hydrodynamic fluid focusing. Utilizing a two-dimensional fluid focusing technique previously applied to aqueous solutions, intersecting microchannels cast in (poly)dimethylsiloxane were utilized to dynamically center core fluids in immiscible sheath fluids prior to electrospinning at the channel outlet. Advantages of using microfluidic channel networks for the electrospinning of composite nanofibers include spatiotemporal control over input reagents, ease of fabrication and the ability to focus the core stream into sheath layer without the need of complex co-annular nozzles.