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A microstructure-based hydrogel was employed to study the relationship between spatial specificity and cellular behavior, including cell fate, proliferation, morphology, and insulin secretion in pancreatic β-cells. To effectively form homogeneous cell clusters in vitro, we made cell-containing hydrogel membrane constructs with an adapted grid structure based on a hexagonal micropattern. Homogeneous cell clusters (average diameter: 83.6 ± 14.2 μm) of pancreatic insulinoma (MIN6) cells were spontaneously generated in the floating hydrogel membrane constructs, including a hexagonal grid structure (size of cavity: 100 μm, interval between cavities: 30 μm). Interestingly, 3D clustering of MIN6 cells mimicking the structure of pancreatic islets was coalesced into a merged aggregate attaching to each hexagonal cavity of the hydrogel grid structure. The fate and insulin secretion of homogeneous cell clusters in the hydrogel grid structure were also assessed. The results of these designable hydrogel–cell membrane constructs suggest that facultative in vitroβ-cell proliferation and maintenance can be applied to biofunctional assessments. [ABSTRACT FROM AUTHOR]

A gentle, but fast means for low-stress, high-throughput platelet purification is of significant clinical and biotechnological utility. Current implementations to sort platelets, however, require an external physical field, specialized buffer, or the harsh separation condition of high shear stress that tends to cause platelet stimulation. Here we report the use of hydrophoretic size separation in a wider channel and its parallelization to augment its throughput capability, maintaining physiological shear-stress range. We demonstrate a parallelized device comprising 10 stacks of the wide-channel hydrophoresis device, yielding a throughput of 2.9 million cells s−1and a platelet purity of 76.8%. The use of the wide channel for hydrophoresis also facilitates clogging-free separation by sorting blood clots and plaques. The wide-channel hydrophoresis offers the potential for gentle, fast, clogging-free sorting of rare blood cells with extreme throughput capabilities. [ABSTRACT FROM AUTHOR]

The lysis of cancer cells inside a sessile droplet was performed using traveling surface acoustic waves (SAWs) without any chemical reagents. Raman spectrum profiling was then carried out to explore detailed cell-derived data. The Rayleigh waves formed by an interdigital transducer were made to propagate along the surface of an LiNbO 3 substrate. Polystyrene microparticles (PSMPs) were used to establish mechanical cell lysis effectively, and gold nanoparticles (AuNPs) were added to enhance the Raman signals from the lysed cells by SAWs. The lysis efficiency was evaluated according to the size and concentration of the PSMPs in experiments where the frequency was varied. Lysis occurred mainly by mechanical collision using PSMPs in a high-frequency domain, and the lysis efficiency was improved by increasing the application time and the energy density of the SAWs. Raman signals from the lysed cells were greatly enhanced by nanogaps formed by the AuNPs, which were evenly distributed irrespective of the SAWs through the frequency-independent behavior of the AuNPs. Finally, detailed Raman spectra of MDA-MB-231, malignant breast cancer cells, were acquired, and various organic matter-derived peaks were observed. The 95% confidence region for cells subjected to lysis was more widely distributed than that of cells not subjected to lysis. The proposed SAW platform is expected to facilitate the detection of small quantities and to be applied in biomedical applications.

We have proposed a novel mobile healthcare platform, combining a pocket-sized colorimetric reader (13.5 × 6.5 × 2.5 cm(3)) and commercially available 10-parameter urinalysis paper strips (glucose, protein, glucose, bilirubin, urobilinogen, ketones, nitrite, pH, specific gravity, erythrocytes, and leukocytes), capable of sending data with a smart phone. The reader includes a novel colorimetric multi-detection module, which consists of three-chromatic light-emitting diodes, silicon photodiodes and a novel poly(methylmethacrylate) (PMMA) optical splitter. We employed data reading methods using conversions of the signal data (red, blue, and green) to the hue (H) color map or the Y model data, and used a curve-fitting method for the quantification. The reader is battery-powered, inexpensive, light-weight, and very speedy in analysis. And, it was applied to detection of a thousand of human urine samples and demonstrated reliable quantification of urinary glucose and protein. The features can be used by unskilled people on-site to transfer the analyzed data to experts off-site.

Extraordinary advances in lab on a chip systems have been made on the basis of the development of micro/nanofluidics and its fusion with other technologies based on electrokinetics and optics. Optoelectrofluidic technology, which has been recently introduced as a new manipulation scheme, allows programmable manipulation of particles or fluids in microenvironments based on optically induced electrokinetics. Herein, the behaviour of particles or fluids can be controlled by inducing or perturbing electric fields on demand in an optical manner, which includes photochemical, photoconductive, and photothermal effects. This elegant scheme of the optoelectrofluidic platform has attracted attention in various fields of science and engineering. A lot of research on optoelectrofluidic manipulation technologies has been reported and the field has advanced rapidly, although some technical hurdles still remain. This review describes recent developments and future perspectives of optoelectrofluidic platforms for chemical and biological applications.

Simple and low-cost implementation of three-dimensional (3D) particle measurement is vital for designing and characterizing microfluidic devices that show spatiotemporally varying characteristics in three dimensions. However, the conventional 3D particle image velocimetry or particle streak velocimetry has proven difficult to address the needs, requiring complex and expensive equipment, precise alignment between optical components, and specialized image-processing algorithms. Here, we report mirror-embedded microchannels and a method of optical path-length (OPL) modulation for 3D particle measurement in the channels. The mirror, ideally at 45 degrees, reflects the side view of the channels and enables 3D positional information to be obtained easily from two different orthogonal-axis images with different optical paths. To offset the optical path difference between two image views, we utilized a cover glass as a medium of high refractive index and placed it in the light path through which the side-view image propagates, thereby prolonging the OPL of the side view and simultaneously shifting its depth of field (DOF) range. This modulation ensures imaging of in-focus side view as well as top view. This 3D imaging principle was verified by observing 3D positions of 6 mum-sized beads in the linear and grooved microchannels. The mirror-embedded scheme can be readily fabricated with existing microfluidic designs, and offer easy and simple implementation of 3D particle measurement.

This paper reports the first use of the abacus-groove structure to handle droplets in a wide microchannel, with no external forces integrated to the system other than the pumps. Microfluidic abacus channels are demonstrated for the sequential addition of droplets at the desired location. A control channel which is analogous to biasing in electronics can also be used to precisely determine the number of added droplets, when all other experimental conditions are fixed including the size of the droplets and the frequency of droplet-generation. The device allows programmable and autonomous operations of complex two-phase microfluidics as well as new applications for the method of analysis and computations in lab-on-a-chip devices.

We demonstrate rapid manipulation and selective concentration of microparticles using AC electrokinetics such as dielectrophoresis (DEP) and AC electro-osmosis (ACEO) in an optoelectrofluidic platform based on a liquid crystal display (LCD). When 10 V bias at 10 kHz was applied to the optoelectrofluidic device, only the 1 microm-diameter polystyrene particles were concentrated into the projected LCD image patterns and closely packed, forming the crystalline structure by ACEO flow, while the 6 microm-diameter particles were repelled by negative DEP forces. We have characterized this frequency-dependency of the optoelectrofluidic particle behavior according to the particle diameter. On the basis of these results, we can rapidly concentrate the 1 microm-diameter particles and separate them from the 6 microm particles, by applying an AC signal of 10 kHz frequency. This novel technique can be applied to rapidly concentrate, separate and pattern micro-/nanoparticles in many biological and chemical applications.

The soft lithographic technique is a collection of simple and cost-effective patterning techniques which applies an elastomeric stamp to transfer a nano/micro-scale pattern. Patterning biological materials using soft lithography provides procedurally simple control of the surface chemistry and the cell environments. However, conventional methods for generating microstructures on a substrate require expensive clean room facilities and skillful training. Here we report a simple and inexpensive clean-room free process using a conventional photomask film as a master to fabricate elastomeric stamps or microfluidic channels. This ultra rapid prototyping technique was applied to print FITC labeled poly-L-lysine with a 10 microm feature size on a glass substrate using soft lithographic processes, such as micro-contact printing and micromolding in capillaries, for patterning human hepatocellular carcinoma cells, human skin fibroblasts and hippocampal neurons from E-18 Sprague-Dawley rat. This novel technique using a photomask film as a master would be very useful 'hands-on' tool for the generation of micro-patterned chemical or biological assays using cells and proteins.

We report an analysis of pressure-driven bubble elimination for a gas-permeable microfluidic device. In this study, we described bubble elimination in a microfluidic device employing a gas permeation model and calculated the removal efficiency of bubbles. The correction factor for the simplified model was estimated with respect to the applied pressure. Based on the established model, the required time to remove a trapped bubble with a certain area was shown to be within an error of 11.58% by comparison with experimental results. Exploiting the model equation, we were able to completely remove the air bubbles appearing during the process of filling a microfluidic device with an aqueous solution.

This paper describes a novel microfluidic immunoassay utilizing binding of superparamagnetic nanoparticles to beads and deflection of these beads in a magnetic field as the signal for measuring the presence of analyte. The superparamagnetic 50 nm nanoparticles and fluorescent 1 microm polystyrene beads are immobilized with specific antibodies. When target analytes react with the polystyrene beads and superparamagnetic nanoparticles simultaneously, the superparamagnetic nanoparticles can be attached onto the microbeads by the antigen-antibody complex. In the poly(dimethylsiloxane)(PDMS) microfluidic channel, only the microbeads conjugated with superparamagnetic nanoparticles by analytes consequently move to the high gradient magnetic fields under the specific applied magnetic field. In this study, the magnetic force-based microfluidic immunoassay is successfully applied to detect the rabbit IgG and mouse IgG as model analytes. The lowest concentration of rabbit IgG and mouse IgG measured over the background is 244 pg mL(-1) and 15.6 ng mL(-1), respectively. The velocities of microbeads conjugated with superparamagnetic nanoparticles are demonstrated by magnetic field gradients in microfluidic channels and compared with the calculated magnetic field gradients. Moreover, dual analyte detection in a single reaction is also performed by the fluorescent encoded microbeads in the microfluidic device. Detection range and lower detection limit can be controlled by the microbeads concentration and the higher magnetic field gradient.