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At least 613 records · Page 34Linked to original sources

PubMed2004

Unsteady transport phenomena in free-flow electrophoresis--prerequisite of ultrafast sample cleaning in microfluidic devices.

The evolution partial differential equations describing the transport processes induced by hydrodynamic flow in free-flow electrophoresis (FFE) are solved by the generalized dispersion theory. Our theoretical analysis demonstrates that the central injection of solutes into a relatively fast hydrodynamic flow enables to transport them to the channel outlet well before they are spread through the width of the channel and their migration is negatively affected by a contact with walls. In this case, the axial zone spreading decreases by increasing the linear velocity of hydrodynamic flow. The resulting dependencies of convective and dispersion coefficients on the velocity of flow and parameters of the separation channel show the optimum separation conditions with respect to resolution and analysis time. Due to the unsteady character of transport processes, effective FFE separations can potentially be performed in a microfluidic device in seconds. This is a reasonable time to separate low-molecular mass impurities in the electric field. Thus, a fast and efficient sample cleaning before subsequent analysis by electrospray ionization-mass spectrometry (ESI-MS) or another separation method can be performed.

Electrophoresis, Microchip↗

PubMed2004

Noninvasive fluid flow measurements in microfluidic channels with backscatter interferometry.

The ability to measure fluid velocity within picoliter volumes or on-chip noninvasively, is important toward fully realizing the potential of microfluidics and micrototal analysis systems, particularly in applications such as micro-high-performance liquid chromatography (HPLC) or in metering mixing where the flow rate must be quantified. Additionally, these measurements need to be performed directly on moving fluids in a noninvasive fashion. We presented here the proof of principle experiments showing nonintrusive fluid flow measurements can be accomplished on-chip using a pump and probe configuration with backscattering interferometry. The on-chip interferometric backscatter detector (OCIBD) is based on a fiber-coupled HeNe laser that illuminates a portion of an isotropically etched 40 microm radius channel and a position sensitive transducer to measure fringe pattern shifts. An infrared laser with a mechanical shutter is used to heat a section of a flowing volume and the resulting refractive index (RI) change is detected with the OCIBD downstream as a time-dependent RI perturbation. Fluid velocity is quantified as changes in the phase difference between the shutter signal and the OCIBD detected signal in the Fourier domain. The experiments are performed in the range of 3-6 microL/h with 3sigma detection limits determined to be 0.127 nL/s. Additionally, the RI response of the system is calibrated using temperature changes as well as glycerol solutions.

Equipment Design↗

PubMed2005

Microfluidic flow focusing: drop size and scaling in pressure versus flow-rate-driven pumping.

We experimentally study the production of micrometer-sized droplets using microfluidic technology and a flow-focusing geometry. Two distinct methods of flow control are compared: (i) control of the flow rates of the two phases and (ii) control of the inlet pressures of the two phases. In each type of experiment, the drop size l, velocity U and production frequency f are measured and compared as either functions of the flow-rate ratio or the inlet pressure ratio. The minimum drop size in each experiment is on the order of the flow focusing contraction width a. The variation in drop size as the flow control parameters are varied is significantly different between the flow-rate and inlet pressure controlled experiments.

Microfluidic Analytical Techniques↗

PubMed2006

Laser processing for bio-microfluidics applications (part I).

This paper reviews applications of laser-based techniques to the fabrication of microfluidic devices for biochips and addresses some of the challenges associated with the manufacture of these devices. Special emphasis is placed on the use of lasers for the rapid prototyping and production of biochips in particular for applications in which silicon is not the preferred material base. Part I of this review addresses applications and devices using UV lasers for laser ablation and surface treatment of microchannels, in particular in polymers.

Lasers↗

PubMed2006

Laser processing for bio-microfluidics applications (part II).

This paper reviews applications of laser-based techniques to the fabrication of microfluidic devices for biochips and addresses some of the challenges associated with the manufacture of these devices. Special emphasis is placed on the use of lasers for the rapid prototyping and production of biochips, in particular for applications in which silicon is not the preferred material base. This review addresses applications and devices based on ablation using femtosecond lasers, infrared lasers as well as laser-induced micro-joining, and the laser-assisted generation of micro-replication tools, for subsequent replication of polymeric chips with a technique like laser LIGA.

Carbon Dioxide↗

PubMed2006

Bio-assay based on single molecule fluorescence detection in microfluidic channels.

A rapid bioassay is described based on the detection of colocalized fluorescent DNA probes bound to DNA targets in a pressure-driven solution flowing through a planar microfluidic channel. By employing total internal reflection excitation of the fluorescent probes and illumination of almost the entire flow channel, single fluorescent molecules can be efficiently detected leading to the rapid analysis of nearly the entire solution flowed through the device. Cross-correlation between images obtained from two spectrally distinct probes is used to determine the target concentration and efficiently reduces the number of false positives. The rapid analysis of DNA targets in the low pM range in less than a minute is demonstrated.

DNA↗

PubMed2006

A quantitative observation and imaging of single tumor cell migration and deformation using a multi-gap microfluidic device representing the blood vessel.

A microfluidic device was developed for quantifying the migratory and deformability capabilities of a single tumor cell using direct imaging. It was fabricated using photolithography and is made of polydimethysiloxane. Chemotaxis approach was used for directing cell movement, using 10 microm microgaps to restrict the migration to a single cell. Each cell's migration rate is quantified as a measure of its distance traveled over time taken. Real-time recording of cell deformation under physiological flow was performed, and the elongation index and surface area change of the cells were compared. Three human tumor cell lines viz. HepG2, HeLa and MDA-MB-435S were used to verify the operation and methodology of the device. Their migration rates ranged from 5 to 15 microm/h, consistent with other scientific reports. By reducing the microgap width to 3 microm, it was found that the cells moved along the row of microgaps but were unable to migrate across the microgaps. Subsequent deformation of the cells through the gaps further showed that their migratory capability might be governed by their deformation ability and the deformation stress on their membranes. The strategy of targeting cancer cell membrane for rupture may provide a therapy for metastasis. Being a valuable tool for rapid quantification of a single cell's migratory capability, this device should be helpful for pharmacologic and drug screening, investigation of factors that regulate cell migration and deformation.

Algorithms↗

PubMed2026

Liquid biopsy-based detection of circulating and exfoliated cholangiocarcinoma tumor cells from blood and bile using heparan sulfate octasaccharides on integrated microfluidic systems.

Early diagnosis of cholangiocarcinoma (CCA) remains challenging because existing diagnostic approaches often lack sufficient sensitivity for reliable detection of early-stage disease. Circulating tumor cells (CTCs) in blood and exfoliated tumor cells (ETCs) in bile represent valuable targets for liquid biopsy-based detection; however, their low abundance and the complexity of clinical sample analysis pose substantial technical challenges for reliable enrichment and identification. Herein, we present a reproducible workflow for isolating and identifying CCA tumor cells from blood for CTCs and bile for ETCs using synthetic cell-surface heparan sulfate (HS) octasaccharide-functionalized magnetic beads (MBs) on integrated microfluidic systems. The method combined sample pre-processing, magnetic bead-based enrichment, controlled low-shear mixing and immunofluorescence-based identification into a unified workflow compatible with distinct clinical sample types. Key operational parameters, including MB concentration, mixing frequency, and pressure settings, were detailed to facilitate consistent performance. Using this workflow, tumor cell capture rates of approximately 70% in bile (for ETCs) and blood (for CTCs) were achieved, with a total processing time of 60-90 min per sample under clinically relevant low-abundance conditions. The platform enables reliable detection of as few as 1 tumor cell per mL of blood or bile. This method provides a practical and adaptable strategy for glycosaminoglycan-mediated liquid biopsy applications and may be extended to other tumor-cell enrichment workflows involving heterogeneous cell-surface interactions.

Humans↗

PubMed2005

Cytometry and velocimetry on a microfluidic chip using polyelectrolytic salt bridges.

This paper reports a polyelectrolytic salt bridge-based electrode (PSBE), which is a key embedded unit in a microchip device that can size-selectively count microparticles and measure their velocities. The construction of salt bridges at specific locations within a microfluidic chip enables dc-driven electrical detection to be performed successfully. This is expected to be a competitive alternative to the optical methods currently used in conventional cell sorters. The PSBEs were fabricated by irradiating ultraviolet light over a patterned mask on the parts of interest, which were filled with an aqueous monomer solution containing diallyldimethylammonium chloride. A pair of such PSBEs was easily formed at the two lateral branches perpendicular to the main microchannel and was found to be very useful for dc impedometry. The human blood cells as well as the fluorescent microbeads passing between the two PSBEs produced impedance signals in proportional to their size. The information about the velocity of a microparticle was extracted from a doublet of the dc impedance signals, which were generated when cells or microbeads sequentially passed through two PSBE pairs separated from each other by a fixed distance. The plot of peak amplitude versus velocity of the moving microbeads and cells indicated only a slight correlation between the size and the velocity, which means that the peak amplitude of the dc impedance signals alone can provide information about the size of the cells in a mixture. The experimental results showed a screening rate of over 1000 cells s(-1) and a velocity of the cells of over 100 mm s(-1). Compared with the previously suggested electrical detection system based on metal electrodes, the sensitivity and selectivity in cell detection were remarkably improved. In addition, the detection unit including the operating circuit became innovatively simple and the whole device could be miniaturized.

Blood Cell Count↗

PubMed2004

Power-free poly(dimethylsiloxane) microfluidic devices for gold nanoparticle-based DNA analysis.

An extremely simple, power-free pumping method for poly(dimethylsiloxane)(PDMS) microfluidic devices is presented. By exploiting the high gas solubility of PDMS, the energy for the pumping is pre-stored in the degassed bulk PDMS, therefore no additional structures other than channels and reservoirs are required. In a Y-shaped microchannel with cross section of 100 microm width x 25 microm height, this method has provided flow rate of 0.5-2 nL s(-1), corresponding to linear velocity of 0.2-0.8 mm s(-1), with good reproducibility. As an application of the power-free pumping, gold nanoparticle-based DNA analysis, which does not rely on the cross-linking mechanism between nanoparticles, has been implemented in a microchannel with three inlets. Target 15mer DNA has been easily and unambiguously discriminated from its single-base substituted mutant. Instead of colorimetric detection in a conventional microtube, an alternative detection technique suitable for microdevices has been discovered-observation of deposition on the PDMS surfaces. The channel layout enabled two simultaneous DNA analyses at the two interfaces between the three laminar streams.

DNA↗

PubMed2005

Laser induced fluorescence photobleaching anemometer for microfluidic devices.

We have developed a novel, non-intrusive fluid velocity measurement method based on photobleaching of a fluorescent dye for microfluidic devices. The residence time of the fluorescent dye in a laser beam depends on the flow velocity and approximately corresponds to the decaying time of the photobleaching of the dye in the laser beam. The residence time is inversely proportional to the flow velocity. The fluorescence intensity increases with the flow velocity due to the decrease of the residence time. A calibration curve between fluorescence intensity and known flow velocity should be obtained first. The calibration relationship is then used to calculate the flow velocity directly from the measured fluorescence intensity signal. The new method can measure the velocity very quickly and is easy to use. It is demonstrated for both pressure driven flow and electroosmotic flow.

Calibration↗

PubMed2005

A microfluidic mixer with grooves placed on the top and bottom of the channel.

A new microfluidic mixer is presented consisting of a rectangular channel with grooves placed in the top and bottom. This not only increases the driving force behind the lateral flow, but allows for the formation of advection patterns that cannot be created with structures on the bottom alone. Chevrons, pointing in opposite directions on the top and bottom, are used to create a pair of vortices positioned side by side. Stripes running the width of the channel generate a pair of vertically stacked vortices. Computational fluid dynamics (CFD) simulations are used to model the behavior of the systems and provide velocity maps at cross-sections within the mixer. Experiments demonstrate the mixing that results when two segregated species enter the mixer side-by-side and pass through two cycles of the mixer (i.e., two alternating sets of four stripes and four chevrons).

Computer Simulation↗

PubMed2005

Microwave plasma treatment of polymer surface for irreversible sealing of microfluidic devices.

Microwave plasma was generated in a glass bottle containing 2-3 Torr of oxygen for plasma treatment of a polymer surface. A "kitchen microwave oven" and a dedicated microwave digestion oven were used as the power source. Poly(dimethylsiloxane)(PDMS) slabs treated by a 30 W plasma for 30-60 s sealed irreversibly to form microfluidic devices that can sustain solution flow of an applied pressure of 42 psi without leaking. Experimental set up and conditions for the production of a homogeneous plasma to activate the PDMS surface for irreversible sealing are described in detail. The surface of a microwave plasma-treated PDMS slab was characterized using atomic force microscopy (AFM) and attenuated total reflection-Fourier Transform infrared spectroscopy (ATR-FTIR). The plasma-treated surface bears silica characteristics.

Dimethylpolysiloxanes↗

PubMed2005

Microfluidic separation of satellite droplets as the basis of a monodispersed micron and submicron emulsification system.

Emulsions are widely used to produce sol-gel, drugs, synthetic materials, and food products. Recent advancements in microfluidic droplet emulsion technology has enabled the precise sampling and processing of small volumes of fluids (picoliter to femtoliter) by the controlled viscous shearing in microchannels. However the generation of monodispersed droplets smaller than 1 microm without surfactants has been difficult to achieve. Normally, the generation of satellite droplets along with parent droplets is undesirable and makes it difficult to control volume and purity of samples in droplets. In this paper, however, several methods are presented to passively filter out satellite droplets from the generation of parent droplets and use these satellite droplets as the source for monodispersed production of submicron emulsions. A passive satellite droplet filtration system and a dynamic satellite droplet separation system are demonstrated. Satellite droplets are filtered from parent droplets with a two-layer channel geometry. This design allows the creation and collection of droplets that are less than 100 nm in diameter. In the dynamic separation system, satellite droplets of defined sizes can be selectively separated into different collecting zones. The separation of the satellite droplets into different collecting zones correlates with the cross channel position of the satellite droplets during the breakup of the liquid thread. The delay time for droplets to switch between the different alternating collecting zones is nominally 1 min and is proportional to the ratio of the oil shear flows. With our droplet generation system, monodispersed satellite droplets with an average radius of 2.23 +/- 0.11 microm, and bidispersed secondary and tertiary satellite droplets with radii of 1.55 +/- 0.07 microm and 372 +/- 46 nm respectively, have been dynamically separated and collected.

Chemical Phenomena↗

PubMed2005

An integrated microfluidic device for influenza and other genetic analyses.

An integrated microfluidic device capable of performing a variety of genetic assays has been developed as a step towards building systems for widespread dissemination. The device integrates fluidic and thermal components such as heaters, temperature sensors, and addressable valves to control two nanoliter reactors in series followed by an electrophoretic separation. This combination of components is suitable for a variety of genetic analyses. As an example, we have successfully identified sequence-specific hemagglutinin A subtype for the A/LA/1/87 strain of influenza virus. The device uses a compact design and mass production technologies, making it an attractive platform for a variety of widely disseminated applications.

Animals↗

PubMed2006

Formation of droplets and bubbles in a microfluidic T-junction-scaling and mechanism of break-up.

This article describes the process of formation of droplets and bubbles in microfluidic T-junction geometries. At low capillary numbers break-up is not dominated by shear stresses: experimental results support the assertion that the dominant contribution to the dynamics of break-up arises from the pressure drop across the emerging droplet or bubble. This pressure drop results from the high resistance to flow of the continuous (carrier) fluid in the thin films that separate the droplet from the walls of the microchannel when the droplet fills almost the entire cross-section of the channel. A simple scaling relation, based on this assertion, predicts the size of droplets and bubbles produced in the T-junctions over a range of rates of flow of the two immiscible phases, the viscosity of the continuous phase, the interfacial tension, and the geometrical dimensions of the device.

Emulsions↗

PubMed2006

Toolbox for the design of optimized microfluidic components.

A computational "toolbox" for the a priori design of optimized microfluidic components is presented. These components consist of a microchannel under low-Reynolds number, pressure-driven flow, with an arrangement of grooves cut into the top and bottom to generate a tailored cross-channel flow. An advection map for each feature (i.e., groove of a particular shape and orientation) predicts the lateral transport of fluid within the channel due to that feature. We show that applying these maps in sequence generates an excellent representation of the outflow distribution for complex designs that combine these basic features. The effect of the complex three-dimensional flow field can therefore be predicted without solving the governing flow equations through the composite geometry, and the resulting distribution of fluids in the channel is used to evaluate how well a component performs a specified task. The generation and use of advection maps is described, and the toolbox is applied to determine optimal combinations of features for specified mixer sizes and mixing metrics.

Microfluidic Analytical Techniques↗

PubMed2006

Open-access microfluidic patch-clamp array with raised lateral cell trapping sites.

A novel open-access microfluidic patch-clamp array chip with lateral cell trapping sites raised above the bottom plane of the chip was developed by combining both a microscale soft-lithography and a macroscale polymer fabrication method. This paper demonstrates the capability of using such an open-access fluidic system for patch-clamp measurements. The surface of the open-access patch-clamp sites prepared by the macroscale hole patterning method of soft-state elastic polydimethylsiloxane (PDMS) is examined; the seal resistances are characterized and correlated with the aperture dimensions. Whole cell patch-clamp measurements are carried out with CHO cells expressing Kv2.1 ion channels. Kv2.1 ion channel blocker (TEA) dosage response is characterized and the binding activity is examined. The results demonstrate that the system is capable of performing whole cell measurements and drug profiling in a more efficient manner than the traditional patch-clamp set-up.

Animals↗