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At least 757 records · Page 42Linked to original sources

PubMed2003

Microfluidic sorting in an optical lattice.

The response of a microscopic dielectric object to an applied light field can profoundly affect its kinetic motion. A classic example of this is an optical trap, which can hold a particle in a tightly focused light beam. Optical fields can also be used to arrange, guide or deflect particles in appropriate light-field geometries. Here we demonstrate an optical sorter for microscopic particles that exploits the interaction of particles-biological or otherwise-with an extended, interlinked, dynamically reconfigurable, three-dimensional optical lattice. The strength of this interaction with the lattice sites depends on the optical polarizability of the particles, giving tunable selection criteria. We demonstrate both sorting by size (of protein microcapsule drug delivery agents) and sorting by refractive index (of other colloidal particle streams). The sorting efficiency of this method approaches 100%, with values of 96% or more observed even for concentrated solutions with throughputs exceeding those reported for fluorescence-activated cell sorting. This powerful, non-invasive technique is suited to sorting and fractionation within integrated ('lab-on-a-chip') microfluidic systems, and can be applied in colloidal, molecular and biological research.

Capsules↗

PubMed2005

Controlled microfluidic interfaces.

The microfabrication technologies of the semiconductor industry have made it possible to integrate increasingly complex electronic and mechanical functions, providing us with ever smaller, cheaper and smarter sensors and devices. These technologies have also spawned microfluidics systems for containing and controlling fluid at the micrometre scale, where the increasing importance of viscosity and surface tension profoundly affects fluid behaviour. It is this confluence of available microscale engineering and scale-dependence of fluid behaviour that has revolutionized our ability to precisely control fluid/fluid interfaces for use in fields ranging from materials processing and analytical chemistry to biology and medicine.

Diffusion↗

PubMed2006

Developing optofluidic technology through the fusion of microfluidics and optics.

We describe devices in which optics and fluidics are used synergistically to synthesize novel functionalities. Fluidic replacement or modification leads to reconfigurable optical systems, whereas the implementation of optics through the microfluidic toolkit gives highly compact and integrated devices. We categorize optofluidics according to three broad categories of interactions: fluid-solid interfaces, purely fluidic interfaces and colloidal suspensions. We describe examples of optofluidic devices in each category.

Animals↗

PubMed2006

Microfluidic diagnostic technologies for global public health.

The developing world does not have access to many of the best medical diagnostic technologies; they were designed for air-conditioned laboratories, refrigerated storage of chemicals, a constant supply of calibrators and reagents, stable electrical power, highly trained personnel and rapid transportation of samples. Microfluidic systems allow miniaturization and integration of complex functions, which could move sophisticated diagnostic tools out of the developed-world laboratory. These systems must be inexpensive, but also accurate, reliable, rugged and well suited to the medical and social contexts of the developing world.

Developing Countries↗

PubMed2005

All-optical control of microfluidic components using form birefringence.

The reflection and refraction of light at a dielectric interface gives rise to forces due to changes in the photon momentum. At the microscopic level, these forces are sufficient to trap and rotate microscopic objects. Such forces may have a profound impact in the emergent area of microfluidics, where there is the desire to process minimal amounts of analyte. This places stringent criteria on the ability to pump, move and mix small volumes of fluid, which will require the use of micro-components and their controlled actuation. We demonstrate the modelling, fabrication and rotation of microgears based on the principle of form birefringence. Using a geometric anisotropy (a one-dimensional photonic crystal etched into the microgear), we can fabricate microgears of known birefringence, which may be readily rotated by manipulating the input polarization in a standard optical trap. This methodology offers a new and powerful mechanism for generating a wide range of microfabricated machines, such as micropumps, that may be driven by purely optical control.

Biocompatible Materials↗

PubMed2002

Microfluidic devices fabricated in poly(methyl methacrylate) using hot-embossing with integrated sampling capillary and fiber optics for fluorescence detection.

High-aspect-ratio microstructures have been prepared using hot-embossing techniques in poly(methyl methacrylate) (PMMA) from Ni-based molding dies prepared using LIGA (Lithographie, Galvanoformung, Abformung). Due to the small amount of mask undercutting associated with X-ray lithography and the high energy X-ray beam used during photoresist patterning, deep structures with sharp and smooth sidewalls have been prepared. The Ni-electroforms produced devices with minimal replication errors using hot-embossing at a turn around time of approximately 5 min per device. In addition, several different polymers (with different glass transition temperatures) could be effectively molded with these Ni-electroforms and many devices (>300) molded with the same master without any noticeable degradation. The PMMA devices consisted of deep and narrow channels for insertion of a capillary for the automated electrokinetic loading of sample into the microfluidic device and also, a pair of optical fibers for shuttling laser light to the detection zone and collecting the resulting emission for fluorescence analysis. Electrophoretic separations of double-stranded DNA ladders Phi X174 digested with Hae III) were performed with fluorescence detection accomplished using near-IR excitation. It was found that the narrow width of the channels did not contribute significantly to electrophoretic zone broadening and the plate numbers generated in the extended length separation channel allowed sorting of the 271/281 base pair fragments associated with this sizing ladder when electrophoresed in methylcellulose entangled polymer solutions. The dual fiber detector produced sub-attomole detection limits with the entire detector, including laser source, electronics and photon transducer, situated in a single box measuring 3'' x 10" x 14".

Dinitrobenzenes↗

PubMed2002

Microfluidic devices for fluidic circulation and mixing improve hybridization signal intensity on DNA arrays.

Reactions of biomolecules with surface mounted materials on microscope slides are often limited by slow diffusion kinetics, especially in low volumes where diffusion is the only means of mixing. This is a particular problem for reactions where only small amounts of analyte are available and the required reaction volume limits the analyte concentration. A low volume microfluidic device consisting of two interconnected 9 mm x 37.5 mm reaction chambers was developed to allow mixing and closed loop fluidic circulation over most of the surface of a microscope slide. Fluid samples are moved from one reaction chamber to the other by the rotation of a magnetic stirring bar that is driven by a standard magnetic stirrer. We demonstrate that circulation and mixing of different reagents can be efficiently accomplished by this closed loop device with solutions varying in viscosity from 1 to 16.2 centipoise. We also show by example of a microarray hybridization that the reaction efficiency can be enhanced 2-5 fold through fluid mixing under conditions where diffusion is rate limiting. For comparison, similar results were achieved with a disposable commercial device that covers only half of the reaction area of the closed loop device.

DNA↗

PubMed2003

Electrowetting-based droplet mixers for microfluidic systems.

Mixing of analytes and reagents is a critical step in realizing a lab-on-a-chip. However, mixing of liquids is very difficult in continuous flow microfluidics due to laminar flow conditions. An alternative mixing strategy is presented based on the discretization of liquids into droplets and further manipulation of those droplets by electrowetting. The interfacial tensions of the droplets are controlled with the application of voltage. The droplets act as virtual mixing chambers, and mixing occurs by transporting the droplet across an electrode array. We also present an improved method for visualization of mixing where the top and side views of mixing are simultaneously observed. Microliters of liquid droplets are mixed in less than five seconds, which is an order of magnitude improvement in reported mixing times of droplets. Flow reversibility hinders the process of mixing during linear droplet motion. This mixing process is not physically confined and can be dynamically reconfigured to any location on the chip to improve the throughput of the lab-on-a-chip.

Electrochemistry↗

PubMed2003

Measurement of density and chemical concentration using a microfluidic chip.

A new microfluidic product for measuring fluid density, specific gravity and chemical concentration has been developed. At the core of this lab-on-a-chip sensor is a vacuum-sealed resonating silicon microtube. Measurements can be made with under a microliter of sample fluid, which is over 1000x less than is conventionally required. Since the product is MEMS-based the overall system size is a fraction of conventional density meters and it weighs much less than the traditional desk-top, temperature controlled, density meters. The syringe or pipette loaded system includes a dynamic temperature control system that operates between 0 degree C and 90 degree C with an accuracy of less than 0.01 degree C. Density measurement accuracies of 4 to 5 digits have been observed with aqueous solutions. Measurement examples and applications will be discussed.

Equipment Design↗

PubMed2003

Counting and sizing of particles and particle agglomerates in a microfluidic device using laser light scattering: application to a particle-enhanced immunoassay.

A microfluidic device for counting and sizing particles and particle agglomerates based on laser light scattering is demonstrated. The particles were confined hydrodynamically and passed through a focused laser beam. Scattering at two different angles, 15 degree and 45 degree, was detected. At an acquisition rate of 10 kHz, a throughput of 150 particles s(-1) was achieved. Scattering intensity was found to depend on particle volume for 2 to 9 microm diameter particles. Size discrimination of particles with a diameter ratio of 1: 2 was accomplished. In addition, the scattering signals of particle agglomerates formed in a particle-enhanced immunoassay for C-reactive protein (CRP) were measured. Scattering intensity was found to be dependent on the CRP concentration, 100 ng CRP per mL could be detected. The particle counting method presented is generic and can be employed in a wide variety of assays as well as for cell counting and particle counting.

C-Reactive Protein↗

PubMed2003

Design of a recursively-structured valveless device for microfluidic manipulation.

A recursively-structured apparatus based on a pneumatic pumping structure has been investigated numerically and experimentally in the present study. For the T-connected channels, this apparatus demonstrated the ability to manipulate the liquid drop from a first channel to a second channel, while simultaneously preventing flow into the third channel. The microTAS research aimed at biochemical analysis miniaturization and integration has recently made explosive progress. However, there is still a considerable technical challenge in integrating these procedures into a multiple-step system. An important issue for this integration is microfluid management techniques. The microTAS method must be designed considering special transport mechanisms to move samples and reagents through the microchannels. The structure of this apparatus was simple and easily fabricated. Moreover, because there is a continuous airflow at the "outlet" during fluid manipulation, it is possible to avoid contamination of the air source similar to the "laminar flow hook" in biological experiments. Utilizing the concept of a recursive structure, one can easily design a device wherein more than three channels are included in the flow network, either intersecting in a single junction or in multiple junctions.

Computer Simulation↗

PubMed2003

Enhancement of microfluidic mixing using time pulsing.

Many microfluidic applications require the mixing of reagents, but efficient mixing in these laminar (i.e., low Reynolds number) systems is typically difficult. Instead of using complex geometries and/or relatively long channels, we demonstrate the merits of flow rate time dependency through periodic forcing. We illustrate the technique by studying mixing in a simple "T" channel intersection by means of computational fluid dynamics (CFD) as well as physically mixing two aqueous reagents. The "T" geometry selected consists of two inlet channel segments merging at 90 degrees to each other, the outlet segment being an extension of one of the inlet segments. All channel segments are 200 microm wide by 120 microm deep, a practical scale for mass-produced disposable devices. The flow rate and average velocity after the confluence of the two reagents are 48 nl s(-1) and 2 mm s(-1) respectively, which, for aqueous solutions at room temperature, corresponds to a Reynolds number of 0.3. We use a mass diffusion constant of 10(-10) m(2) s(-1), typical of many BioMEMS applications, and vary the flow rates of the reagents such that the average flow rate remains unchanged but the instantaneous flow rate is sinusoidal (with a DC bias) with respect to time. We analyze the effect of pulsing the flow rate in one inlet only as well as in the two inlets, and demonstrate that the best results occur when both inlets are pulsed out of phase. In this case, the interface is shown to stretch, retain one fold, and sweep through the confluence zone, leading to good mixing within 2 mm downstream of the confluence, i.e. about 1 s of contact. From a practical viewpoint, the case where the inlets are 180 degrees out of phase is of particular interest as the outflow is constant.

Computer Simulation↗

PubMed2004

Optical tweezers applied to a microfluidic system.

We will demonstrate how optical tweezers can be combined with a microfluidic system to create a versatile microlaboratory. Cells are moved between reservoirs filled with different media by means of optical tweezers. We show that the cells, on a timescale of a few seconds, can be moved from one reservoir to another without the media being dragged along with them. The system is demonstrated with an experiment where we expose E. coli bacteria to different fluorescent markers. We will also discuss how the system can be used as an advanced cell sorter. It can favorably be used to sort out a small fraction of cells from a large population, in particular when advanced microscopic techniques are required to distinguish various cells. Patterns of channels and reservoirs were generated in a computer and transferred to a mask using either a sophisticated electron beam technique or a standard laser printer. Lithographic methods were applied to create microchannels in rubber silicon (PDMS). Media were transported in the channels using electroosmotic flow. The optical system consisted of a combined confocal and epi-fluorescence microscope, dual optical tweezers and a laser scalpel.

Cell Separation↗

PubMed2004

A flexible sample introduction method for polymer microfluidic chips using a push/pull pressure pump.

A push/pull sample introduction method based on push/pull pressure flow for microfluidic systems (cross, double T and multichannel structures) is presented. This leads to well-defined and controllable sample plugs even when dealing with long channels. By tuning the relative push/pull pressure, it is shown that the size of the sample plug can effectively be controlled. Good signal reproducibility upon continued sample introduction and subsequent chip electrophoresis employing fluorescence detection is demonstrated for different chip geometries (i.e. short channels and long channels). Since the performance of the method is relatively insensitive to chip geometry, it is particularly useful for polymeric prototype microchips as tedious optimization is not required. Furthermore, the push/pull sample introduction is extended to multichannel chips thus demonstrating the possibilities of applying the methodology for realizing single chip high throughput sample analysis.

Equipment Design↗

PubMed2003

Controlled microfluidic reconstitution of functional protein from an anhydrous storage depot.

A novel method has been developed for preserving molecules in microfluidic devices that also enables the control of the spatial and temporal concentrations of the reconstituted molecules within the devices. In this method, a storage cavity, embedded in a microchannel, is filled with a carbohydrate matrix containing, for example, a reagent. When the matrix is exposed to flowing liquid, it dissolves, resulting in the controlled reconstitution and release of the reagent from the cavity. The technique was demonstrated using two different model systems; the successful preservation and controlled release of beta-galactosidase was achieved. This method has possible applications for simple point-of-care drug delivery and immunoassays, and could be used to pattern the surfaces of microchannels. More broadly, this preservation and controlled release technique can be applied where the preservation and/or spatial and temporal control of chemical concentrations are desired.

Dimethylpolysiloxanes↗

PubMed2003

Integration of single cell injection, cell lysis, separation and detection of intracellular constituents on a microfluidic chip.

A microfluidic system was developed for the analysis of single biological cells, with functional integration of cell sampling, single cell loading, docking, lysing, and capillary electrophoretic (CE) separation with laser induced fluorescence (LIF) detection in microfabricated channels of a single glass chip. Channels were 12 microm deep and 48 microm wide, with a simple crossed-channel design. The effective separation channel length was 35 mm. During sampling with a cell suspension (cell population 1.2 x 10(5) cells per mL in physiological salt solution), differential hydrostatic pressure (created by adjusting liquid levels in the four reservoirs) was used to control cell flow exclusively through the channel crossing. Single cell loading into the separation channel was achieved by electrophoretic means by applying a set of potentials at the four reservoirs, counteracting the hydrostatic flow. A special docking (adhering) procedure for the loaded cell was applied before lysis by repeatedly connecting and disconnecting a set of low potentials, allowing precise positioning of the cell within the separation channel. Cell lysis was then effected within 40 ms under an applied CE separation voltage of 1.4 kV (280 V cm(-1)) within the working electrolyte (pH 9.2 borate buffer) without additional lysates. The docked lysing approach reduced dispersion of released intracellular constituents, and significantly improved the reproducibility of CE separations. Glutathione (GSH) was used as a model intracellular component in single human erythrocyte cells. NDA derivatized GSH was detected using LIF. A throughput of 15 samples h(-1), a retention time precision of 2.4% RSD was obtained for 14 consecutively injected cells. The average cellular concentration of GSH in human erythrocytes was found to be 7.2 [times] 10(-4)+/- 3.3 x 10(-4) M (63 +/- 29 amol per cell). The average separation efficiency for GSH in lysed cells was 2.13 x 10(6)+/- 0.4 x 10(6) plates per m, and was about a factor of 5 higher than those obtained with GSH standards using pinched injection.

Electrophoresis, Capillary↗

PubMed2004

Microfluidic chip for high efficiency DNA extraction.

A high efficiency DNA extraction microchip was designed to extract DNA from lysed cells using immobilized beads and the solution flowing back and forth. This chip was able to increase the extraction efficiency by 2-fold when there was no serum. When serum existed in the solution, the extraction efficiency of immobilized beads was 88-fold higher than that of free beads. The extraction efficiency of the microchip was tested under different conditions and numbers of E. coli cells. When the number of E. coli cells was between 10(6) and 10(8) in 25 microl of whole blood, the extraction efficiency using immobilized beads was only slightly higher than that using free beads (10(0) to 10(1) fold). When the number of E. coli cells was in the range 10(4) to 10(6) in 25 microl of whole blood, the extraction efficiency of immobilized beads was greater than that of the free beads (10(1) to 10(2) fold). When the number of E. coli cells was lower, in the range 10(3) to 10(4) in 25 microl of whole blood, the extraction efficiency of immobilized beads was much higher than that of the free beads (10(2) to 10(3) fold). This study indicated that DNA could be efficiently extracted even when the number of bacterial cells was smaller (10(5) to 10(3)). This microfluidic extraction chip could find potential applications in rare sample genomic study.

Blood↗

PubMed2004

Cell immersion and cell dipping in microfluidic devices.

Combining deflective dielectrophoretic barriers with controlled pressure driven liquid flows in microfluidic devices allows accurate handling of particles such as biological cells in suspensions. Working towards cell-based lab-on-a-chip applications, a platform permitting rapid testing of devices having different dielectrophoretic and fluidic subunits was developed. The performance of such a system is shown in the cases of (A) flooding a small number of immobilised cells with a dye and (B) transient buffer swapping of a large number of cells in flow. The transition times for moving cells from one reagent to the other are below 0.5 s in the case of flow-through cell dipping.

Biotechnology↗