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Silicon couplers for microfluidic applications.

Several types of silicon fluidic coupler have been designed, fabricated, and tested to facilitate external connections to MEMS (microelectromechanical systems) fluidic devices. By using both bulk micromachining and DRIE (deep reactive ion-etching) techniques, couplers of different geometry have been produced for use with any standard MEMS fluidic port. In addition, couplers are easily modified to accommodate any arbitrary fluidic port geometry. For ease of use, these couplers interface with PEEK (polyetheretherketone) and fused-silica capillary tubing, both of which are commonly used in HPLC (high-performance liquid chromatography) systems and are supported by a wide range of plumbing products. Coupler performance was evaluated and an operating range of at least 0-8,963 kPa (0-1,300 psig) is attainable.

Journal Article↗

Breakup of carbon nanotube flocs in microfluidic traps.

The critical stress to break flocs of multiwalled-carbon nanotubes suspended in low-molecular-weight polymer fluid is measured in planar elongational flow. Through image analysis of aggregates and their fragments, the extension rate of the flow and the size and aspect ratio of the aggregates are measured in real time. While trapping an aggregate at the stagnation point of the device, the flow rate is increased continually and breaking events are recorded, establishing a correlation between aggregate size and the critical elongation stress for fragmentation sigma. This relationship resembles that for the breakup of flocs comprising spherical particles, yet it indicates that the strength of these fibrous flocs depends much more strongly on the local particle concentration. Fracture avalanches (or cascades) are also observed.

Journal Article↗

Flow-through sampling for electrophoresis-based microfluidic chips using hydrodynamic pumping.

This work presents a novel electrophoretic microchip design which is capable of directly coupling with flow-through analyzers for uninterrupted sampling. In this device, a 3 mm wide sampling channel (SC) was etched on quartz substrate to create the sample inlet and outlet and the 75 microm wide electrophoretic channels were also fabricated on the same substrate. Pressure was used to drive the sample flow through the external tube into the SC and the flow was then split into outlet and electrophoretic channels. A gating voltage was applied to the electrophoretic channel to control the sample loading for subsequent separations and inhibit the sample leakage. The minimum gating voltage required to inhibit the sample leakage depended on the solution buffer and increased with the hydrodynamic flow-rate. A fluorescent dye mixture containing Rhodamine B and Cy3 was introduced into the sample stream at either a continuous or discrete mode via an on-line injection valve and then separated and detected on the microchip using laser-induced fluorescence. For both modes, the relative standard deviation of migration time and peak intensity for consecutive injections was determined to be below 0.6 and 8%, respectively. Because the SC was kept floating, the external sampling equipment requires no electric connection. Therefore, such an electrophoresis-based microchip can be directly coupled with any pressure-driven flow analyzers without hardware modifications. To our best knowledge, this is something currently impossible for reported electrophoretic microchip designs.

Electrophoresis↗

A simple microfluidic system for patterning populations of neurons on silicon micromachined substrates.

The purpose of this paper is to describe a low-cost simple technique based on the hydraulically driven deposition of adhesion molecules for patterning populations of neurons on silicon micromachined substrates. First, the design and fabrication process of the silicon micromachined substrates and the design of a flow-through chamber for the localised deposition of adhesive proteins are described. The experimental protocol for the deposition of the adhesive proteins is then presented. Finally, the results of experiments of 'entrapment' of chick embryo spinal cord neurons in microstructures of the silicon substrates and of formation of patterned biological neural networks are shown.

Animals↗

Chromatography and electrophoresis on chips: critical elements of future integrated, microfluidic analytical systems for life science.

Liquid chromatography and electrophoresis played a major role in the life-science revolution, most strikingly in protein purification, peptide fractionation and sequencing, amino acid analysis, and DNA sequencing. The objective of this article is to examine the potential role of separation systems in the continuing evolution of biochemistry, biotechnology and molecular biology. Very small chip-based systems may change how chemical analyses in biology, medical research and health care evolve over the next decade.

Biological Science Disciplines↗

Microfluidic devices for DNA analysis.

Microfabricated electrophoresis devices allow us to perform short-tandem-repeat genotyping assays in under 2 min and sequence single-stranded DNA in under 15 min. This is 10-100 times faster than standard slab-gel and capillary systems. The microdevice format is the natural extension of 100 years of gradual improvements to electrophoresis but operates in an almost-perfect way, limited only by the sieving medium.

Acrylic Resins↗

A microfluidic cartridge to prepare spores for PCR analysis.

A prototype cartridge system is described that rapidly disrupts Bacillus spores by sonication, adds PCR reagent to the disrupted spores, and dispenses the mixture into a PCR tube. The total time to automatically process the spores in the cartridge and then detect the spore DNA by real-time PCR was 20 min.

Bacillus↗

Microfluidic separation of DNA.

DNA separation is important for numerous applications in biotechnology and medicine. Efforts to improve DNA separation in microdevices have led to advances in capillary electrophoresis and the development of novel separation strategies. Current research on microcapillary electrophoresis materials is focused on the development of separation matrices with low injection viscosities and wall-coating capabilities. Microcapillary injector geometries are being designed to allow increased control of sample plug volumes. Novel separation strategies using entropic traps, arrays of pillars and Brownian ratchets are also being developed.

DNA↗

Miniaturized FRET assays and microfluidics: key components for ultra-high-throughput screening.

Assay miniaturization applicable across a wide range of target classes, along with automation and process integration, are well-recognized goals for ultra-high-throughput screening on an industrial scale. This report summarizes the implementation of fluorescence resonance energy transfer (FRET)-based biochemical and cell-based assays in 3456-well NanoWelltrade mark assay plates using key components of Aurora's ultra-high-throughput screening system.

Journal Article↗

Microfluidic combinatorial chemistry.

Microreactors are finding increasing application in the field of combinatorial chemistry. In the past few years, microreactor chemistry has shown great promise as a novel method on which to build new chemical technology and processes. It has been conclusively demonstrated that reactions performed within microreactors invariably generate relatively pure products in high yield. One of the immediate and obvious applications is therefore in combinatorial chemistry and drug discovery.

Combinatorial Chemistry Techniques↗

Microfluidic device for combinatorial fusion of liposomes and cells.

We describe an electrofusion-based technique for combinatorial synthesis of individual liposomes. A prototype device with containers for liposomes of different compositions and a fusion container was constructed. The sample containers had fluid contact with the fusion container through microchannels. Optical trapping was used to transport individual liposomes and cells through the microchannels into the fusion container. In the fusion container, selected pairs of liposomes were fused together using microelectrodes. A large number of combinatorially synthesized liposomes with complex compositions and reaction systems can be obtained from small sets of precursor liposomes. The order of different reaction steps can be specified and defined by the fusion sequence. This device could also facilitate single cell-cell electrofusions (hybridoma production). This is exemplified by fusion of transported red blood cells.

Cells↗

Lysing bacterial spores by sonication through a flexible interface in a microfluidic system.

Cell disruptions using ultrasonic energy transmitted through a flexible interface into a liquid region has limitations because the motion of the vibrating tip is not completely transferred into the liquid. To ensure that some degree of contact will be maintained between the ultrasonic horn tip and the flexible interface, the liquid must be pressurized. The pressure conditions that yield consistent coupling between the ultrasonic horn tip and the liquid region were explored in this study by using an analytical model of the system and test fixture experiments. The nature of the interaction between the horn tip and the flexible interface creates pulses of positive pressure rises, increase in temperature, streaming flow, and almost no cavitation in the liquid. There was sufficient energy to create a cloud of microspheres, or beads, that maintain a consistent pattern of ballistic motion in the liquid. The sonication was found to be repeatable by studying video recordings of bead motion and was shown to be statistically consistent using measurements of temperature rise. Sonication of bacterial spores to obtain measurements of released nucleic acid and SEM images of damaged spores were used to verify the effects of liquid pressure on the horn-interface-liquid coupling.

Hydrolysis↗