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At least 1,243 records · Page 69Linked to original sources

PubMed2006

Steady flow generation in microcirculatory systems.

In this paper we explore the mechanical generation of steady-non pulsatile-flow in microfluidic systems. The rationale of the paper is inspired in the example of cardiovascular systems where at the microscale (i.e. capillaries) the flow is steady rather than pulsatile to optimize performance. We present a solution to the generation of steady flow in engineered microfluidic systems either in open or closed loop configurations via the use of disc pumps. The disc pump consists of a flat rotating disc and utilizes both viscous drag and centrifugal force to achieve pumping. Experiments using single loop and double loop microfluidic systems are presented to characterize the disc pump. Continuous flow generated by the disc pumps can be used to separate particles based on size using recirculating loops and for extraction of small particles without disturbing the concentration of bigger particles. The potential impact of this technology includes sample separation and extraction techniques into portable microfluidic labs-on-a-chip, and long term culture systems for cells in suspension.

Biomimetic Materials↗

PubMed2006

Rapid heterogeneous liver-cell on-chip patterning via the enhanced field-induced dielectrophoresis trap.

Biomimetic heterogeneous patterning of hepatic and endothelial cells, which start from randomly distributed cells inside the microfluidic chamber, via the chip design of enhanced field-induced dielectrophoresis (DEP) trap is demonstrated and reported in this paper. The concentric-stellate-tip electrode array design in this chip generates radial-pattern electric fields for the DEP manipulation of the live liver cells. By constructing the geometric shape and the distribution of stellate tips, the DEP electrodes enhance the desired spatial electric-field gradients to guide and snare individual cells to form the desired biomimetic pattern. With this proposed microfluidic chip design, the original randomly distributed hepatocytes inside the microfluidic chamber can be manipulated in parallel and align into the desired pearl-chain array pattern. This radial pattern mimics the lobular morphology of real liver tissue. The endothelial cells, then, are snared into the additional pearl-chain array and settle at the space in-between the previous hepatic pearl-chain array. By this cell-lab chip, we demonstrate the in vitro reconstruction of the heterogeneous lobule-mimetic radial pattern with good cell viability after cell patterning. This work reports the rapid in-parallel patterning of the dual types of live liver cells via the enhanced DEP trap inside the microfluidic chip.

Biomimetic Materials↗

PubMed2006

Continuous sorting of magnetic cells via on-chip free-flow magnetophoresis.

The ability to separate living cells is an essential aspect of cell research. Magnetic cell separation methods are among some of the most efficient methods for bulk cell separation. With the development of microfluidic platforms within the biotechnology sector, the design of miniaturised magnetic cell sorters is desirable. Here, we report the continuous sorting of cells loaded with magnetic nanoparticles in a microfluidic magnetic separation device. Cells were passed through a microfluidic chamber and were deflected from the direction of flow by means of a magnetic field. Two types of cells were studied, mouse macrophages and human ovarian cancer cells (HeLa cells). The deflection was dependent on the magnetic moment and size of the cells as well as on the applied flow rate. The experimentally observed deflection matched well with calculations. Furthermore, the separation of magnetic and non-magnetic cells was demonstrated using the same microfluidic device.

Animals↗

PubMed2006

Lab on a CD.

In this paper, centrifuge-based microfluidic platforms are reviewed and compared with other popular microfluidic propulsion methods. The underlying physical principles of centrifugal pumping in microfluidic systems are presented and the various centrifuge fluidic functions, such as valving, decanting, calibration, mixing, metering, heating, sample splitting, and separation, are introduced. Those fluidic functions have been combined with analytical measurement techniques, such as optical imaging, absorbance, and fluorescence spectroscopy and mass spectrometry, to make the centrifugal platform a powerful solution for medical and clinical diagnostics and high throughput screening (HTS) in drug discovery. Applications of a compact disc (CD)-based centrifuge platform analyzed in this review include two-point calibration of an optode-based ion sensor, an automated immunoassay platform, multiple parallel screening assays, and cellular-based assays. The use of modified commercial CD drives for high-resolution optical imaging is discussed as well. From a broader perspective, we compare technical barriers involved in applying microfluidics for sensing and diagnostic use and applying such techniques to HTS. The latter poses less challenges and explains why HTS products based on a CD fluidic platform are already commercially available, whereas we might have to wait longer to see commercial CD-based diagnostics.

Biological Assay↗

PubMed2004

Characterization of a novel intraocular drug-delivery system using crystalline lipid antiviral prodrugs of ganciclovir and cyclic cidofovir.

PURPOSE: In an earlier study, a novel intraocular drug-delivery system was reported in which hexadecyloxypropyl-phospho-ganciclovir (HDP-P-GCV) was used as a prototype. The hypothesis was that many biologically effective compounds could be modified to crystalline lipid prodrugs and could be delivered directly into the vitreous in a long-lasting, slow-release form. This study was undertaken to characterize this new drug-delivery system further, by using small particles of HDP-P-GCV and hexadecyloxypropyl-cyclic cidofovir (HDP-cCDV). METHODS: HDP-P-GCV was microfluidized into 4.4-microm (median) particles, injected into rabbit vitreous. The vitreous drug level was then measured at different time points. Crystalline HDP-cCDV was synthesized, suspended in 5% dextrose, and injected into the rabbit's vitreous at 10, 55, 100, 550, or 1000 microg in 50 microL vehicle per eye, to determine the highest nontoxic dose. The dose, 100 microg, was injected into 24 rabbit eyes, to evaluate pharmacokinetics; into 14 rabbit eyes with established HSV retinitis, to evaluate its efficacy; and into 58 rabbit eyes before herpes simplex virus (HSV) infection to evaluate its intraocular antiviral duration. RESULTS: Microfluidized particles of HDP-P-GCV showed an increased drug release rate compared with the large-particle drug formulation, with area under concentration-time curve (AUC) of 219.8 +/- 114.1 (n=3) versus 108.3 +/- 47.2 (n=3) for unmodified HDP-P-GCV during the 12-week period after a 2.8-micromole intravitreal injection. There was a 103% increase of the drug released from the microfluidized formulation of HDP-P-GCV versus the unmodified formulation. Intravitreal injections of HDP-cCDV at doses of 100 microg/eye or lower were not toxic. After the 100 microg/eye injections, HPLC analysis showed a vitreous HDP-cCDV level of 0.05 microM at week 5, which declined to 0.002 microM at week 8. The concentration at week 8 (0.002 microM) remained above the IC50 for cytomegalovirus (0.0003 microM). The pretreatment study demonstrated an antiviral effect that lasted 100 days after a single intravitreal injection. CONCLUSIONS: This crystalline lipid prodrug intravitreal delivery system is an effective approach to achieving sustained, therapeutic drug levels in the eye. Small microfluidized particles of HDP-P-GCV provide more rapid dissolution and higher vitreous drug levels.

Animals↗

PubMed2002

Passive electrophoresis in microchannels using liquid junction potentials.

The formation of the liquid junction potential (LJP) is a well-studied phenomenon that occurs in the presence of ionic concentration gradients. Although the LJP has been well characterized, its impact has generally been overlooked in microfluidic applications. The characteristics of flow in microfluidic channels cause this phenomenon to be particularly important, both as a source of deviation from anticipated results and as a tool capable of being harnessed to perform useful tasks. It is demonstrated that LJPs formed in microchannels can induce appreciable electrophoretic transport of charged species without the use of electrodes or an external power supply. This process is demonstrated in an H-filter (an H-shaped microfluidic channel used to bring two fluids into contact allowing extraction of diffusing species from one stream to another) by generating junction potentials between two flowing streams containing different concentrations of strong electrolytes and observing the mass transport of the charged dye fluorescein between those streams. It is shown that the LJP can be controlled to either accelerate or decelerate mass transport across a fluid interface in the absence of an interposed membrane. A preliminary mathematical description of the phenomena is offered to support the hypothesis that the observed mass transport is a result of the LJP. Possible practical microfluidic applications of electrophoretic transport without electrodes are discussed.

Diffusion↗

PubMed2001

Optical measurement of transverse molecular diffusion in a microchannel.

Quantitative analysis of molecular diffusion is a necessity for the efficient design of most microfluidic devices as well as an important biophysical method in its own right. This study demonstrates the rapid measurement of diffusion coefficients of large and small molecules in a microfluidic device, the T-sensor, by means of conventional epifluorescence microscopy. Data were collected by monitoring the transverse flux of analyte from a sample stream into a second stream flowing alongside it. As indicated by the low Reynolds numbers of the system (< 1), flow is laminar, and molecular transport between streams occurs only by diffusion. Quantitative determinations were made by fitting data with predictions of a one-dimensional model. Analysis was made of the flow development and its effect on the distribution of diffusing analyte using a three-dimensional modeling software package. Diffusion coefficients were measured for four fluorescently labeled molecules: fluorescein-biotin, insulin, ovalbumin, and streptavidin. The resulting values differed from accepted results by an average of 2.4%. Microfluidic system parameters can be selected to achieve accurate diffusion coefficient measurements and to optimize other microfluidic devices that rely on precise transverse transport of molecules.

Biochemistry↗

PubMed2003

Thermal bonding of polymeric capillary electrophoresis microdevices in water.

A new method for thermally bonding poly(methyl methacrylate) (PMMA) substrates to form microfluidic systems has been demonstrated. A PMMA substrate is first imprinted with a Si template using applied pressure and elevated temperature to form microchannel structures. This embossing method has been used to successfully pattern over 65 PMMA pieces using a single Si template. Thermal bonding for channel enclosure is accomplished by clamping together an imprinted and a blank substrate and placing the assembly in boiling water for 1 h. The functionality of these water-bonded microfluidic substrates was demonstrated by performing high-resolution electrophoretic separations of fluorescently labeled amino acids. Testing of bond strength in four microdevices showed an average failure pressure of 130 kPa, which was comparable to the bond strength for devices sealed in air. Subsequent profilometry of separated substrates revealed that the dimensions of the channels were well preserved during the bonding process. This new methodology for generation of microfluidic constructs should facilitate the permanent incorporation of hydrated, molecular size-selective membranes in microdevices, thus circumventing problems associated with membrane swelling in microfluidic systems upon exposure to water.

Journal Article↗

PubMed2004

Quantitative mass spectrometric determination of methylphenidate concentration in urine using an electrospray ionization source integrated with a polymer microchip.

We have demonstrated the use of a simple microfabricated electrospray ionization source for coupling microfluidic chips to mass spectrometry (MS). A polymer-based microchip, coupled to a triple quadrupole mass spectrometer, has been employed for direct infusion quantitative bioanalysis of methylphenidate (Ritalin) extracted from human urine samples. The approach used a microfabricated polymer electrospray emitter to couple a microfluidic channel to a stable electrospray ionization source. The microchip was fabricated from cycloolefin plastic plate by hot embossing and thermal bonding. This microfluidic chip contained two independent microfluidic channels, integrated with two corresponding electrospray emitters and an internal gold electrode. Liquid-liquid extraction was used to prepare urine samples, spiked with methylphenidate. A trideuterated analogue of methylphenidate (methylphenidate-d(3)) was used as the internal standard for the analysis. The system showed good electrospray stability and reproducibility with different spray tips. Four different electrospray tips were used to analyze the same sample, and the results showed very small variation with a relative standard deviation of 1.4%. A standard curve prepared for methylphenidate in urine (R(2) = 0.999) was linear over the range of 0.4-800 ng/mL. The precision of the quality control samples for three different concentrations ranged from 19.1% at 20 ng/mL, 3.2% at 200 ng/mL, to 3.5% at 667 ng/mL while the accuracy was 96.3% at 20 ng/mL, 101.2% at 200 ng/mL, and 101.6% at 667 ng/mL. No system carryover was detected even when the same device was used for sequential analysis. These results suggest the potential of this microdevice for MS-based quantitative analysis in drug discovery and development.

Electrophoresis, Microchip↗

PubMed2004

A nanoliter-scale nucleic acid processor with parallel architecture.

The purification of nucleic acids from microbial and mammalian cells is a crucial step in many biological and medical applications. We have developed microfluidic chips for automated nucleic acid purification from small numbers of bacterial or mammalian cells. All processes, such as cell isolation, cell lysis, DNA or mRNA purification, and recovery, were carried out on a single microfluidic chip in nanoliter volumes without any pre- or postsample treatment. Measurable amounts of mRNA were extracted in an automated fashion from as little as a single mammalian cell and recovered from the chip. These microfluidic chips are capable of processing different samples in parallel, thereby illustrating how highly parallel microfluidic architectures can be constructed to perform integrated batch-processing functionalities for biological and medical applications.

Animals↗

PubMed2004

Solid supports for micro analytical systems.

The development of micro analytical systems requires that fluids are able to interact with the surface of the microfluidic chip in order to perform analysis such as chromatography, solid phase extraction, and enzymatic digestion. These types of analyses are more efficient if there are solid supports within the microfluidic channels. In addition, solid supports within microfluidic chips are useful in producing devices with multiple functionalities. In recent years there have been many approaches introduced for incorporating solid supports within chips. This review will explore several state of the art methods and applications of introducing solid supports into chips. These include packing chips with beads, incorporating membranes into chips, creating supports using microfabrication, and fabricating gels and polymer monoliths within microfluidic channels.

Journal Article↗

PubMed2006

Liposomal delivery systems for encapsulation of ferrous sulfate: Preparation and characterization.

Liposomal delivery systems for water-soluble bioactives were prepared using the pro-liposome and the microfluidization technologies. Iron, an essential micronutrient as ferrous sulfate and ascorbic acid, as an antioxidant for iron were encapsulated in the liposomes. Liposomes prepared by the microfluidization technology using 6% (w/w) concentration of the lipid encapsulated with ferrous sulfate and ascorbic acid had particle size distributions around 150 to 200 nm, whereas liposomes from the pro-liposome technology resulted in particle sizes of about 5 microm. The encapsulation efficiency of ferrous sulfate was 58% for the liposomes prepared by the microfluidization using 6% (w/w) lipid and 7.5% of ferrous sulfate concentrations, and it was 11% for the liposomes from pro-liposome technology using 1.5% (w/v) lipid and 15% of ferrous-sulfate concentration. Both the liposomes exhibited similar levels of oxidative stability, demonstrating the feasibility of microfluidization-based liposomal delivery systems for large-scale food/nutraceutical applications.

Drug Delivery Systems↗

PubMed2006

Interfacing microchip capillary electrophoresis with electrospray ionization mass spectrometry.

Microfluidic devices are a unique enabling technology for chemical separations, modification, and synthesis that are ideally suited for the manipulation of low volume samples on the order of a few nanoliters in volume. Complex patterns of capillary-sized channels with zero dead volume connections are the distinguishing features of many microfluidic devices. Concurrently, mass spectrometry has undergone further development, and is now arguably the method of choice for structural characterization of mass- and volume-limited samples. The production of ions in the gas phase from the solution phase is critical for direct coupling of fluidic devices with the mass spectrometer, and the electrospray ionization (ESI) sources are well suited for this application. Micro- and nanoflow ESI interfaces are ideal for these applications as they cover flow rate ranges from the hundreds to a few nanoliters per minute, which are the same as the flow rates used by most microfluidic devices. Herein, the assembly and operation of a simple ESI interface for coupling a microfluidic device and mass spectrometer is described.

Electrophoresis, Microchip↗

PubMed2005

Phase-changing sacrificial materials for solvent bonding of high-performance polymeric capillary electrophoresis microchips.

A new method for solvent bonding polymeric substrates to form microfluidic systems has been demonstrated. Prior to device sealing, channels in an embossed poly(methyl methacrylate) (PMMA) piece are filled with a heated liquid (paraffin wax) that forms a solid sacrificial layer at room temperature. The sacrificial material prevents the bonding solvent (acetonitrile) and softened PMMA from filling the channels. Once the sealing step is complete, the sacrificial layer is melted and removed, leaving enclosed microfluidic channels. We found that PMMA substrates welded together using this method could withstand internal pressures of >2250 psi, more than 1 order of magnitude higher than their thermally bonded counterparts. To demonstrate the usefulness of this method, microchip capillary electrophoresis (CE) devices in PMMA were created and tested. Amino acid and peptide mixtures were separated in <15 s, with >40,000 theoretical plates in a 2.5-cm separation distance. Electric fields as high as 1.5 kV/cm were applied in these microchips, and >300 CE runs were performed on a single device with no degradation of separation performance. The simplicity of the methods presented here and the improved robustness of the resulting devices should facilitate the broader implementation of polymer microchips in microfluidic analyses.

Acetonitriles↗

PubMed2004

Manipulation of liquid droplets using amphiphilic, magnetic one-dimensional photonic crystal chaperones.

The controlled manipulation of small volumes of liquids is a challenging problem in microfluidics, and it is a key requirement for many high-throughput analyses and microassays. One-dimensional photonic crystals made from porous silicon have been constructed with amphiphilic properties. When prepared in the form of micrometre-sized particles and placed in a two-phase liquid such as dichloromethane/water, these materials will accumulate and spontaneously align at the interface. Here we show that superparamagnetic nanoparticles of Fe(3)O(4) can be incorporated into the porous nanostructure, allowing the materials to chaperone microlitre-scale liquid droplets when an external magnetic field is applied. The optical reflectivity spectrum of the photonic crystal displays a peak that serves to identify the droplet. Two simple microfluidics applications are demonstrated: filling and draining a chaperoned droplet, and combining two different droplets to perform a chemical reaction. The method provides a general means for manipulating and monitoring small volumes of liquids without the use of pumps, valves or a microfluidic container.

Crystallization↗

PubMed2005

Optofluidic control using photothermal nanoparticles.

Photothermal metallic nanoparticles have attracted significant attention owing to their energy-conversion properties. Here, we introduce an optofluidic application based on a direct optical-to-hydrodynamic energy conversion using suspended photothermal nanoparticles near the liquid-air interface. Using light beams with submilliwatt power, we can drive and guide liquid flow in microfluidic channels to transport biomolecules and living cells at controlled speeds and directions. Previously, a variety of methods for controlling microscale liquid flow have been developed owing to the increasing interest for microfluidics-based biochemical analysis systems. However, our method dispenses with the need for complex pump and valve devices, surface chemistry and electrode patterning, or any other further effort towards substrate fabrication. Instead, our optofluidic control method will allow the fabrication of all-optical large-scale integrated microfluidic circuits for biomolecular and cellular processing without any physical valve or mechanical pumping device.

Electrochemistry↗

PubMed2006

Monolithically integrated dye-doped PDMS long-pass filters for disposable on-chip fluorescence detection.

We report the fabrication of high quality monolithically integrated optical long-pass filters, for use in disposable diagnostic microchips. The filters were prepared by incorporating dye molecules directly into the microfluidic chip substrate, thereby providing a fully integrated solution that removes the usual need for discrete optical filters. In brief, lysochrome dyes were added to a poly(dimethylsiloxane) (PDMS) monomer prior to moulding of the microchip from a structured SU-8 master. Optimum results were obtained using 1 mm layers of PDMS doped with 1200 microg mL(-1) Sudan II, which resulted in less than 0.01% transmittance below 500 nm (OD 4), >80% above 570 nm, and negligible autofluorescence. These spectral characteristics compare favourably with commercially available Schott-glass long-pass filters, indicating that high quality optical filters can be straightforwardly integrated into the form of PDMS microfluidic chips. The filters were found to be robust in use, showing only slight degradation after extended illumination and negligible dye leaching after prolonged exposure to aqueous solutions. The provision of low cost high quality integrated filters represents a key step towards the development of high-sensitivity disposable microfluidic devices for point-of-care diagnostics.

Azo Compounds↗

PubMed2005

Study of the electroosmotic flow as a means to propel the mobile phase in capillary electrochromatography in view of further miniaturization of capillary electrochromatography systems.

In this paper, we investigate the phenomenon of electroosmosis as a means to propel a mobile phase, in particular in view of an application in microfluidic systems, which are characterized by significantly smaller volumes of the reservoirs and the separation channels compared to conventional instrumentation. In the microfluidic chip, pH changes due to water electrolysis quickly showed an effect on the electroosmotic flow (EOF), which could be counteracted by either regularly exchanging or buffering the mobile phase. Surface treatment was of no effect in regard to EOF stabilization in empty channels but may have an influence in channels filled with a charged monolith. In fused-silica capillaries the EOF was generally found to decrease from 'naked' to surface-treated to monolith-filled capillaries. The EOF tended to be higher when an organic solvent (acetonitrile) was added to the mobile phase and could be further increased by substituting the water with equal amounts of methanol. In addition, the hydrostatic pressure exerted by the EOF was investigated. In a microfluidic chip with empty (cross-)channels such an effect could be responsible for a redirection of the flow. In capillaries partially filled with a noncharged (non-EOF-generating) monolith, a linear relationship could be established between the EOF created in the empty section of the capillary (apparent mobility) and the length of the monolith (backpressure). In capillaries partially filled with a charged (EOF-producing) monolith, flow inhomogeneities must be expected as a consequence of a superimposition of hydrodynamic pressure and EOF as mobile phase driving force.

Chromatography, Micellar Electrokinetic Capillary↗