Micronics has developed a wide variety of microfluidic devices and integrated systems for clinical diagnostics and life sciences applications. They fall into two general classes: machine-controlled disposable cartridges, and passive self-contained disposable cards. They include particle separators, flow cytometers, valves, detection channels, mixers, and diluters. Current applications for these devices include a hematology analyzer, stand-alone blood plasma separators, and a variety of chemical and biological assays. In this paper, we will focus on microfluidic structures for chemical and cellular analysis. Experimental data as well as the results of fluid modeling will be shown.
The oxyradical production by leukocytes is crucial for killing invading bacteria, while it has been widely discussed as a tissue injuring factor. Despite such importance of the event, it is still unclear, probably because of lack of simple and reliable measurement methods, to what extent it varies among different subjects and either to what extent it is affected by environmental factors including diet. The present paper describes use of microfabricated channel arrays, that have been developed for use in studies of blood rheology, in the oxyradical measurement by chemiluminescence.
Self-assembled monolayers (SAMs) of alkanthiols have been studied and applied to enzyme modification on metal electrode. The construction of enzyme electrode using SAM is one of the considerable approaches for enzyme sensors. Glucose electrode and lactate electrode were fabricated on gold electrode by alkanthiols. The electrode response allowed to differentiate between long and short alkyl chains of alkanthiols. This result suggests that SAM with different chain length change their surface properties and affect electrochemical response of enzyme modified electrodes. On the basis of the result, micro machined glucose electrode was fabricated and its response was measured.
Microfabrication techniques which permit the creation of therapeutic delivery systems that possess a combination of structural, mechanical, and perhaps electronic features may surmount challenges associated with conventional delivery of therapy. In this review, delivery concepts are presented which capitalize on the strengths of microfabrication. Possible applications include micromachined silicon membranes to create implantable biocapsules for the immunoisolation of pancreatic islet cells--as a possible treatment for diabetes--and sustained release of injectable drugs needed over long time periods. Asymmetrical, drug- loaded microfabricated particles with specific ligands linked to the surface are proposed for improving oral bioavailability of peptide (and perhaps protein) drugs.
Isotachophoresis is an electrokinetic separation technique in which a sample volume is placed between two electrolytes. The resulting separation consists of contiguous zones of constant composition whose length is proportional to component concentration in the sample. This paper describes the development of miniaturized formats consisting of microchannel structures fabricated in polymer substrates.
Tissue cells cannot survive without the attachment to extracellular matrix (ECM). Furthermore, the geometry of ECM is known to play an essential role in the regulation for these cells to proliferate and differentiate so that tissues with normal morphologies can be formed or maintained. We have introduced microfabricated surface structures coated with ECM protein collagen into cell culture studies to examine a possibility of 3D patterning of ECM.
The differences in hydrophobicity produced by the e-beam patterning exposure of the surface of poly[(tert-butyl methacrylate)-co-(methyl methacrylate)] -a common e-beam and deep-UV resist, resulted in the selective attachment of heavy meromyosin on hydrophobic, unexposed surfaces. The movement of the actin filaments on myosin-rich and myosin- poor surfaces was statistically characterized in terms of velocity, acceleration, and angle of movement. The actin filaments have a smooth motion on myosin-rich surfaces and an uneven motion on myosin-poor surfaces. Interestingly, an excess of myosin sites has a slowing, albeit mild, effect on the motion of the action filaments. It was also found that the myosin-rich/myosin-poor boundary has an alignment- enforcement effect, especially for the filaments approaching the border from the myosin-rich side. Based on these results we discuss the feasibility of building purposefully designed molecular motor arrays and the testing of the hypothesis regarding the functioning of the biomolecular dynamic biodevice.
Over the last year, a team of scientists and engineers has built the first battery-powered, hand-held multichamber PCR instrument. It is the culmination of nearly a decade of R&D into PCR instrumentation. Each of the instruments over this time was based on bulk micromachining of single-crystal silicon to produce the heart of the instrument, a thermal- cycling chamber. When fluorescent reagents were developed to perform real-time PCR, we added this capability to our instruments.
The sensitivity and speed of methods for the detection of microorganisms and/or cells need to be constantly improved to provide timely and accurate analysis in large number of important applications. Such applications range from detection of pathogens in drinking water, biological warfare agents, biomedical diagnostics and food industry. The trends toward miniaturization of sensors using microfluidic and nanofluidic on-chip devices will push current detection limits to lower concentrations than what is offered by the present analytical equipment and/or detection kids. Microfluidic devices have been used to perform DNA analysis, polymerase chain reaction analysis, capillary electrophoresis and hybridization to oligonucleotide probes. This paper describes a new approach for the detection of pathogens on contaminated surfaces, which will integrated sampling, concentration and detection of targeted microorganisms.
We are developing a method for high-throughput screening using arrays of `nanowells' built into a silicon substrate. These wells can serve as bioreactors for studying a variety of biochemical reactions such as the enzymatic activity that occurs in yeast metabolism. For a variety of studies it is important to know the volume of liquid that has been deposited in a given well and/or to monitor the evaporation of the liquid. Using silicon as our substrate means that we can take advantage of the ability to build microelectronics into the wells in order to develop `smart' wells.
The emerging field of microfluidics may provide for the rapid, automated analysis of samples. Here we describe the microfabrication and operation of a nanoelectrospray device formed from the planar surface of a monolithic silicon substrate for electrospray mass spectrometry sample analysis at low nanoliter per minute flow rates. To generate a useful electrospray from a microchip, a high aspect ratio nozzle structure of small dimensions is required. Deep reactive ion etching technologies allow these high aspect ratio structures to be fabricated in parallel and are widely available for the etching of silicon.
A prototype evanescent-wave sensor using resonant whispering-gallery modes of a fused-silica microsphere has been developed and is being applied to the detection of trace amounts of carbon dioxide, carbon monoxide, ammonia, and acetylene in the 1530 - 1580 nm wavelength region. Its sensitivity is comparable to that of typical multipass-cell systems, but our sensor is much more compact because of resonant cavity enhancement. It represents a significant improvement over current total-internal-reflection or fiber evanescent-wave sensors, owing to the longer effective absorption path length (tens of meters in a sphere less than a millimeter in diameter). The present sensitivity is about a hundred parts per million, equivalent to the level detected by a household carbon monoxide sensor. This sensitivity is for direct absorption measurements; wavelength-modulation spectroscopy is being implemented and should provide two or three orders of magnitude improvement. By extending the same techniques, using fluorozirconate- glass microspheres and stronger transitions in the mid- infrared, the sensitivity is expected to improve to about a part per billion.
The artificial resonances of dielectric optical microcavities can be used to enhance the detection sensitivity of evanescent-wave optical fluorescence biosensors to the binding of a labeled analyte to a biospecific monolayer. Microcavity sensors offer the high sensitivity of a slab waveguide evanescent fluorescence sensor of much larger sensing surface area. Alternatively, when compared to a slab waveguide of the same area, microcavity based sensors offer much improved sensitivity. In either case, the required number of bound analytes is dramatically reduced. These scaling relations are highly conducive to achieving large sensing arrays with small sample volumes.
A new nano technique based on enhanced metal cluster absorption was used to detect antibody-food allergen interactions, resulting in a optical signal, which is observed directly as a color change of the chip surface either with the eye or using an optical scanner.
Biomaterials are substances that are produced synthetically or biologically for use in the medical and the other fields. The use of biomaterials to interface with living systems, such as fluids, cells, and tissues of the body, has played an increasingly important role in medicine and pharmaceutics. In particular, the design of biocompatible synthetic surfaces to control the interaction between a living system and an implanted material remains the major theme for biomaterial applications in medicine. The novel and low-cost electrostatic self-assembly (ESA) technique provides an effective approach to incorporate various biomaterials on substrate surfaces, and gives greater opportunity to develop unique biocompatible materials with well-controlled interfaces between the living system and the implanted materia. This paper presents the design, synthesis, and characterization of multilayer thin films fabricated layer-by-layer by the ESA process using ceramics, polymers and functionalized fullerenes as candidate biomaterials.
The development of microsystems that merge biological materials with microfabricated structures is highly dependent on the successful interfacial interactions between these innately incompatible materials. Surface passivation of semiconductor and glass surfaces with thin organic films can attenuate the adhesion of proteins and cells that lead to biofilm formation and biofouling of fluidic structures. We have examined the adhesion of glial cells and serum albumin proteins to microfabricated glass and semiconductor surfaces coated with self-assembled monolayers of octadecyltrimethoxysilane and N-(triethoxysilylpropyl)-O- polyethylene oxide urethane, to evaluate the biocompatibility and surface passivation those coatings provide.
The speed of light through a biofluid or biological cell is inversely related to the biomolecular concentration of proteins and other complex molecules comprising carbon- oxygen double bonds that modify the refractive index at wavelengths accessible to semiconductor lasers. By placing a fluid or cell into a semiconductor microcavity laser, these decreases in light speed can be sensitively recorded in picoseconds as frequency red-shifts in the laser output spectrum. This biocavity laser equipped with microfluidics for transporting cells at high speed through the laser microcavity has shown potential for rapid analysis of biomolecular mass of normal and malignant human cells in their physiologic condition without time-consuming fixing, staining, or tagging.
The precision of soft tissue dissection with pulsed lasers in endo-microsurgery is typically limited by collateral damage from vapor bubbles created during energy deposition. Expansion and collapse of the cavitation bubble introduces collateral damage extending far beyond the primary energy deposition zone in both, axial and radial directions. We present an alternative technique that allows for creating of only axial pulsed liquid flow with well-defined radial dimensions and axial velocity.