A silicon microneedle array with integrated microfluidic channels is presented, which is designed to extract dermal interstitial fluid (ISF) for biochemical analysis. ISF is a cell-free biofluid that is known to contain many of the same constituents as blood plasma, but the scope and dynamics of biomarker similarities are known for only a few components, most notably glucose. Dermal ISF is accessible just below the outer skin layer (epidermis), which can be reached and extracted with minimal sensation and tissue trauma by using a microneedle array. The microneedle arrays presented here are being developed to extract dermal ISF for off-chip profiling of nucleic acid constituents in order to identify potential biomarkers of disease. In order to assess sample volume requirements, preliminary RNA profiling was performed with suction blister ISF. The microneedles are batch fabricated using established silicon technology (low cost), are small in size, and can be integrated with sensors for on-chip analysis. This approach portends a more rapid, less expensive, self-administered assessment of human health than is currently achievable with blood sampling, especially in non-clinical and austere settings. Ultimately, a wearable device for monitoring a person’s health in any setting is envisioned.
KEYWORDS: Carbon, Electrodes, Nanoparticles, Ion channels, Silicon, Nanofabrication, Signal detection, Scanning electron microscopy, Solid state electronics, Nanowires
Rapid and cost-effective DNA sequencing is a pivotal prerequisite for the genomics era. Many of the recent
advances in forensics, medicine, agriculture, taxonomy, and drug discovery have paralleled critical advances
in DNA sequencing technology. Nanopore modalities for DNA sequencing have recently surfaced including
the electrical interrogation of protein ion channels and/or solid-state nanopores during translocation of DNA.
However to date, most of this work has met with mixed success. In this work, we present a unique
nanofabrication strategy that realizes an artificial nanopore articulated with carbon electrodes to sense the
current modulations during the transport of DNA through the nanopore. This embodiment overcomes most of
the technical difficulties inherent in other artificial nanopore embodiments and present a versatile platform for
the testing of DNA single nucleotide detection. Characterization of the device using gold nanoparticles, silica
nanoparticles, lambda dsDNA and 16-mer ssDNA are presented. Although single molecule DNA sequencing
is still not demonstrated, the device shows a path towards this goal.
Solid phase direct-write (SPDW) patterning is a promising technique for nanoscale device fabrication. It enables the deposition of a range of materials with the precision and relatively low cost inherent in scanning force microscopy. The ability to deposit controlled 2D and 3D patterns at the nanometer scale and image them with the same instrument adds versatility to nanodevice design and fabrication. This technique works by loading an atomic force microscopy tip with a solid phase "ink" then reversing the process to write a pattern. Linewidths between 40nm and 500nm can be written, with the dimension varied by user specified parameters. To date, four materials have been successfully deposited: carbon, silicon, tungsten oxide and molybdenum oxide. This report presents an overview of SPDW and its application to the direct write fabrication of electronic devices.
Microfabrication not only enables the miniaturization of sensors and instruments, it also enables novel function and capability not accessible to the macro versions. For biomedical applications small size means less invasive, greater spatial resolution, and/or the ability to process small sample volumes. Miniaturization has additional advantages for space applications such as reduced launch payload, compact flight storage, and ease of redundancy. Several, demonstrated biomedical microinstruments are described here illustrating new capabilities arising from descending scale.
A miniature linear synchronous motor was designed, fabricated and tested. Actuation was achieved through interaction of traveling magnetic wave, generated by linear array of microcoils on a stator, and permanent magnets on a rotor. Two configurations of the motor were investigated. One with a single, hand assembled permanent magnet on rotor and corresponding array of multiturn microcoils, the other, a fully microfabricated rotor with embedded array of screenplated permanent magnets and serpentine microcoils on stator. Motion of the rotor is constrained by silicon dovetail microjoints. A numerical model was developed for modeling and control. The motor was tested under various operating conditions with both open and closed loop control.
The early '70s witnessed the introduction of the 'ion- selective field-effect transistor,' ISFET, which melded ion- selective electrode technology with standard microfabricated electronics and subsequently ushered in the era of integrated transducers. The futuristic allure of integrated transducers soon permeated the literature generating a literal zoo of unique sensors and actuators all purporting a litany of 'smaller, cheaper, better.' Capitalizing on the forte of microfabrication, the simple microdevice quickly evolved into arrays of microdevices and then on to integrated microsystems, complete with multiple transducers, actuators, and controls. However, the initial visions for integrated microsystems far outstripped available technical resources. For example, the simple ISFET required over twenty years to realize even limited commercialization. Process incompatibilities, materials issues, and fabrication limitations still present formidable challenges to any practical commercialization of most academic microsystem concepts. These limitations have generally mandated two strategic adaptations: (1) Limit products to simple, single-function/process microdevices such as in ink-jet printers, solid state pressure sensors, etc., or (2) Follow the example of high speed electronics and adopt a hybrid approach where the individual microdevices are individually fabricated and later assembled/packaged into the complex system. The latter approach is particularly apropos to optical microsystems which inherently demand a diverse range of nontraditional materials, photonic, and electro-optical components.
KEYWORDS: Silicon, Glasses, Microfluidics, Semiconducting wafers, Deep reactive ion etching, Microfluidic imaging, Photography, Digital signal processing, Reactive ion etching, Control systems
Microfabrication technology is implemented to realize a fluidic microinstrument for the study of endothelial cell elongation and cell responsiveness to fluid flow. The microinstrument contains arrays of microchannels, 30 - 300 micrometer wide, that are fabricated by deep reactive ion etching (DRIE) of silicon and anodic bonding to glass. Silicon fluidic input/output modules, also micromachined in silicon, provide modular connections between the microchannels and off- chip devices for flow monitoring and control. Image analysis of cells cultured in microchannels shows that the cells become progressively more elongated as channel width decreases. When subjected to a fluid shear stress of 2 N/m2, cuboidal cells grown in 200 micrometer wide microchannels progressively align and elongate in the direction of flow.
A long range translation actuator designed for optic and robotic applications is presented. Specifically, the microstage is designed to operate as the moving mirror in a miniature version of a traditional Michelson Fourier transform spectrometer. The translational microstage utilizes an electromagnetic actuation mechanism to realize linear translation of centimeters of precision travel. Motion is constrained in the normal and lateral directions using silicon dovetail microjoints. The electromagnetic actuation is based on macro linear synchronous motor design using a linear array of microcoils. Microcoils are arranged in a 3-phase configuration to enable both velocity and direction control. The electromagnetic force is characterized by finite element computer simulations to develop the input signal for translational travel at constant velocity. Optical position detection was used to measure the translation with time. Operation was demonstrated at various drive frequencies.
We describe the development and performance of microchips that interface capillary electrophoresis (CE) with matrix-assisted laser desorption/ionization (MALDI) mass spectrometry. The chip contains an open channel where CE is performed. The open channel functions as the CE column and is used to separate the mixture. Once separation occurs, the solvent is evaporated and the chip placed in the ionization source of a Fourier transform mass spectrometer. To perform the MALDI, a buffer will be used in the CE that will also function as matrix once the solvent is evaporated. Preliminary results will be described showing: (1) the design and construction of a new ionization source for an external source FTMS that will handle the microchip, (2) the feasibility of the CE on an open channel and (3) the feasibility of MALDI on an open channel. Two chips made of glass with groves cut on the surface have been fabricated for these experiments. The rates of evaporation of different solvent mixtures indicate that evaporation will not be a problem during the CE analysis. The rates of evaporation are considerably slower than the speed of the separation. To determine the feasibility of CE, a colored dye was placed on a 2 cm long column and high voltages attached to the two ends. Movement of a colored dye on the chip was observed under an electric field correspond to about 500 V/cm. This experiment indicates that CE can be performed on an open channel. The first experiments with MALDI of biomolecules, in this case oligosaccharides have been performed. (beta) -Cyclodextrin, a seven-membered cyclic oligosaccharide, was mixed with 3,5-dihydroxybenzoic acid (matrix) on an open channel. Striking the grove with a 337 nm beam from a N2 laser produces the mass spectrum of the compound with excellent resolution and high signal-to-noise.
At this early phase in the development of microfabricated fluidic systems, only a few components or functions have been microfabricated. Some sort of interface to the remaining 'off chip' components is required. For example, a variety of analysis techniques have been demonstrated in microfabricated channels, and cells, but sample preparation is to date still mostly performed off chip, involving pipetting, tubing and titer plate interfacing. The transition from micro to macro components has been to date rather crude, consisting mostly of tubing glued into or over holes etched into silicon or glass substrates. This paper presents new, micromachinable, joining and interconnecting structures that enable the modular, plug-in assembly of fluidic components to one another, to tubing, and into a fluid channel breadboard. Micro-to-miniature interfacing elements for making connections between microchannels and standard tubing, and both horizontal and vertical channel- to-channel interconnects will be demonstrated. Excellent seals are created using photopatternable silicone O-rings that are held in compression by the connecting structure. This technology allows one to assemble a fluidic microsystem with both custom and off the shelf, micro or miniature components. The connections are all reversible, making the system design reconfigurable and components easily exchanged.
A new technology for the fabrication of optical microcomponents is presented. This technology combines a number of standard and new techniques to produce microstructures based scaled down versions of macro joints such as dovetail, dado, etc. and has been coined MicroJoinery. This technique along with the collected 'toolbox' of associated technologies is presented through the fabrication and characterization of two fundamental optical components: and xyz positioning microstages and a 1 x fiber optic switch. Other microstructures and components which demonstrate MicroJoinery are also presented.
A micromachined optical 'trap' to capture and move micron sized dielectric particles is presented. The trap consists of four single mode optical fibers mutually aligned to have a common optical beam intersection at the center of a micromachined housing. The intersection of the beams forms an optical 'cross-hair' which captures dielectric microparticles with a strong optical gradient force field, and holds them for further manipulation, visualization, and/or analysis. The stability and magnitude of the trapping force fields are comparable to the single beam 'optical tweezers' technique, but are considerably more versatile.
This paper presents a new method for obtaining highly efficient electrochemiluminescence (ECL) of tris(2,2'- bipyridine) ruthenium (TBR) in aqueous solutions and a biosensor which utilizes this method. An interdigitated, microelectrode array is employed with electrode widths and spacings of 5 micrometer. The microelectrode is supported on a silicon nitride coated silicon substrate and occupies 1 mm2. Each microelectrode is 1 mm long and 5 microns wide. The diffusion enhancement produced by the microelectrode geometry, the small electrode spacing and the electrode material are all critical parameters for high ECL efficiency. ECL has been detected from TBR concentrations as low as 1 (mu) M, using a silicon PIN photodiode detector at room temperature. For biosensing applications, TBR is attached to the molecule of interest and ECL is then generated at the electrode surfaces. Cell configuration and the results of preliminary studies of the detection of TBR labeled DNA, attached to paramagnetic beads are presented.
The fabrication and characterization of a microfabricated, fexural plate, acoustic wave delay line is presented for use in the physical translation of fluids and/or biological cells. The device consists of dual interdigitated transducers patterned on a thin film composite membrane of silicon nitride, platinum, and sol gel derived piezoelectric ceramic (PZT). The acoustic properties of the device are presented along with preliminary applications to mechanical transport and liquid delivery systems. Improved acoustic signals and improved mass transport are achieved with PZT over present fexural plate wave devices employing ZnO as the piezoelectric material.
A high sensitivity, batch fabricated, micromachined pressure sensor with interferometric readout is described. The transducer consists of a fiber V-groove, a 45 degree(s) stationary mirror and a silicon membrane, which are micromachined in two separate silicon wafers by anisotropic etching in KOH solution. The 45 degree(s) mirror provides a means of directing the light to and from the membrane with a horizontally mounted fiber, which is compatible with etched V-groove fiber alignment and positioning. A Fabry-Perot optical cavity is formed between the end of the fiber and the silicon membrane. The generated optical interference fringes are used to detect and measure the change in membrane deflection. The pressure range of operation and sensitivity are dictated by the thickness, size and material of the membrane and the wavelength of the light source. The sensor described here is designed for implantation in living bone tissue for the detection of necrosis. The ultimate, minimum size for this sensor is dictated by the diameter of one, single mode fiber, e.g. 125 microns.
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