Bio-Micro Electro Mechanical System (Bio-MEMS) technology was applied to the problem of early breast cancer detection and diagnosis. A micro-device is being developed to identify and specifically collect tumor cells of low abundance (1 tumor cell among 107 normal blood cells) from circulating whole blood. By immobilizing anti-EpCAM (Epithelial Cell Adhesion Molecule) antibodies on polymer micro-channel walls by chemically modifying the surface of the PMMA, breast cancer cells from the MCF-7 cell line, which over-express EpCAM, were selected from a sample volume by the strong binding affinity between the antibody and antigen. To validate the capture of the breast cancer cells, three fluorochrome markers, each identified by a separate color, were used to reliably identify the cancer cells. The cancer cells were defined by DAPI+ (blue), CD45- and the FITC-cell membrane linker+ (green). White blood cells, which may interfere in the detection of the cancer cells, were identified by DAPI+ (blue), CD45+ (red), and the FITC-cell membrane linker+ (green). EpCAM/anti-EpCAM binding models from the literature were used to estimate an optimal velocity, 2mm/sec, for maximizing the number of cells binding and the critical binding force. At higher velocities, shear forces (> 0.48 dyne) will break existing bonds and prevent the formation of new ones. This detection micro-device can be assembled with other lab-on-a-chip components for follow-up gene and protein analysis.
Passive (diffusional) mixing has been used in designing high-aspect-ratio micro-mixers for the purpose of performing Liagase Detection Reaction (LDR). The types of mixers considered are simple, cheap, and durable and can perform over a broad range of volumetric flow rates at reasonably modest pressure drops. The fluids to be mixed have a very low typical diffusion coefficient of=1.2x10-10m2/s and diffusional mixing is only effective in high-aspect-ratio micro-channels. A very modestly high aspect ratio of 6 has been considered initially because it is easily releasable using the LIGA technique. Numerical simulations of a few basic diffusional mixer configurations are going to be presented in this paper. Two variants of a Y-type mixer with contraction and several variants of a mixer employing jets in cross-flow have been simulated. The various mixers have been evaluated in terms of volumetric mixing efficiencies and maximum pressure drops. One of the mixers with jets-in-cross-flow was found to perform best.
The objective was to design and manufacture a microscale Ligase Detection Reaction (LDR) device for detection of cancer-associated rare gene mutations. The LDR module will be incorporated with other devices such as a Continuous Flow Polymerase Chain Reaction (CFRCR) unit and a Capillary Electrophoresis (CE) chip in a modular lab-on-a-chip technology. During LDR, devloped by Francis Barany, several primers are mixed with the analyte, exposed to a thermal cycle consisting of two steps of 95°C and 65°C for 20 cycles, and cooled to 0°C. The first step in the design was to determine if the baseline time for the LDR reaction could be reduced from the 2½ hours required for the orignal reaction. Experiments have shown that it is posssible to obtain useable product from the LDR after 40 minutes, a 75% reduction, before going to the microscale, which should allow further improvements. Due to the extensive mixing needed prior to the reaction a set of alternative diffusion mixers was identified and microfabricated to determine which geometry was the most effective. Simulations of the thermal response of the device were done using finite element analysis (FEA) to compare to experimental results. The required temperature profile will be obtained by using resistive heaters and thermoelectric modules. A prototype LDR device was laid out based on the results of the studies.
Two types of Microfluidic bioanalytical systems were designed and fabricated in polymer substrates using the LIGA process. A continuous flow polymerase chain reaction (CFPCR) Microfluidic device was fabricated in polycarbonate (PC), which utilized isothermal zone and shuttling the sample through each zone to achieve amplification. A 20-cycle PCR amplification of a fragment of a plasmid DNA template was achieved in 5.3 min. The results were comparable to those obtained in commercial laboratory-scale PCR system. The second system consisted of a microchip contating a low-density array assembled into the Microfluidic channel, which was hot-embossed in poly(methyl methacrylate) (PMMA). The detection of low-abundant mutations in gene fragments (K-ras) that carry point mutations with high diagnostic value for colorectal cancer was successfully performed. The array accessed microfluidics in order to enhance the kinetic associated with hybridization.
A continuous flow polymerase chain reaction (CFPCR) system was designed, fabricated from molded polycarbonate, and tested. Finite element modeling was used to simulate the thermal and Microfluidic response of the system. The mold insert for the initial prototypes was fabricated using the X-ray LIGA microfabrication process and device components produced by hot embossing polycarbonate. Commercial thin film heaters under PID control were used to supply the necessary heat flux to maintain the steady-state temperatures in the PCR.
The simulated transient temperature response at start up was compared to the experimental response. The simulated steady state temperature profile along the channel generated by the finite element analysis was compared to the experimental temperature profile displayed by liquid crystals. Experimental and simulated results were within 5% of each other, validating the thermal design of the CFPCR device.
The objective of this work was to develop a thermally-driven bimetallic actuator for application in high temperature environments. The actuator was designed to drive distributed air flow control valves in a gas turbine combustor. The valves control localized cooling air flows in response to rises in temperature, leading to more uniform and complete combustion. The actuator is a passive thermo-mechanical device formed from bimorph elements concatenated in a recurve architecture to obtain the required forces and deflections. An electroplating process for depositing an Invar-like alloy in deep recess was developed and used in the fabrication of prototypes. Fabrication of additional protypes and testing are continuing.
Furl injector nozzles fabricate with micrometer-scale swirler channels are being fabricated using a combination of micro-fabrication and precision machining. Arrays of fuel injector nozzles are an integral component of the Trapped- Vortex (TV) gas turbine combustor for use in advanced aircraft engines. The principle of TV is to improve flame stabilization through interaction between the main and secondary combustion processes. The fabrication of an array of fuel injectors requires nickel microstructures to be electro deposited on both sides of a nickel substrate in order to segregate the inlet air and fuel flows. The microstructures assist in the atomization of the fuel and induce swirl in the fluids. For each injector, a micrometer- scale cone drilled through the plate facilitates mixing of swirling fuel and air. The mixture is then injected into the secondary combustion chamber with a low-pressure air supply, which is required in order to obtain stoichiometric conditions. The prototype fuel injectors are composed of four individual plates. Two plates seal the air and fuel channels. Another plate contains the micro fabricated swirlers. The fourth plate is used to define the low- pressure air reservoir. The plates were mechanically fastened together using alignment pins for accurate plate positioning. Precision machining was used to position and drill the holes required for alignment, fluid flow, and connectors.
This paper reports on a research effort to design, microfabricate and test an AC-type magnetohydrodynamic (MHD) micropump using UV-LIGA microfabrication. The micropump is driven using the Lorentz force and can be used to deliver electrically conductive fluids. In the AC-type MHD micropump developed in our laboratory, a diffuser/nozzle is integrated with a MHD driving chamber. With a magnetic field supplied by an external permanent magnet, and an AC electrical current supplied across two copper side-walls, the distributed body force generated will produce a pressure difference on the fluid in the pumping chamber. The directional dependence of the flow resistance of the diffuser/nozzle allows for a net output flow in response to the oscillating pressure generated by the sinusoidal current. The major advantage of a MHD-based micropump is that it does not contain any moving parts. It may have potential applications in medicine delivery, and biological or biomedical studies. An AC-driven micropump may be used to improve on the performance obtained in tests of a DC-driven prototype micropump, that showed pumping performance was significantly degraded by bubble generation.
Masks made from graphite stock material have been demonstrated as a cost-effective and reliable method of fabricating X-ray masks for deep and ultra-deep x-ray lithography (DXRL and UDXRL, respectively). The focus on this research effort was to fabricate masks that were compatible with the requirements for deep and ultra deep X-ray lithography by using UV optical lithography and gold electroforming. The major focus was on the uniform application of a thick resist on a porous graphite substrate. After patterning the resist, gold deposition was performed to build up the absorber structures using pulsed- electroplating. In this paper we will report on the current status of the mask fabrication process and present some preliminary exposure results.
This paper reports a research effort to microfabricate a nozzle-diffuser type of micropumps based on the magnetohydrodynamic (MHD) principle using LIGA technologies. The micropump is driven using the Lorentz force and can be used to deliver electrically conductive fluids. The major advantage of a MHD-based micropump is that it does not contain any moving parts. It may have potential applications in medicine delivery, biological and biomedical studies. Prototypes of MHD micropumps have been fabricated and tested. Significant bubble generation was observed due to electrolysis effect. These bubbles made the flow two-phase one and resulted in flow rate reduction. To overcome bubble generation, a new generation of MHD micropumps is currently under development. This new, diffuser/nozzle type of the MHD micropumps is based on the similar design as widely used in the diffuser/nozzle pumps with diaphragm.
KEYWORDS: Cartilage, Surgery, Ultrasonography, Instrument modeling, Curium, Actuators, In vivo imaging, Microfabrication, Transducers, Systems modeling
An instrument to estimate the dynamic properties of articular cartilage in vivo is proposed. Through the use of a mechanical indenter adapted from in vitro testing methods and an ultrasound data acquisition system, a time constant for articular cartilage can be obtained. Dynamic lumped parameter models of articular cartilage and the instrument were developed using bond graph techniques for evaluating the feasibility of microfabricating the tool. Simulation results showed that a characteristic time constant for cartilage reswelling could be measured using the probe. Measurement protocols were designed to isolate fluid resistance and cartilage stiffness. Scaling the size of the instrument down lowered the amplitude of the forces required to indent the cartilage and reduced the length of the time the surgeon would need to hold the instrument in a single position in order to perform a test.
This paper reports a lumped-parameter mathematical model for a magnetohydrodynamic (MHD) micropump being developed by the authors. The micropump can be used to deliver electrically conductive fluids. The major advantage of a MHD based micropump is that it does not contain any moving parts. It may have potential applications in medicine delivery, biological and biomedical studies. To develop a design guideline for the MHD micropump, it is desired that the dynamic behavior of the flow in a microsystem driven with MHD body force. A bond graph model has been developed for the MHD micropump. A commercial software, 20 SIM, was used as the simulation tools. The simulation results for two different sizes of micropumps with a 1 percent salt-water solution used as a pumping fluid are presented in the paper.
This paper reports a microfabricated array of probes suitable for highly localized temperature manipulation (cooling or heating) or temperature manipulation of micro- sized subject. These microprobes were fabricated with `LIGA' (German acronym for Lithographie, Galvanoformung, Abformung) process--one of the MEMS (microelectromechanical systems) technologies. The LIGA technology is based on X-ray lithography and electroplating and suitable for making high- aspect-ratio metal or alloy structures with aspect-ratio up to 100 times. The array of microprobes with a height of 1000 m was fabricated on the top surface of a conventional electronic cooling device based on Peltier effect. Electrical current supplied to the cooling chip causes a cooling effect and thermal conduct effect of the microprobes carries the heat from the sample subject to be cooled to the cooling chip surface. A one-stage semiconductor-cooling device with a maximum temperature difference of 20 degree(s)C was used. It was found that the maximum temperature difference that could be achieved was very close to the temperature at the surface of the electronic device and the difference is small.
High aspect-ratio microposts of bismuth-telluride alloy with a height of up to 750 micrometer and a diameter of 150 micrometer have been fabricated with the LIGA technique. This work is the part of an on-going research effort to develop a microprobe based on Peltier effect for highly localized temperature manipulation on the microscale. Bismuth-telluride alloys were electrodeposited galvanostatically on a titanium substrate using an acidic solution containing Bi3+ and HTeO2- ions in 1 mol dm-3 nitric acid (pH equals 0). The Bi-Te alloy microposts were found to be monophasic, exhibit a polycrystalline structure, demonstrate excellent adhesion on the substrate and with good mechanical strength. The chemical composition of the microposts was dependent on the electrolyte composition of deposition bath and the current density used in the electroplating; by controlling these two factors either p- or n-type Bi-Te alloy microposts may be produced. This research demonstrates that the microfabrication of Peltier effect probes is feasible.
A LIGA based tool-set of tips for various scanning probe applications is under investigation by the LSU (mu) SET. This involves fabrication of `micro-columns' using LIGA, followed by an electrochemical sharpening process. Micro-columns ranging from 1.8 micrometers diameter and 14 micrometers tall to 165 micrometers X 165 micrometers and 1000 micrometers tall have been fabricated. In order to understand the sharpening mechanism, commercially available wires with diameters ranging from 25 - 800 micrometers were sharpened. A computer aided design tool, based on deforming finite elements, was developed to simulate the sharpening process.
The reliable, high resolution concentration measurement of carbon dioxide is of critical importance in several life sciences and advanced life support related applications ranging from cabin air quality on extended duration space flights to monitoring and controlling plant growth and efficiency in closed life support systems. The design of a LIGA (German acronym for lithography, electrodeposition and plastic molding) micromachined, integrated optical bench for a carbon dioxide concentration sensor, based on the principle of infrared absorption, is presented in this paper as a compact solution to the need for high resolution CO2 instrumentation. The micromachining approach takes advantage of the superior performance of optical infrared absorption sensing technology. In addition, creating an integral, micro- fabricated optical bench along with the source, detector and other necessary components on the same substrate will eliminate the size and alignment problems of the current designs. The design of the CO2 sensor uses a folded optical system consisting of five parallel micro- mirrors placed 1.6 cm apart. A parametric evaluation of the beam divergence shows that the use of 1000 micrometers mirrors and a laser beam with a spot radius of 300 micrometers would result in a sensor design that can easily be fabricated by the LIGA process.
Biomechanical analysis of motion is based on the approximation of skeletal segments as rigid links moving through space, interconnected through a series of low-friction joints. Measurement systems that are aimed at capturing the spatial trajectories of body segments usually involve a camera system that tracks a series of body-fixed markers. Using stereophotogramxnetric cameras, the planar projections of markers at each camera are used to reconstruct the spatial coordinates of each marker. The derivation of segmental kinematics (i.e. linear translation and angular orientation) necessary to document the motion of the body segments has been done in most cases by attaching the markers to anatomic landmarks, and using geometric assumptions to characterize the spatial motion of given limbs. For example, by tagging the hip, knee and ankle statements have been made about the motion of the knee joint, and therefore the shank and thigh segments. This approach suffers from serious shortcomings, including the approximation of body segments as lines (as opposed to rigid bodies), the underlying assumption that axes of rotation remain constant throughout the motion, and that joint centers can be tagged by skin-mounted markers.
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