Abstract: An analysis device comprises a body having a reaction chamber for chemically reacting a sample, a separation region for separating components of the sample, and a transition region connecting the reaction chamber to the separation region. The transition region includes at least one valve for controlling the flow of fluid between the reaction chamber and the separation region. Further, the transition region thermally isolates the reaction chamber from the separation region. In a preferred embodiment, the reaction chamber is an amplification chamber for amplifying nucleic acid in the sample, and the separation region comprises an electrophoresis channel containing a suitable matrix material, such as electrophoresis gel or buffer, for separating nucleic acid fragments. Electrodes are embedded in the body for separation of sample components. The body may also be surrounded by external, functional components such as an optical detector for detecting separated components of the sample.

Abstract: The present invention provides a cartridge for analyzing a fluid sample. The cartridge provides for the efficient separation of cells or viruses in the sample from the remaining sample fluid, lysis of the cells or viruses to release the analyte (e.g., nucleic acid) therefrom, and optionally chemical reaction and/or detection of the analyte. The cartridge is useful in a variety of diagnostic, life science research, environmental, or forensic applications for determining the presence or absence of one or more analytes in a sample.

Abstract: A microfabricated biopsy/histology instrument which has several advantages over the conventional procedures, including minimal specimen handling, smooth cutting edges with atomic sharpness capable of slicing very thin specimens (approximately 2 &mgr;m or greater), micro-liter volumes of chemicals for treating the specimens, low cost, disposable, fabrication process which renders sterile parts, and ease of use. The cutter is a “cheese-grater” style design comprising a block or substrate of silicon and which uses anisotropic etching of the silicon to form extremely sharp and precise cutting edges. As a specimen is cut, it passes through the silicon cutter and lies flat on a piece of glass which is bonded to the cutter. Microchannels are etched into the glass or silicon substrates for delivering small volumes of chemicals for treating the specimen. After treatment, the specimens can be examined through the glass substrate.

Abstract: A method for separating a desired analyte from a fluid sample comprises the steps of introducing the sample into a cartridge having a sample flow path and a lysing chamber in the sample flow path. The lysing chamber contains at least one filter for separating cells or viruses from the sample. The sample is forced to flow through the sample flow path, thereby capturing the cells or viruses with the filter as the sample flows through the chamber. The ratio of the volume of sample forced to flow through the chamber to the volume capacity of the chamber is preferably at least 2:1, and the volume of sample forced to flow through the chamber is preferably at least 100 microliters. The captured cells or viruses are disrupted to release the analyte therefrom, and the analyte is eluted from the chamber.

Abstract: Microfabricated therapeutic actuators are fabricated using a shape memory polymer (SMP), a polyurethane-based material that undergoes a phase transformation at a specified temperature (Tg). At a temperature above temperature Tg material is soft and can be easily reshaped into another configuration. As the temperature is lowered below temperature Tg the new shape is fixed and locked in as long as the material stays below temperature Tg. Upon reheating the material to a temperature above Tg, the material will return to its original shape. By the use of such SMP material, SMP microtubing can be used as a release actuator for the delivery of embolic coils through catheters into aneurysms, for example. The microtubing can be manufactured in various sizes and the phase change temperature Tg is determinate for an intended temperature target and intended use.

Abstract: Fabrication and use of porous silicon structures to increase surface area of heated reaction chambers, electrophoresis devices, and thermopneumatic sensor-actuators, chemical preconcentrates, and filtering or control flow devices. In particular, such high surface area or specific pore size porous silicon structures will be useful in significantly augmenting the adsorption, vaporization, desorption, condensation and flow of liquids and gasses in applications that use such processes on a miniature scale. Examples that will benefit from a high surface area, porous silicon structure include sample preconcentrators that are designed to adsorb and subsequently desorb specific chemical species from a sample background; chemical reaction chambers with enhanced surface reaction rates; and sensor-actuator chamber devices with increased pressure for thermopneumatic actuation of integrated membranes.

Abstract: A microfabricated biopsy/histology instrument which has several advantages over the conventional procedures, including minimal specimen handling, smooth cutting edges with atomic sharpness capable of slicing very thin specimens (approximately 2 .mu.m or greater), micro-liter volumes of chemicals for treating the specimens, low cost, disposable, fabrication process which renders sterile parts, and ease of use. The cutter is a "cheese-grater" style design comprising a block or substrate of silicon and which uses anisotropic etching of the silicon to form extremely sharp and precise cutting edges. As a specimen is cut, it passes through the silicon cutter and lies flat on a piece of glass which is bonded to the cutter. Microchannels are etched into the glass or silicon substrates for delivering small volumes of chemicals for treating the specimen. After treatment, the specimens can be examined through the glass substrate. For automation purposes, microvalves and micropumps may be incorporated.

Abstract: A micromachined electrical cauterizer. Microstructures are combined with microelectrodes for highly localized electro cauterization. Using boron etch stops and surface micromachining, microneedles with very smooth surfaces are made. Micromachining also allows for precision placement of electrodes by photolithography with micron sized gaps to allow for concentrated electric fields. A microcauterizer is fabricated by bulk etching silicon to form knife edges, then parallelly placed microelectrodes with gaps as small as 5 .mu.m are patterned and aligned adjacent the knife edges to provide homeostasis while cutting tissue. While most of the microelectrode lines are electrically insulated from the atmosphere by depositing and patterning silicon dioxide on the electric feedthrough portions, a window is opened in the silicon dioxide to expose the parallel microelectrode portion. This helps reduce power loss and assist in focusing the power locally for more efficient and safer procedures.

Abstract: Devices for performing tissue biopsy on a small scale (microbiopsy). By reducing the size of the biopsy tool and removing only a small amount of tissue or other material in a minimally invasive manner, the risks, costs, injury and patient discomfort associated with traditional biopsy procedures can be reduced. By using micromachining and precision machining capabilities, it is possible to fabricate small biopsy/cutting devices from silicon. These devices can be used in one of four ways 1) intravascularly, 2) extravascularly, 3) by vessel puncture, and 4) externally. Additionally, the devices may be used in precision surgical cutting.

Abstract: Microfabricated therapeutic actuators are fabricated using a shape memory polymer (SMP), a polyurethane-based material that undergoes a phase transformation at a specified temperature (Tg). At a temperature above temperature Tg material is soft and can be easily reshaped into another configuration. As the temperature is lowered below temperature Tg the new shape is fixed and locked in as long as the material stays below temperature Tg. Upon reheating the material to a temperature above Tg, the material will return to its original shape. By the use of such SMP material, SMP microtubing can be used as a release actuator for the delivery of embolic coils through catheters into aneurysms, for example. The microtubing can be manufactured in various sizes and the phase change temperature Tg is determinate for an intended temperature target and intended use.

Abstract: Fabrication and use of porous silicon structures to increase surface area of heated reaction chambers, electrophoresis devices, and thermopneumatic sensor-actuators, chemical preconcentrates, and filtering or control flow devices. In particular, such high surface area or specific pore size porous silicon structures will be useful in significantly augmenting the adsorption, vaporization, desorption, condensation and flow of liquids and gasses in applications that use such processes on a miniature scale. Examples that will benefit from a high surface area, porous silicon structure include sample preconcentrators that are designed to adsorb and subsequently desorb specific chemical species from a sample background; chemical reaction chambers with enhanced surface reaction rates; and sensor-actuator chamber devices with increased pressure for thermopneumatic actuation of integrated membranes.

Abstract: Micromachined thin film cantilever actuators having means for individually controlling the deflection of the cantilevers, valve members, and rudders for steering same through blood vessels, or positioning same within a blood vessel, for example. Such cantilever actuators include tactile sensor arrays mounted on a catheter or guide wire tip for navigation and tissues identification, shape-memory alloy film based catheter/guide wire steering mechanisms, and rudder-based steering devices that allow the selective actuation of rudders that use the flowing blood itself to help direct the catheter direction through the blood vessel. While particularly adapted for medical applications, these cantilever actuators can be used for steering through piping and tubing systems.

Abstract: Micromachined thin film cantilever actuators having means for individually controlling the deflection of the cantilevers, valve members, and rudders for steering same through blood vessels, or positioning same within a blood vessel, for example. Such cantilever actuators include tactile sensor arrays mounted on a catheter or guide wire tip for navigation and tissues identification, shape-memory alloy film based catheter/guide wire steering mechanisms, and rudder-based steering devices that allow the selective actuation of rudders that use the flowing blood itself to help direct the catheter direction through the blood vessel. While particularly adapted for medical applications, these cantilever actuators can be used for steering through piping and tubing systems.

Abstract: An integrated microfabricated instrument for manipulation, reaction and detection of microliter to picoliter samples. The instrument is suited for biochemical reactions, particularly DNA-based reactions such as the polymerase chain reaction, that require thermal cycling since the inherently small size of the instrument facilitates rapid cycle times. The integrated nature of the instrument provides accurate, contamination-free processing. The instrument may include reagent reservoirs, agitators and mixers, heaters, pumps, and optical or electromechanical sensors. Ultrasonic Lamb-wave devices may be used as sensors, pumps and agitators.

Abstract: A mold assembly with micro-sized features in which the hollow portion thereof is fabricated from a sacrificial mandrel which is surface treated and then coated to form an outer shell. The sacrificial mandrel is then selectively etched away leaving the outer shell as the final product. The sacrificial mandrel is fabricated by a precision lathe, for example, so that when removed by etching the inner or hollow area has diameters as small as 10's of micros (.mu.m). Varying the inside diameter contours of the mold can be accomplished with specified ramping slopes formed on the outer surface of the sacrificial mandrel, with the inside or hollow section being, for example, 275 .mu.m in length up to 150 .mu.m in diameter within a 6 mm outside diameter (o.d.) mold assembly. The mold assembly itself can serve as a micronozzle or microneedle, and plastic parts, such as microballoons for angioplasty, polymer microparts, and microactuators, etc., may be formed within the mold assembly.

Abstract: An integrated microfabricated instrument for manipulation, reaction and detection of microliter to picoliter samples. The instrument is suited for biochemical reactions, particularly DNA-based reactions such as the polymerase chain reaction, that require thermal cycling since the inherently small size of the instrument facilitates rapid cycle times. The integrated nature of the instrument provides accurate, contamination-free processing. The instrument may include reagent reservoirs, agitators and mixers, heaters, pumps, and optical or electromechanical sensors. Ultrasonic Lamb-wave devices may be used as sensors, pumps and agitators.

Abstract: An integrated microfabricated instrument for manipulation, reaction and detection of microliter to picoliter samples. The instrument is suited for biochemical reactions, particularly DNA-based reactions such as the polymerase chain reaction, that require thermal cycling since the inherently small size of the instrument facilitates rapid cycle times. The integrated nature of the instrument provides accurate, contamination-free processing. The instrument may include reagent reservoirs, agitators and mixers, heaters, pumps, and optical or electromechanical sensors. Ultrasonic Lamb-wave devices may be used as sensors, pumps and agitators.

Abstract: A silicon-based sleeve type chemical reaction chamber that combines heaters, such as doped polysilicon for heating, and bulk silicon for convection cooling. The reaction chamber combines a critical ratio of silicon and silicon nitride to the volume of material to be heated (e.g., a liquid) in order to provide uniform heating, yet low power requirements. The reaction chamber will also allow the introduction of a secondary tube (e.g., plastic) into the reaction sleeve that contains the reaction mixture thereby alleviating any potential materials incompatibility issues. The reaction chamber may be utilized in any chemical reaction system for synthesis or processing of organic, inorganic, or biochemical reactions, such as the polymerase chain reaction (PCR) and/or other DNA reactions, such as the ligase chain reaction, which are examples of a synthetic, thermal-cycling-based reaction. The reaction chamber may also be used in synthesis instruments, particularly those for DNA amplification and synthesis.

Abstract: The liquid of a flow cytometer itself acts as an optical waveguide, thus transmitting the light to an optical filter/detector combination. This alternative apparatus and method for detecting scattered light in a flow cytometer is provided by a device which views and detects the light trapped within the optical waveguide formed by the flow stream. A fiber optic or other light collecting device is positioned within the flow stream. This provides enormous advantages over the standard light collection technique which uses a microscope objective. The signal-to-noise ratio is greatly increased over that for right-angle-scattered light collected by a microscope objective, and the alignment requirements are simplified.

Abstract: A process is provided for forming a long-lasting, stable, pH-sensitive dye-acrylamide copolymer useful as a pH-sensitive material for use in an optrode or other device sensitive to pH. An optrode may be made by mechanically attaching the copolymer to a sensing device such as an optical fiber.