Abstract: The invention provides a device and method for the manipulation of materials (e.g., particles, cells, macromolecules, such as proteins, nucleic acids or other moieties) in a fluid sample. The device comprises a substrate having a plurality of microstructures and an insulator film on the structures. Application of a voltage to the structures induces separation of materials in the sample. The device and method are useful for a wide variety of applications such as dielectrophoresis (DEP) or the separation of a target material from other material in a fluid sample.

Abstract: A cartridge (101) for separating a desired analyte from a fluid sample includes a sample port (103) and a sample flow path extending from the port through the body of the cartridge. The sample flow path includes at least one flow-through component (122), e.g., filter paper or a microfabricated chip, for capturing the desired analyte from the sample as the sample flows through the cartridge. The cartridge also includes an elution flow path for carrying elution fluid through the component (122) to release captured analyte from the component into the elution fluid. The elution flow path diverges from the sample flow path after passing through the component (122). Flow controllers (41A) and (41B) direct the remaining fluid sample into a waste chamber (139) after the sample flows through the component (122) and direct the elution fluid and eluted analyte into a reagent chamber (141) and reaction chamber (143).

Abstract: An apparatus for thermally controlling and optically interrogating a reaction mixture includes a vessel [2] having a chamber [10] for holding the mixture. The apparatus also includes a heat-exchanging module [37] having a pair of opposing thermal plates [34A, 34B] for receiving the vessel [2] between them and for heating/and or cooling the mixture contained in the vessel. The module [37] also includes optical excitation and detection assemblies [46,48] positioned to optically interrogate the mixture. The excitation assembly [46] includes multiple light sources [100] and a set of filters for sequentially illuminating labeled analytes in the mixture with excitation beams in multiple excitation wavelength ranges. The detection assembly [48] includes multiple detectors [102] and a second set of filters for detecting light emitted from the chamber [10] in multiple emission wavelength ranges.

Abstract: A cartridge for separating a desired analyte from a fluid sample has a sample flow path and a lysing chamber in the sample flow path. The lysing chamber contains at least one filter for capturing cells or viruses from the sample as the sample flows through the lysing chamber. Beads are also disposed in the lysing chamber for rupturing the cells or viruses to release the analyte therefrom. An analyte flow path extends from the lysing chamber and diverges from the sample flow path. The analyte flow path preferably leads to a reaction chamber for chemically reacting and optically detecting the analyte. The cartridge also includes at least one flow controller (e.g., valves) for directing the sample into the waste chamber after the sample flows through the lysing chamber and for directing the analyte separated from the sample into the analyte flow path.

Abstract: A device for separating an analyte from a fluid sample comprises a cartridge having a sample port and a first flow path extending from the sample port. A microfluidic chip is positioned in the first flow path. The microfluidic chip includes an extraction chamber having an array of microstructures for capturing the analyte from the sample as the sample flows through the extraction chamber and for subsequently releasing the captured analyte into an elution fluid as the elution fluid flows through the extraction chamber. Each of the microstructures has an aspect ratio of at least 2:1. The cartridge also includes a second flow path for eluting the captured analyte from the microfluidic chip, the second flow path diverging from the first flow path after passing through the chip. At least one flow controller directs the sample into the first flow path and the eluted analyte into the second flow path.

Abstract: A device for use with an ultrasonic transducer to lyse components of a fluid sample comprises a cartridge having a lysing chamber, an inlet port in fluid communication with the lysing chamber, and an outlet port for exit of the sample from the lysing chamber. The inlet and outlet ports are positioned to permit flow of the sample through the lysing chamber, and the chamber contains at least one solid phase for capturing the sample components to be lysed as the sample flows through the chamber. The lysing chamber is defined by at least one wall having an external surface for contacting the transducer to effect the transfer of ultrasonic energy to the chamber.

Abstract: An analyte is separated from a fluid sample by introducing the sample into a cartridge having a sample port and a first flow path extending from the sample port. The first flow path includes an extraction chamber containing a solid support for capturing the analyte from the sample. The cartridge has a second flow path for eluting the captured analyte from the extraction chamber, the second flow diverging from the first flow path after passing through the extraction chamber. The sample is forced to flow through the extraction chamber and into a waste chamber, thereby capturing the analyte with the solid support as the sample flows through the extraction chamber. The captured analyte is then eluted from the extraction chamber by forcing an elution fluid to flow through the extraction chamber and along the second flow path.

Abstract: This invention comprises an apparatus and method for the manipulation of materials, including particles, cells, macromolecules, such as proteins, nucleic acids and other moieties, in fluid samples. The apparatus comprises an enclosed chamber on a chip having an internal microstructure with surface area substantially greater than the facial surface area of the internal structure. Generally the internal microstructure comprises a continuous network of channels, each of which has a depth substantially greater than its width. The network may comprise a single channel, a single channel with multiple branches, multiple channels, multiple channels with multiple branches, and any combination thereof. The internal structure may present an inert, non-reactive surface, or be coated with a reactive ligand, or be electrically conductive and optionally be coated with an electrical insulator. Discrete portions of the internal structure may differ in structural and surface properties.

Abstract: An apparatus for thermally controlling and optically interrogating a reaction mixture includes a vessel [2] having a chamber [10] for holding the mixture. The apparatus also includes a heat-exchanging module [37] having a pair of opposing thermal plates [34A, 34B] for receiving the vessel [2] between them and for heating/and or cooling the mixture contained in the vessel. The module [37] also includes optical excitation and detection assemblies [46,48] positioned to optically interrogate the mixture. The excitation assembly [46] includes multiple light sources [100] and a set of filters for sequentially illuminating labeled analytes in the mixture with excitation beams in multiple excitation wavelength ranges. The detection assembly [48] includes multiple detectors [102] and a second set of filters for detecting light emitted from the chamber [10] in multiple emission wavelength ranges.

Abstract: A device for lysing components (e.g., cells, spores, or microorganisms) of a fluid sample comprises a cartridge having a lysing chamber for receiving the sample and having at least one solid phase in the lysing chamber for capturing the sample components to be lysed. An ultrasonic transducer is coupled to a wall of the lysing chamber to transfer ultrasonic energy to the captured sample components.

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.