Abstract: A cartridge for analyzing a fluid sample has a body defining at least first and second channels and a cavity separating the channels. An end of the first channel is positioned on a first side of the cavity, and an end of the second channel is positioned on a second side of the cavity. The cavity is defined by a first curved surface positioned adjacent the end of the first channel, a second curved surface positioned adjacent the end of the second channel, and at least a third surface between the first and second curved surfaces. The cartridge also comprises an elastic membrane for establishing a seal with the first and second curved surfaces to prevent the flow of fluid between the channels. The third surface is recessed from the first and second surfaces to provide a gap between the membrane and the third surface when the membrane is pressed against the first and second surfaces. A cartridge having a conical valve seat is also disclosed.

Abstract: A device for separating an analyte from a fluid sample comprises a cartridge incorporating a flow-through microfluidic chip. The microfluidic chip includes an extraction chamber having an array of microstructures for capturing the analyte and for subsequently releasing the captured analyte into an elution fluid. Each of the microstructures has an aspect ratio of at least 2:1. The cartridge also includes channels and at least one low controller (e.g., one or more valves) for directing the flow of the sample and elution fluid through the microfluidic chip. The cartridge may optionally include a lysing region for lysing sample components (e.g., cells spores, or microorganisms), a waste chamber for storing waste fluid, and reaction or detection chambers for amplifying or detecting the analyte.

Abstract: The present invention provides an apparatus for performing heat-exchanging chemical reactions, such as nucleic acid amplification. The apparatus includes a reaction vessel having a chamber for holding a sample for chemical reaction and optical detection. The vessel has a rigid frame defining the side walls of the chamber, and flexible sheets attached to opposite sides of the frame to form opposing major walls of the chamber. The frame further includes a port and a channel connecting the port to the chamber. The temperature of the sample is controlled by opposing plates positioned to receive the chamber of the vessel between them. The apparatus also includes a plunger which is inserted into the channel of the vessel to seal the port and increase pressure in the chamber. The increased pressure forces the flexible major walls of the chamber to contact and conform to the surfaces of the plates, thus ensuring optimal thermal conductance between the plates and the chamber.

Abstract: A reaction vessel having a reaction chamber for holding a sample is fabricated by producing a housing having a rigid frame defining the minor walls of the chamber. The housing also defines a port for introducing fluid into the chamber. At least one sheet or film is attached to the rigid frame to form at least one major wall of the chamber. In preferred embodiments, two sheets or films are attached to opposite sides of the rigid frame to form two opposing major walls of the chamber, the major walls being connected to each other by the minor walls.

Abstract: A fluid control and processing system for controlling fluid flow among a plurality of chambers comprises a body including a fluid processing region continuously coupled fluidicly with a fluid displacement region. The fluid displacement region is depressurizable to draw fluid into the fluid displacement region and pressurizable to expel fluid from the fluid displacement region. The body includes at least one external port. The fluid processing region is fluidicly coupled with the at least one external port. The fluid displacement region is fluidicly coupled with at least one external port of the body. The body is adjustable with respect to the plurality of chambers to place the at least one external port selectively in fluidic communication with the plurality of chambers.

Abstract: This invention provides an apparatus for rapidly heating and/or cooling a sample in a reaction vessel. In some embodiments, the apparatus includes optics for the efficient detection of a reaction product in the vessel. The invention also provides a reaction vessel having a reaction chamber designed for optimal thermal conductance and for efficient optical viewing of reaction products in the chamber.

Abstract: The present invention provides a reaction vessel and apparatus for performing heat-exchanging reactions. The vessel has a chamber for holding a sample, the chamber being defined by a plurality of walls, at least two of the walls being light transmissive to provide optical windows to the chamber. The apparatus comprises at least one heating surface for contacting at least one of the plurality of walls, a heat source for heating the surface, and optics positioned to optically interrogate the chamber while the heating surface is in contact with at least one of the plurality of walls. The optics include at least one light source for transmitting light to the chamber through a first one of the light transmissive walls and at least one detector for detecting light exiting the chamber through a second one of the light transmissive walls.

Abstract: A container for holding cells or viruses for disruption comprises a chamber defined by two spaced apart, opposing major walls and side walls connecting the major walls to each other. At least one of the major walls has an external surface to which the transducer may be coupled and is sufficiently flexible to flex in response to vibratory motion of the transducer. The container also has at least one port for introducing the cells or viruses into the chamber. In some embodiments, the chamber contains beads for aiding the disruption of the cells or viruses.

Abstract: A reaction vessel has a reaction chamber, a loading reservoir connected to the reaction chamber via a first channel, and an aspiration port connected to the chamber via a second channel. To load the sample into the reaction chamber, the sample is dispensed into the loading reservoir and then drawn into the chamber by application of a vacuum to the aspiration port. A system for controlling the temperature of the sample in the reaction vessel includes one or more thermal elements for heating or cooling the sample and optionally optics for detecting one or more analytes in the 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: The present invention provides an apparatus and method for disrupting cells or viruses to release the nucleic acid therefrom. The apparatus includes a container having a chamber for holding the cells or viruses. The apparatus also includes an ultrasonic transducer for contacting a wall of the chamber and for transmitting ultrasonic energy into the chamber through the wall. A support structure holds the container and the transducer against each other such that the transducer contacts the wall of the chamber. The support structure includes an elastic body, such as a spring, for applying to the container or to the transducer a substantially constant force to press together the transducer and the wall. The chamber also preferably contains beads for enhancing the disruption of the cells or viruses. The apparatus performs rapid and consistent lysis of cells or viruses, often in as little time as 5 to 10 seconds.

Abstract: The invention provides a reaction vessel and temperature control system for performing heat-exchanging chemical reactions, such as nucleic acid amplification. The vessel has a body defining a reaction chamber, and a loading structure extending from the body for loading a sample into the chamber. The loading structure has a loading reservoir, an aspiration port, and respective fluid channels connecting the loading reservoir and aspiration port to the chamber. To load the sample into the vessel, the sample is first dispensed into the loading reservoir and then drawn into the chamber by application of a vacuum to the aspiration port. The vessel also includes a seal aperture extending over the outer ends of the loading reservoir and aspiration port. A plug is inserted into the aperture after loading the sample into the chamber to simultaneously seal the chamber, loading reservoir, and aspiration port from the external environment.

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: 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: 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.