Abstract: The invention provides apparatus and methods for subsecond lysis of selected cells in a cell chamber using a voltage pulse of 10 ms to 10 &mgr;s in duration followed by nearly simultaneous collection of the lysed cellular contents into a capillary electrophoresis tube or other suitable micro-collection device. Cell chambers and capillary electrophoresis tubes configured with electrodes for performing the electrical lysis are described. The influence of variables that govern the rate of cell lysis, such as inter-electrode distance, pulse duration, and pulse strength are also described. The methods are illustrated using fluorophores that are loaded into a cell then collected following electrical lysis, separated by electrophoresis, and then detected by laser-induced fluorescence detection in a capillary electrophoresis system.

Abstract: A device and method are disclosed for selective exposure of a biological sample, preferably biological cell material, to sound waves. The device is provided with a receptacle for the sample, in which the biological sample is in a suspended form, and having an electroacoustic transducer device, which generates sound waves and which is disposed outside the receptacle of the sample in such a manner that sound-wave coupling into said sample occurs through the wall of said receptacle.

Abstract: Cell lysis may be brought about by contacting a suspension of cells with a lysis reagent such as sodium hydroxide solution; subsequent treatment enables organic molecules such as plasmid DNA to be separated from other cell components. Intimate mixing of the cell suspension with lysis reagent is achieved by passage through a fluidic vortex mixer arranged so the residence time of the cell suspension in the mixer is less than the time for lysis to be completed, and may be less than 0.1 seconds. Such a vortex mixer comprises a cylindrical chamber with an axial outlet duct and at least one tangential inlet duct, but with no internal baffles. The low shear stress to which the cell suspension is subjected minimizes loss of product through denaturation or fragmentation of the product, and indeed of contaminants. The subsequent treatment may also utilize a fluidic vortex mixer.

Abstract: An apparatus including at least one sonotrode (2) designed to generate ultrasound of variable power in at least one biological sample (5) containing cells to be lysed, the sample (5) being contained in at least one receptacle (4 or 10) such that the sonotrode (2) is in direct contact with the receptacle(s) (4). Also disclosed is a method for using ultrasound to lyse a biological sample (5) contained in a receptacle (4), which includes placing the receptacle (4) in direct contact with the sonotrode (2), and activating the sonotrode (2) for long enough to lyse the cells in the sample (5) but preserve the DNA and/or RNA molecules released for subsequent operations, e.g. amplification. The invention is particularly applicable in the discipline of molecular biology.

Abstract: The invention concerns a device for lysis (1) of micro-organism to release at least one intracellular biological constituent, comprising a container (2) wherein are present a biological sample, in liquid medium, containing the micro-organism to be lyzed, and a material in the form of particles, relatively hard and inert with respect to the sample. The invention also concerns a grinding method. The material in the form of particles comprises at least two types of grinding means into different dimensions: at least large dimension magnetic means (3) automatically controlled by a magnetic field; and at least small dimension means (4) actuated by the large dimension grinding means (3). The invention is useful for separating biological constituents.

Abstract: A micromachined cell lysis device with electrodes that are spaced by less than 10 &mgr;m from one another. The cells are attracted to the space between the electrodes and then lysed.

Abstract: Proteins can be purified and concentrated from crude cell lysates using high-throughput, automated process control systems that use software application programs to instruct one or more processors, controllers, and actuators to control and/or monitor the operations of filtration, purification, and concentration modules in such systems. The high-throughput production of concentrated proteins can be enabled by filtering the lysates and using compressed, non-reactive gas to concentrate the purified proteins, rather than using more complex centrifugation techniques.

Abstract: Microfluidic systems and methods are disclosed which are adapted to transport and lyse cellular components of a test sample for analysis. The disclosed microfluidic systems and methods, which employ an electric field to rupture the cell membrane, cause unusually rapid lysis, thereby minimizing continued cellular activity and resulting in greater accuracy of analysis of cell processes.

Abstract: A micromachined cell lysis device with electrodes that are spaced by less than 10 &mgr;m from one another. The cells are attracted to the space between the.electrodes and then lysed.

Abstract: A loading system for providing a cell suitable for delivery of an agent to a vertebrate, the system comprise a loading module for loading a cell with an agent; and a sensitisation module in fluid communication with the loading module, the sensitisation module for sensitising a cell to an energy field, such that said cell is induced to release the agent upon exposure to said energy field. The system can be used to transform a cell, such as a red blood cell, into a delivery vehicle for delivering a therapeutic agent and/or an imaging agent to a vertebrate, and in particular, to a mammal, such as a human being.

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 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: A microwave device has a monolithic microwave integrated circuit (MMIC) disposed therein for applying microwave radiation to a microfluidic structure, such as a chamber, defined in the device. The microwave radiation from the MMIC is useful for heating samples introduced into the microfluidic structure and for effecting lysis of cells in the samples. Microfabrication techniques allow the fabrication of MMICs that perform heating and cell lysing of samples having volumes in the microliter to picoliter range.

Abstract: An assembly device and method for collecting and testing fluid samples more specifically for preparing and stabilizing nucleic acid components in a closed system. The assembly comprises a sample collection container with preloaded testing reagents and a safety separator to contain the testing reagents during sample collection. A fluid sample is delivered to the container and the assembly is subjected to centrifugation whereby the centrifugal load causes the separator to deform so that the separator migrates through the test reagents mixing the sample and reagents, and comes to rest atop the solids at the bottom of the tube.

Abstract: The invention relates to a vessel for mixing a cell lysate. The invention also relates to a method of using the vessel to mix a cell lysate in order to obtain high-purity products such as nucleic acids or proteins for use in a variety of applications. The invention also relates to a method for monitoring the degree of cell lysis in a cell suspension by measuring the viscosity of the cell suspension.

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: 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: Manipulation of DNA molecules in solution has become an essential aspect of genetic analyses used for biomedical assays, the identification of hazardous bacterial agents, and in decoding the human genome. Currently, most of the steps involved in preparing a DNA sample for analysis are performed manually and are time, labor, and equipment intensive. These steps include extraction of the DNA from spores or cells, separation of the DNA from other particles and molecules in the solution (e.g. dust, smoke, cell/spore debris, and proteins), and separation of the DNA itself into strands of specific lengths. Dielectrophoresis (DEP), a phenomenon whereby polarizable particles move in response to a gradient in electric field, can be used to manipulate and separate DNA in an automated fashion, considerably reducing the time and expense involved in DNA analyses, as well as allowing for the miniaturization of DNA analysis instruments.

Abstract: A micromachined cell lysis device with electrodes that are spaced by less than 10 &mgr;m from one another. The cells are attracted to the space between the electrodes and then lysed.

Abstract: A process and system for electrical extraction of intracellular matter from biological matter, and intracellular matter products formed thereby, based on preparing a mixture of biological matter featuring cells, and an electro-conductive liquid, and electrifying the mixture by transmitting controlled cycles of pulses and pauses of electrical current into the mixture by using electrodes, whereby the pulses of electrical current pierce holes into or perforate the cell membranes of the cells, enabling the release of intracellular matter for collecting and separating into target intracellular matter extract and solid waste. Pauses included in each cycle of transmitting pulses of electrical current enable firm control of electrical extraction processing conditions, including extent of extraction, temperature effects, and pressure effects, during the electrical extraction process.

Abstract: A micromachined cell lysis device with electrodes that are spaced less than 100 &mgr;m from one another. The cells are attracted to the space between the electrodes and then lysed.

Abstract: This invention provides an apparatus for extracting nucleic acids from nucleic acid-containing samples. The nucleic acid extraction apparatus of the invention comprises (1) a group of extraction vessels each comprising a reactor tube in which a sample, a reagent solution, and a magnetic carrier are admixed and reacted, a drain cup for pooling an unwanted component solution, and a nucleic acid recovery tube all as secured to a support, (2) a distribution means for introducing a solution into each of the extraction vessels, (3) a stirring means for mixing the solution and magnetic carrier in the reactor tube, (4) a holding means for holding the magnetic carrier stationary within the vessel, (5) a discharging means for discharging the solution from the reactor tube while the magnetic carrier is held stationary, (6) a heating means for heating the solution and magnetic carrier in the reactor tube, and (7) a transfer means for serially transferring the vessels to the given positions.

Abstract: The present invention comprises devices and methods for performing channel-less separation of cell particles by dielectrophoresis, DC high voltage-pulsed electronic lysis of separated cells, separation of desired components from crude mixtures such as cell lysates, and/or enzymatic reaction of such lysates, all of which can be conducted on a single bioelectronic chip. A preferred embodiment of the present invention comprises a cartridge (10) including a microfabricated silicon chip (12) on a printed circuit board (14) and a flow cell (16) mounted to the chip (12) to form a flow chamber. The cartridge (10) also includes output pins (22) for electronically connecting the cartridge (10) to an electronic controller. The chip (12) includes a plurality of circular microelectrodes (24) which are preferably coated with a protective permeation layer which prevents direct contact between any electrode and a sample introduced into the flow chamber.

Abstract: A filtration process for the preparation of nucleic acids from natural sources is disclosed. The sources containing nucleic acids are lysed; the lysate is left to rest for some time; the resulting lysate passes a filter layer. The filter layer is selected from silica gel, aluminum oxide or packed diatomaceous earth, or interwoven or cemented non-wovens of glass fibers and silica gel. Other filter layers include cellulose, paper, compressed paper, and paper non-wovens. The fraction leaving the filter layer is then collected and the nucleic acid is subsequently isolated and purified from the collected fraction. Furthermore, the filter layer has not been modified with anion exchange groups.

Abstract: This invention provides an apparatus for extracting nucleic acids from nucleic acid-containing samples, particularly biological samples, and more particularly to a nucleic acid extraction apparatus well suited for the nucleic acid extraction method utilizing a nucleic acid-binding magnetic carrier.

Abstract: A process is disclosed for the large scale isolation and purification of plasmid DNA from large scale microbial fermentations. The process exploits a rapid heating method to induce cell lysis and precipitate genomic DNA, proteins and other debris while keeping the plasmid in solution. Suspending the microbial cells in buffer and then heating the suspension to about 70-100° C. in a flow-through heat exchanger results in excellent lysis. Continuous flow or batch-wise centrifugation of the lysate effects a pellet that contains the cell debris, protein and most of the genomic DNA while the plasmid remains in the supernatant. This invention offers a number of advantages including higher product recovery than by chemical lyses, inactivation of Dnases, operational simplicity and scaleability.

Abstract: This invention relates to methods for the cultivating cells, and in particular to methods for propagating recombinant viruses for gene therapy.