Abstract: This invention relates to a method and device for separating charged particles according to their diffusivities in a separation medium by means of a spatially and temporally varying electric potential. The method is particularly suited to sizing and separating DNA fragments, to generating DNA fragment length polymorphism patterns, and to sequencing DNA through the separation of DNA sequencing reaction products. The method takes advantage of the transport of charged particles subject to an electric potential that is cycled between an off-state (in which the potential is flat) and one or more on-states, in which the potential is preferably spatially periodic with a plurality of eccentrically shaped stationary potential wells. The potential wells are at constant spatial positions in the on-state. Differences in liquid-phase diffusivities lead to charged particle separation. A preferred embodiment of the device is microfabricated. A separation medium fills physically defined separation lanes in the device.

Abstract: A serpentine electrophoresis channel, e.g., for a microchip format, is disclosed. The channel includes pairs of linear segments, e.g., parallel or right-angle segments, each joined by an angled channel region having a first curved channel portion subtending an angle &agr;f>&agr;, where &agr; is the angle between segments in a pair, and a second curved channel portion subtending an angle &agr;s=&agr;f−&agr;. The angles and cross-sections of the two channel portions are such that &dgr;tf, the time differential of analyte migration at inner and outer tracks in the first curved portion is equal to &dgr;ts, the time differential of analyte migration at outer and inner tracks in the second curved portion, respectively.

Abstract: The present invention relates to the electrophoretic separation of bio-organic molecules using a slab gel electrophoresis apparatus having a pair of spaced, confronting plates defining a multi-lane separation zone adapted to hold a separation medium and an upper loading zone. In one aspect of the invention, at least one of the plates is shaped to provide an expanded loading zone. The plate-to-plate distance within the expanded loading zone is greater than the plate-to-plate width within the separation zone. In another aspect of the invention, a comb is provided with each tooth having a gradual taper beginning at a support member and extending along most of the tooth's longitudinal axis, and a sharp taper beginning immediately beyond the gradual taper and extending to the end of the tooth.

Abstract: The invention relates to improved methods and compositions for loading samples into an analytical instrument having a plurality of sample receiving loading ports. In a principle embodiment of the invention, first and second sample markers are added to sample to be loaded onto an analytical instrument having a plurality of sample receiving loading ports. The first and second samples are compounds are selected so as to produce a distinctive signal upon combination thus a sample containing a first sample marker and a sample containing a second marker are mistakenly loaded into the same sample receiving loading port, a detectable signal indicative of the misloading is produced.

Abstract: A multi-channel capillary electrophoresis apparatus is disclosed. The apparatus includes a capillary array assembly comprising a plurality of capillaries, each capillary having a capillary outlet, and an outlet support for supporting the capillary outlets. The apparatus further includes a cuvette defining a receiving slot, a gap region, and a detection zone, where the receiving slot is adapted to removably receive the outlet support, and wherein when the outlet support is inserted into the receiving slot, the capillary outlets are positioned in the gap region in proximity to the detection zone, and a flow channel is formed by the outlet support and the receiving slot such that the flow channel is in fluid communication with the gap region. In addition, the apparatus includes a front plumbing block in fluid communication with the flow channel for supplying a fluid flow through the gap region sufficient to transport material downstream from the capillary outlets to the detection zone.

Abstract: Flat plates serving as molds and enclosures for slab gels are held together by a clamping frame in which the side edges of the plates slide into facing channels and are clamped by lever-operated cams that compress the channel walls against the plate surfaces. The joined plates are held on a vertical support rack containing a finger-operated spring-loaded notched clamp that presses down on the plates to seal the opening at the bottom edges of the plates against a gasket. A well-forming comb for insertion between the plates contains flexible outwardly angled fingers to seal against the spacers between the plates.

Abstract: The present invention generally provides microfluidic devices which incorporate improved channel and reservoir geometries, as well as methods of using these devices in the analysis, preparation, or other manipulation of fluid borne materials, to achieve higher throughputs of such materials through these devices, with lower cost, material and/or space requirements.

Abstract: A method for observing and determining the size of individual molecules and for determining the weight distribution of a sample containing molecules of varying size, which involves placing a deformable or nondeformable molecule in a medium, subjecting the molecule to an external force, thereby causing conformational and/or positional changes, and then measuring these changes. Preferred ways to measure conformational and positional changes include: (1) determining the rate at which a deformable molecule returns to a relaxed state after termination of the external force, (2) determining the rate at which a molecule becomes oriented in a new direction when the direction of the perturbing force is changed, (3) determining the rate at which a molecule rorates, (4) measuring the length of a molecule, particularly when it is at least partially stretched, or (5) measuring at least one diameter of a spherical or ellipsoidal molecule.

Abstract: Disclosed is a process for manipulating microscopic dielectric particles in which particles are exposed to an electric field. In disadvantaged processes the particles are exposed to inhomogeneous electric field and are polarized by them. The polarized particles are moved in the direction of higher field strength. These processes permit no reversal of the traveling direction of the particles. The particles are enriched at the electrode so that they cannot be retained in free space. In the invented process the particles are exposed to high-frequency field traveling in one or more prescribed direction, by which the particles are subject to a force which sets them in a motion that is strongly synchronous to the field. With the aid of a device for carrying out the invented process, the particles can be manipulated very flexibly.

Abstract: A mass spectrometer includes a sample passage through which a sample solution flows towards a tip of the sample passage, a gas passage which produces a gas flow along the sample passage towards an orifice of the gas passage, a gas supplier which supplies a gas to the gas passage so that the gas flow has a velocity effective for spraying the sample solution near the tip of the sample passage, and an analyzer which analyzes a mass of gaseous ions formed from the sample solution sprayed by the gas flow. The gas flow has a characteristic value F/S between 350 meters/second (m/s) and 700 m/s, where F is a flow rate of the gas at standard conditions (20.degree. C., 1 atmosphere), and S is a difference between a cross section of the orifice and a cross section of the sample passage at the orifice. An exposed length of the sample passage between an external opening of the orifice and the tip of the sample passage may be between -0.25 mm and 1.2 mm.

Abstract: A micromachined system for electrical field-flow fractionation of small test fluid samples is provided. The system includes a microchannel device comprising a first substrate having a planar inner surface with an electrode formed thereon. A second substrate having a planar inner surface with an electrode formed thereon is positioned over the first substrate so that the respective electrodes face each other. An insulating intermediate layer is interposed between the first and second substrates. The intermediate layer is patterned to form opposing sidewalls of at least one microchannel, with the electrodes on the substrates defining opposing continuous boundaries along the length of the microchannel. Inlet and outlet ports are formed in one or both substrates for allowing fluid flow into and out of the microchannel. The microchannel device can be fabricated with single or multiple microchannels therein for processing single or multiple test fluids.

Abstract: A liquid is separated into its constituent species by electrophoresis along a capillary channel. A plurality of the channels is provided in the thickness of an injection molded plastics disc. The disc is rotatably mounted such that samples are dispensed into successive channels. When all twelve channels have been used, the disc is replaced with a fresh one.

Abstract: A sample handling system in a multi-channel capillary electrophoresis apparatus is disclosed. The sample handling system includes a work surface for supporting a plurality of samples located at a plurality of work surface coordinates and a sample loading assembly comprising a plurality of loading wells. At least one of the loading wells includes a capillary fixedly positioned therein. The system further includes a programmable sample transfer device for automatically transferring a sample from a work surface coordinate to a loading well. The invention further includes methods for using the sample handling system.

Abstract: A method and apparatus for measuring electrochemiluminescence from a sample composition are described wherein magnetically responsive electrochemiluminescent active species are captured on the electrode with the aid of a capture magnet having a configuration such that the magnetic flux lines (or the magnetic field gradient) of at least one magnetic field source therein are compressed and/or dispersed. This capture magnet improves the distribution of the magnetically responsive electrochemiluminescent active species on the electrode surface and reduces interference with the photomultiplier tube, thereby enhancing the ECL signal and improving sensitivity. The improved capture and distribution also allows for shorter assay times.

Abstract: Systems and methods for the electronic sample preparation of biological materials utilize the differential charge-to-mass ratio and/or the differential affinity of sample constituents to separation materials for sample preparation. An integrated system is provided for performing some or all of the processes of: receipt of biological materials, cell selection, sample purification, sample concentration, buffer exchange, complexity reduction and/or diagnosis and analysis. In one embodiment, one or more sample chambers adapted to receive a buffer solution are formed adjacent to a spacer region which may include a trap or other affinity material, electrophoretic motion of the materials to be prepared being effected through operation of electrodes. In another aspect of this invention, a transporter or dipstick serves to collect and permit transport of materials, such as nucleic acids, most preferably DNA and/or RNA.

Abstract: A new approach and instrument for field identification of micro-organisms and DNA fragments using a small and disposable device containing integrated polymerase chain reaction (PCR) enzymatic reaction wells, attached capillary electrophoresis (CE) channels, detectors, and read-out all on/in a small hand-held package. The analysis instrument may be made inexpensively, for example, of plastic, and thus is disposable, which minimizes cross contamination and the potential for false positive identification between samples. In addition, it is designed for multiple users with individual applications. The integrated PCR/CE is manufactured by the PCR well and CE channels are "stamped" into plastic depressions where conductive coatings are made in the wells and ends of the CE microchannels to carry voltage and current to heat the PCR reaction mixtures and simultaneously draw DNA bands up the CE channels.

Abstract: An ultra-miniaturized surface structure with controllable adhesion having extremely miniaturized (in the sub atomic range) planar electrode strips applied to the surface to which high frequency pulse trains may be applied to generate progressive or stationary standing waves. The electrodes in themselves are combined with dielectric insulating materials with controlled bio-compatibility. The type of electric drive, together with the properties of the surface layers that cover the electrodes, determines the adhesion properties of the surface to a large extent regardless of the used base material. Particle movement is gently influenced, so that for the first time it becomes possible to influence particles in highly physiological nutritive solutions.

Abstract: An electrospray apparatus uses a microchannel formed in a microchip. Fluid is pumped through the channel to an outlet orifice using either hydraulic or electrokinetic means. An electrospray is generated by establishing a sufficient potential difference between the fluid at the outlet orifice and a target electrode spaced from the outlet orifice. Electrokinetic pumping is also utilized to provide additional benefits to microchip devices.

Abstract: An anchoring device to be placed atop a slab of electrophoresis gel in a submerged electrophoresis process chamber includes a planar frame member shaped and sized to distribute weight evenly across the gel slab, particularly having a width dimension generally the same as the slab, and a plurality of legs spaced evenly around the frame. The legs have a length sufficient to raise the frame above the level of buffer liquid in process chamber, and have a blunt bottom surface in contact with the gel slab. The weight of the device and the even distribution of that weight is sufficient to anchor the gel slab and keep it submerged in the buffer liquid in the electrophoresis process chamber while making minimal contact with the slab and not distorting the electrical field through the gel, and without penetrating or lacerating the slab. The frame encloses one or more open window areas above the sample wells in the gel slab to permit easy access to load biological samples.

Abstract: The present invention concerns an apparatus for conducting a microfluidic process. The apparatus comprises integral first and second plates. The first plate comprises an array of sample receiving elements for receiving a plurality of samples from an array of sample containers and dispensing the samples. The second plate comprises a planar array of microfluidic networks of cavity structures and channels for conducting a microfluidic process. Also disclosed is a method for processing an array of samples. At least a portion of each sample in an array of sample wells is simultaneously transferred to a corresponding array of microfluidic networks of cavity structures and channels by means of a corresponding array of sample receiving elements that is in integral fluid communication with the array of microfluidic networks. The samples are then processed.