Abstract: A fully automated protein and/or DNA gene fragment analyzing machine and method are disclosed in which, in a simple machine structure, a plurality of electrophoresis calls each containing such fragments, are robotically, under computer programming, inserted into an electrophoresis housing and subjected to voltage for producing electrophoretic migration in one dimension (horizontally), and then preferably after robotic 90.degree. rotating of the cells, are voltage migrated in an orthogonal direction to separate the fragments vertically, and then robotically presented to an optical image scanner for identifying the brightest fragments and classifying the same, with comparison with reference image fragment locations of normal or variant fragments, and for computer storing all relevant data.

Abstract: A microchip laboratory system and method provide fluid manipulations for a variety of applications, including sample injection for microchip chemical separations. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis and electrochromatography are performed in channels formed in the substrate. Analytes are loaded into a four-way intersection of channels by electrokinetically pumping the analyte through the intersection, followed by switching of the potentials to force an analyte plug into the separation channel.

Abstract: In a method of forming a microchannel and/or microcavity structure by bonding together two elements (1, 2) having opposed plane surfaces of the same or different material, one or both surfaces having open channels and/or cavities, bonding is effected by applying to one or both element surfaces (1, 2) a thin layer (3) of a solution of a material capable of fusing with and having a lower melting point than that of the material or materials of the two element surfaces (1, 2) in a solvent which substantially does not dissolve the element surface material or materials. The solvent is then removed, and the two elements (1, 2) are brought together and heated to a temperature where the dissolved material is caused to melt but not the element surface material or materials.

Abstract: A gel cassette for electrophoresis includes opposed plastic plates holding a gel therebetween. An upper buffer tank can be adhered to one of the plates by double backed tape that is sandwiched between the tank and plate, thereby avoiding the use of a rubber sealing gasket between the tank and plate. As a result, the distance between the tank and the plate is kept constant. A buffer solution in the tank communicates with the gel. The cassette can then be placed in a lower buffer tank and an electric field applied to the buffer solutions to effect electrophoresis of DNA fragments that have been placed in the gel. In an alternate embodiment, a window is formed in one of the plastic plates to allow laser light to pass into the cassette and excite a fluorescent tag in the DNA. The fluorescence then passes back through the window for detection by a sensor, to automatically determine the DNA sequence of the sample in the gel in accordance with auto DNA sequencing principles.

Abstract: In acordance with the teachings of the present invention, there are provided mathods, gels, and transferring devices for loading gels. The mathods and devices of the present invention involve the use of ultra-thin, miniature, disposable, slab gels for the quick, inexpensive and high resolution analysis of polynucleotide samples.

Abstract: An automated electrophoretic system is disclosed. The system employs a capillary cartridge having a plurality of capillary tubes. The cartridge has a first array of capillary ends projecting from one side of a plate. The first array of capillary ends are spaced apart in substantially the same manner as the wells of a microtitre tray of standard size. This allows one to simultaneously perform capillary electrophoresis on samples present in each of the wells of the tray. The system includes a stacked, dual carousel arrangement to eliminate cross-contamination resulting from reuse of the same buffer tray on consecutive executions from electrophoresis. The system also has a gel delivery module containing a gel syringe/a stepper motor or a high pressure chamber with a pump to quickly and uniformly deliver gel through the capillary tubes. The system further includes a multi-wavelength beam generator to generate a laser beam which produces a beam with a wide range of wavelengths.

Abstract: A device for fractionating macromolecules in a fluid medium includes a plurality of individual obstacles which are arranged on a substrate in rows and columns. An electric field is provided and oriented to move the macromolecules in migration through fluid channels that are established between the columns of obstacles. Each obstacle has mutually symmetrical right and left front walls which are inclined to a respective fluid channel. Consequently, as macromolecules diffuse through the fluid medium from a fluid channel during their migration through the device, the front walls of the obstacles redirect them back into the same fluid channel from which they diffused. As a result, the faster diffusing, smaller macromolecules take longer to migrate through the fluid channels of the device. Eventually, because the diffusion rate of the macromolecules depends on their size, the positions of the macromolecules in the device reflect their respective diffusion rates, and therefore their size.

Abstract: This invention is an integrated instrument for the high-capacity electrophoretic analysis of biopolymer samples. It comprises a specialized high-voltage, electrophoretic module in which the migration lanes are formed between a bottom plate and a plurality of etched grooves in a top plate, the module permitting concurrent separation of 80 or more separate samples. In thermal contact with the bottom plate is a thermal control module incorporating a plurality of Peltier heat transfer devices for the control of temperature and gradients in the electrophoretic medium. Fragments are detected by a transmission imaging spectrograph which simultaneously spatially focuses and spectrally resolves the detection region of all the migration lanes. The spectrograph comprises a transmission dispersion element and a CCD array to detect signals. Signal analysis comprises the steps of noise filtering, comparison in a configuration space with signal prototypes, and selection of the best prototype.

Abstract: A gel for electrophoresis in a horizontal mode which contains at least one sample well with an enlarged loading area that is formed in an elevated gel segment. At least a front wall of the sample well consists of a substantially vertical part and a non-vertical part, where the non-vertical part is declined at an angle sufficiently steep that the sample loaded on the non-vertical part slides down into the sample well. Any sample molecules that during electrophoresis enter the gel through the non vertical part of the front wall migrate only through the elevated gel segment. They also exit this segment, so that substantially no double bands, which could complicate the interpretation of experimental results, are detected.

Abstract: The present invention relates to an electrophoretic method to effect differential net migration, the extent of said migration being dependent on molecular size, of electrically charged macromolecules through a gel support in a single dimension, which method comprises subjecting electrically charged macromolecules applied to a gel support to an electric field oriented along a single axis within the gel for a time period sufficient to effect migration in the direction of the oriented field and form a separation pattern in order of the respective molecular weights of the macromolecules in a distance of about 0.5 to about 20 millimeters, said gel support comprising about 3 to about 40 percent polyacrylamide, said electric field being applied in an amount of about 5 to about 100 volts per millimeter of gel support along the axis length, and said gel support having a width perpendicular to said axis of about 0.1 to 1.5 millimeters.

Abstract: A microchip laboratory system and method proved fluid manipulations for a variety of applications, including sample injection for microchip chemical separations. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis and electrochromatography are performed in channels formed in the substrate. Analytes are loaded into a four-way intersection of channels by electrokinetically pumping the analyte through the intersection, followed by switching of the potentials to force an analyte plug into the separation channel.

Abstract: A microchip laboratory system and method provide fluid manipulations for a variety of applications, including sample injection for microchip chemical separations. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis and electrochromatography are performed in channels formed in the substrate. Analytes are loaded into a four-way intersection of channels by electrokinetically pumping the analyte through the intersection, followed by switching of the potentials to force an analyte plug into the separation channel.

Abstract: The subject invention provides methods and kits for conveniently diagnosing various physiological conditions that produce altered levels of specific carbohydrates, known as diagnostic carbohydrates. Measurement of the levels of the diagnostic carbohydrates is performed by fluorophore assisted carbohydrate electrophoresis. Physiological conditions of particular interest that may be ascertained by the subject invention include carbohydrate metabolism diseases, autoimmune diseases, neoplasia, toxic chemical exposure and microbial infections. Fluorophore assisted carbohydrate electrophoresis diagnosis may be applied to various patient specimens, including blood, urine and skin.

Abstract: Integrated microfluidic devices comprising at least an enrichment channel and a main electrophoretic flowpath are provided. In the subject integrated devices, the enrichment channel and the main electrophoretic flowpath are positioned so that waste fluid flows away from said main electrophoretic flowpath through a discharge outlet. The subject devices find use in a variety of electrophoretic applications, including clinical assays, high throughput screening for genomics and pharmaceutical applications, point-or-care in vitro diagnostics, molecular genetic analysis and nucleic acid diagnostics, cell separations, and bioresearch generally.

Abstract: To sequence DNA, DNA samples marked with flourscent infrared dye are applied at a plurality of locations for electrophoresing in a plurality of channels through a gel electrophoresis slab. The channels are scanned with a laser and a sensor, that include a microscope focused on the gel slab. The focal point and slab are adjusted with respect to each other so that the focal point of the microscope remains on the gel slab during a scan. The data from the scan is directly used to amplitude modulate density readings on a display, and the scan is displayed in a horizontal sweep of a cathode ray tube, whereby said cathode ray tube provides intensity displays of bands representing DNA. Different sizes of glass gel sandwiches may be mounted to the same console for different sequencing tasks.

Abstract: A microchip apparatus and method provide fluidic manipulations for a variety of applications, including sample injection for microchip liquid chromatography. The microchip is fabricated using standard photolithographic procedures and chemical wet etching, with the substrate and cover plate joined using direct bonding. Capillary electrophoresis is performed in channels formed in the substrate. Injections are made by electro-osmotically pumping sample through the injection channel that crosses the separation channel, followed by a switching of the potentials to force a plug into the separation channel.

Abstract: An integrated apparatus for capillary electrophoresis which is automated using conveyors which carry vials containing electrolytes and samples, a capillary contained in a modular, portable, and interchangeable cartridge, and actuators for bringing the capillary into flow communication with the fluids in the vials. Electropotential is applied to the ends of the capillary to cause electrophoretic separation. The cartridge may include an opening to allow detection of fluid in the capillary using a detector provided in the apparatus.

Abstract: A viscosity-adjustable medium for use in separation methods is described. In particular, a block copolymer composition is described which exists as a low viscosity solution at a temperature outside of the temperature range of electrophoresis and which self-assembles into a gel-like polymer network at electrophoresis operating temperatures. A system is described for conducting molecular separation in a capillary column using the viscosity-adjustable medium. In addition, a method is also described for separating charged molecules.

Abstract: This invention is an integrated instrument for high-capacity electrophoretic analysis of biopolymer samples. It comprises a specialized high-voltage, electrophoretic module in which the migration lanes are formed between a bottom plate and a plurality of etched grooves in a top plate, the module permitting concurrent separation of 80 or more separate samples. In thermal contact with the bottom plate is a thermal control module incorporating a plurality of Peltier heat transfer devices for the control of temperature and gradients in the electrophoretic medium. Fragments are detected by a transmission imaging spectrograph which simultaneously spatially focuses and spectrally resolves the detection region of all the migration lanes. The spectrograph comprises a transmission dispersion element and a CCD array to detect signals. Signal analysis comprises the steps of noise filtering, comparison in a configuration space with signal prototypes, and selection of the best prototype.

Abstract: A capillary electrophoresis method for resolving transferrin glycoforms in a sample is described. The capillary comprises a lumen, an inlet and an outlet. The lumenal surface of the capillary is charge-neutral and the capillary contains a buffer containing a polymeric matrix. The transferrin sample is contacted with the inlet of the capillary. A voltage is applied to the capillary such that the inlet is a cathode and the outlet is an anode and such that the voltage is effective for resolving transferrin glycoforms. A method for diagnosing chronic alcoholism or carbohydrate-deficient glycoprotein syndrome using CE to resolve abnormal populations of transferrin glycoforms is also described.