Abstract: A method for verifying an ILS signal for DNA processing includes obtaining the ILS signal, determining acquisition times between peaks of the ILS signal, obtaining acquisition times between peaks in reference ILS information for the ILS signal, and verifying the ILS signal based on the ILS acquisition times and the reference ILS acquisitions times. An ILS signal processor includes a false peak remover that removes any false peaks in an ILS signal and a signal verifier that verifies the ILS signal includes only true peaks based on reference ILS information for the ILS signal.

Abstract: The invention relates to a microfabricated device and methods of using the device for analyzing and sorting polynucleotide molecules by size.

Abstract: An electrophoretic notch filter apparatus including a gel cartridge having at least one sample channel, an electrode and a counter electrode each engagable with the sample channel, a user interface for programming one or more steps for a sample channel into a processor to form a programmed sequence and an electrophoretic controller for implementing the programmed sequence.

Abstract: Particles of interest such as DNA, RNA may be detected in trace quantities by subjecting the particles to concentration by scodaphoresis, detecting a signal indicative of the presence of the particles in a scodaphoresis focus spot and performing phase-sensitive detection on the signal using a reference signal tied to the scodaphoresis fields. Specificity may be enhanced by using a medium having high affinity for the particles and/or markers having specific affinity for the target particles. In some embodiments a fluorescence signal is detected and subjected to phase-sensitive analysis. The signal may be detected by a camera or other imaging system.

Abstract: Particles may be injected into a matrix for concentration by scodaphoresis using a quadrupole injection field. Particles may be injected from two or more sample chambers simultaneously. Particle injection may be performed simultaneously with performing scodaphoresis. In some embodiments the particles are concentrated into a well containing fluid. The well can extend out of a plane of the matrix. Altering the relative phases of components of a scodaphoresis field permits concentration of selected particles and exclusion of other particles. Scodaphoresis methods may be applied to DNA, other bio-molecules and other particles.

Abstract: Particles of interest, such as DNA molecules, are injected into a medium by applying a first field. Once in the medium the particles are concentrated by applying one or more fields that cause mobilities of the particles in the medium to vary in a manner that is correlated with motions of the particles. Particle injection and particle concentration may be performed concurrently or in alternation.

Abstract: A device for addressing an electrode array of 2n lines of an electro-fluidic device, each line having N electrodes (n?N). The device includes, on each line, n selection electrodes, all of the line selection electrodes being connected to 2n line selection conductors, 2n?1 line selection electrodes of 2n?1 lines being connected to each line selection conductor, and selection devices for selecting one or more line selection conductors.

Abstract: Particles may be injected into a matrix for concentration by scodaphoresis using a quadrupole injection field. Particles may be injected from two or more sample chambers simultaneously. Particle injection may be performed simultaneously with performing scodaphoresis. In some embodiments the particles are concentrated into a well containing fluid. The well can extend out of a plane of the matrix. Altering the relative phases of components of a scodaphoresis field permits concentration of selected particles and exclusion of other particles. Scodaphoresis methods may be applied to DNA, other bio-molecules and other particles.

Abstract: The present teachings provide methods, devices, systems, and materials for performing electrophoresis in an automated fashion. The electrophoresis system may simultaneously image gel during an electrophoresis run. In some embodiments, the electrophoresis system may analyze an imaged gel during or after electrophoresis. The device may comprise a gel processing system, a gel illumination system, an image capture system, and an image analysis all housed within a housing.

Abstract: Particles may be injected into a matrix for concentration by scodaphoresis using a quadrupole injection field. Particles may be injected from two or more sample chambers simultaneously. Particle injection may be performed simultaneously with performing scodaphoresis. In some embodiments the particles are concentrated into a well containing fluid. The well can extend out of a plane of the matrix. Altering the relative phases of components of a scodaphoresis field permits concentration of selected particles and exclusion of other particles. Scodaphoresis methods may be applied to DNA, other bio-molecules and other particles.

Abstract: Components of a mixture are separated by feeding charged molecules of the components into a end surface of a suitable medium, for example a gel. The molecules are drawn in a first direction through the medium by means of an DC electric field, while at the same time being subjected to an alternating voltage with a strongly asymmetric profile in a direction transverse to the first direction. The nonlinear behavior of the electrically-generated migration causes a large number of molecules to migrate transversely out of the medium while only a small number of molecules reach the opposite end surface of the medium. A superimposed DC voltage in the transverse direction selects which of the mixture components migrate all the way through the medium in the first direction. The separated components can be sampled from the opposite end surface and from points on the upper and lower medium surfaces.

Abstract: The present teachings describe gel processing systems comprising at least an electrophoresis device and a computer system operably linked to perform electrophoresis. Systems of the disclosure may also comprise gel imaging systems, image capture systems, gel illumination systems and/or gel/image analysis systems. A computer system of the disclosure may comprise software components including graphical user interface (GUI) specifications and functional specifications. The disclosure also describes methods for gel processing performed on a gel processing system. Methods of the disclosure may comprise performing electrophoresis and in some embodiments, one or more additional steps, such as imaging, analysis, report generation and transfer of data to external sources. Methods and workflows of the disclosure may be user controlled and customized by using the GUI and other software and hardware functional components of the computer system.

Abstract: Particles of interest, such as DNA molecules, are injected into a medium by applying a first field. Once in the medium the particles are concentrated by applying one or more fields that cause mobilities of the particles in the medium to vary in a manner that is correlated with motions of the particles. Particle injection and particle concentration may be performed concurrently or in alternation.

Abstract: A technique for producing multiple protein blots from a single gel, including entering the number ‘n’ membranes to be blotted into microprocessor memory, determining calibration constants for a gel batch, inputting calibration constants into microprocessor memory, and calculating ‘n’ voltage/time profiles for simultaneous blotting. A gel layer from the gel batch is treated with a protein sample, ‘n’ membranes are placed onto the gel layer to yield a gel pack, and the gel pack is placed between an electrode plate maintained at a fixed first voltage and an array of ‘n’ spaced generally parallel electrodes. The voltage to each respective ‘n’ spaced generally parallel electrodes is varied over time according to a respective ‘n’ voltage/time profile to transfer proteins to each respective ‘n’ membranes to yield blotted membranes to yield ‘n’ respective blotted membranes.

Abstract: Methods and apparatus for moving and concentrating particles apply an alternating driving field and an alternating field that alters mobility of the particles. The driving field and mobility-varying field are correlated with one another. The methods and apparatus may be used to concentrate DNA or RNA in a medium, for example. Methods and apparatus for extracting particles from one medium into another involve applying an alternating driving field that causes net drift of the particles from the first medium into the second medium but no net drift of the particles in the second medium.

Abstract: Particles of interest such as DNA, RNA may be detected in trace quantities by subjecting the particles to concentration by scodaphoresis, detecting a signal indicative of the presence of the particles in a scodaphoresis focus spot and performing phase-sensitive detection on the signal using a reference signal tied to the scodaphoresis fields. Specificity may be enhanced by using a medium having high affinity for the particles and/or markers having specific affinity for the target particles. In some embodiments a fluorescence signal is detected and subjected to phase-sensitive analysis. The signal may be detected by a camera or other imaging system.

Abstract: An electrophoretic notch filter apparatus including a gel cartridge having at least one sample channel, an electrode and a counter electrode each engagable with the sample channel, a user interface for programming one or more steps for a sample channel into a processor to form a programmed sequence and an electrophoretic controller for implementing the programmed sequence.

Abstract: A system for displaying the positions of substances in electrophoretic separations comprises a gel (635) a substance to be separated into a region (450), plates (400, 401) with electrodes (405-420 and 430-445) placed on either side of the gel. A source (315) applies a voltage to an electrode on one side of the gel, and an electrode on the other side of the gel is connected to the input of an amplifier (320). Multiplexers (605, 610) connect the source and amplifier to electrodes on either side of the gel. A computer (600) issues commands to the multiplexers to connect the source and amplifier to individual electrodes, and while a pair of electrodes is so connected, the computer activates a sample-and-hold circuit (620) and an A/D converter (630) to record the value of the electrical impedance within the gel at the location of the selected electrodes. The impedance value is stored in the computer's memory and also displayed on a monitor (635) connected to the computer.

Abstract: A new approach is proposed that contemplates systems and methods to support a fully automated two dimensional gel electrophoresis instrument with modular scalability to support laboratory needs. Each instrument integrates a plurality of “plug-n-play” removable all-in-one precast “unigel” cassettes that each houses one or more of first and second dimension gels casted on a gel supports, wherein the cassette capacities of the instrument can be expanded to accommodate increasing numbers of cassettes. Here, each of the cassettes integrates a first dimension gel unit of the isoelectric focusing process and a second dimension gel unit of the polyacrylamide gel electrophoresis process and allows for automatic insertion, removal, cooling, staining and distaining of the gels as well as addition of samples and operational buffers.

Abstract: A method is provided for separating single- and double-stranded nucleic acid molecules based on their strandness and length.

Abstract: A microcapillary device includes a microcapillary tube. An anode is positioned at a first end of the microcapillary tube. A cathode is positioned at a second end of said microcapillary tube. A plurality of electric field reducing components are spaced apart along a length of the microcapillary tube. The anode and the cathode generate an electric field along the length of the microcapillary tube, and the plurality of electric field reducing components selectively reduce the electric field at spatial intervals along the length of the microcapillary tube.

Abstract: An electrophoresis device is disclosed that is capable of reducing waves occurring in a fluid in which the capillary tips of a capillary assay are immersed. A plurality of partition plate members can be provided in a container containing the fluid to divide the surface of the fluid into several sections. The container can be transported at a high speed, and the capillary tips can be immersed in the fluid quickly, thereby preventing resolution degradation caused by a long period of exposure of the capillary tips to air. Throughput of sample analysis can also be improved because it is not necessary to wait until waves disappear before conducting an analysis.

Abstract: Methods of use, accessories and chambers, optimal for performing Pulsed Field Gel Electrophoresis (PFGE) of DNA molecules in ‘Contour Clamped Homogeneous Electric Field’ (CHEF) and ‘Transversal Alternating Field Electrophoresis’ (TAFE) systems, are provided herein. DNA molecules are rapidly separated in the minigels of these chambers. The sizes of chambers and accessories are determined by the separation between the opposite polarity electrodes; which is comprised between 6.2 and 15 cm. Reproducibility of molecule separation is achieved because the accessories warrant homogeneous electric resistance in the buffer and minigels. Chambers allow a high-throughput sample format using the reagents efficiently. It is attained excluding the non-useful electrophoresis zones For a better optimization, TAFE chambers have several useful electrophoresis zones (UEZ), each carrying a minigel.

Abstract: A method and apparatus for fractionation of charged macro-molecules such as DNA is provided. DNA solution is loaded into a matrix including an array of obstacles. An alternating electric field having two different fields at different orientations is applied. The alternating electric field is asymmetric in that one field is stronger in duration or intensity than the other field, or is otherwise asymmetric. The DNA molecules are thereby fractionated according to site and are driven to a far side of the matrix where the fractionated DNA is recovered. The fractionating electric field can be used to load and recover the DNA to operate the process continuously.

Abstract: A fluidic channel patterned with a series of thin-film electrodes makes it possible to move and concentrate DNA in a fluid passing through the fluidic channel. The DNA has an inherent negative charge and by applying a voltage between adjacent electrodes the DNA is caused to move. By using a series of electrodes, when one electrode voltage or charge is made negative with respect to adjacent electrodes, the DNA is repelled away from this electrode and attached to a positive charged electrode of the series. By sequentially making the next electrode of the series negative, the DNA can be moved to and concentrated over the remaining positive electrodes.

Abstract: The invention relates to a capillary electrophoresis-based method of screening complex materials for any unidentified affinity ligand that binds to a target of interest. The method subjects a plug of a mixture of the target and a complex material sample, and a separate plug of a known, tight-binding competitive ligand, to capillary electrophoresis under conditions optimized to allow mingling of the two plugs during the capillary electrophoresis run. Preferably, migration of the competitive ligand is tracked.

Abstract: Circuit to clamp the voltages in the electrodes of the CHEF system chambers of Pulsed Field Gel Electrophoresis (PFGE) which is formed by two identical clamping circuits that are connected to a power supply through an alternator and only one of the two circuits receives electric power at the same time. Each clamping circuit is formed by several resistors and diodes connected in series to form a voltage divider. Voltage repeaters are connected to the nodes formed in the union of two resistors. Each repeater is connected to a pair of electrodes that should be polarized at the same potential. Diodes are introduced to correct small errors in the voltage pattern applied to the electrodes. The circuit is able to maintain the potential of each electrode in front of the variations of conductivity that occur inside the chamber during the electrophoresis. This way each imposition circuit generates a homogeneous electric field of same value and different direction in a PFGE chamber of the CHEF system.

Abstract: The invention relates to capillary electrophoretic methods for detecting ligands or hit compounds that can bind to a selected target at or above a selected binding strength. The method allows one to rank various ligands based on their relative affinity, i.e., the relative stability of the target/ligand complex during capillary electrophoresis under selected conditions. The method also enables selective detection of strong-to-moderate binding hit compounds, even in the presence of high concentrations of weaker, competitive hit compounds.

Abstract: An automated laboratory system and method allow high-throughput and fully automated processing of materials, such as liquids including genetic materials. The invention includes a variety of aspects that may be combined into a single system. For example, processing may be performed by a plurality of robotic-equipped modular stations, where each modular station has its own unique environment in which processes are performed. Transport devices, such as conveyor belts, may move objects between modular stations, saving movement for robots in the modular stations. Gels used for gel electrophoresis may be extruded, thus decreasing the time needed to form such gels. Robotically-operated well forming tools allow wells to be formed in gels in a registered and accurate way.

Abstract: The present invention provides an integrated, fully automated, high-throughput system for two-dimensional electrophoresis comprised of gel-making machines, gel processing machines, gel compositions and geometries, gel handling systems, sample preparation systems, software and methods. The system is capable of continuous operation at high-throughput to allow construction of large quantitative data sets.

Abstract: The present invention provides an integrated, fully automated, high-throughput system for two-dimensional electrophoresis comprised of gel-making machines, gel processing machines, gel compositions and geometries, gel handling systems, sample preparation systems, software and methods. The system is capable of continuous operation at high-throughput to allow construction of large quantitative data sets.

Abstract: A compact, low cost, automated electrophoresis apparatus provides for the optical detection of multiple DNA samples. A substantially cylindrical gel cartridge houses multiple sample lanes that are sealed on the outer periphery by a shrink tube, which allows for straightforward gel casting, as well as for the pre-casting of sequencing gels. The radial column design of the gel cartridge also facilitates the use of a light source to illuminate one or more sample lanes at the same time. The radial column design further provides for an increased sample lane depth that allows for reading through a greater optical path length of the migrated samples, yielding greater optical signal strength, and an increased signal to noise ratio. The gel lanes can be designed to vary in depth as a function of longitudinal length, allowing for a variable current density. Additionally, this radial design allows for different types of optical detection techniques to be performed on the sample, including transmittance and fluorescence.

Abstract: An apparatus for electroporation stores a level of charge, specified by a user, on a capacitor, which is delivered to a cuvette through an optically isolated high voltage switch. The capacitor is charged through a charging system, including a current mode pulse width modulation control circuit, which monitors the current in the primary winding of a transformer and supplies a pulse width modulated signal, limiting the current on every pulse to a level set by the microcontroller, to the controlling transistor in order to generate the drive to the primary winding of the transformer. A controlled amount of energy is transferred through each pulse to the capacitor. The microcontroller monitors the voltage on the capacitor up to a threshold level to predict the number of pulses necessary to store the requested amount of charge on the capacitor. The microcontroller will then count the number of pulses until the number of pulses necessary to store the requested amount of charge on the capacitor has been reached.

Abstract: An apparatus for electrophoresing a sample and for thereafter either scanning in the visible mode or the fluorescent mode, under control of a central processor, to provide scanning densitometry of the electrophoresed sample, and with the fluorescent mode scanning being performed in situ. The apparatus includes a gantry which moves from left to right in the XY plane. The gantry draws, delivers and deposits the samples and reagents, and includes safety devices to prevent the gantry from movement and damage when there are obstructions in the path of the gantry. A fluorescent scanning unit is moved by X- and Y-direction motors to position a photomultiplier over an electrophoresed sample. In this way, the electrophoretic sample can remain fixed in place during sample delivery, ultraviolet exposure and measurement operations.

Abstract: An apparatus for the rapid preparation of electrophoresis gels comprises: (a) a housing; (b) a support fixture removably disposed within the housing and adapted to receive a gel holder having an internal gel compartment, the support fixture being optionally adapted to permit filling of the gel holder within the housing; (c) an optional injection system, which is connectible to a reservoir for holding a polymerizable solution; (d) an optional solution injection connector adapted to couple the injection system to a gel holder placed within the filling fixture, (e) an optional controller for the injection system, which causes the injection system to inject polymerizable solution from the reservoir into the gel compartment; and (f) a radiation source disposed within the housing in a location effective to irradiate polymierizable solution within the gel compartment of a gel holder in the support fixture.

Abstract: A system for measuring and analyzing an image of a gel electrophoresis, includes measuring apparatus and a processor. The measuring apparatus includes a frame mountable in a fixed location relative to the image, including a bar extending along a first axis, a carriage coupled to the bar and slidable along the first axis, an alignment device extending transversely from the carriage along a second axis for aligning selected components of the image, and a distance sensor operatively coupled to the carriage for sensing the distance travelling by the carriage and generating distance signals. The processor is operatively coupled to the measuring apparatus and processes the distance signals and generates maps based thereon. The subject system is well suited for constructing restriction enzyme maps for an image of bands created by subjecting DNA to gel electrophoresis.

Abstract: A method and apparatus for carrying out electrophoretic separation is provided which imparts a fractal field component to the particles themselves or to the medium in which the particles are to be separated which, in combination with a steady field component, provides for a fast electrophoretic separation method that can be used on molecules and particles of a larger size than currently available electrophoretic methods.

Abstract: A virtual DNA sequencer combines a plurality of individual DNA sequencers. Samples of DNA or other nucleic acid from subjects are prepared and allocated in real time to particular lanes or sets of lanes in electrophoresis plates of the individual sequencers, with records kept of the allocations. The data resulting from the electrophoresis runs is collected and collated according to the identities of the subjects. The individual sequencers are networked, and each individual sequencer is preferably equipped with a data buffer large enough to accommodate all or substantially all of a data run, thus protecting the virtual sequencer from loss of valuable data in the event that the network is disrupted for some portion of the time of the data run. In this way, a plurality of sequencers is virtually the same as a single sequencer with a very large number of tracks each of which can run for a much longer sequencing run than an individual sequencer.

Abstract: The method and apparatus for preparative electrophoresis is especially useful for proteins. An electrophoretic potential with an initial polarity is applied across an electrophoretic medium (13) to induce at least two species of macromolecules (1,2) in a mixture (3) with a first electrolyte solution to move into the medium (13) and towards a second electrolyte solution on an opposite side of the medium (13). The at least two species of macromolecules (1,2) have similar transport properties, although at least one (1) of the species moves through the medium (13) at a faster rate than the other species (2). The initial polarity is maintained until just before any of the other species of macromolecules have emerged into the second electrolyte solution whereupon the polarity of the electrophoretic potential is reversed while preventing the proportion of the at least one species of macromolecules (1) which has already emerged into the second electrolyte solution from being drawn back into the medium (13).

Abstract: A method for extending the useful lifetime and improving the reproducibility of electrophoresis gels, particularly gel-filled capillaries. The polarity of the applied electric field imposed across the gel is periodically reversed between one or more electrophoretic runs.

Abstract: An apparatus for collecting samples by gel electrophoresis has a base table, a cutting tool or an extractor disposed above the base table, a moving mechanism, a pattern detector and a control device. The base table is for placing thereon a gel in the form of a slab with one of its sandwiching support plates removed therefrom in such a way that the gel is exposed in the upward direction. The cutter is for cutting out a specified portion of the gel, and the extractor is for extracting a specified migration band in such a specified portion of the gel by electrophoresis. The moving mechanism is for moving the cutter, or the extractor, three-dimensionally. The pattern detector is for optically detecting migration patterns in the gel on the base table so as to enable the user to determine which part of the gel or which migration band thereon is of interest.

Abstract: A gel electrophoresis method and apparatus is described in which the shape and orientation of the electric field is controlled by contour clamping. Electrodes are arranged around a closed contour. Two or more electrodes, the driving electrodes, are clamped at a potential difference .phi..sub.0 to establish the general orientation and strength of the electric field. The remaining electrodes are clamped to intermediate potentials to control the shape of the field established by the driving electrodes. The field is varied in accordance with the purpose of the electrophoresis, depending upon the size of the particles and the information to be determined concerning the particles.

Abstract: An apparatus for detecting fluorescently-labeled molecules moving in an electrophoretic separation medium. The apparatus utilizes a scanning detection system in which multiple fluorophores are efficiently and simultaneously detected using dichroic mirrors to allow simultaneous detection of fluorescently-labeled molecules in ultrathin gels labeled with several fluorophores and to permit operation at speeds ten times faster than prior art gel separations. The apparatus also utilizes a detection system where lightweight collection optics are in motion while detection optics are fixed in a remote location, thereby allowing exceptionally high-speed scanning.

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: Electrophoresis apparatus with a gel support configured and arranged to hold a gel, a buffer chamber configured and arranged to hold a buffer, with the buffer contacting each end of the gel, and a buffer shaper configured to be positioned near the gel support and in contact with the buffer. The buffer shaper is positioned nearer to one portion of the gel support than to another portion of the gel support to cause the depth of buffer between the gel support and the buffer shaper to vary along the length or width of the gel support and buffer shaper.