Abstract: A method of DNA fragmentation is provided. The method comprising incubating a semi-solid biological sample which comprises the DNA with an auxiliary domain-directed nuclease having a binding affinity and selectivity to pre-defined sites in the DNA so as to yield a DNA fragment-of-interest, to thereby fragment the DNA.

Abstract: The invention provides columns (including pipette tip columns) and automated methods for the purification of nucleic acids including plasmids. Nucleic acids can be purified from unclarified, clarified or partially-clarified cell lysates that contain cell debris. The columns typically include a bed of medium positioned above a bottom frit and with an optional top frit. Plasmid preparation scales include miniprep, midiprep, maxiprep, megaprep and gigaprep.

Abstract: The invention provides an electrophoretic medium comprising at least two types of particles having substantially the same electrophoretic mobility but differing colors. The invention also provides article of manufacture comprising a layer of a solid electro-optic medium, a first adhesive layer on one surface of the electro-optic medium, a release sheet covering the first adhesive layer, and a second adhesive layer on an opposed second surface of the electro-optic medium.

Abstract: Methods and apparatus providing for the isolation of an unknown mutation from a sample comprising wild type nucleic acids and mutated nucleic acids through the application of time-varying driving fields and periodically varying mobility-altering fields to the sample within in an affinity matrix.

Abstract: A system for preparing and analyzing a sample of biological material, including a test cartridge having a first housing defining a flow-through chamber, a second housing defining a central space within which the first housing is at least partially located. The first housing is rotatable relative to the second housing, and the second housing defines a plurality of circumferentially spaced chambers, one of the chambers having an inlet for receiving a sample, at least one of the chambers containing a liquid reagent, and at least one of the chambers comprising an analysis module, the chambers of the second housing each having an opening into the central space. The first housing has one or more openings into the central space so that openings can be selectively aligned with one of the openings into the chambers of the second housing by relative rotation of the first housing and second housings.

Abstract: Two-dimensional gel electrophoresis apparatus includes an electrophoresis zone having four edges defined by a plurality of electrodes. A pair of opposed edges are defined by groups of discrete electrodes. Discrete electrodes within each group are electrically isolated from each other while the other pair of opposed edges are used to generate an electrical field. As a result, the electrical field is less distorted than would be the case if each edge was defined by a single elongate electrode. The apparatus can be provided as a cassette with electrodes configured to guide gas generated during electrolysis out of the cassette through apertures, to reduce the build up of combustible gases.

Abstract: Methods and apparatus for moving and concentrating particles by applying 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: A specified proton concentration in a volume (80) is produced by passing a controlled electrophoresis current through an adjacent electrophoresis volume (28) between a working electrode (26) and a counter electrode (24). An array of such volumes with specified proton concentration is used to provide the pH gradient for isoelectric focusing.

Abstract: Methods and apparatus providing improved fidelity and specificity when separating nucleic acids from a sample, but without need for amplification. In particular, using the disclosed methods, it is possible to isolate a variant nucleic acid (i.e., a mutation) from a non-target nucleic acid (i.e., a wild-type) when the variant is present in the original sample at a much lower concentration than the non-target, e.g., 1:10,000, without substantial loss of the variant.

Abstract: An electrophoresis control device, on the basis of a current value of current flowing due to applying a voltage to a conducting medium, controls an amount of electric power to supply to that conducting medium.

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: A control device for a sample separation apparatus, the sample separation apparatus including a first separation unit and a second separation unit downstream of the first separation unit and supplied with the fluidic sample after treatment by the first separation unit. A control device is configured for controlling the first separation unit to execute a primary separation sequence within a time interval for separating the fluidic sample into fractions, and for controlling the second separation unit to execute secondary separation sequences within the time interval for further separating the separated fractions into sub-fractions, wherein the secondary separation sequences form part of a common sample separation method defined by a common specification of the sample separation involving a set of parameters, and adjusting, over a progress of the primary separation sequence, at least one parameter according to which at least one of the plurality of secondary separation sequences is executed.

Abstract: In one general aspect, an electrophoretic measurement method is disclosed that includes providing a vessel that holds a dispersant, providing a first electrode immersed in the dispersant, and providing a second electrode immersed in the dispersant. A sample is placed at a location within the dispersant between the first and second electrodes with the sample being separated from the electrodes, an alternating electric field is applied across the electrodes, and the sample is illuminated with temporally coherent light. A frequency shift is detected in light from the step of illuminating that has interacted with the sample during the step of applying an alternating electric field, and a property of the sample is derived based on results of the step of detecting.

Abstract: Methods and apparatus providing improved fidelity and specificity when separating nucleic acids from a sample, but without need for amplification. In particular, using the disclosed methods, it is possible to isolate a variant nucleic acid (i.e., a mutation) from a non-target nucleic acid (i.e., a wild-type) when the variant is present in the original sample at a much lower concentration than the non-target, e.g., 1:10,000, without substantial loss of the variant.

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: Methods and apparatus for separating, concentrating and/or detecting molecules based on differences in binding affinity to a probe are provided. The molecules may be differentially modified. The molecules may be differentially methylated nucleic acids. The methods can be used in fields such as epigenetics or oncology to selectively concentrate or detect the presence of specific biomolecules or differentially modified biomolecules, to provide diagnostics for disorders such as fetal genetic disorders, to detect biomarkers in cancer, organ failure, disease states, infection or the like.

Abstract: Methods and apparatus providing improved fidelity and specificity when separating nucleic acids from a sample, but without need for amplification. In particular, using the disclosed methods, it is possible to isolate a variant nucleic acid (i.e., a mutation) from a non-target nucleic acid (i.e., a wild-type) when the variant is present in the original sample at a much lower concentration than the non-target, e.g., 1:10,000, without substantial loss of the variant.

Abstract: Methods and apparatus for separating, concentrating and/or detecting molecules based on differences in binding affinity to a probe are provided. The molecules may be differentially modified. The molecules may be differentially methylated nucleic acids. The methods can be used in fields such as epigenetics or oncology to selectively concentrate or detect the presence of specific biomolecules or differentially modified biomolecules, to provide diagnostics for disorders such as fetal genetic disorders, to detect biomarkers in cancer, organ failure, disease states, infection or the like.

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: 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 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 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 biochip for the integration of all steps in a complex process from the insertion of a sample to the generation of a result, performed without operator intervention includes microfluidic and macrofluidic features that are acted on by instrument subsystems in a series of scripted processing steps. Methods for fabricating these complex biochips of high feature density by injection molding are also provided.

Abstract: The invention provides an electrophoresis cassette, methods for making the electrophoresis cassette, and method of fractionating analytes from a sample based upon electrophoretic mobility in a single application of the sample to an electrophoretic system.

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: The invention provides an electrophoresis cassette, methods for making the electrophoresis cassette, and method of fractionating analytes from a sample based upon electrophoretic mobility in a single application of the sample to an electrophoretic system.

Abstract: A family of PCR assays is disclosed for determining, both qualitatively and quantitatively, presence of material from a predetermined species source and for quantifying the amount of such material. The assays are based respectively on SINEs uniquely characteristic of pig species, cow species, chicken species, and ruminant sub-order, and having a high copy number. The assays disclosed permit rapid, inexpensive evaluation of meat samples to facilitate elimination from their diet of pork or beef by persons desiring to avoid such food sources; as well as the assay of cattle feed to determine presence therein of ruminant-source proteins, which are a potential source of bovine spongiform encephalopathy (BSE), commonly referred to as “mad cow disease.” The assays amplify the predetermined unique SINEs and the resulting amplified mixture is then evaluated qualitatively by electrophoresis on gel containing ethidium bromide or quantitatively by SYBR Green-based detection or TaqMan chemistry.

Abstract: Provided is a method for determining a zeta potential generated between a solid wall and a solution. The method includes (a) injecting an electrolyte solution into a first inlet of a T channel, which is provided with first and second inlet electrodes and a grounded outlet electrode, and a mixed solution of the electrolyte solution and a fluorescent dye into a second channel of the T channel and maintaining a steady-state of the two solutions; (b) applying a direct current electric field from the first and second electrodes to the outlet electrode to form an interface between the electrolyte solution and the mixed solution; (c) applying an alternating current electric field from one of the two inlet electrodes to the outlet electrode to oscillate the interface; and (d) measuring an amplitude of oscillation of the interface and determining the zeta potential from the standard relationship between the zeta potential and the amplitude.

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: 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 to collect a plurality of target zones from a plurality of channels. The method includes introducing a plurality of compound mixtures into a plurality of microchannels on a microfabricated chip or a capillary tube. Optical signal measured at a detector window provides a signal of the position of a target zone. When a target zone has migrated to the location of a detector window, the detector senses an optical signal from the target zone and signals the system to disconnect a driving force from that channel. Once a plurality of zones in a plurality of channels are aligned, the driving force is reconnected and the zones are coeluted into a collection container.

Abstract: A method for separating a chemical or biological compound present in a mixture of similar compounds by diffusion in a medium, the method comprising reacting the compounds of the mixture with a component (P) present in the medium to obtain products (Qi), wherein the reactions Ci+P?Qi are reversible and have kinetic constants k1 and k2, and applying to the medium a varying field to which the compounds are sensitive, wherein the period of the field and the concentration of component (P) in the medium are determined from the kinetic constants (k1,k2) of the compound (C) to be separated in order to establish resonance condition between said reactions and the field and for giving compound C an apparent diffusion coefficient (Da) in the medium that is maximum.

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: An electrophoretic method for purifying a nucleic acid sample is disclosed. According to the method, the electrophoresis is effective to substantially reduce the concentration of contaminants relative to the concentration of desired nucleic acid in the nucleic acid sample, thereby producing a purified nucleic acid. In the method, the loading and recovery wells may be the same or different, and the electric fields may be DC or alternating.

Abstract: A process for rapid typing of yeast, parasites and bacteria is provided. It comprises the following steps: a) Preparing immobilized intact DNA in 5 to 60 minutes aided by a method involving a reagent kit that only contains buffer solution, a detergent, a metal chelating agent and an agent to disrupt the hydrogen bonds. b) Separating intact DNA molecules or their restriction fragments in miniequipments for Pulsed Field Gel Electrophoresis of the CHEF (Contour Clamped Homogeneous Electric Field) and TAFE (Transversal Alternating Field Electrophoresis) systems in times comprised between 2.5 and 7 hours. c) Selecting the optimal conditions that should be set in miniCHEF with the aid of a method to simulate the electrophoresis patterns d) Providing reorientation times, migration velocities and sizes of the molecules calculated with the aid of a method to analyze the migrated distances without the use of size markers.

Abstract: The apparatus and method of the present invention disclose a system in which multiple injections may be made into a capillary array. The injections are spaced in time with each injection followed by an interval of electrophoresis. Once all samples are loaded into the capillaries, continuous electrophoresis and detection is used to separate and detect target compounds within the sample. The interval between injections is matched to the target compound migration rate to be sufficient to allow the target compounds to be detectably separated when the compounds reach the detector.

Abstract: The electrophoresis apparatus comprises rectifier (A) which rectifies an AC current from a universal AC power source and outputs a rectified wave, an electrophoresis cell and an electric controller which applies an electric output from the rectifier (A) to a carrier disposed in the electrophoresis cell, the elastic controller comprising a controller (3) for indirectly controlling, in accordance with external inputs, a driving section (6) which controls an electric output from the rectifier circuit. The electrophoresis cell unit defines a recess for receiving the electric controller, and a cover is positionable over the electrophoresis cell unit. The cover includes a cover terminal, where the cover and cover terminal are shaped to electrically connect an output terminal of the electric controller to an input terminal of the electrophoresis cell unit when the; cell covers the electrophoresis cell unit.

Abstract: In a method for positioning or controlling the motion of an object in a multi-electrode arrangement for forming a field cage, the basic potentials for driving the electrodes are modulated with drive potentials in such a way that the object position in the field cage changes in relation to a predetermined position or path. A device for arranging objects at predetermined positions in a multi-electrode arrangement has a switching device by which basic potentials, produced by generator means, can be modulated according to predetermined drive potentials (FIG. 1).

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: 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 method for screening a plurality of compounds is used in conjunction with microfluidic devices for performing high throughput screening assays. A conveyor system is used to transport and dispense libraries of compounds into one or more sample port of a microfluidic device. The microfluidic device accesses the compounds in order to screen large numbers of different compounds for their effects on a variety of chemical and biochemical systems.

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 method of stacking or condensing DNA or other samples prior to electrophoresis to improve electrophoretic resolution. A sample material is placed on a separation medium, e.g., polyacrylamide or agarose gel. A relatively low voltage is applied across the sample for a short period to stack or condense the sample material without significantly transporting the sample material into the separation medium. A large voltage is then applied to inject the stacked sample material into the separation medium.