Abstract: An electrophoresis apparatus is provided in which negative effects caused by abnormalities in a current-carrying path in an electrophoresis apparatus can be avoided or reduced. The current flowing in the current-carrying path during electrophoresis can be measured to detect the state of a separating medium, and the application of a voltage to the current-carrying path can be interrupted.

Abstract: A droplet/electrospray device and a liquid chromatography-electrospray system are disclosed. The droplet/electrospray device comprises a substrate defining a channel between an entrance orifice on an injection surface and an exit orifice on an ejection surface, a nozzle defined by a portion recessed from the ejection surface surrounding the exit orifice, and an electrode for application of an electric potential to the substrate to optimize and generate droplets or an electrospray. A plurality of these electrospray devices can be used in the form of an array of miniaturized nozzles. The liquid chromatography-electrospray device comprises a separation substrate defining an introduction channel between an entrance orifice and a reservoir and a separation channel between the reservoir and an exit orifice, the separation channel being populated with separation posts perpendicular to the fluid flow.

Abstract: A method and device is disclosed for rapidly identifying a large number of proteins by placing a protein mixture in a sample chamber of an electrophoresis gel, and performing electrophoresis to separate the mixture by molecular weight, in a direction of separation, into a two-dimensional separation pattern in the gel. The separation pattern is transferred to a membrane, such as a sheet of nitrocellulose, and a plate with a set of separate, side-by-side slots is then applied to the membrane. A different antibody mixture is introduced into each of the slots by perfusing each antibody mixture under pressure through the slots. The antibody mixture that is perfused through each slot recognizes several different proteins of sufficiently different molecular weights that different protein bands can be resolved by the antibody mixture in each slot.

Abstract: The invention provides an electrophoresis apparatus comprising an electrophoretic chamber containing at least on two-plate housing for a sieving matrix, each said at least one two-plate housing consisting of a cover plate and a plate for housing said sieving matrix, wherein said plate includes an optical waveguide array which is characterized by being aligned with respect to a reference direction such as to enable one or more light beams incident on the sieving matrix along said reference direction to be maintained well-confined along said reference direction within any desired length of interaction along the width of said sieving matrix.

Abstract: With a method of controlling the flow in a flow system where a liquid flow contains a particle concentration, the liquid flow is surrounded by a carrier liquid. The liquid flow and carrier liquid are led into a central channel in which there is provided an observation area (4) where measurements of the liquid flow are effected. The result of the measurements are used to lead the liquid flow into one of several channels, in that control liquids are introduced into the liquid flow before this reaches the channels, the control liquids being derived from a capillary pump structure which pumps on the basis of an electro-kinetic effect, e.g. an electro-osmotic effect. In a preferred embodiment, the pump structure consists of two capillary structures, to each of which an electrical field can be applied. Depending on the strength of the field, the amount of control liquid will be able to be controlled so that the liquid flow with the particle concentration can be led to one of two channels.

Abstract: The invention provides a method of performing one- and two-dimensional electrophoresis with or without gel in an automated way. The two dimensional electrophoresis can be performed either separately or continuously. Both electrokinetic and hydrodynamic forces can be used to facilitate sample transfer from the first to the second dimension. The samples can be detected on-line by using common detectors like UV-Vis, laser induced fluorescence (LIF), and mass spectrometry (MS).

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: A modular multiple lane or capillary electrophoresis (chromatography) system that permits automated parallel separation and comprehensive collection of all fractions from samples in all lanes or columns, with the option of further on-line automated sample fraction analysis, is disclosed. Preferably, fractions are collected in a multi-well fraction collection unit, or plate (40). The multi-well collection plate (40) is preferably made of a solvent permeable gel, most preferably a hydrophilic, polymeric gel such as agarose or cross-linked polyacrylamide.

Abstract: The invention provides uncharged water-soluble silica-adsorbing polymers for suppressing electroendoosmotic flow and to reduce analyte-wall interactions in capillary electrophoresis. In one aspect of the invention, one or more of such polymers are employed as components of a separation medium for the separation of biomolecules, such as polynucleotides, polysaccharides, proteins, and the like, by capillary electrophoresis. Generally, such polymers are characterized by (i) water solubility over the temperature range between about 20° C. to about 50° C., (ii) concentration in a separation medium in the range between about 0.001% to about 10% (weight/volume), (iii) molecular weight in the range of about 5×103 to about 1×106 daltons, and (iv) absence of charged groups in an aqueous medium having pH in the range of about 6 to about 9.

Abstract: The present invention relates to microfabrication and utilization of microscale electrophoresis devices as well as the separation and detection of biomolecules in microscale electrophoresis devices. The device of the present invention utilizes novel fabrication and detection methods.

Abstract: Embodiments of a device and method are described which provide for control over the distortion of a sample zone upon exiting an electrophoresis separation channel. According to the teachings herein (i) the downstream regions of the channels, near the outlet ends, and/or (ii) the detection chamber, is/are configured so that distortion of one or more sample zones passing from the channels into and across the detection chamber can be controlled (e.g., reduced) in a fashion affording enhanced detectability. In certain embodiments, the lumens along the end regions of the separation channels progressively expand.

Abstract: A method for determining a DNA sequence includes providing a sample which contains first DNA fragments having adenines at an end and labeled by first fluorophores, second DNA fragments having thymines at an end and labeled by second fluorophores, third DNA fragments having cytosines at an end and labeled by third fluorophores, and fourth DNA fragments having guanines at an end and labeled by fourth fluorophores, wherein each of the first to fourth fluorophores is different. The sample is supplied into a capillary and the sample is made to migrate in the capillary. A sheath flow is formed around an end of the capillary where the sample migrates, a light is irradiated into the sheath flow to excite the fluorophores. Fluorescence emitted from the fluorophores is detected and the fluorophores are identified.

Abstract: A capillary array capable of being easily mounted on an electrophoresis apparatus without damaging the capillaries. The capillary array can include a plurality of capillaries that can be fixed via hollow electrodes on a load header in a matrix arrangement. The load header can be disposed on the electrophoresis apparatus. The capillary array can include a capillary frame onto which a capillary head and a detection portion can be detachably mounted. The structure allows the load header, the capillary head, the detection unit and other portions of the capillary array to be handled as a unit, thereby making it easier to mount the capillary array on the electrophoresis apparatus.

Abstract: A method and apparatus are disclosed for screening separation media for performance in capillary electrophoresis. In one aspect the invention comprises concurrently loading a plurality of capillaries from one corresponding end of each with a respective plurality of separation media, adding a sample to each capillary, advancing the samples through the capillaries under an applied electric field, measuring a property of the samples or components thereof as they advance through the capillaries, and using the measured properties to identify one or more preferred sets of separation media. At least one of the steps of loading or advancing are carried out simultaneously over the plurality of capillaries.

Abstract: The invention relates to methods used for mass spectrometric analysis of substances separated by capillary electrophoresis, in particular biopolymers such as proteins, proteoglycanes or other protein conjugates or their digest peptides. The invention consists in reducing the electrophoresis voltage upon appearance of the first analytically interesting substance, thereby maintaining the high separation power and gaining sensitivity. With direct coupling, e.g. by electrospray, the electrophoretic voltage may be directly controlled by the ion current measured by the mass spectrometer.

Abstract: A microfluidic component having a microfluidic channel is bonded to an electronics component having a circuit for processing signals related to the microfluidic component. In an embodiment, the electronics component is a prefabricated integrated circuit chip that includes signal processing and/or process control functionality. The bonding of the microfluidic component to the electronics component provides a modular architecture in which different combinations of microfluidic components and electronics components can be used to create customized processing and analysis tools.

Abstract: A capillary electrophoresis system comprises capillaries positioned in parallel to each other forming a plane. The capillaries are configured to allow samples to migrate. A light source is configured to illuminate the capillaries and the samples therein. This causes the samples to emit light. A lens is configured to receive the light emitted by the samples and positioned directly over a first group of the capillaries and obliquely over a second group of the capillaries. The light source is further configured to illuminate the second group of capillaries more than the first group of the capillaries such that amount of light received by the lens from the first group of capillaries is substantially identical to amount of light received from the second group of capillaries when an identical amount of the samples is migrating through the first and second group capillaries.

Abstract: The invention concerns a multiple capillary electrophoresis system including many juxtaposed capillaries, at least one source for transmitting a beam designed to excite the molecules present in its path and inside the capillaries, and detection of the fluorescence of the molecules excited by said beam. The invention is arranged so as to detect the light emerging at the output of said capillaries and propagated along a direction wherein the capillaries extend and the detection resolution is sufficient for distinguishing the light emerging at the output of the capillaries from that coming from the walls thereof and/or their surrounding medium.

Abstract: A method of imaging molecules of interest within a biological sample includes shining a UV light onto the sample and detecting the molecular UV absorption. Where the molecules of interest are themselves UV absorbers, the intrinsic absorption of those molecules may be used. If the molecules of interest are not good UV absorbers, UV-aborbing tag molecules may be use. The method may be used in molecular imaging devices of all types, and in DNA sequences. A novel diamond-based detector is disclosed which is suitable for many applications.

Abstract: An improved rotary confocal fluorescence scanner capable of detecting analytes separated on over a 1,000 capillaries simultaneously. This system uses a confocal microscope objective and mirror assembly that rotates inside a vertical ring of capillaries to provide rapid and efficient excitation and detection of fluorescently labeled fragments separated within a cylindrical capillary array. Use of automated procedures to load and run all capillaries permits one to read more than 350,000 base pairs of raw sequence data per hour.

Abstract: A multiplexed capillary electrophoresis system with cooling sufficient to prevent overheating during chiral separation. The system includes a thermally insulated enclosure enclosing a bundle of capillary tubes, a light source and photodetector. A heat transfer system is provided for cooling closely spaced portions and spread apart portions of the capillary tubes to an extent sufficient to prevent overheating of the tubes and contents thereof due to the heat generated during chiral separation.

Abstract: Embodiments of a device and method are described which provide for control over the distortion of a sample zone upon exiting an electrophoresis separation channel. According to the teachings herein (i) the downstream regions of the channels, near the outlet ends, and/or (ii) the detection chamber, is/are configured so that distortion of one or more sample zones passing from the channels into and across the detection chamber can be controlled (e.g., reduced) in a fashion affording enhanced detectability. In certain embodiments, the lumens along the end regions of the separation channels progressively expand.

Abstract: The invention relates to a method for the qualitative and/or quantitative analysis of a protein and/or peptide pattern of a liquid sample that is derived from the human or animal body. The proteins and peptides of the liquid sample are separated by capillary electrophoresis, then directly ionized and transferred for analysis online via an interface to a mass spectrometer coupled thereto.

Abstract: The invention relates to a method by which a sample can be taken from a process and be analyzed by means of a capillary electrophoresis apparatus on-line, and to a capillary electrophoresis apparatus which comprises containers containing a background electrolyte solution, the containers communicating with each other by mediation of a separation capillary (1), current electrodes (E) connected to a source of voltage, and a detector (4) substantially in the vicinity of the exit end of the separation capillary (1), as well as one or more solution containers on the injection side of the apparatus, at least one of the containers being a sample collector in which the sample coming from the process is collected, and one or more solution containers on the detector side of the apparatus, the ends of the said separation capillary (1) being located in expansions (5, 6) continuing from the lower ends of capillary ducts (2, 3) intended for feeding in various solutions from the containers, the said expansions continuing as

Abstract: A capillary electrophoresis device having a substrate layer and a cover layer, with a plurality of electrophoresis channels formed in the substrate layer, includes an optical waveguide system that transmits excitation radiation from a source port into each one of the electrophoresis channels. The optical waveguide system is defined by regions, within either the cover or substrate, that have an index of refraction higher than that of the surrounding material.

Abstract: A multi-channel and multi-color bio-separation detection method and apparatus in which a single detector is coupled to a plurality of radiation sources, in a one detector/many radiation sources configuration. Each radiation source directs radiation at a detection zone of a single separation channel, and a single detector is applied to detect light emissions from the detection zones associated with several radiation sources. The radiation sources are activated to direct radiation at the detection zone in a predetermined sequence and further in a cyclic manner, with the detector output synchronized to the radiation sources by a controller. Bio-separation may be conducted simultaneously in all the channels in parallel, with detection time-staggered and/or time multiplexed with respect to the light sources. In one embodiment, low cost light emitting diodes may be used as radiation sources.

Abstract: The present method provides methods and apparatus for separating proteins using a series of electrophoretic methods that utilize controlled fractionation and labeling techniques to resolve mixtures of proteins. The samples for each electrophoretic method other than the initial method, contain only a subset of proteins resolved in the preceding method. The methods can be used in a variety of different applications including, creating proteomic databases, comparative expression studies, diagnostics, structure activity relationships and metabolic engineering investigations.

Abstract: An electrophoresis apparatus includes an optical cell having an outlet for fluid and filled with a buffer solution, and a plurality of electrophoresis lanes, each including a separation medium, which separate samples labeled with fluorophores, one end of each of the electrophoresis lanes being disposed in the optical cell to enable the separated samples labeled with the fluorophores to migrate from the electrophoresis lanes into the buffer solution in the optical cell. There is also provided a vessel containing a buffer solution, the vessel being disposed so that a level of the buffer solution in the vessel is higher than the ends of the electrophoresis lanes disposed in the optical cell, a passage connecting the vessel with the optical cell, a light source which emits light which excites the fluorophores to emit fluorescence, and a photodetector which detects the fluorescence emitted by the fluorophores.

Abstract: An apparatus and a method for reading a gel electrophoresis pattern can read the gel electrophoresis pattern of a sample, such as a nucleic acid and a protein, with high sensitivity and without requiring the use of an expensive device structure such as a laser light source of unique type.

Abstract: An improved rotary confocal fluorescence scanner capable of detecting analytes separated on over a 1,000 capillaries simultaneously. This system uses a confocal microscope objective and mirror assembly that rotates inside a vertical ring of capillaries to provide rapid and efficient excitation and detection of fluorescently labeled fragments separated within a cylindrical capillary array. Use of automated procedures to load and run all capillaries permits one to read more than 350,000 base pairs of raw sequence data per hour.

Abstract: A cuvette cartridge for optical measurements is disclosed herein, the cartridge comprising a flat, adhesive sheet having a selected thickness that defines an optical path length perpendicular to the longitudinal axis of such sheet; wherein a portion of the adhesive sheet is cut out to define at least one optical chamber of a desired length; wherein the adhesive sheet is placed between a first flat sheet and a second flat sheet, the first flat sheet comprising at least one inlet hole and at least one outlet hole, the vent hole being located at a first end of the optical chamber and the inlet hole being located at a second end of the optical chamber. An integrated analytical system employing this cartridge and optionally including a vacuum chuck for holding and registering the cartridge are also disclosed.

Abstract: Analytical systems and methods that use a modular interface structure for providing an interface between a sample substrate and an analytical unit, where the analytical unit typically has a particular interface arrangement for implementing various analytical and control functions. Using a number of variants for each module of the modular interface structure advantageously provides cost effective and efficient ways to perform numerous tests using a particular substrate or class of substrates with a particular analytical and control systems interface arrangement. Improved optical illumination and detection system for simultaneously analyzing reactions or conditions in multiple parallel microchannels are also provided.

Abstract: The present invention concerns methods and apparatus for the high resolution, high output electrophoretic separation of molecules. In preferred embodiments, the methods and apparatus are of use for DNA sequencing. The apparatus comprises a hybrid device, comprising a microfabricated chip injector attached to an array of one or more capillaries. The chip injector is designed with incorporation and injector channels that precisely match the capillaries, to minimize or eliminate dead volume in the system. DNA sequencing runs of over 700 bases, with a run time of less than one hour, may be accomplished with the methods and apparatus disclosed herein.

Abstract: The electrophoresis apparatus includes plural capillaries for separating fluorephore-labeled samples by electrophoresis, fluorescence detecting parts provided in a part of these capillaries arranged in the same place for detecting a fluorescence emitted by fluorephore labels when a part of the plural capillaries is scanned and irradiated by a laser beam, and a fluorescence detection system for detecting this fluorescence. The fluorescence detecting parts are scanned and repeatedly irradiated by the laser bean where a scanning period of the fluorescence detecting parts by the laser bean is t1, and the fluorescence is detected by the fluorescence detecting system where an acquisition time of fluorescence signal is t2 (t1≦t2). The laser bean from a laser source is narrowly converged by a light collecting lens, and a galvanomirror is rotated in a rotation directional of the galvanomirror around the rotation axis of the galvanomirror so as to repeatedly scan the fluorescence detecting parts.

Abstract: A parallel capillary electrophoresis system for separating and analyzing the components of multiple chemical samples. The system comprises a bundle of capillary tubes arrayed to have at least portions of the tubes extending generally parallel to one another, a light source for emitting light to pass through the capillary tubes, and a photodetector comprising a linear array of photodetector elements for receiving light passing through the capillary tubes. The improvement involves mounting the photodetector for rotation whereby the angular position of the linear array of photodetector elements can be adjusted to an optimal position for analyzing the light passing through the capillary tubes.

Abstract: Provided are methods of screening and identification of bioactivities and bioactive molecules of interest using a capillary array system. More specifically, disclosed are methods of using optical detection and capillary array-based techniques for screening libraries and recovering bioactive molecules having a desired activity or a nucleic acid sequence encoding such bioactive molecules.

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: Microfluidic devices and systems having enhanced detection sensitivity, particularly for use in non-fluorogenic detection methods, e.g., absorbance. The systems typically employ planar microfluidic devices that include one or more channel networks that are parallel to the major plane of the device, e.g., the predominant plane of the planar structure, and a detection channel segment that is substantially orthogonal to that plane. The detection system is directed along the length of the detection channel segment using a detection orientation that is consistent with conventional microfluidic systems.

Abstract: A self-adjusting, free-flowing pneumatic nebulizer interface is described for coupling fluid phase separation apparatus such as capillary electrophoresis apparatus or fluid-phase analyte delivery apparatus such as flow-injection analysis apparatus to gas phase, post-separation detection apparatus such as mass spectrometers, chemiluminescence detectors, or other similar gas phase detection apparatus. The interface combines the analytes with only the needed amount of sheath fluid to produce a combined flow whose magnitude automatically matches the self-aspiration rate of the pneumatic nebulizer interface, and which is combined with a gas flow to produce an aerosol. The resulting aerosol can then be either deposited directly on a surface, forwarded directly to a detection system or forwarded first to a conversion apparatus such as an oxidizer and the oxidized sample components are then forwarded to a detector.

Abstract: A high-efficiency, high-sensitivity absorbance detection system in a lab-on-a-chip is provided. The absorbance detection system includes detection cells having an optical pathlength ten times and/or much longer than the width of a separation channel to improve detection sensitivity, lens structures for collimating light in the detection cells, and slit structures for preventing scattered light from entering detectors. The detection cells, the lens structures, and the slit structures of the absorbance detection system are fabricated and integrated in a lab-on-a-chip. The absorbance detection system exhibits excellent absorption efficiency, detection limit, and linearity, compared to existing absorbance detection systems, and can be applied for the detection of a variety of samples. The absorbance detection system does not need labeling of the samples which saves time and costs. The absorbance detection system can be used effectively in detecting trace compounds with a high sensitivity.

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 of characterizing a polypeptide, comprising providing a first capillary channel having a separation buffer disposed within, wherein the separation buffer comprises a non-crosslinked polymer solution, a buffering agent, a detergent, and a lipophilic dye. The separation buffer is provided such that, at the time of detection, the detergent concentration in the buffer is not above the critical micelle concentration. The polypeptide is introduced into one end of the capillary channel. An electric field is applied across a length of the capillary channel, which transports polypeptides of different sizes through the polymer solution at different rates. The polypeptide is then detected as it passes a point along the length of the capillary channel.

Abstract: A data processing part comprises a time-series data production part for producing time-series data as to each capillary column from a scan waveform obtained by an optical measuring part, further comprises a correction data storage part for storing correction data indicating the relation between the number of data points of saturated parts and light intensity data obtained on the assumption that a peak is unsaturated as to a saturated scan waveform peak and a saturated data correction part obtaining light intensity data as to the saturated peak included in the scan waveform on the basis of the correction data stored in the correction data storage part, and employs the light intensity data obtained by the saturated data correction part as the time-series data.

Abstract: The claims provide for detecting prions in a sample by (a) subjecting a sample to membrane-based electrophoresis to separate and/or concentrate at least some prions present in the sample; and (b) detecting and or identifying the presence of the separated and/or concentrated prions.

Abstract: A sieving medium for use in the separation of analytes in a sample containing at least one such analyte comprises a monomeric non-ionic surfactant of the of the general formula, B-A, wherein A is a hydrophilic moiety and B is a hydrophobic moiety, present in a solvent at a concentration forming a self-assembled micelle configuration under selected conditions and having an aggregation number providing an equivalent weight capable of effecting the size separation of the sample solution so as to resolve a target analyte(s) in a solution containing the same, the size separation taking place in a chromatography or electrophoresis separation system.

Abstract: An electrospray device, a liquid chromatography device and an electrospray-liquid chromatography system are disclosed. The electrospray device comprises a substrate defining a channel between an entrance orifice on an injection surface and an exit orifice on an ejection surface, a nozzle defined by a portion recessed from the ejection surface surrounding the exit orifice, and an electrode for application of an electric potential to the substrate to optimize and generate an electrospray; and, optionally, additional electrode(s) to further modify the electrospray.

Abstract: Microfluidic devices and systems having enhanced detection sensitivity, particularly for use in non-fluorogenic detection methods, e.g., absorbance. The systems typically employ planar microfluidic devices that include one or more channel networks that are parallel to the major plane of the device, e.g., the predominant plane of the planar structure, and a detection channel segment that is substantially orthogonal to that plane. The detection system is directed along the length of the detection channel segment using a detection orientation that is consistent with conventional microfluidic systems.

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 acrylamide, 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: An electrophoretic system having a plurality of separation lanes is provided with an automatic color calibration feature in which each lane is separately calibrated. For each lane, a dye matrix standard is created using reference fragments which migrate either before, or after, the sample fragments being electrophoresced, during the same electrophoresis run. These dye standards are detected automatically for the purpose of determining coefficients used to identify sample fragments mixed together with the reference fragments. This allows for calibrating the dye standard matrix for each of a plurality of lanes each time the electrophoresis system is used.

Abstract: Embodiments of a device and method are described which provide for control over the distortion of a sample zone upon exiting an electrophoresis separation channel. According to the teachings herein (i) the downstream regions of the channels, near the outlet ends, and/or (ii) the detection chamber, is/are configured so that distortion of one or more sample zones passing from the channels into and across the detection chamber can be controlled (e.g., reduced) in a fashion affording enhanced detectability. In certain embodiments, the lumens along the end regions of the separation channels progressively expand.