Abstract: The field of the present invention relates generally to a microstructure apparatus which may be used in a high-throughput screening context to monitor the rate of reaction of an enzyme with its substrate in cases where the product of the reaction has an altered net charge. For example, the systems and methods disclosed herein may be used to detect the activity of phosphatase enzymes, proteases and kinases on charged peptide substrates. The microstructure devices of the present invention comprise a plurality of microstructures, wherein each microstructure comprises a capture matrix located between two electrodes.

Abstract: This invention relates to an electrophoresis separation medium having a gel matrix of at least one random, linear copolymer comprising a primary comonomer and at least one secondary comonomer, wherein the comonomers are randomly distributed along the copolymer chain. The primary comonomer is an acrylamide or an acrylamide derivative that provides the primary physical, chemical, and sieving properties of the gel matrix. The at least one secondary comonomer imparts an inherent physical, chemical, or sieving property to the copolymer chain. The primary and secondary comonomers are present in a ratio sufficient to induce desired properties that optimize electrophoresis performance. The invention also relates to a method of separating a mixture of biological molecules using this gel matrix, a method of preparing the novel electrophoresis separation medium, and a capillary tube filled with the electrophoresis separation medium.

Abstract: Improved sealing for microstructures in microfluidic devices having a plurality of units is provided by providing collars surrounding the openings to the microstructures, such as reservoirs. The collars are protrusions extending from the surface of the devices and the internal walls of the collars generally aligned with the internal walls of the microstructure. Conformable and/or adhesive lids are employed for sealing the microstructures.

Abstract: An apparatus for conducting a microfluidic process and analysis, including at least one elongated microfluidic channel, fluidic transport means for transport of fluids through the microfluidic channel, and at least one thick-film electrode in fluidic connection with the outlet end of the microfluidic channel. The present invention includes an integrated on-chip combination reaction, separation and thick-film electrochemical detection microsystem, for use in detection of a wide range of analytes, and methods for the use thereof.

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: 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: A method of injecting, isolating and separating mixed analytes from one or more samples. The method includes collecting successive fractions from each of a plurality of samples at discrete points in time. Fractions may be analyzed at the time of collecting, or later, using one or more detector systems. In one embodiment, a processor controls the elutions of fractions by modulating the migration field in a separation pathway. The processor also controls distribution of the fraction into a particular collection well of a plurality of collection wells.

Abstract: A medium comprises an electrolyte wherein is dissolved at least an assembly of block copolymers characterized in that the block copolymers: are present in the electrolyte at a concentration level to provide the medium with the property of reversibly passing from a state of viscosity V1, obtained at a temperature T1, to a viscosity state V2 greater by at least 100% than V1, obtained at a temperature T2, and comprise in their structure at least: two non-contiguous polymeric segments having in the electrolyte a lower critical solubility temperature (LCST) and having an average number of atoms along their skeleton more than 50; and a polymeric segment soluble in the electrolyte at temperatures T1 and T2. The invention also concerns the use of the medium for separating analytes.

Abstract: The present invention relates to an electrophoretic device in the form of a casing having inside sealed spaces isolated by an electrophoretic carrier, wherein the device comprises at least one liquid injection/discharge opening, communicable with the outside, on the outer wall of said sealed spaces, and an electrophoretic method and a specimen detection method using the device. Additionally, the present invention relates to an electrophoresis apparatus having a structure for sandwiching the electrophoretic carrier between a pair of electrodes, and having a space capable of holding liquid between the sandwiched electrophoretic carrier and the respective electrodes, and to an electrophoretic method using the same device.

Abstract: The structure of a capillary head section is made such that the liquid contacting surfaces of a capillary holder, a capillary, and an adhesive form a plane surface, and this shared liquid contacting surface is made a mirror surface with a surface roughness of 3.2 s or less. In the shared liquid contacting surface, the ratio of the total area of the capillaries to the internal diameter area of the capillary holder is made 60 to 73%.

Abstract: Compositions and methods are provided for performing capillary electrophoresis using a composition comprising in combination in an aqueous buffered medium a coating polymer and a sieving polymer, where the sieving polymer is more hydrophilic than the coating polymer and is present in greater amount. Of particular interest are uncrosslinked acrylamide polymer mixtures for coating plastic channels and providing sieving for performing DNA separations in microfluidic devices. Polyacrylamide or N,N-dimethyl acrylamide is used with a N,N-dialkyl acrylamide copolymer, either separately or together for sieving and coating, serving as the medium in capillary electrophoresis DNA separations.

Abstract: Methods for selectively separating at least one component from a multi-component componant fluidic sample are provided. In the subject methods, the fluidic sample is introduced into a micro-fluidic device that includes at least one micro-valve made up of a phase reversible material. The multi-component fluidic sample is then contacted with the microvalve in a microfluidic device under conditions sufficient for the at least one component to enter the microvalve, while the remaining constituents of the fluidic sample remain outside of the microvalve. Also provided are kits for use in practicing the subject methods, where the kits include at least a microfluidic device having a microvalve and instructional material (or means for obtaining the same) on how to use the device in the subject methods. The subject devices find use in a variety of applications, including sample desalting and concentration applications.

Abstract: The present invention provides a method for producing a high-quality capillary tube used in an electrophoresis apparatus in a safe and inexpensive manner.

Abstract: Disclosed herein are multidimensional electrophoresis devices and methods of using thereof. The multidimensional electrophoresis devices comprise short microchannels having lengths of less than about 1 millimeter to about 5 centimeters. The microchannels may comprise solid sieving medium having different sieving characteristics. IEF and PAGE, including SDS-PAGE and native PAGE, using the multidimensional electrophoresis devices takes only a few minutes or less to perform.

Abstract: The capillary electrophoresis device using one pressure-resistant syringe (125) is capable of automatically suctioning in polymer solution and injecting polymer solution into a capillary array (100). An electric hook (131) is installed for pulling up the syringe plunger on a push-in action type syringe (125). A check valve (124) is inserted between a polymer bottle (123) and syringe to prevent solution from flowing back into the polymer bottle. As a result, one syringe portion of polymer solution can be suctioned and injected, a large volume of polymer solution can be continuously used and device processing capability is improved.

Abstract: An injection syringe 14 for injecting a gel into a capillary 111, a charging syringe 15 for charging the injection syringe 14 with the gel 10 are attached to a block 17. A check valve 16 is inserted between the both syringes, and the check valve 16 works so as to prevent the gel 10 from flowing back to the charging syringe 15. As the result, the gel charging can be automated, and accordingly the processing ability of the electrophoretic instrument can be improved.

Abstract: The present invention provides, in one aspect, an apparatus for electrophoretic separation of analytes. In one aspect, the apparatus comprises a disc-shaped substrate defining (1) a central reservoir region, (2) a plurality of electrophoretic channels in fluid communication with, and emanating substantially radially from, the central reservoir region, the channels being coplanar with each other, and each channel having (i) a proximal end which is linked to the reservoir region, and (ii) a distal end, and preferably (3) for each channel, at least one chamber, and preferably three chambers, linked by a passageway in fluid communication with the distal end of that channel.

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: An electrochromatographic device is provided for conducting enantioselective separation of enantiomers. The device is comprised of a conduit containing a monolithic enantioselective separation medium, and may be, for example, a capillary tube or a microchannel in a substrate. The enantioselective separation medium is prepared by copolymerization of (a1) an ionizable chiral monomer or (a2) a chiral monomer and an ionizable comonomer, along with (b) a crosslinking comonomer and (c) a polymerization initiator, in (d) a porogenic solvent. Following ionization, the enantioselective separation medium serves as a charge carrier as well as a chiral separation medium, and further acts as an electroosmotic pump to facilitate the flow of a fluid. The invention also provides methods for preparing the enantioselective separation medium and electrochromatographic devices fabricated therewith.

Abstract: The invention concerns a method for separating particles or molecules whereby these particles or molecules are introduced in a separating medium and a moving force is applied to them in said medium. The method is characterised in that the separating medium is a ferrofluid, i.e. a colloidal suspension of magnetic particles and a magnetic field is applied to this ferrofluid generating therein at least an alternation of a zone rich in magnetic particles and a zone poor in magnetic particles, part at least of the region of the ferrofluid in which this alternation is generated is passed through by the particles or molecules to be separated during their migration.

Abstract: The invention relates to a method and a device for detecting marked biopolymers, especially nucleic acid fragments in a gel matrix. A parallel separation takes place in a number of microcapillaries that are filled with a gel matrix.

Abstract: Various embodiments provide, for example, buffer compositions and/or sieving formulations useful in connection with electrophoresis instruments, such as capillary electrophoresis (CE) devices. In various embodiments, a buffer composition can include Bis-Tris, TAPS and/or TAPSO, and, optionally, a chelating agent, such as EDTA. Methods of separating samples containing bio-molecules, such as DNA or RNA, are also described.

Abstract: An apparatus and method are described for capillary separation of macromolecules and precise post-separation blotting. Apparatus include disposable separating element (capillary), which contains a sieving or interaction matrix inside, an external layer of blotting material, positioned close to the boundary of said sieving or interaction matrix, and the membrane with changeable permeability for separated material; said membrane separates blotting layer from the sieving or interaction matrix. After separation of macromolecules in capillary with initially non-permeable walls, chemical or physical modification of the membrane is performed, which is followed by changing the vector of driving forces for transfer, so that separated molecules are moved through the walls of the capillary and blotted to the outer layer of separating element, which contains blotting material. Means of modification of the membrane include chemical or physical modification, leading to changes in permeability.

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 multi-capillary electrophoresis apparatus is provided for reducing errors during analysis caused by fluctuations in electrophoresis time among plural capillaries of the apparatus. The multi-capillary electrophoresis apparatus can contain a multi-capillary array that has a separation medium filled therein for isolating a sample. A detector component can be provided at a position remote from a sample injecting end of the array for acquiring information from the sample. A buffer container can be provided for holding a buffer solution into which the sample injecting end can be immersed. One or more temperature controlling component devices can be arranged for controlling a temperature of the buffer solution, of the detector component, or of both the buffer solution and the detector component.

Abstract: The present invention includes apparatus for simultaneous loading of multiple samples for molecular separation, including a separation area with walls wherein at least one of the walls has apertures having loading sites, a gel located within the separation area, and a plurality of wells within the gel. The apertures are connected to the plurality of wells by channels structurally configured to convey samples from the apertures to the wells.

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: Apparatus for simultaneous loading of multiple samples for molecular separation, including a separation area with walls, at least one of the walls has apertures having loading sites, a gel located within the separation area, and a plurality of wells within the gel. The loading sites are offset with respect to the wells. The apertures are connected to the plurality of wells by channels structurally configured to convey samples from the apertures to the wells, and apparatus for electrophoresis separation having an electrophoresis area, an electrophoresis gel located within the electrophoresis area, and multiple rows of wells within the electrophoresis gel, wherein the rows are arranged in an alternating staggered format. A method for simultaneous loading of multiple samples into the electrophoresis apparatus.

Abstract: The present invention provides for a column for use in capillary electrochromatography including a tube, wherein the tube includes an inner surface having a positively or negatively charged, chemically-bonded stationary coating thereon. The present invention further provides for a method of making a column for use in capillary electrochromatography, including a tube, wherein the tube includes an inner surface having a positively or negatively charged chemically-bonded stationary coating thereon, wherein the steps include filling the column with a sol-gel solution, maintaining the sol-gel solution within the column, and forcing the sol-gel solution out of the column with an inert gas. Further, the present invention provides for a method of analytical separation with a column including an inner layer having a positively charged chemically-bonded stationary coating thereon that reverses the direction of electroosmotic flow in the column compared with a column without the positive surface charge.

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: 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: One embodiment of the invention relates to a microfluidic apparatus for performing two dimensional biomolecular separations. According to one aspect of the invention, after a first dimension separation in a first microchannel, the sample material is electrokinetically and simultaneously transferred to an array of microchannels in the second dimension (e.g., by changing the electric potentials at the reservoirs connected to the microchannels). Preferably any separation accomplished in the first dimension is completely retained upon transfer to the second dimension. According to another aspect of the invention, the separation in the second dimension is performed using a temperature gradient (e.g., a spatial or temporal temperature gradient). According to one embodiment of the invention, the biomolecular material comprises DNA and the first dimension separation is a sized-based separation and the second dimension separation is a sequence-based separation.

Abstract: A low molecular weight non-entangled polyvinylpyrrolidone for use as a separation media for microchannel electrophoretic separation. The separation media may be used in a system in which multiple samples of small compounds are injected into a single microchannel at time spaced intervals followed by a continuous detection interval.

Abstract: The invention provides a device and method for the manipulation of materials (e.g., particles, cells, macromolecules, such as proteins, nucleic acids or other moieties) in a fluid sample. The device comprises a substrate having a plurality of microstructures and an insulator film on the structures. Application of a voltage to the structures induces separation of materials in the sample. The device and method are useful for a wide variety of applications such as dielectrophoresis (DEP) or the separation of a target material from other material in a fluid sample.

Abstract: The invention provides a microfluidic apparatus for performing 2-D biomolecular separations. The microfluidic 2-D device may include first and second planar substrates which include at least a first dimension microchannel extending in a first direction and an array of second dimension microchannels extending in a second direction, preferably, orthogonal to the first dimension. The ends of at least some of the microchannels are in fluid communication with a plurality of reservoirs. The substrates may further include a number of microchannels and reservoirs. The reservoirs are in electrical communication with a plurality of electrodes and voltage power sources. The device enables two dimensional separations of proteins and other biomolecules. According to another aspect of the invention, an isoelectric point based separation is enabled in a first dimension, and a size based separation in a second dimension.

Abstract: An apparatus and method are described for capillary separation of macromolecules and precise post-separation blotting. Apparatus include disposable separating element (capillary), which contains a sieving or interaction matrix inside, an external layer of blotting material, positioned close to the boundary of said sieving or interaction matrix, and the membrane with changeable permeability for separated material; said membrane separates blotting layer from the sieving or interaction matrix. After separation of macromolecules in capillary with initially non-permeable walls, chemical or physical modification of the membrane is performed, which is followed by changing the vector of driving forces for transfer, so that separated molecules are moved through the walls of the capillary and blotted to the outer layer of separating element, which contains blotting material. Means of modification of the membrane include chemical or physical modification, leading to changes in permeability.

Abstract: The present invention relates to an electrophoresis apparatus having a filling/refilling system and methods of using the same. The electrophoresis apparatus comprises a first buffer chamber comprising a solid portion, at least one inlet channel in said solid portion, and at least one outlet channel in said solid portion, wherein said at least one inlet channel is in fluid communication with at least one inlet port, said at least one outlet channel is in fluid communication with at least one outlet port and said at least one inlet channel is in fluid communication with said at least one outlet channel. The electrophoresis apparatus also comprises a plurality of capillaries having first ends, second ends, and intermediate portions disposed between said first ends and said second ends, wherein said first ends extend into said first buffer chamber and are in fluid communication with said at least one inlet channel and said at least one outlet channel.

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: Microfluidic devices are provided where barriers are introduced between different compartments of the device to prevent fluid flow between the two compartments. Different materials and methods are employed for the introduction and removal of the barriers, including reversible gel particle expansion, reversible gellation, in situ polymerization, magnetic beads, and the like. In this way mixing of agents may be temporally controlled during the operation of the device, where the barriers may be used in a passive manner or as an active agent involved in the operation being performed in the device.

Abstract: The method entails using capillary electrophoresis or capillary isoelectric focusing to separate intact microbes. The capillary system can be a conventional capillary tube or a microfluidic device.

Abstract: A method of injecting, isolating and separating mixed analytes from one or more samples. The method includes collecting successive fractions from each of a plurality of samples at discrete points in time. Fractions may be analyzed at the time of collecting, or later, using one or more detector systems. In one embodiment, a processor controls the elutions of fractions by modulating the migration field in a separation pathway. The processor also controls distribution of the fraction into a particular collection well of a plurality of collection wells.

Abstract: A multi-capillary electrophoresis apparatus arranged with a fixed sample injection holder opposite a detection side holder within the same plane and an epi-optical detection system. A sample is injected sequentially and separated components are successively fed to the detection part for analysis by fluorescence. The epi-optical system adjusts the parallelism between the detection side holder and scanning axis of the detector. Thus, a capillary electrophoretic apparatus can detect fluorescence from a fluorochrome bonded to samples as a label without influence by Raman scattering or Rayleigh scattering.

Abstract: A sample is separated and separated components thereof are successively fed to a part to be detected. A laser beam of at least 600 nm from a laser beam source of an optical measuring part is applied to the part to be detected through a dichroic mirror and a lens, for making a fluorochrome bonded to the separated components absorb multiphotons, exciting the fluorochrome and making the same fluoresce. The optical measuring part captures the fluorescence so that photomultipliers detect fluorescence of not more than 510 nm in wavelength, fluorescence longer than 510 nm and not more than 560 nm in wavelength, fluorescence longer than 560 nm and not more than 580 nm in wavelength and fluorescence longer than 580 in wavelength respectively. Thus, a capillary electrophoretic apparatus can detect fluorescence from a fluorochrome bonded to samples as a label without influence by Raman scattering or Rayleigh scattering.

Abstract: The present invention provides methods of electrophoretically separating macromolecular species, as well as compositions and systems useful in carrying out such methods. Specifically, the methods of the present invention comprise providing a substrate that has at least a first capillary channel disposed therein. The surface of the channel has a first surface charge associated therewith, and is filled with a water soluble surface adsorbing polymer solution that bears a net charge that is the same as the charge on the capillary surface.

Abstract: The present invention provides an on-chip packed reactor bed design that allows for an effective exchange of packing materials such as beads at a miniaturized level. The present invention extends the function of microfluidic analysis systems to new applications including on-chip solid phase extraction (SPE) and on-chip capillary electrochromatography (CEC). The design can be further extended to include integrated packed bed immuno- or enzyme reactors.

Abstract: A holder for a capillary cassette closes a chamber, and is fixed to a detection side holder fixing member. An acidic solution container, an alkaline solution container, a pure water container and a drain container are arranged on a reservoir stage having a dry chamber. A holder up/down mechanism and a stage moving mechanism successively bring an end of a capillary array into contact with an acidic solution, an alkaline solution, pure water and nitrogen gas, and the chamber is decompressed for successively introducing these into capillary columns and performing pretreatment. Thereafter a gel container is arranged in the chamber, which in turn is pressurized for charging the capillary columns with a gel.

Abstract: A microchannel that can be used for separating two or more substances present in a sample has a first substrate and a second substrate with printed component printed on one or both of the substrates and is shaped to define a perimeter of the channel. The substrates are affixed to one another so that the component is sandwiched between the substrates and is in contact with both substrates. The microchannel is constructed using printing techniques to define the channel on one or both of the substrates.

Abstract: An electrophoresis apparatus is generally disclosed for sequentially analyzing a single sample or multiple samples having one or more analytes in high or low concentrations. The apparatus comprises a relatively large-bore transport capillary which intersects with a plurality of small-bore separation capillaries. Analyte concentrators, having antibody-specific (or related affinity) chemistries, are stationed at the respective inter-sections of the transport capillary and separation capillaries to bind one or more analytes of interest. The apparatus allows the performance of two or more dimensions for the optimal separation of analytes.

Abstract: A fully integrated monolithic small volume PCR-CE device in glass, or the like materials, is fabricated using thin film metal heaters and thermocouples to thermally cycle sub-microliter PCR volumes. Successful amplification of a PCR fragment is demonstrated on a PCR-CE chip. The process utilizes a linear polyacrylamide surface coating coupled with addition of BSA to the amplification buffer was necessary to obtain amplification efficiencies comparable to a positive control. The micro-reactor reduced significantly the time required for amplification and the reaction volume was in the sub-microliter regime. Likewise addressed are the known problems connected with reliable microfabrication of metal coatings and the insulating layers required to shield these layers from the PCR reaction mix, and the longstanding unresolved issue of exposed metal regions in the PCR-CE chip resulting in electrolysis of water and bubble formation whenever a voltage is applied.

Abstract: The filling of an internally coated capillary with a gel in its polymerized state without damaging the gel. The coating prevents bonding of the gel to the inside of the capillary, The gel comprises up to 6% acrylamide and 0-5% crosslinker. The gel can be advantageously and conveniently used in automated electrophoresis systems for automatic replacement of spent gel.