Abstract: A method for extracting proteins from heterogeneous fluids by precipitation using microfluidics. The method uses an automated protocol for precipitation of proteins onto surfaces, rinsing the precipitates to remove impurities, and resolubilization in buffer for further analysis. The method is compatible with proteins representing a range of different physicochemical properties, as well as with complex mixtures such as fetal bovine serum and cell lysate. In all cases, the quantitative performance (measured using a fluorescent assay for % recovery) was comparable to that of conventional techniques, which are manual and require more time.

Abstract: The present invention concerns microfluidic systems with printed surface structured electronically controllable wettability switches for efficient manipulation of small amounts of fluids. The high performance microfluidic systems of the invention can be used in many applications, e.g. in rapid DNA separation and sizing, cell manipulation, cell sorting and molecule detection.

Abstract: Compounds having the general formula (I): wherein X is S, Se or NH, and stereoisomers thereof, and de-O-sulfonated analogues of all of the foregoing, but excluding naturally occurring kotalanol and de-O-sulfonated kotalanol, and methods for synthesizing same. The compounds are useful as glycosidase inhibitors, and may be used in the treatment of diabetes. The synthetic compounds may also be used as standards in the calibration or grading of natural or herbal remedies produced from natural sources of glycosidase inhibitors such as kotalanol.

Abstract: The methods and compositions provided herein relate to the discovery of 13 STR are markers found on the human Y chromosome with surprisingly high mutation rates when compared with 173 other Y-STR markers known today, including those that are in common use in forensics. In addition to theoretical expectations based on elevated mutation rates, these 13 rapidly-mutating (RM) Y-STRs proved to be suitable for differentiating between closely related males, as well as between more distant male relatives and much more so than the most-commonly used Y-STRs in forensics. Our new set of RM-Y-STRs is expected to overcome the current dilemma of Y-chromosome analysis in forensic applications from current male lineage identification towards male individual identification in many cases, due to their extraordinary mutation properties as discovered here.

Abstract: The present invention refers to a droplet-based miniaturized device with on-demand droplet-trapping, -fusion, and -releasing. The device makes use of different electrical fields for directing droplets into microwells and releasing them from the same. In another aspect, the present invention refers to a system comprising such a microfluidic device and a method of operating it.

Abstract: A compound of the formula: wherein R1 is independently selected from C1-C10 alkyl or substituted alkyl, R2 is independently selected from the group consisting of —H and C1-C6 alkyl or substituted alkyl, Y? is an anion, m is an integer from 1 to 8 and n is an integer from 1 to 8 is described. Methods of making and using the compound are also described. The compound may comprise a zwitterionic acid-labile surfactant suitable for purification and identification techniques used in proteomics.

Abstract: Blood plasma of pregnant women contains fetal and (generally>90%) maternal circulatory extracellular DNA. Most of said fetal DNA contains ?500 base pairs, said maternal DNA having a greater size. Separation of circulatory extracellular DNA of <500 base pairs results in separation of fetal from maternal DNA. A fraction of a blood plasma or serum sample of a pregnant woman containing, due to size separation (e.g. by chromatography, density gradient centrifugation or nanotechnological methods), extracellular DNA substantially comprising ?500 base pairs is useful for non-invasive detection of fetal genetic traits (including the fetal RhD gene in pregnancies at risk for HDN; fetal Y chromosome-specific sequences in pregnancies at risk for X chromosome-linked disorders; chromosomal aberrations; hereditary Mendelian genetic disorders and corresponding genetic markers; and traits decisive for paternity determination) by e.g. PCR, ligand chain reaction or probe hybridization techniques, or nucleic acid arrays.

Abstract: The present invention provides exchangeable, reagent pre-loaded carriers (10), preferably in the form of plastic sheets, which can be temporarily applied to an electrode array (16) on a digital microfluidic (DMF) device (14). The carrier (10) facilitates virtually un-limited re-use of the DMF devices (14) avoiding cross-contamination on the electrode array (16) itself, as well as enabling rapid exchange of pre-loaded reagents (12) while bridging the world-to-chip interface of DMF devices (14). The present invention allows for the transformation of DMF into a versatile platform for lab-on-a-chip applications.

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 and includes a valve system. Analyte concentrators, having antibody-specific (or related affinity) chemistries, are stationed at the respective intersections 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. The apparatus may also include a plurality of valves surrounding each of the analyte concentrators to localize each of the concentrators to improve the binding of one or more analytes of interest.

Abstract: In some embodiments, an analyte detection system is provided that includes a nanochannel, an electrode arrangement, and a plurality of nanoFET devices disposed in the nanochannel. A plurality of nucleic acid base detection components can be used that include a plurality of nanopores, a plurality of nanochannels, a plurality of hybridization probes, combinations thereof, and the like. According to other embodiments of the present teachings, different coded molecules are hybridized to a target DNA molecule and used to detect the presence of various sequences along the target molecule. A kit including mixtures of coded molecules is also provided. In some embodiments, devices including nanochannels, nanopores, and the like, are used for manipulating movement of DNA molecules, for example, in preparation for a DNA sequencing detection. Nanopore structures and methods of making the same are also provided as are methods of nucleic acid sequencing using the nanopore structures.

Abstract: Disclosed herein are compositions and methods for the rapid screening of candidate protein therapeutics. In particular, the instant invention provides compositions and methods for assaying the behavior of candidate protein therapeutics in complex biological fluids and for identifying those candidate protein therapeutics exhibiting desirable pharmacokinetic properties in such fluids.

Abstract: There is provided a novel target recognition molecule. The target recognition molecule has a specific reactivity, and can be densely self-assembled and immobilized reversibly or irreversibly at a predetermined site in a microfluidic device. And The target recognition molecule including: (1) a target recognition peptide segment having an amino acid sequence which specifically interacts with a target substance capable of causing an immune reaction; and (2) an electrostatically-charged segment which is provided with three or more electrostatically-charged functional groups capable of being electrically charged to the same polarity in the same solution.

Abstract: The invention provides a microfabricated device for sorting cells based on a desired characteristic, for example, reporter-labeled cells can be sorted by the presence or level of reporter on the cells. The device includes a chip having a substrate into which is microfabricated at least one analysis unit. Each analysis unit includes a main channel, having a sample inlet channel, typically at one end, and a detection region along a portion of its length. Adjacent and downstream from the detection region, the main channel has a discrimination region or branch point leading to at least two branch channels. The analysis unit may further include additional inlet channels, detection points, branch points, and branch channels as desired. A stream containing cells is passed through the detection region, such that on average one cell occupies the detection region at a given time.

Abstract: A method of carrying out a chemical reaction on a microfluidic device in which a first reactant at a first concentration is delivered into a reaction channel; within the reaction channel the concentration of the first reactant is changed from the first concentration to a second concentration; and while at the second concentration the first reactant is exposed to a second reactant.

Abstract: A multiplexed concentration interface that can connect with a plurality of microchannels, conventional 96 well plates or other microarrays is disclosed. The interface can be used in biosensing platforms and can be designed to detect single or multiple targets such as DNA/RNA, proteins and carbohydrates/oligosaccharides. The multiplexed concentration device will provide a set of volume-matched sample preparation and detection strategies directly applicable by ordinary researchers. Furthermore, a multiplexed microfluidic concentrator without buffer channels is disclosed.

Abstract: Aspects of the disclosure provide a microfluidic chip. The microfluidic chip includes a first domain configured for polymerase chain reaction (PCR) amplification of DNA fragments, and a second domain for electrophoretic separation. The first domain includes at least a first reaction reservoir designated for PCR amplification based on a first sample, and a second reaction reservoir designated for PCR amplification based on a second sample. The second domain includes at least a first separation unit coupled to the first reaction reservoir to received first amplified DNA fragments based on the first sample, and a second separation unit coupled to the second reaction reservoir to received second amplified DNA fragments based on the second sample. The first separation unit is configured to perform electrophoretic separation for the first amplified DNA fragments, and the second separation unit is configured to perform electrophoretic separation for the second amplified DNA fragments.

Abstract: The present invention provides methods for diagnosing human hepatic disorders, such as non-alcoholic steatohepatitis (NASH), identifying a human subject at risk of an adverse drug reaction, and determining an appropriate dosage of a therapeutic drug for a human subject. The marker is an increased level of acetaminophen-glucuronide in a plasma or urine sample from a human subject.

Abstract: A novel method for visualizing electrokinetic process zones (e.g., for isotachophoresis (ITP)) is provided. We introduce negligibly small concentrations of a fluorophore that is not focused by isotachophoresis. This non-focusing tracer (NFT) migrates through multiple isotachophoresis zones. As it enters each zone, the NFT concentration adapts to the local electric field in each zone. ITP zones can then be visualized with a point detector or camera. The method can be used to detect, identify, and quantify unknown analyte zones, and can visualize complex and even transient electrophoresis processes. This visualization technique is particularly suited to microfluidic and lab-on-a-chip applications, as typical fluorescence microscopes and CCD cameras can provide high-resolution spatiotemporal data.

Abstract: The process for the diagnosis of a renal cell carcinoma comprises the step of determining the presence or absence or amplitude of at least three polypeptide markers in a urine sample, wherein said polypeptide markers are selected from the markers as characterized in Table 1 by molecular masses and migration times.

Abstract: A lateral flow device includes a porous medium layer having a two-dimensional shape in plan view that is capable of supporting near-constant velocity capillary-driven fluid flow and can be combined with electrodes in a manner to achieve to achieve electrokinetic molecule separation.

Abstract: A plurality of particles of from about 5 nm to 100 ?m possessing predetermined isoelectric points in the pH range of from about 2.5 to 11 is used in a method of detection of a plurality of analytes, wherein the isoelectric particles of each isoelectric point further contain as label and a member of a binding pair capable of interacting with a selected analyte. The particles that form specific binding pairs are recovered and separated by isoelectric focusing followed by the detection of the labels associated with the particles. A flow cytometer may be used as a detector of the isoelectric particles.

Abstract: Various pentosan polysulfate (PPS) formulations useful for treatment of osteoarthritis, interstitial cystitis, and other conditions of mammals are provided. These formulations showed improved resistance to degradation and discoloration and improved stability at physiological pH, even after sterilization. Capillary electrophoresis analysis of these formulations indicates that various formulations remain stable under conditions that caused degradation of PPS in prior art PPS formulations.

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 and includes a valve system. Analyte concentrators, having antibody-specific (or related affinity) chemistries, are stationed at the respective intersections 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. The apparatus may also include a plurality of valves surrounding each of the analyte concentrators to localize each of the concentrators to improve the binding of one or more analytes of interest.

Abstract: Methods of evaluating heparin preparations, e.g., for suitability for use as a drug or for use in making a drug, by determining the absence, presence or amount of a structural signature that is indicative of the methods used to make the heparin preparation.

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: Exemplary embodiments provide systems and methods for concentrating, focusing and/or separating proteins using nanofluidic channels and/or their arrays. In embodiments, low-abundance proteins can be focused and separated with high resolution using separation techniques including isoelectric focusing (IEF), and/or dynamic field gradient focusing (DFGF) in combination with nanofluidic channels and/or multi-gate nanofluidic field-effect-transistors (FETs).

Abstract: Techniques for manipulating a molecule in a nanopore embedded in a lipid bilayer are described. In one example, an acquiring electrical stimulus level is applied across a lipid bilayer wherein a region of the lipid bilayer containing the nanopore is characterized by a resistance and wherein the acquiring electrical stimulus level tends to draw the molecule from a surrounding fluid into the nanopore, a change in the resistance of the lipid bilayer resulting from the acquisition of at least a portion of a molecule into the nanopore is detected, the acquiring electrical stimulus level is changed to a holding electrical stimulus level wherein the portion of the molecule remains in the nanopore upon the changing of the acquiring electrical stimulus level to the holding electrical stimulus level.

Abstract: The present invention is related to a method of separation of compounds by electrophoresis in which the compounds such as genes, proteins, etc. may be analyzed very precisely as samples are introduced directly into the separation tubes of the chip at the collection site, and therefore, it is not necessary to have separate fluid paths or individual sample storing apparatus that have been necessary for the conventional electrophoresis; it is easy to make the chips as the structure of the chip becomes extremely simple, and high-density arrangement of the separation tubes is enabled; and further, the compounds such as genes, proteins, etc. may be analyzed very precisely without interference in the storage tubs by using a non-polar solvent as the solvent of the sample storage tub.

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: The present invention relates to methods and devices for separating particles according to size. More specifically, the present invention relates to a microfluidic method and device for the separation of particles according to size using an array comprising a network of gaps, wherein the field flux from each gap divides unequally into subsequent gaps. In one embodiment, the array comprises an ordered array of obstacles in a microfluidic channel, in which the obstacle array is asymmetric with respect to the direction of an applied field.

Abstract: An embodiment of the invention is directed to a capillary electrophoresis apparatus comprising a plurality of separation micro-channels. A sample loading channel communicates with each of the plurality of separation channels. A driver circuit comprising a plurality of electrodes is configured to induce an electric field across each of the plurality of separation channels sufficient to cause analytes in the samples to migrate along each of the channels. The system further comprises a plurality of detectors configured to detect the analytes.

Abstract: The invention relates to an enhanced method of detecting and/or quantifying at least one analyte in a sample.

Abstract: The present invention provides diagnostic in vitro methods as well as kits and devices to be used in the methods of the present invention for diagnosis or prognosis of a pathologic condition characterized by the presence/absence of an endogenous hormone and/or hormone analog(s) thereof involved in diabetes or metabolic syndrome. The methods comprise a quantitative separation of at least those analytes of interest whose common presence interferes with measuring the presence/absence or concentration of one of the analytes of interest by a subsequent analytical method.

Abstract: The present invention provides microfabricated substrates and methods of conducting reactions within these substrates. The reactions occur in plugs transported in the flow of a carrier-fluid.

Abstract: The present invention provides microfabricated substrates and methods of conducting reactions within these substrates. The reactions occur in plugs transported in the flow of a carrier-fluid.

Abstract: A sample analysis method with improved separation accuracy is provided. The method relates to a method for analyzing a sample by electrophoresis using an electrophoresis apparatus provided with a channel and a sample reservoir formed in the channel. The method includes: placing the sample in the sample reservoir of the electrophoresis apparatus with the channel being filled with an electrophoresis running buffer; and performing electrophoresis by applying a voltage to both ends of the channel. The concentration of at least one of a) and b) is set to be approximately the same between the sample and the electrophoresis running buffer; wherein a) and b) are defined as follows: a) an ion that moves in the same direction as an analyte in the sample by the electrophoresis and has a smaller degree of mobility than the analyte, and b) an ion that moves in the opposite direction to the analyte.

Abstract: An electrolytic system includes an analyte chamber having an access port for introducing a sample containing a molecules of interest, such as DNA. Electrodes create an electric field along a length of the analyte chamber to drive molecules toward an interaction region containing a nanopore, thereby increasing the arrival rate of molecules at the nanopore. Additional electrodes may be utilized to create an electric field through the nanopore to drive a molecule into the nanopore. A current sensor may be utilized to count, discriminate or characterize the molecules as they interact with the nanopore. Advantageously, system can be utilized for unamplified DNA sequencing.

Abstract: A method for analyzing hemoglobin by electrophoresis, capable of analyzing hemoglobin A1c (HbA1c) and modified hemoglobin with improved accuracy in a shortened analysis time is provided. The method for analyzing hemoglobin by electrophoresis includes performing electrophoresis under conditions in which an acidic substance having two or more carboxyl groups is present in an electrophoresis solution. At least two of the carboxyl groups of the acidic substance each have an acid dissociation constant (pKa) lower than the pH of the electrophoresis solution at the time of analysis.

Abstract: The invention provides methods and apparatus for characterizing complex polymeric mixture of interest. Candidate solutions are eliminated from a solution space using one or more experimental measurements of a polymeric mixture of interest. The elimination step can be repeated one or more times using different experimental measurements produced by various chemical and physical protocols, so that the remaining candidate solutions converge to describe the actual polymeric mixture under investigation. Once the composition of the complex polymeric mixture has been characterized, the information thus generated can be used to facilitate, for example, the manufacture of a bio-equivalent of the complex polymeric mixture.

Abstract: Provided is a first reservoir for containing a liquid solution including a molecule to be characterized and a second reservoir for containing a liquid solution. A solid state support includes a nanopore having a molecular inlet providing a fluidic connection to the first reservoir and a molecular outlet providing a fluidic connection to the second reservoir. An electrical connection is disposed between the first and second reservoirs to apply a molecular translocation voltage across the nanopore between the molecular inlet entrance and outlet exit. At least one electrical probe is disposed at the nanopore to apply a first voltage bias with respect to translocation voltage to slow progression of a molecule through the nanopore between the molecular inlet and outlet and to apply a second voltage bias with respect to translocation voltage to cause the molecule to proceed through the nanopore between the molecular inlet and outlet.

Abstract: A microfluidic system for creating encapsulated droplets whose shells can be further removed comprises: two electrode plates and a spacing structure disposed between the two electrode plates. One of the electrode plates has three reservoir electrodes and a plurality of channel electrodes. The three electrodes are respectively used for accommodating a shell liquid, a core liquid, and a removing liquid which is able to remove the shell liquid. The channel electrodes are used for communicating droplets among the three reservoir electrodes. Via these arrangements, the microfluidic system can create a quantitative shell droplet and a quantitative core droplet, and then merge the shell and core droplets to form an encapsulated droplet. Moreover, the shell of the encapsulated droplet can be removed by mixing it with the removing liquid. This invention is further provided with a method for creating an encapsulated droplet with a removable shell.

Abstract: A microfluidic cell for the dielectrophoretic separation, accumulation, and/or lysis of polarizable bioparticles, including an interdigital electrode system composed of two electrode groups having interdigitated electrodes, a flat electrode in which the interdigital electrode system and the flat electrode are situated on opposite sides of the cell in order to improve the separation, accumulation and/or lysis characteristics. Moreover, a microfluidic system which includes such a microfluidic cell, and use thereof, and a method for separating, accumulating, and/or lysing polarizable bioparticles is also described.

Abstract: A microfluidic cell for the dielectrophoretic separation, accumulation, and/or lysis of polarizable bioparticles, including an interdigital electrode system composed of two electrode groups having interdigitated electrodes, and a micromixer having microchannels and microelevations. The interdigital electrode system and the micromixer are situated on the same side of the cell to improve the separation, accumulation, and/or lysis characteristics. Moreover, also described is a microfluidic system which includes such a microfluidic cell, and use thereof, and a method for separating, accumulating, and/or lysing polarizable bioparticles.

Abstract: The invention provides methods for detecting an interaction between an analyte and a biomolecule. The method comprises separating at least one biomolecule according to its isoelectric point in the presence of a given analyte and detecting an interaction between the analyte and a biomolecule using fluorescence anisotropy. The method may further comprise collecting the analyte-biomolecule complex and analyzing the biomolecule.

Abstract: Methods for detecting one or more analytes, such as a protein, in a fluid path are provided. The methods include resolving, immobilizing and detecting one or more analytes in a fluid path, such as a capillary. Also included are devices and kits for performing such assays.

Abstract: A microfluidic device comprising a set of one or more, preferably more than 5, covered microchannel structures manufactured in the surface of a planar substrate. The device is characterized in that a part surface of at least one of the microchannel structures has a coat exposing a non-ionic hydrophilic polymer. The non-ionic hydrophilic polymer is preferably attached covalently directly to the part surface or to a polymer skeleton that is attached to the surface.

Abstract: The present invention includes an apparatus and corresponding method for fluid flow control in microfluidic applications. A microchamber, filled with a fluid, is in fluid contact with a flexible plate. A transducer is acoustically coupled to the flexible plate. A function generator outputs a signal to excite the transducer, which in turn induces drumhead vibration of the flexible plate, creating a flow pattern within the fluid filled microchamber.

Abstract: The micro-channel chip for electrophoresis of the present invention comprises a first substrate formed of a gas-permeable material and a second substrate formed of a gas-permeable or a gas-impermeable material, the first and the second substrate being glued together, the mating surface of either one of the first and second substrates having a sample-feeding channel having a port at both ends and an electrophoretic channel also having a port at both ends, the sample-feeding channel and the electrophoretic channel being allowed to communicate with each other via a narrower channel having a smaller cross-sectional area than those two channels. The micro-channel chip for electrophoresis of the present invention requires only one power source to perform electrophoresis and can use samples with minimum waste of their quantity.

Abstract: This invention provides a method and an apparatus for quickly continuously fractionating biomolecules, such as DNAs, proteins and carbohydrates by taking advantage of differential bidirectional transport of biomolecules with varying physico-chemical characteristics, for example size, charge, hydrophobicity, or combinations thereof, through periodic arrays of microfabricated nanofilters. The passage of biomolecules through the nanofilter is a function of both steric and electrostatic interactions between charged macromolecules and charged nanofilter walls, Continuous-flow separation through the devices of this invention are applicable for molecules varying in terms of any molecular properties (e.g., size, charge density or hydrophobicity) that can lead to differential transport across the nanofilters.

Abstract: A method and apparatus for determining the concentration of an analyte in a sample is provided. This method involves combining enhanced chemiluminescence with microchip capillary electrophoresis or microchip liquid chromatography.