Abstract: Improved methods for the separation, isolation, enrichment, or detection of target molecules, such as nucleic acids and proteins, within dilute or heterogeneous samples, such as bodily fluids, excreta or tissue samples, are disclosed. The methods include repetitively and rapidly passing a sample across at least one region of a conduit in which at least one region includes a binding partner specific for the target molecule. In certain methods, at least one other region includes binding partners specific for non-target molecules. The sample may be passed over the binding partner in the same direction if the conduit is a loop or in an antiparallel direction (i.e., back and forth over the binding partner). In an embodiment, the sample is electrophoresed through or over an electrophoretic medium, in which at least one region includes a binding partner for the target molecule. The invention also provides apparatus and sample preparation systems adapted for use in the methods.

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

Abstract: The present invention is directed to a droplet actuator and methods of making and using the droplet actuator including one or more substrates configured to form a droplet operations gap and including a physical or chemical feature that may be provided at a predetermined locus within or exposed to the droplet operations gap and configured to retain a bubble in position within the droplet operations gap.

Abstract: A new method of diagnosing postprandial hyperglycemia by indirectly measuring a blood glucose level is provided. Postprandial hyperglycemia is detected by measuring a glycation degree of lysine in hemoglobin, in which a side chain amino group of lysine is glycated (GHbLys %). Measurement of GHbLys % can be performed by cleaving hemoglobin by protease, treating a glycated part of a lysine residue in the obtained cleavage product of hemoglobin with fructosyl amino acid oxidase, and measuring a redox reaction between the glycated part and fructosyl amino acid oxidase.

Abstract: A micro fluidic chip (100) for handling fluidic droplets (101), the micro fluidic chip (100) comprising a plurality of electrodes (103) being arranged in a Back End of the Line portion (104) of the microfluidic chip (100), and a control unit (106) adapted for controlling electric potentials of the plurality of electrodes (103) to generate electric forces for moving the fluidic droplets (101) along a predefined trajectory.

Abstract: The present invention relates to a method for the diagnosis, prognosis, and monitoring of bladder cancer, such as early or late stage bladder cancer, by detecting in a urine sample from a subject at least one biomarker for bladder cancer identified herein, such as alpha-1B-glycoprotein, haptoglobin, serotransferrin, or alpha-1-antitrypsin. The biomarkers may be detected and, optionally, measured using an agent that detects or binds to the biomarker protein or an agent that detects or binds to encoding nucleic acids, such as antibodies specifically reactive with the biomarker protein or a portion thereof. The invention further relates to kits for carrying out the methods of the invention. The invention further relates to a device for the rapid detection of one or more bladder cancer biomarkers in urine and methods for rapidly measuring bladder cancer biomarkers in urine.

Abstract: The invention relates to a microelectronic device for manipulating a sample, the device comprising an array of actuator units (AU) and an array of sensitive units (SU). The actuator units (AU) may particularly exert dielectrophoretic forces on a sample (1) in an adjacent sample chamber, and the sensitive units (SU) optionally measure properties of said sample. Furthermore, the actuator units (AU) are linked to a set of power lines (PL) and the sensitive units (SU) are linked to a set of signal lines (SL), wherein the routing of these lines is such that the effects of parasitic couplings are minimized for a given set of alternating electrical power signals on the power lines. The power lines (PL) may particularly be supplied with alternating electrical signals that are identical besides a phase shift. Optionally, the couplings between the power lines and the signal lines are adapted to provide a maximal compensation of cross-talk effects.

Abstract: The invention includes methods and kits for making and analyzing primer extension products incorporating one or more universal bases, including methods and kits for nucleic acid sequencing and microsatellite analysis.

Abstract: Methods for performing microfluidic sampling are provided. The method includes providing a substrate including an arrangement of first, second and third electrodes, wherein the second electrode is interposed between the first and third electrodes. The method additionally includes causing a fluid input to continuously flow to the first electrode and biasing the first, second and third electrodes to a first voltage to cause a portion of the fluid input to spread across the second and third electrodes. The method further includes biasing the second electrode to a second voltage different from the first voltage to form a droplet on the third electrode, the droplet being separate from the fluid input.

Abstract: The invention includes a method for sequencing DNA by partially sequencing the bases of complementary strands of double-stranded DNA and combining the partial information from both strands of the double strand DNA to fully sequence the DNA. The invention also includes DNA sequences sequenced by the methods, computer readable mediums including program instructions for such methods, and kits adapted to perform such methods.

Abstract: The present invention provides methods of determining the size of a particular nucleic acid segment of interest in a sample of nucleic acids through fragmentation of DNA, size fractionation, an optional second fragmentation, and identification using a marker sequence. In particular aspects, an expansion or reduction of tandem repeat sequences can be detected. In further aspects, carriers and individuals afflicted with fragile X syndrome or other diseases associated with tandem repeats can be distinguished from normal individuals.

Abstract: The invention relates to a microelectronic device, particularly a microelectronic biosensor, comprising an array of field electrodes (FE) for generating an alternating electrical field (E) in an adjacent sample chamber (SC). The field electrodes (FE) are coupled to associated local oscillators (OS), which are preferably tunable and connected in a matrix pattern to an external control unit (CU). The local oscillators (OS) allow high frequencies of the generated electrical fields (E), such that for example dielectrophoretic forces can be generated.

Abstract: A method for performing electrophoretic separation of ionic compounds which involves varying a bulk fluid flow though a separation path into which ionic species are continuously introduced and separated. The method can also include the introduction of a leading electrolyte into the separation path to form an ionic interface with the sample and an optional terminating electrolyte to enrich ionic species for higher detection resolution.

Abstract: A microchip for capillary electrophoresis is provided. The microchip comprises an injection channel and a separation channel configured to receive a sample through a sample well disposed on a first end of the separation channel; wherein the injection channel and the separation channel intersect to form a ‘T’ junction. The microchip further comprises a first valve disposed adjacent to the ‘T’ junction and on the separation channel and a second valve disposed at the ‘T’ junction. The second valve is a two-way valve. A sample plug is injected into an area between the ‘T’ junction and a second end of the separation channel.

Abstract: Various particle transport systems and components for use in such systems are described. The systems utilize one or more traveling wave grids to selectively transport, distribute, separate, or mix different populations of particles. Numerous systems configured for use in two dimensional and three dimensional particle transport are described.

Abstract: A first electrophoretic medium comprises an electrically charged particle suspended in a suspending fluid, the particle having a polymeric shell having repeating units derived from at least one monomer the homopolymer of which is incompatible with the suspending fluid. A second, similar electrophoretic medium comprises a suspending fluid, and first and second types of electrically charged particle suspended in the suspending fluid, the two types of particle having differing optical characteristics but both having polymeric shells. The polymeric shells are arranged such that homoaggregation of the two types of particles is thermodynamically favored over heteroaggregation.

Abstract: Various particle transport systems and components for use in such systems are described. The systems utilize one or more traveling wave grids to selectively transport, distribute, separate, or mix different populations of particles. Numerous systems configured for use in two dimensional and three dimensional particle transport are described.

Abstract: A liquid conveying substrate comprises: rectangular electrodes which are disposed on the substrate surface and whose surfaces are covered with a dielectric with a water repellent surface; first axial electrode columns where the rectangular electrodes are coupled in an x direction; and second axial electrode columns where the rectangular electrodes are coupled in a y direction. Accordingly, electrodes necessary for conveying liquid droplets can be arranged on one substrate, and the number of mechanisms for controlling the potential can be suppressed.

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 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.

Abstract: An electrolytic sensing system for measuring a blocking signal allows for controlled translocation of a molecule, such as DNA, through a fluid channel. A substantially constant electric field supplied by a DC source is applied across the fluid channel and induces translocation of the molecule within the system. An oscillating electric parameter (e.g. current or voltage) supplied by an AC source is also applied across the fluid channel as a means for measuring a blocking signal. The substantially constant electric field can be altered to provide more detailed control of the molecule and, optionally, run a select portion of the molecule through the channel multiple times to provide numerous signal readings. A temperature control stage cools the system, providing further control of molecule translocation. A modified or non-modified protein pore may be utilized in the fluid channel. The system allows for long DNA strands to be sequenced quickly without amplification.

Abstract: A diagnostic device is provided that includes a plurality of retainment regions interconnected through at least one fluid processing passageway or separated by at least one barrier. A fluid flow modulator can be provided in the fluid processing passageway if a fluid processing passageway is provided. The barrier and/or fluid flow modulator can comprise a polysaccharide, a derivative of a polysaccharide, or a combination thereof. For example, the barrier can comprise a chitosan material.

Abstract: The present teachings relate to systems and methods for separation of substances such as cells, nucleic acids, and carbon nanotubes. The substances are combined with a separation medium in a liquid sample cavity, for example a microchannel, and transit through the separation by optically activated dielectrophoretic forces. The substances are advantageously labeled and visualized using a microscope and camera.

Abstract: Alternative approaches to fabricating printed circuit boards for use in droplet actuator operations are provided. In one embodiment, a method of manufacturing a droplet actuator for conducting droplet operations includes positioning a dielectric material between a first metal layer configured to include an electrode and a second metal layer configured to include an interconnect pad. The method additionally includes forming a connection between the first and second metal layers. Droplet actuators and methods of fabricating and supporting printed circuit boards of droplet actuators are also provided.

Abstract: A microfluidic device for carrying a liquid, the device comprising a microfluidic channel having an interior wall and a polyelectrolyte film on the interior wall whereby liquid carried by the channel contacts the polyelectrolyte film, the polyelectrolyte film having a thickness of about 1 to about 1000 nanometers and comprising an interpenetrating network of a predominantly positively charged polymer and a predominantly negatively charged polymer, the predominantly positively charged polymer, the predominantly negatively charged polymer or both containing (i) a pH insensitive positively or negatively charged repeat unit having a pKa greater than 9 or less than 3, and (ii) a pH sensitive repeat unit, the pH sensitive repeat unit having a pKa of 3 to 9, whereby the pH of liquid in the microfluidic channel may be used to control the velocity or direction of electroosmotic flow of the liquid within said microfluidic channel.

Abstract: Devices with lateral flow elements and integral fluidics are disclosed. The integral fluidics consist of injector pumps comprised of fluidic elements under instrument control. The fluidic element of an injector pump is fluidically connected to lateral flow elements and can be used to control fluid entry into containment chambers referred to as micro-reactors. The lateral flow elements comprise conductor elements that can be used for sample application and transport of analyte contained in the sample to the micro-reactor. Fluidic transport through the fluidic element of the injector pump is under instrument-control. Both the lateral flow element and the fluidic element may contain chemical entities incorporated along their length. The chemical reactions that can be used for analyte detection using the devices are described. Also described are methods of manufacture of these devices.

Abstract: An electrophoresis plate has a plurality of separation channels provided inside a substrate. The separation channels are arranged along the surface of the substrate without intersecting each other, and the separation channels have openings on both ends on the substrate surface. When a voltage is applied between the two ends of the channel, a sample is separated by electrophoresis along the channel. The openings on one end are placed in a matrix pattern as sample inlet ports, and the pitch of that placement is set equal to the pitch of the wells of a sample plate containing the samples to be injected into the sample inlet ports. Since the pitch of the sample inlet ports pattern is equal to the pitch of the sample plate wells, sample injection can be performed quickly and conveniently even with a large number of separation channels.

Abstract: A novel label-free sensitive detection method by employing a novel sensitive charge sensor is provided. Dissociation constant information is provided by a simple measurement of the dissociation of the target molecule form the target's receptor. The later process is affected by a novel system and its configuration as described herein. Basic objectives are to provide a drug discovery and characterization system that is an improvement over the current state of the art, low cost, highly sensitive, accurate, fast and easy to use. This invention involves both a physical system and a methodology.

Abstract: A method and device are provided for affinity gradient focusing for directing at least one analyte in a solution containing a pseudostationary phase and located in a channel such as a capillary or a microchannel. The method includes establishing a steady-state spatial gradient in a retention factor of the pseudostationary phase for the at least one analyte. The analyte is caused to be moved within the channel whereby the concentration of the at least one analyte changes at one or more positions along the gradient. The pseudostationary phase is charged and the analyte is either neutral or charged or alternatively, the pseudostationary phase is neutral and the analyte is charged. The device may include a fluid channel, a pseudostationary phase having a retention factor gradient, an electrical current source and a pump system for establishing the bulk flow in the solution in the channel.

Abstract: Reversible flow may be provided in certain EHD device configurations that selectively energize corona discharge electrodes arranged to motivate flows in generally opposing directions. In some embodiments, a first set of one or more corona discharge electrodes is positioned, relative to a first array of collector electrode surfaces, to when energized, motivate flow in a first direction, while second set of one or more corona discharge electrodes is positioned, relative to a second array of collector electrode surfaces, to when energized, motivate flow in a second direction that opposes the first. In some embodiments, the first and second arrays of collector electrode surfaces are opposing surfaces of individual collector electrodes. In some embodiments, the first and second arrays of collector electrode surfaces are opposing surfaces of respective collector electrodes.

Abstract: An electrophoretic fluid separation structure (100) comprising a substrate (101) and a plurality of vertical nanowires (102) grown on the substrate (101).

Abstract: The present invention relates to a method for separating components of a sample. The method includes obtaining a first separation of the sample components along a first dimension wherein the sample components are at least partially resolved, wherein the first separation can be performed in the absence of an electric field applied to the first dimension. An electric field is used to obtain a second separation of the sample components along a second dimension comprising a plurality of substantially isolated volumes. An intensity-time data record is obtained from each of the isolated volumes, the intensity-time data records containing peaks, each peak being indicative of a migration time. The migration time of a first peak is normalized with respect to a migration time of at least a second peak to correct for migration time differences between the isolated volumes.

Abstract: The present invention is directed to droplet actuators with droplet retention structures, and methods related thereto. In an exemplary embodiment, the invention provides a droplet actuator with one or more substrates arranged to form a droplet operations gap comprising gap-facing surfaces; droplet operations electrodes configured to conduct droplet operations in the droplet operations gap; at least one barrier included on at least one of the substrate surfaces and having dimensions selected to: permit droplet transport from atop a first droplet operations electrode to a second droplet operations electrode when the second droplet operations electrode is activated; and prevent movement of a droplet from atop a first droplet operations electrode when the first and second droplet operations electrodes are inactive.

Abstract: Methods and devices are described for concentration and cleanup of samples containing bio-molecule analytes (e.g., polynucleotides, such as DNA, RNA, PNA). Various embodiments provide for pH-mediated sample concentration and cleanup of nucleic acid samples with channel devices (e.g., cross-T format, microchannel devices).

Abstract: The disclosure teaches a method for the analysis of a sample by electrophoresis, making use of a binding partner for a target compound or group of target compounds which may be present in the sample. The disclosure further teaches a kit for use in an electrophoretic analysis, to a modified antibody or fragment thereof, and to specific uses of the kit or modified antibody or fragment thereof.

Abstract: The present invention describes an actuator in a microfluidic system for inducing an electroosmotic liquid movement in a microchannel.

Abstract: This invention provides devices and apparatuses comprising the same, for efficient pumping and/or mixing of relatively small volumes of fluid. Such devices utilize nonlinear electrokinetics as a primary mechanism for driving fluid flow. Methods of cellular analysis and high-throughput, multi-step product formation using devices of this invention are described.

Abstract: To provide an electrophoresis method being capable of rapidly analyzing a protein in a native state without carrying out a heat-denaturing pretreatment step, and having even higher sensitivity. The electrophoresis method of the present invention is useful for proteosome analysis and medical diagnosis.

Abstract: The present invention relates to an apparatus having a nanodevice (1) for controlling the flow of charged particles in an electrolyte. Such apparatus comprises an electrolytic bath container (2) divided by a polymeric membrane foil (3) into a first (4) and a second compartment (5), wherein each compartment (4, 5) comprises an electrode (6, 7) connected to a voltage supply (8). Further the apparatus comprises at least one asymmetric pore (9) forming a via hole through said foil (3), wherein said pore (9) provides a narrow opening (10) of a diameter in the range of several nanometers down to about one nanometer on a front side (11) of said foil (3) and a wide opening (12) in the range of several ten nanometers up to several hundred nanometers on a back side (13) of said foil (3).

Abstract: An electrophoretic cell and methods of switching an electrophoretic cell and moving charged species in an electrophoretic cell employ differential electrophoretic mobilities and a time-varying electric field. The methods include providing first and second charged species that are oppositely charged and have different mobilities. The method of switching further includes inducing a net motion of both of the charged species using the time-varying applied electric field. The induced net motion results in either the first charged species being moved toward the electrode and the second charged species remaining essentially motionless or both of the charged species being moved toward the same electrode. The electrophoretic cell includes the first and second charged species with opposite charge and different mobilities, and further includes the time-varying applied electric field that provides the net motion of the charged species.

Abstract: In accordance with the invention there are systems and methods of separating a mixture of carbon nanotubes comprising dispersing carbon nanotubes into a fluid to form a dispersion of individually-suspended carbon nanotubes and focusing the dispersion of individually-suspended carbon nanotubes into a single file stream of carbon nanotubes. The methods can also include characterizing the single file stream of carbon nanotubes and sorting the carbon nanotubes based on their properties.

Abstract: Electrophoresis systems and methods comprise an electrophoresis device, wherein the electrophoresis device comprises a loading channel, an injection channel, and a separation channel. The loading channel is in fluid communication with a first and second sample port. The injection channel is connected to the loading channel to form a first intersection. The separation channel is connected to the injection channel to form a second intersection and in fluid communication with a first and second reservoir, and wherein the injection channel is in fluid communication with a third reservoir. The electrophoresis system further comprises electrodes coupled to the first sample port and the third reservoir, and the first reservoir and the second reservoir, respectively, that are adapted to move the sample into the loading channel towards the third reservoir and form a sample plug in the second intersection, and to further move the sample plug into the separation channel towards the second reservoir.

Abstract: Devices and methods for separating sample constituents are provided. The subject devices are characterized by having a fluid flow path with at least one electrophoretic separation element positioned at a region thereof. The separation element includes an element for applying an electric field across the fluid flow path and a trapping element for trapping sample constituents that migrate out of the flow path when an electric field is applied across the fluid flow path. In using the subject devices, sample is moved past the separation element and an electric field is applied across the flow path such that constituents of the sample migrate into the trapping element. The subject devices and methods find use in a variety of applications, including protein separation applications.

Abstract: A method is disclosed for effecting the concentration of a polar analyte in an alternating electric field. In the method, a relative translation of the polar analyte and an alternating electric field along a translation path is effected. A portion of the polar analyte is then trapped and concentrated in a concentration zone formed by the intersection of the translation path and the alternating electric field. Also disclosed are various devices for carrying out the forgoing method.

Abstract: Methods are disclosed for screening of the occurrence of gene silencing (e.g. post transcriptional gene silencing) in an organism. Also provided are methods for isolating silencing agents so identified.

Abstract: Method for simultaneously determining alleles present in a set of loci from at least one nucleic acid sample comprising the steps: a) providing said at least one sample, b) subjecting said sample to a nucleic acid amplification reaction using a primer pair simultaneously primer pairs specific and optimized for each of the loci of a set of at least three loci selected from the group consisting of D2S1360, D7S1517, D8S1132, D9S1118, D10S2325, D11S554, D12S1064, D12S391, D17S1290, D19S253, MYCLl, P450CYP19 and SE-33, and c) evaluating the length and optionally the relative quantity of amplification products obtained from step b) or from the analysis of one or two of the above loci to determine and/or optionally quantify the alleles present at each of the loci analyzed in the set within said sample.

Abstract: This invention relates generally to cutting single-wall carbon nanotubes (SWNT). In one embodiment, the present invention provides for preparations of homogeneous populations of short carbon nanotube molecules by cutting and annealing (reclosing) the nanotube pieces followed by fractionation. The cutting and annealing processes may be carried out on a purified nanotube bucky paper, on felts prior to purification of nanotubes or on any material that contains single-wall nanotubes. In one embodiment, oxidative etching with concentrated nitric acid is employed to cut SWNTs into shorter lengths. The annealed nanotubes may be disbursed in an aqueous detergent solution or an organic solvent for the fractionation. Closed tubes can also be derivatized to facilitate fractionation, for example, by adding solubilizing moieties to the end caps.

Abstract: Sintering self-assemblies of calcined colloidal silica particles results in sintered colloidal crystals that are free of cracks that can be resolved using optical microscopy. The sintered colloidal crystals have significantly improved strength and durability, and withstand aggressive handling. Surface rehydroxylation of the sintered colloidal crystals enables subsequent chemical modification.

Abstract: Electroosmotic flow controllers and methods of fluid flow control are described. The invention uses an electroosmotically generated flow component in conjunction with a pressure driven flow component to modulate fluid flow. The devices and methods of the invention may include salt bridges for making electrical connection between a power supply and a channel filled with a porous dielectric material and a fluid. Embodiments including flow controllers and flow splitters are described as is their use in a variety of fluid handling applications.

Abstract: A method for detecting HIV infection in a mammal is disclosed. The method contains the steps of isolating exosomes from a urine sample of a mammal and detecting the presence of HIV-specific biomarker in said isolated exosomes. A method for diagnosing a mammal with an HIV-associated disease, in particular, HIV-associated nephropathy is also disclosed.

Abstract: This invention provides devices and apparatuses comprising the same, for the mixing and pumping of relatively small volumes of fluid. Such devices utilize nonlinear electrokinetics as a primary mechanism for driving fluid flow. Methods of cellular analysis and high-throughput, multi-step product formation using, devices of this invention are described.