Abstract: The present invention provides an integrated microfluidic analysis system. The system contains at least a first (pre-reaction treatment) domain for treating a sample prior to subjecting the sample to a chemical reaction. The following domains are optionally added to the first domain: a second (reaction) domain for reacting the chemical of interest in the sample; and a third (post-reaction separation) domain for separating products and reactants coming out of the reaction domain. The integrated microfluidic analysis system of the present invention is most applicable to PCR analysis.

Abstract: Methods of forming a chip with fluidic channels include forming (e.g., milling) at least one nanofunnel with a wide end and a narrow end into a planar substrate, the nanofunnel having a length, with width and depth dimensions that both vary over its length and forming (e.g., milling) at least one nanochannel into the planar substrate at an interface adjacent the narrow end of the nanofunnel.

Abstract: A system that incorporates the subject disclosure may include, for example, a method for selectively applying an electrical potential to a top surface of a membrane having a nanopore to repel or attract a molecular strand from the top surface of the membrane, applying a second electrical potential to a bottom surface of the membrane to repel or attract the molecular strand from the bottom surface of the membrane, applying a third electrical potential to an electrolyte solution to apply a transport force on the molecular strand to displace a section of the molecular strand into the nanopore, arresting the section of the molecular strand in the nanopore by adjusting of the first electrical potential, the second electrical potential, the third electrical potential, or combinations thereof, and measuring a signal at the nanopore to identify the section of the molecular strand. Other embodiments are disclosed.

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: A digital microfluidics system for manipulating samples in liquid droplets within a gap between a first hydrophobic surface of a bottom layer and a second hydrophobic surface of at least one disposable cartridge. Disposable cartridges comprise a body and/or a rigid cover plate. The bottom layer of each disposable cartridge is a flexible film that is sealingly attached to the body or plate. The cartridge has no spacer between the first and second hydrophobic surfaces. When using these cartridges, the bottom layers configured as a working film for manipulating samples in liquid droplets thereon, is placed on an electrode array of a digital microfluidics system. The array has individual electrodes. The digital microfluidics system also comprises a central control unit for controlling the selection of the individual electrodes of the electrode array and for providing these electrodes with individual voltage pulses for manipulating liquid droplets by electrowetting.

Abstract: A device for generating an adjustable adhesion force on a wet substrate is described. The device has a main body with an adhesion surface which, in use, arranges itself facing the substrate, at such adhesion surface the main body having a plurality of channels generating a capillary return for water present on the substrate. A delivery and/or reservoir system for silicone oil, providing the latter at the adhesion surface, so that silicone oil arranges itself interposed between the surface itself and the water on the substrate. A static electric field generating system generates a static electric field at the adhesion surface. Such electric field modifies the wettability of silicone oil with respect to the adhesion surface.

Abstract: An electrophoresis apparatus that applies voltage from electrodes that are provided in a capillary flow channel and causes component separation by performing electrophoresis on a specimen that is injected into the capillary flow channel comprises: a physical quantity acquisition unit and a physical quantity determination unit. The physical quantity acquisition unit, with migration solution and specimen injected inside the capillary flow channel, acquires an electrical quantity that occurs in the capillary flow channel at a specified time when voltage is being applied to the electrodes. The physical quantity determination unit determines whether or not the electrical quantity that the physical acquisition unit acquires is within a specified range.

Abstract: A method for multiplex characterization of individual particles by their size, shape, mechanical properties (deformability), and chemical affinity to recognition agents. The analysis can be performed from concentrated solutions. The method detects transient sticking of particles in the pore and points to its location along a pore axis. If a pore is decorated with a recognition agent for an analyte present in a solution, it is possible to distinguish specific binding at the place of the recognition agent, and non-specific adsorption of the analyte. The method confirms whether any individual particle or hydrogel completely translocates the pore and allows unambiguous detection and characterization of multiple particles or hydrogels in the pore, which would previously corrupt the results, so that higher analyte concentrations can be used for faster analysis.

Abstract: Microfluidic devices and methods for using the same are provided. Embodiments include microfluidic devices that have a first separation region configured to separate a sample along a first directional axis based on a first property, and a second separation region in fluid communication with the first separation region and configured to separate the sample along a second directional axis based on a second property. Also provided are methods of using the devices as well as systems and kits that include the devices. The devices, systems and methods find use in a variety of different applications, including diagnostic and validation assays.

Abstract: The present disclosure relates to systems and methods for high efficiency electronic sequencing of nucleic acids and molecular detection. In an example embodiment of the instant disclosure, the NanoNeedle may be utilized to detect a change in impedance resulting from the modulation of the counter ion concentration or Debye length associated with a biomolecule of interest, such as DNA or protein, for an application of interest, such as DNA sequencing, DNA hybridization, or protein detection.

Abstract: A nanosensor for detecting molecule characteristics includes a membrane having an opening configured to permit a charged molecule to pass but to block a protein molecule attached to a ligand connecting to the charged molecule, the opening being filled with an electrolytic solution. An electric field generator is configured to generate an electric field relative to the opening to drive the charged molecule through the opening. A sensor circuit is coupled to the electric field generator to sense current changes due to charged molecules passing into the opening. The current changes are employed to trigger a bias field increase to cause separation between the ligand and the protein to infer an interaction strength.

Abstract: Provided herein is technology relating to depositing and/or placing a macromolecule at a desired site for an assay and particularly, but not exclusively, to methods and systems for placing or guiding a macromolecule such as a protein, a nucleic acid, or a protein:nucleic acid complex to an assay site, such as near a nanopore, a nanowell, or a zero mode waveguide.

Abstract: Provided is a device comprising a channel through and defined by a plurality of layers surrounding the channel, the channel connecting a first and a second chambers separated by the plurality of layers, wherein the plurality of layers comprise a first layer, a second layer; and a conductive middle layer disposed between the first and second layers, wherein the channel comprises (a) a first region defined by the first layer, denoted as an inlet, that is about 0.5 nm to about 100 nm in diameter and (b) a second region defined by the second layer, denoted as an outlet, wherein the inlet and the outlet are about 10 nm to about 1000 nm apart from each other, and wherein the first and second chambers and the middle layer are connected to a power supply. Also provided are methods of preparing and using the device, in particular for nucleic acid sequencing.

Abstract: One embodiment of the present invention is directed to methods for ionophorically screening pore forming bacterial protein toxins and receptors. The method includes: a) forming a membrane comprising a lipid and a receptor, b) contacting the membrane with the pore forming bacterial protein toxin and an ion solution, and c) measuring ion flow through the membrane.

Abstract: Flow step focusing isolates and concentrates a molecule of interest by flowing a liquid comprising a molecule of interest through a main channel having an inlet and an outlet with application of a first pressure at the inlet; applying a voltage along the channel during the flowing, wherein the voltage is configured to have a polarity such that it drives the molecule of interest in a direction opposite the flow of the liquid; controlling the first pressure and/or the voltage in a manner so as to trap and concentrate the molecule of interest in a region of the main channel; and removing the concentrated molecule of interest from the channel by recovering a portion of the liquid from a side channel diverging from the main channel, wherein the side channel is maintained at a pressure lower than the first pressure. Also disclosed is an apparatus for such.

Abstract: A method of determining water quality of a water sample, comprising exposing the water sample to a test cell system; generating at least one profile of ensuing changes in activities of transcription factors in said test cell system in response to said exposing; and determining from the generated at least one profile the water quality of the water sample. Computer systems and kits for carrying out the water quality determination of water specimens are also described, in which water quality can be readily and accurately determined by transcription factor activity analysis.

Abstract: Various aspects of the present invention relate to the control and manipulation of fluidic species, for example, in microfluidic systems. In one aspect, the invention relates to systems and methods for making droplets of fluid surrounded by a liquid, using, for example, electric fields, mechanical alterations, the addition of an intervening fluid, etc. In some cases, the droplets may each have a substantially uniform number of entities therein. For example, 95% or more of the droplets may each contain the same number of entities of a particular species. In another aspect, the invention relates to systems and methods for dividing a fluidic droplet into two droplets, for example, through charge and/or dipole interactions with an electric field. The invention also relates to systems and methods for fusing droplets according to another aspect of the invention, for example, through charge and/or dipole interactions. In some cases, the fusion of the droplets may initiate or determine a reaction.

Abstract: Provided herein are Mycobacterium smegmatis porin nanopores, systems that comprise these nanopores, and methods of using and making these nanopores. Such nanopores may be wild-type MspA porins, mutant MspA porins, wild-type MspA paralog porins, wild-type MspA homolog porins, mutant MspA paralog porins, mutant MspA homolog porins, or single-chain Msp porins. Also provided are bacterial strains capable of inducible Msp porin expression.

Abstract: Metabolites and signatures (panels) of metabolites are applicable as biomarkers in clinical diagnosis, in particular for neonatal encephalopathy. They are useful tools in differential clinical diagnosis for early detection of brain injury, determination of brain areas affected by the insults and prediction of adverse neurological outcome and may also be applied in diagnosing disease progression and treatment effect. An in vitro method for predicting the likelihood of neonatal encephalopathy of distinct brain areas, identification of affected brain area(s) of neonatal encephalopathy and risk of brain damage and prognosis and neurological outcome due to identification of the type and extent of damage of distinct brain tissues, in particular of hippocampus and/or basal ganglia, is provided.

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: Devices for detecting a particle in a fluid sample are provided. The device includes a segmented microfluidic conduit configured to carry a flow of a fluid sample, where the conduit includes one or more nodes and two or more sections, and a node is positioned between adjacent sections of the conduit. The device also includes a detector configured to detect a change in current through the conduit. Also provided are methods of using the devices as well as systems and kits that include the devices. The devices, systems and methods find use in a variety of different applications, including diagnostic assays.

Abstract: A method is provided of controlling the functionality of a substrate containing at least one nanopore. The method includes the steps of: introducing to the substrate a solution containing a molecular construct having a body formation which defines an aperture and a tail formation extending from the body formation; applying a potential difference across the substrate to thread the tail formation through the nanopore thereby docking the molecular construct to the substrate with the aperture aligned with the nanopore such that the sleeve formation lines the nanopore; and expelling the molecular construct from the substrate by varying the potential difference. A DNA construct for docking to a substrate having a nanopore is also provided, the construct having a body formation which defines an aperture, and a tail formation extending from the body formation for threading through the nanopore to dock the construct to the substrate with the aperture and nanopore in alignment.

Abstract: Methods and microfluidic circuitry for inline injection of nucleic acids for capillary electrophoresis analysis are provided. According to various embodiments, microfabricated structures including affinity-based capture matrixes inline with separation channels are provided. The affinity-based capture matrixes provide inline sample plug formation and injection into a capillary electrophoresis channel. Also provided are methods and apparatuses for a microbead-based inline injection system for DNA sequencing.

Abstract: A mechanism is provided for utilizing a nanodevice to distinguish molecules with different structure. The molecules translocate through or across a nanochannel filled with a electrolyte solution. An electrical signal through the nanochannel is measured for every translocation event. Inner surfaces of the nanochannel include a functional layer, which is a coating to functionalize the nanochannel, in which the functional layer is configured to interact with predetermined ones of the molecules during translocation events. It is determined that a combination of at least two different molecules is formed based on predetermined ones of the molecules interacting with the functional layer to change the electrical signal and/or change a translocation time for the translocation event.

Abstract: The invention provides dry compositions for preparing and loading a sample on a gel for electrophoretic separation. The dry compositions preferably include a tracking dye and a sedimenting agent selected from a five-carbon polyol (e.g., ribitol, arabitol, or xylitol),iso-erythritol, maltitol, and saccharine. Methods for making and using, as well as kits comprising the disclosed compositions, are also provided.

Abstract: Methods and systems are provided for concentrating particles (e.g., bacteria, viruses, cells, and nucleic acids) suspended in a liquid. Electric-field-induced forces urge the particles towards a first electrode immersed in the liquid. When the particles are in close proximity to (e.g., in contact with) the first electrode, the electrode is withdrawn from the liquid and capillary forces formed between the withdrawing electrode and the surface of the liquid immobilize the particles on the electrode. Upon withdrawal of the electrode from the liquid, the portion of the electrode previously immersed in the liquid has particles immobilized on its surface.

Abstract: This invention discloses a highly efficient method, system and apparatus for nucleic acid analysis, including sequencing (both automated re-sequencing and de-novo sequencing). The system is capable of sequencing DNA sizes ranging from fragments to mammalian size genomes having mouse draft quality at a much reduced cost. The system comprises a massive parallel capillary electrophoretic separation using two-dimensional monolith multi-capillary arrays (2D-MMCA). Sequence identification can be performed using fluorescent or otherwise labeled dideoxynucleotide-terminated DNA extension product generated by gel matrix-, or beads-, or substrate tethered-, or otherwise immobilized colonies of single template molecules.

Abstract: A microdevice for supporting a flowing nonpolar fluid is disclosed. The microdevice includes a substrate that is at least partially coated by one or more amphiphilic layers. Methods for using the device in biological and chemical assays are also disclosed.

Abstract: Technologies are generally described for microfluidic channel devices. Some example devices may include a substrate having a substrate surface, with an array of drive electrode assemblies disposed upon the substrate surface. The drive electrode assemblies may be arranged along a path. Each drive electrode assembly may include one or more of a drive electrode layer, a dielectric layer and/or a stationary phase layer. The device may further include a plate including a plate surface. The device may further include a reference electrode configured on the plate surface to face the stationary phase layer of the drive electrode assemblies and separated from the substrate surface by a distance. The device may further include a voltage source effective to output a voltage potential, the voltage source configured in communication with the drive electrode assembly and the reference electrode. The device may further include an electrode selector effective to control the voltage source.

Abstract: Provided are device components, devices and methods characterized by a high contrast signal to noise ratio (CNR).

Abstract: The invention relates generally to polymers and copolymers comprising N-vinylamide-type monomers, their preparation, and compositions, such as electrophoresis separation media, containing the same; to supports, such as capillaries, containing these polymers; and methods for separating a mixture of biomolecules, especially polynucleotides, using capillary electrophoresis. Separation media comprising such polymers yield advantageous performance in the analysis and separation of biomolecules by capillary electrophoresis.

Abstract: Provided are a sample analysis method using capillary electrophoresis capable of enhancing analysis accuracy, a solution for capillary electrophoresis, and a sample analysis kit. The sample analysis method includes separating and/or detecting a substance to be analyzed in a sample through capillary electrophoresis, in which the substance to be analyzed is separated and/or detected in the presence of a pH buffer substance and a non-surfactant-type zwitterionic substance. Further, the solution for capillary electrophoresis contains a pH buffer substance, a non-surfactant-type zwitterionic substance, and water.

Abstract: The present invention concerns a device and a method of single-molecule analysis by detection of a target molecule on functionalized nanopores in such a way that it interacts with the target molecule and has an effective diameter smaller than the dimension of the target molecule.

Abstract: A detection optics configuration for bio-analysis, in which the direction of incident radiation, the axis of the separation channel, and the direction of collection of the output radiation are coplanar at the detection zone. The detection configuration incorporates ball-end optical fibers to direct incident radiation at and collection of output radiation from the detection zone. The detection optics configuration may be implemented in an improved bio-separation instrument, in particular a capillary electrophoresis instrument.

Abstract: A sample stacking method using on-line automatic solid phase extraction coupled to nonaqueous capillary electrophoresis, and an interface structure between a solid-phase preconcentration cartridge and a capillary therefor. The sample analysis method using solid phase extraction coupled to nonaqueous capillary electrophoresis by connecting a solid-phase preconcentration cartridge with a capillary includes: extracting a sample on a solid phase; injecting an elution solvent at an outlet terminal of the capillary, the elution solution desorbing analytes adsorbed onto a solid-phase material of a solid-phase preconcentration cartridge; and injecting a nonaqueous buffer solution from the outlet terminal of the capillary to push the elution solvent to the solid-phase material.

Abstract: A cartridge-based bio-separation system configured to utilize a pen shaped bio-separation cartridge that is easy to assemble and use with no moving parts and that has an integrated reagent (separation buffer) reservoir. The cartridge includes a body, defining an opening as a detection window for receiving external detection optics, at least one capillary column supported in the body, having a first end extending beyond a first end of the body, wherein the detection window exposes a section along the capillary column, to which the external optics are aligned through the detection window, and a reservoir attached to a second end of the body in fluid flow communication with a second end of the capillary column. The reservoir is structured to be coupled to an air pressure pump that pressurizes the gel reservoir to purge and fill the capillaries with buffer as the separation support medium.

Abstract: A direct contact segmented column heater is described. The heater is capable of a broad heating and cooling range, and exhibits a very rapid response, with heating and cooling rates better than 350° C. min?1. In one configuration one or more of the individual heating devices are provided with full independent control and temperature feedback, and developed to provide excellent thermal stability at all temperatures. The heating devices or in other words active thermal transfer devices are capable of bi-directional operation, selectively heating (i.e., providing heat to) or cooling (i.e., withdrawing heat from) a column and/or contents of a column.

Abstract: Antibody-free processes are disclosed that provide accurate quantification of a wide variety of low-abundance target analytes in complex samples. The processes can employ high-pressure, high-resolution chromatographic separations for analyte enrichment. Intelligent selection of target fractions may be performed via on-line Selected Reaction Monitoring (SRM) or off-line rapid screening of internal standards. Quantification may be performed on individual or multiplexed fractions. Applications include analyses of, e.g., very low abundance proteins or candidate biomarkers in plasma, cell, or tissue samples without the need for affinity-specific reagents.

Abstract: The present invention provides control methods, control systems, and control software for microfluidic devices that operate by moving discrete micro-droplets through a sequence of determined configurations. Such microfluidic devices are preferably constructed in a hierarchical and modular fashion which is reflected in the preferred structure of the provided methods and systems. In particular, the methods are structured into low-level device component control functions, middle-level actuator control functions, and high-level micro-droplet control functions. Advantageously, a microfluidic device may thereby be instructed to perform an intended reaction or analysis by invoking micro-droplet control function that perform intuitive tasks like measuring, mixing, heating, and so forth. The systems are preferably programmable and capable of accommodating microfluidic devices controlled by low voltages and constructed in standardized configurations.

Abstract: A method of mixing a droplet, the method comprising providing a droplet on a surface, forming the droplet into a first “U” shape having a bottom region and two terminal ends, and simultaneously merging the terminal ends and splitting the droplet at the bottom region to form a second “U” shape which is substantially opposite the first “U” shape.

Abstract: An analysis apparatus is provided with a storage tank, an injection nozzle, a syringe, a collection nozzle, a test sample tank, a microchip having two or more separation channels, detectors, a waste liquid tank, a controller, and a power supply. The collection nozzle collects a specimen which becomes a test sample from a test sample container housing the specimen, and transfers the specimen to the test sample tank. The separation channels separate characteristic components contained in the test sample. The injection nozzle is distanced from the collection nozzle and injects the test sample from the test sample tank into the separation channels. The detectors detect the separated characteristic components in the separation channels.

Abstract: An electrokinetics-assisted sensor for sensing a target material. The sensor may include a microstructure deflectable in response to added mass on its body. The sensor may also include one or more features on or near the microstructure designed to generate an electric field giving rise to one or more electrokinetic effects to drive material towards the microstructure, when an electrical signal is applied to the feature(s). Presence of the target material on the body of the microstructure may cause a response in the microstructure, including a detectable change in deflection of the microstructure.

Abstract: Microfluidic methods of assaying molecule switching are provided. Aspects of the methods include microfluidically separating a sample containing the molecule of interest and then employing the resultant separation pattern to determine a switching characteristic of the molecule. Also provided are microfluidic devices, as well as systems and kits that include the devices, which find use in practicing embodiments of the methods. The methods, devices, systems and kits find use in a variety of different applications, such as analytical and diagnostic assays.

Abstract: Fluidic nanotube devices and methods for their use are provided wherein the flow of charged molecules through a channel is controlled by the voltage potential of a gate electrode. In at least some embodiments, a molecular transistor is provided that includes a channel having a diameter such that only one target molecule at a time may traverse the channel. The channel may be a carbon nanotube that is electrically isolated from, and in communication with, a gate electrode. Methods are provided for controlling the flow of an individual molecule through the channel and for detecting a single chemical reaction.

Abstract: A mechanism is provided for manipulating a molecule. The molecule is driven into a nanochannel filed with electrically conductive fluid. A first vertical electric field is created inside the nanochannel to slow down the molecule and/or immobilize the molecule. The molecule is stretched into non-folded linear chains by the first vertical electric field and a horizontal electric field. Monomers of the molecule are sequentially read.

Abstract: The invention provides microfluidic devices, systems, and methods for manipulating an object within a channel of a microfluidic device using an external electrode. The device has a channel disposed within the device, the channel having no included electrodes. The channel has a wall, at least a portion of which is penetrable by an electric field generated external to the device, the wall being penetrable such that the electric field extends through the wall portion and into a region within the channel. The system includes the microfluidic device and an electrode external to and not bonded to the device. In the method, the external electrode is placed adjacent to the device and energized to generate an electric field that extends through the wall of the device and into the channel, thereby manipulating an object within the channel.

Abstract: A mechanism is provided for manipulating a molecule. The molecule is driven into a nanochannel filed with electrically conductive fluid. A first vertical electric field is created inside the nanochannel to slow down the molecule and/or immobilize the molecule. The molecule is stretched into non-folded linear chains by the first vertical electric field and a horizontal electric field. Monomers of the molecule are sequentially read.

Abstract: A mechanism is provided for capturing a molecule via an integrated system. An alternating voltage is applied to a Paul trap device in an electrically conductive solution to generate electric fields. The Paul trap device is integrated with a nanopore device to form the integrated system. Forces from the electric fields of the Paul trap device position the molecule to a nanopore in the nanopore device. A first voltage is applied to the nanopore device to capture the molecule in the nanopore of the nanopore device.

Abstract: Methods, structures, devices and systems are disclosed for rapid enrichment and mass transport of biomolecules (e.g., such as proteins) or other small molecules and particles using electrodeless dielectrophoresis (eDEP). In one aspect, a device to aggregate molecules includes a substrate that is electrically insulating, an electrically insulative material formed on the substrate and structured to form a channel to carry an electrically conducting fluid containing particles, a constriction structure formed of the electrically insulative material and located in the channel to narrow a channel dimension and forming an opening with a size in the nanometer range, and a circuit coupled to the substrate to apply an ac electric field and a dc bias electric field along the channel, in which the constriction structure is structured to magnify the applied ac electric field to produce forces that operate collectively to aggregate the particles.

Abstract: A mechanism is provided for capturing a molecule via an integrated system. An alternating voltage is applied to a Paul trap device in an electrically conductive solution to generate electric fields. The Paul trap device is integrated with a nanopore device to form the integrated system. Forces from the electric fields of the Paul trap device position the molecule to a nanopore in the nanopore device. A first voltage is applied to the nanopore device to capture the molecule in the nanopore of the nanopore device.