Abstract: Disclosed is a sensor for sensing the presence of an analyte component without relying on redox mediators. This sensor includes (a) a plurality of conductive polymer strands each having at least a first end and a second end and each aligned in a substantially common orientation; (b) a plurality of molecular recognition headgroups having an affinity for the analyte component and being attached to the first ends of the conductive polymer strands; and (c) an electrode substrate attached to the conductive polymer strands at the second ends. The electrode substrate is capable of reporting to an electronic circuit reception of mobile charge carriers (electrons or holes) from the conductive polymer strands. The electrode substrate may be a photovoltaic diode.

Abstract: Approaches are described for separating plasma from whole blood samples and include the use of magnetically attractable particles associated with an agglutinating agent. The magnetically attractable particles bind the cellular components in a whole blood sample. Application of a magnetic field gradient to a container with the blood sample and the magnetically attractable particles draws the particles to the surface of the container near the source of the magnetic field gradient. The plasma can be removed and stored or used for monitoring or detecting analytes in the plasma.

Abstract: Materials and methods are provided for producing patterned multi-array, multi-specific surfaces for use in diagnostics. The invention provides for electrochemiluminescence methods for detecting or measuring an analyte of interest. It also provides for novel electrodes for ECL assays. Materials and methods are provided for the chemical and/or physical control of conducting domains and reagent deposition for use multiply specific testing procedures.

Abstract: The invention provides a reagentless assay kit for analyte in a sample comprising a modular affinity assembly including at least one sensor unit comprising a ligand having binding affinity for the analyte (affinity module) operatively associated with a reporter probe (reporter module) responsive to changes in the sensor unit induced by analyte/receptor complex formation by transduction of a characteristic detectable signal. Assays employing the modular assembly are also provided.

Abstract: The invention relates generally to methods, systems, and devices for measuring the concentration of target analytes present in a biological system using a series of measurements obtained from a monitoring system and a Mixtures of Experts (MOE) algorithm. In one embodiment, the present invention describes a method for measuring blood glucose in a subject.

Abstract: A method and apparatus for extracting, identifying, and manipulating proteins or peptides from a solution uses paramagnetic beads having a coating with an affinity for the target component. In one embodiment, paramagnetic beads coated with C18 are used to adsorb proteins and peptides. The beads can be used to purify, immobilize and assay antibodies. By cycling the beads, many times greater molar amount of binding partner may be separated from a solution. A magnetic probe is used to capture the beads and transfer the beads to selected processing stages.

Abstract: The present invention relates to an assay for at least one predictive marker in a sample from a mammal wherein a specific reaction for at least one predictive marker indicates when non-fertilizable ova capable of in vitro maturation (IVM) and subsequent in vitro fertilization (IVF) are present in the mammal. This is particularly useful in the determination of when non-fertilizable ova, if aspirated, after in vitro maturation to MF-II will be capable of fertilization and pregnancy after implantation into the female mammal. The assay is based on a sample selected from the group consisting of body secrete, sputum, blood, urine, uterus secretes and cells.

Abstract: The excitation of label molecules usable in chemical and biochemical analysis by electrical pulses at electrodes covered with a thin insulating film, and the use of such electrodes in chemical, clinical and biochemical analysis. The electrodes include a conducting base material that has been coated with an organic or inorganic insulating film or multiple layers of such films, so that either one or several label compounds can be excited to an excited state which is deexcited by emission of ultraviolet, visible or infrared light, in aqueous solution providing the basis for reproducible analytical applications in bioaffinity assays such as immunoassays and DNA-probing assays.

Abstract: A magnetic focusing immunosensor for the detection of pathogens comprising a laser, an exciting fiber and a collecting fiber, a fiber optic magnetic probe in communication with the collecting and exciting fibers and means for detecting, collecting and measuring fluorescent signals in communication with the collecting fiber. The probe and the collecting and exciting fibers are configured to focus paramagnetic microspheres attached to antigen/antibody/optically labeled complexes in a predetermined pattern in the field of view of the collecting fiber while blocking background interference.

Abstract: The present invention provides a method for detecting a molecular event, comprising (1) applying an electromagnetic test signal to a sample in which a molecular event is being detected, whereby the sample interacts with and modulates the test signal to produce a modulated test signal, and (2) detecting the modulated test signal, wherein the applying and detecting take place in a temperature-controlled environment, wherein the temperature-controlled environment comprises the sample, a radiating portion of a signal generating circuit, and a receiving portion of a signal detection circuit and wherein the applying and detecting take place in the environment at a temperature controlled to within ±0.5° C.

Abstract: The present application describes novel uses of ruthenium bipyridyls or palladium porphyrins as photo-activatable crosslinking agents. Crosslinking can be between any two molecules including peptides, proteins, or compounds. Crosslinking occurs in the presence of an electron donor such as ammonium persulfate, and requires only moderate intensity visible light. Crosslinking can be between peptides, polypeptides or lead candidate compounds to unknown target molecules. Reagents utilyzing ruthenium bipyridyls and palladium porphyrins crosslinkers for use in diagnostic and detection scenarios are also disclosed.

Abstract: Electrochemiluminescent label compounds containing multimetallic centers separated by bridging ligands are described. An example of a multimetallic electrochemiluminescent label suitable for use in electrochemiluminescence (ECL) methods, [(bpy)2Ru]2(bphb)4+, demonstrates ECL efficiencies 2 to 3 times greater than those for Ru(bpy)32+ in acetonitrile and aqueous media. Such multimetallic ECL compounds may be especially useful in the design of new labels for bioanalytical applications, such as immunoassays and DNA probes.

Abstract: A method for analyzing a liquid test sample by electrochemiluminescence. The method includes at least one specific biochemical binding reaction that leads to the formation of a complex which contains a chemiluminescence marker and the binding of the complex to a magnetic microparticle. Detection is carried out in a measuring cell having a working electrode in order to determine the concentration of the marked microparticle. The detection cycle includes a purification step, a conditioning step, a recovery step and a measuring step. A specified potential profile is applied to the working electrode during these steps. Between the conditioning step and the recovery step, an additional potential pulse with an oxidizing and/or a reducing potential is inserted into the voltage shape of the detection cycle in order to improve the deposit of the microparticle.

Abstract: The present invention provides methods and devices for detecting a target nucleic acid molecule. A set of oligonucleotide probes integrated into an electric circuit, where the oligonucleotide probes are positioned such that they can not come into contact with one another, are contacted with a sample. If the sample contains a target nucleic acid molecule, one which has sequences complimentary to both probes, the target nucleic acid molecule can bridge the gap between the probes. The resulting bridge can then carry electrical current between the two probes, indicating the presence of the target nucleic acid molecule.

Abstract: A sensor element is provided including a polymer exhibiting a measurable property from the group of luminescence and electrical conductivity, the polymer being complexed with a unit including a recognition element, a tethering element and a property-altering element bound thereto so as to alter the measurable property, the unit being susceptible of subsequent separation from the polymer upon exposure to an agent having an affinity for binding to the recognition element whereupon the separation of the unit from the polymer results in a detectable change in the measurable property.

Abstract: An electrochemical affinity assay system for detection of ligand—ligand receptor binding.

Abstract: The present invention relates to a filtration-detection device for detecting or quantifying an analyte in a test sample including a filtration device having a first binding material immobilized thereto, wherein the first binding material is capable of binding to a portion of the analyte, and a detection assembly positioned relative to the filtration device to detect or quantify analyte bound to the first binding material. The present invention also relates to methods of using the filtration-detection device.

Abstract: A magnetic biological particle separation device comprising positioning a magnetic arrangement comprising a first magnet to generate a first north-south magnetic field in a plane co-planer with a horizontal cross-sectional plane of a container, positioning a second magnet in the magnetic arrangement to generate a second north-south magnetic field substantially opposing the first north-south magnetic field in a plane co-planer with the horizontal cross-sectional plane of the container, positioning a third magnet in the magnetic arrangement to generate a third north-south magnetic field substantially perpendicular to the first and the second north-south magnetic fields, directed radially away from the container, in a plane co-planer with the horizontal cross-sectional plane of the container, and pouring from the container a fluid containing magnetic beads, without a substantial loss of the magnetic beads.

Abstract: The present invention provides an analyte detection device. The device comprises first and second zones, means to allow addition of a probe to the first zone, means to allow addition of a sample suspected to contain an analyte and means to allow passage of the probe from the first zone to the second zone. The first zone contains ligands reactive with the analyte and the second zone includes a membrane the impedance of which is dependent on the presence or absence of the probe and means to measure the impedance of the membrane. It is preferred that the probe includes an ionophore, preferably gramicidin. The present invention also relates to methods of detecting the presence of an analyte.

Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.

Abstract: Disclosed is a component for a device for detecting the presence of an analyte of interest in a sample, the component comprising an electrically conducting solid support having immobilized thereon a chemical moiety, said chemical moiety comprising an electroactive portion with an electrochemical property capable of being directly modulated in a detectable manner by the binding thereto of a binding partner having a specific binding activity for the electroactive portion, together with apparatus comprising the component, and a method of detecting the presence of an analyte of interest.

Abstract: Disclosed are devices for detecting the presence of a preselected analyte in a fluid sample. The devices comprise a substrate microfabricated to define a sample inlet port, and a mesoscale flow system that includes a sample flow channel extending from the inlet port. The mesoscale flow system further includes an analyte detection region in fluid communication with the flow channel comprised of a binding moiety for specifically binding the analyte. The detection region is constructed with a mesoscale dimension sufficiently small to enhance binding of the binding moiety and the analyte. The binding moiety may be immobilized in the detection region. The mesoscale detection systems of the invention may be used in a wide range of applications, including the detection of cells or macromolecules, or for monitoring reactions or cell culture growth.

Abstract: The present invention provides biosensors which include or are fabricated using optically sensitive moieties. The use of optically sensitive moieties provides advantages in the synthesis of the biosensors. Further the inclusion of optically sensitive moieties in the biosensor membrane provides an increase in the sensitivity of detection.

Abstract: The invention provides methods, compositions, and apparatus for performing sensitive detection of analytes, such as biological macromolecules and other analytes, by labeling a probe molecule with an up-converting label. The up-converting label absorbs radiation from an illumination source and emits radiation at one or more higher frequencies, providing enhanced signal-to-noise ratio and the essential elimination of background sample autofluorescence. The methods, compositions, and apparatus are suitable for the sensitive detection of multiple analytes and for various clinical and environmental sampling techniques.

Abstract: A chemical sensor utilizing a substrate and a fluoropolymer coating is disclosed. Transducers may be connected to the substrate to generate an alternating potential across the substrate, which in turn causes the substrate to resonate due to the converse piezoelectric effect. The polymer coating absorbs the analyte, thus changing the mass of the sensor, and accordingly changing its resonant frequency. The transducers detect this change in resonant frequency to indicate to the operator that the analyte is present. The use of amorphous copolymers of 2,2-bistrifluoromethyl-4,5-difluoro-1,3-dioxole (PDD), and tetrafluoroethylene (TFE) allows for improved sensitivity and responsiveness while also allowing for robust characteristics enabling the sensor to be used in a variety of environmental conditions.

Abstract: Methods and composition for inducing, detecting and modulating seizure in animal systems are provided. Methods for inducing seizure comprise (1) electrically stimulating an unanesthetized fly and detecting seizure induction in the fly (2) electrically stimulating a fly with less than 10V and detecting seizure induction in the fly; (3) electrically stimulating a population of wild-type flies and detecting seizure induction in most of the flies and (4) electrically stimulating a population of flies and quantitatively detecting seizure induction in the flies across genotypes or experience. Methods for modulating seizure induction comprise changing the activity of a novel seizure regulator in an animal system and confirming a resultant change in seizure inducibility of the system.

Abstract: A system and method for removing contaminants from a surface. The system is designed to use particles having means thereon which are capable of selectively binding to a contaminant or contaminants of interest. The particles are applied to the surface whereupon the contaminants bind to the particle. When the particle is removed, the desired contaminants are also removed. Preferably, the present invention utilizes magnetic particles having iron therein. The particles may then be readily removed using magnets. The means for binding the contaminant to the particle preferably comprise a ligand or a charge specifically designed to remove the contaminant of interest. The particles may be included in a carrier to facilitate their application to the surface. The invention is especially useful for the removal of contaminants from skin.

Abstract: Disclosed is a method of selecting analgesic agents based on their selective ability to block tetrodotoxin-insensitive sodium channels, particularly in comparison to blocking tetrodotoxin-sensitive sodium channels. Also disclosed is a novel class of compounds that is selective for blocking tetrodotoxin-insensitive sodium channels.

Abstract: A bio-assay test system includes a test fixture, a measurement system, and a computer. The test fixture includes a bio-assay device having a signal path and a retaining structure configured to place a sample containing molecular structures in electromagnetic communication with the signal path. The measurement system is configured to transmit test signals to and to receive test signals from the signal path at one or more predefined frequencies. The computer is configured to control the transmission and reception of the test signals to and from the measurement system.

Abstract: A process for magnetorelaxometric quantitative detection of analytes in the liquid and solid phases, compounds for magnetorelaxometric detection, and their use in analysis and immunomagnetography is described.

Abstract: The invention concerns a method for the immunological determination of an analyte in a sample using magnetic particles coated with the analyte to be determined or analyte-specific bonding partners and directly detectable non-magnetic particles coated with analyte-specific bonding partners or the analyte to be determined or using a non-magnetic substance which is indirectly detectable, and incubation of the reaction mixture. The method is characterized in that the magnetic particles are subsequently separated from the reaction mixture using a magnetic test strip and the analyte concentration is determined directly.

Abstract: Microfluidic devices having predisposed assay components for increased throughput and prolonged shelf life are provided.

Abstract: The present invention relates to an arrangement (10, 20) for preparing samples (15, 27), submergible in a liquid medium. The arrangement comprises a section provided with a device (13, 23) for controllable generation of a magnetic field through influence of a control signal, said magnetic field being generated to trap at least part of said samples (15, 27).

Abstract: A method is provided for modifying cells retained in a high gradient magnetic cell separation column (HGMS). Selected cells within a heterogeneous mixture are labeled with a label comprising a magnetic particle and specific for the selected cells. The labeled, selected cells are applied to the magnetic cell separation column, which retains the selected cells. The selected cells are then modified while retained in the column and then removed to the original suspension or to a purified, homogenous suspension.

Abstract: The present invention concerns a high throughput electrorotation chip having an array of electrorotation units and methods of use thereof. To make the high throughput electrorotation chip, a plurality of electrorotation units (EU) are fabricated on a substrate or support and each EU is capable of producing a rotating electric field upon the application of an appropriate electrical signal. Exemplary embodiments include a row-column configuration of EUs having four electrode elements realized through two conductive-layers. The electrode elements may be linear, concave, or convex. Thin plates having one or multiple holes are bound to high-throughput electrorotation chips to form assay chambers having one or multiple wells. Particles can be introduced to the wells and electrorotation measurements can be performed on the particles.

Abstract: A method for detecting the presence of a target analyte comprising binding a target analyte to a binding ligand comprising at least a first electron donor moiety and a second electron acceptor moiety; and detecting the electron transfer between the donor and acceptor, wherein there is a change in the amount of electron transfer between the donor and acceptor as a result of altering the structured state of the donor and acceptor caused by a conformational change in the binding ligand upon binding of the target ligand.

Abstract: Electrode membrane combinations for use in biosensors to detect analytes in a sample and methods for making and storing same are disclosed. In one aspect, a method is provided for producing a first layer electrode membrane comprising: (1) Forming a solution containing Linker Lipid A, the disulfide of mercaptoacetic acid (MAAD) or similar molecule, linker Gramicidin B, membrane spanning lipid C (MSL-C) and membrane spanning lipid D (MSL-D) or other suitable linker molecules and other ion channel combinations; (2) Contacting an electrode containing a clean gold surface with the solution, the disulfide containing components in the solution thus adsorbing onto the gold surface of the electrode; (3) Rinsing the electrode with a suitable organic solvent; and (4) Removing the excess organic solvent used for rinsing.

Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.

Abstract: This invention relates to an improved method and system for sensing of one or more analytes. A host molecule, which serves as an adapter/carrier, is used to facilitate interaction between the analyte and the sensor element. A detectable signal is produced reflecting the identity and concentration of analyte present.

Abstract: A linker lipid for use in attaching a membrane including a plurality of ionophores to an electrode and providing a space between the membrane and the electrode in which the membrane is either in part or totally made up of the linker lipid. The linker lipid has within the same molecule a hydrophobic region capable of spanning the membrane, an attachment group used to attach the molecule to an electrode surface, a hydrophilic region intermediate the hydrophobic region and the attachment group, and a polar head group region attached to the hydrophobic region at a site remote from the hydrophilic region. The attachment group has a cross sectional area greater than the cross sectional area of the hydrophilic region, and has the structure recited in the specification.

Abstract: A magnetic biological particle separation device comprising a permanent magnet structure substantially surrounding a vessel containing a liquid and a biological sample in colloidal suspension in the liquid is described. The magnetic separation device comprises a window through which to view the liquid. The permanent magnet structure comprises a plurality of permanent magnets arranged in such a manner to provide for superpositioning of the external magnetic field generated by each magnet. The external magnetic field acts on magnetic beads attached to the biological sample, causing the sample to move toward the inner wall of the vessel. The permanent magnets do not completely surround the outside of the vessel to allow the liquid to be poured out of the vessel, substantially leaving the sample.

Abstract: The present invention is based on the discovery of a simplified assay for identifying modulators of ubiquitin ligase activity. This assay allows detection of compounds that affect ubiquitination and thus, cell cycle regulation in cells. An increase in ubiquitination, in comparison to a test sample lacking a test compound, indicates a stimulation of activity, whereas a reduction in ubiquitination indicates an inhibitor of activity. Also disclosed herein are methods of identifying proteins having ubiquitin ligase activity, methods of identifying substrates for ubiquitination, methods for identifying an activity relationship between a particular ubiquitin ligase and a particular ubiquitin conjugating enzyme, and chimeric proteins comprising a ubiquitin conjugating enzyme and a ubiquitination substrate, which are useful in all of the disclosed methods.

Abstract: Microfluidic devices for analyzing a plurality of compounds are manufactured for performing high throughput screening assays. The methods are used to manufacture devices that screen large numbers of different compounds for their effects on a variety of chemical and biochemical systems.

Abstract: A method for detecting or assaying one constituting member in a specific binding pair, for example, the antigen in an antigen/antibody pair, by utilizing specific binding such as binding between an antigen and an antibody, together with redox reaction for detecting a label, wherein an oxygen micro-electrode with a sensing surface area of 1 mm2 or less is used; and an apparatus to which the method is applicable. According to the method and by using the apparatus, redox reaction for assaying the label can be completed in such a short time as several minutes. Therefore, an inexpensive disposable apparatus for household use can be realized.

Abstract: The present invention provides novel microfluidic devices and methods that are useful for performing high-throughput screening assays. In particular, the devices and methods of the invention are useful in screening large numbers of different compounds for their effects on a variety of chemical, and preferably, biochemical systems.

Abstract: The present invention provides methods and devices for detecting a target nucleic acid molecule. A set of oligonucleotide probes integrated into an electric circuit, where the oligonucleotide probes are positioned such that they can not come into contact with one another, are contacted with a sample. If the sample contains a target nucleic acid molecule, one which has sequences complimentary to both probes, the target nucleic acid molecule can bridge the gap between the probes. The resulting bridge can then carry electrical current between the two probes, indicating the presence of the target nucleic acid molecule.

Abstract: A cartridge for separating a desired analyte from a fluid sample has a sample flow path and a lysing chamber in the sample flow path. The lysing chamber contains at least one filter for capturing cells or viruses from the sample as the sample flows through the lysing chamber. Beads are also disposed in the lysing chamber for rupturing the cells or viruses to release the analyte therefrom. An analyte flow path extends from the lysing chamber and diverges from the sample flow path. The analyte flow path preferably leads to a reaction chamber for chemically reacting and optically detecting the analyte. The cartridge also includes at least one flow controller (e.g., valves) for directing the sample into the waste chamber after the sample flows through the lysing chamber and for directing the analyte separated from the sample into the analyte flow path.

Abstract: A method and apparatus for the manipulation of colloidal particulates and biomolecules at the interface between an insulating electrode such as silicon oxide and an electrolyte solution. Light-controlled electrokinetic assembly of particles near surfaces relies on the combination of three functional elements: the AC electric field-induced assembly of planar aggregates; the patterning of the electrolyte/silicon oxide/silicon interface to exert spatial control over the assembly process; and the real-time control of the assembly process via external illumination. The present invention provides a set of fundamental operations enabling interactive control over the creation and placement of planar arrays of several types of particles and biomolecules and the manipulation of array shape and size. The present invention enables sample preparation and handling for diagnostic assays and biochemical analysis in an array format, and the functional integration of these operations.

Abstract: The present invention provides methods and compositions for detecting the presence of biologically-important analytes by using redox liposome biosensors. In particular, the present invention provides liposome/sol-gel electrodes suitable for the detection of a wide variety of organic molecules, including but not limited to bacterial toxins.

Abstract: The present disclosure relates to a method for determining cholesterol in low density lipoprotein comprising the steps of (a) measuring total cholesterol level in a sample containing at least high density lipoprotein, low density lipoprotein, very low density lipoprotein and chylomicron, and (b) measuring cholesterol levels in the high density lipoprotein, very low density lipoprotein and chylomicron in the sample, wherein the cholesterol level in the low density lipoprotein is determined by subtracting a value obtained in step (b) from a value obtained in step (a). The present invention enables concurrent determination of cholesterol level in low density lipoprotein and total cholesterol level, facilitating acquisition of two types of biological information at a time.