Abstract: Compositions and methods are disclosed which enhance the microscopic observation and analysis of biological entities such as cells, bacteria and viruses by eliminating interfering magnetic clusters created by naturally occurring aggregators of colloidal magnetic particles. Additionally means for significantly enhancing the magnetic isolation of low antigen density target cells from biological samples are disclosed.

Abstract: Compositions and methods are disclosed which enhance the microscopic observation and analysis of biological entities such as cells, bacteria and viruses by eliminating interfering magnetic clusters created by naturally occurring aggregators of colloidal magnetic particles. Additionally means for significantly enhancing the magnetic isolation of low antigen density target cells from biological samples are disclosed.

Abstract: An assay element for analyzing a charged analyte employs an immobilized receptor and a material having a net charge which is the same as that of the analyte. In a preferred embodiment, the analyte is an aminoglycoside and the material is a polymer having a net positive charge.

Abstract: Electrokinetic devices having a computer for correcting for electrokinetic effects are provided. Methods of correcting for electrokinetic effects by establishing the velocity of reactants and products in a reaction in electrokinetic microfluidic devices are also provided. These microfluidic devices can have substrates with channels, depressions, and/or wells for moving, mixing and monitoring precise amounts of analyte fluids.

Abstract: This invention relates to a method for establishing and using a decision marker by which positive samples can be discriminated from negative samples. The method employs the analysis of multiple samples from confirmed positive and negative samples. A fluorescence channel is selected so that the desired sensitivity and specificity are achieved. A microparticle having this fluorescence channel then is made and is used in conjunction with a fluorescence marker which is specific for the population of interest.

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: A multilayer analytical element for determining a level of an analyte on a substrate and adapted for use with hydrogen peroxide and an affinity-enzymatic compound of formula A-C-B, wherein A is a detecting agent having affinity for the analyte, B is an enzymatic visualizing agent consisting of peroxidase and C is a binding agent linking the detecting and visualizing agents together. The multilayer analytical element of the invention comprises a solid support and a hydrophilic layer thereon, the hydrophilic layer being formed of gelatin, polyvinyl alcohol or a mixture thereof and containing a developing agent and a hydrophobic color-producing agent in a total amount of 5 to 30 weight %, the developing agent and the color-producing agent being present in a weight ratio of 1:0.3 to 1:3.0.

Abstract: A method and device for fluorimetric determination of a biological, chemical or physical parameter of a sample utilize at least two different luminescent materials, the first of which is sensitive to the parameter, at least with respect to luminescence intensity, and the second of which is insensitive to the parameter, at least with respect to luminescence intensity and decay time. The luminescent materials have different decay times. The time- or phase behaviour of the resulting luminescence response is used to form a reference value for determination of a parameter.

Abstract: A testing apparatus 10 having an absorbent matrix 12, including a membrane 14 which contains a plurality of counter-ions 16. Chromionophore (or fluorionophore)s 18 and affinophores 22 compete to carry ions into the membrane 14 and neutralize the charge of the counter-ions 16. Biological recognition molecules 42 bind to a portion of the affinophores 22 and prevent them from entering the membrane 14, thereby allowing more chromionophore (or fluorionophore)s 18 to enter the membrane 14. The portion of affinophores 22 bound to the biological recognition molecules 42 is inversely proportional to the amount or concentration of analyte 40 occurring within the solution or medium 30. The result of this is that the color of the membrane-covered matrix changes in a manner related to the concentration of the analyte. One application of this apparatus is a strip test for prediction of ovulation.

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: Methods and compositions are provided for determining the potential of a membrane. In one aspect, the method comprises: (a) introducing a first reagent comprising a hydrophobic fluorescent ion capable of redistributing from a first face of the membrane to a second face of the membrane in response to changes in the potential of the membrane, as described by the Nernst equation, (b) introducing a second reagent which labels the first face or the second face of the membrane, which second reagent comprises a chromophore capable of undergoing energy transfer by either (i) donating excited state energy to the fluorescent ion, or (ii) accepting excited state energy from the fluorescent ion, (c) exposing the membrane to radiation; (d) measuring energy transfer between the fluorescent ion and the second reagent, and (e) relating the energy transfer to the membrane potential. Energy transfer is typically measured by fluorescence resonance energy transfer.

Abstract: Imaging apparatus and method which uses change of polarization state of a light beam passed through a total internal reflection structure by a single reflection at a TIR surface in which a specimen is placed in the evanescent field associated with the total internal reflection of the light beam, the specimen being the subject of biological, chemical or genetic investigation.

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: A device for dosing at least a particular constituent in a product sample has a receptacle and a cover assembled to form a closed container having a vertical axis. The receptacle and cover bear coaxial cylindrical walls defining concentric annular chambers inside the container, the walls separating chambers each having an opening, the cover and the container being rotatable relative to each other about the vertical axis, said openings being placed in a predetermined manner so that by relative displacement of the walls, the openings are positioned in a straight line or offset to communicate, or isolate said successive chambers. A method for using such a device and an apparatus for implementing said method are disclosed.

Abstract: A method for identifying one or a small number of molecules, especially in a dilution of ≦1 &mgr;M, using laser excited FCS with measuring times ≦500 ms and short diffusion paths of the molecules to be analyzed, wherein the measurement is performed in small volume units of preferably ≦10−14 l, by determining material-specific parameters which are determined by luminescence measurements of molecules to be examined.

Abstract: The present invention provides a method for identifying a test compound that binds to a target species. The method includes: incubating at least one test mixture under isothermal denaturing conditions, each test mixture comprising at least one test compound, and at least one target species, wherein the isothermal denaturing conditions are effective to cause at least a portion of the target species to denature to a measurable extent; detecting a denaturation signal of each target species in the presence of the at least one test compound by a change in the diffusion properties of the target molecule using fluorescence correlation spectroscopy; and comparing the denaturation signal of each target species in the presence of at least one test compound with a denaturation signal of the same target species in the absence of the at least one test compound under the same isothermal denaturing conditions.

Abstract: The invention provides methods and reagents for the enhancement of surface plasmon resonance (SPR)-based detection assays. The methods and reagents can be used in any molecular recognition assay that uses a solid support. The invention also provides an SPR instrument that operates in imaging mode.

Abstract: The present invention provides an inexpensive and sensitive device and method for detecting and quantifying analytes present in a medium. The device comprises a metalized film upon which is printed a specific, predetermined pattern of an antibody-binding proteins. Upon attachment of a target analyte to select areas of the plastic film upon which the protein is printed, diffraction of transmitted and/or reflected light occurs via the physical dimensions and defined, precise placement of the analyte. A diffraction image is produced which can be easily seen with the eye or, optionally, with a sensing device.

Abstract: A method for performing screening of one or more cell groups of interest obscured by a cell population such as one or more subsets of interest of a WBC population utilizing at least one light sensing parameter. The cell group of interest is enumerated by utilizing microspheres having monoclonal antibodies bound thereto to modify the sensed characteristics of specified cells to differentiate the cell group of interest from the obscuring cell population.

Abstract: Methods for detection and analysis of allosteric receptor/ligand binding by changes in surface refractive index are provided. When analyzed by surface plasmon resonance, binding of such allosteric binding agents to their ligands may result in a negative deviation in the optical response (i.e., a decrease in resonance angle) or in an increase in the optical response (i.e., an increase in resonance angle) depending on the binding properties of the selected allosteric receptor. Other methods for analysis of surface refractive index are also useful in the invention. The methods of the invention are particularly useful for small ligands which would not be expected to produce detectable changes in refractive index because they do not add significant mass upon 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: The biosensor involves a specially designed surface which can be optically coupled to a Surface Plasmon Resonance spectrometer. The key components of the biosensor are a bimetallic layer, a self assembled monolayer of chemicals and a layer of biomolecules such as special antibodies. The innovative bimetallic layer combines the sensitivity of silver metal and durability of gold and thus make it an ideal biosensor layer not only for a low volatility gas phase detection but also for a liquid phase detection. The successful application of the biosensor in high explosive substance detection proves that the biosensor is a sensitive and highly specific device for security and anti-terrorism applications, when it is combined with a Surface Plasmon Resonance Spectroscope.

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: An optical fiber is tapered, preferably adiabatically, and has a material coated on it for chemical bonding with fluorophores. When the fluorophores couple with the material, evanescent radiation generated fibers causes the fluorophores to fluoresce, and the fluorescence is coupled back into the fiber.

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: Described herein are assays and components for encoding and decoding microspheres. Each assay or component described utilizes at least one nanocrystal.

Abstract: Novel sensor devices composed of a crystalline colloidal array (CCA) polymerized in a hydrogel are disclosed. The hydrogels are characterized as being capable of shrinking and swelling in response to specific stimuli applied thereto. As the hydrogels shrink or swell, the lattice structure of the CCA embedded therein changes, thereby changing the wavelength of light diffracted by the CCA. Thus by monitoring the change in diffracted wavelength, the concentration of a stimulus is determined. The gels can be modified to sense numerous different stimuli. The sensor devices are specific in that they are modified to react with only one species or family of species. These sensors have various applications in areas including, for example, environmental and chemical systems, chemomechanical systems, sensor devices and medical diagnostic tools. Various methods for making and using these devices are also disclosed.

Abstract: An immunochemical assay device comprising a base member, an array disposed on the base member, and at least one assay indicia zone. The array comprises (I) a reservoir pad to receive sample liquid, (ii) a wicking membrane, and (iii) at least one filter zone interposed between the wicking membrane and the reservoir pad. The filter zone being operable to permit passage of any specific immunocomplex to the wicking membrane while impeding passage of larger components.

Abstract: An immunoassay device which comprises a Chromatography strip having a substrate adhered to the under surface thereof and a protective laminate adhered to the top surface thereof, wherein a space is arranged on the top and/or under surface of at least a partial region of a coloring region of the chromatography strip.

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: An agglutination assay method for quantitatively determination of an analyte in a liquid sample using particles bearing an anti-analyte. A non-fluid substance which retains the particles while suppressing the diffusion of the particles therein is used as a medium which is to be a place where the agglutination of the particles takes place. Upon analysis, a solation agent is added to the non-fluid substance medium to increase the fluidity of the non-fluid substance, thereby the particles bearing the anti-analyte can diffuse in the medium to cause the agglutination with the analyte. Preferably, the solation agent is added to the non-fluid medium together with the sample. The non-fluid substance medium containing the particle-labeled anti-analyte can be stored with a higher stability in the dry state. A dry analysis element for enabling such analysis method is also provided.

Abstract: A chromatographic assay device according to the present invention provides a unidirectional immunoassay for an analyte in a whole blood sample with improved sensitivity and freedom from interference.

Abstract: A test strip adapted to receive a sample and detect an analyte therein is provided. The test strip comprises a sample addition zone to which a sample may be added; an absorbent zone proximal to the sample addition zone; one or more test zones distal to the sample addition zone, at least one of the test zones including a first analyte binding agent immobilized therein which is capable of binding to the analyte to be detected; and a terminal sample flow zone distal to the one or more test zones, the absorbent zone being positioned relative to the sample addition zone and having an absorption capacity relative to the other zones of the test strip such that a distal diffusion front of a sample added to the sample addition zone diffuses from the sample addition zone to a distal diffusion point within the terminal sample flow zone and then reverses direction and diffuses proximal relative to the one or more test zones.

Abstract: Electrokinetic devices having a computer for correcting for electrokinetic effects are provided. Methods of correcting for electrokinetic effects by establishing the velocity of reactants and products in a reaction in electrokinetic microfluidic devices are also provided. These microfluidic devices can have substrates with channels, depressions, and/or wells for moving, mixing and monitoring precise amounts of analyte fluids.

Abstract: Organic electroluminescent (OEL) devices are proposed herein to be fabricated either as a light source or a heating source for biochips. Under the proposed approach, an OEL-emitting member is fabricated as the substrate of the biochip on which the biological samples, such as DNA, proteins and other related small molecules, are processed for the desired applications, including but not limited to, analysis of biological molecules, such as electrophoretic separation, PCR amplification and hybridization.

Abstract: The present invention relates to a glucose biosensor comprising a genetically engineered Glucose Binding Protein (GBP). In a specific embodiment, the invention relates to a GBP engineered to include mutations that allow site specific introduction of environmentally sensitive reporter groups. The signal of these prosthetic groups changes linearly with the degree of glucose binding. Thus, the glucose sensor of the invention can be used, for example, for detection of glucose in blood or industrial fermentation processes.

Abstract: An array bundle is provided for creating multiple arrays for testing. The array bundle is adapted to be cut transversely to form a series of identical arrays of cells. In one embodiment, the array bundle is used in detecting predetermined components from sample mixtures.

Abstract: A test strip platform for a testing apparatus of the type using test strips, wherein the platform has a shroud defining a strip track for positioning an inserted strip over an optical aperture for making analytical determinations. The platform has a hood permanently mounted to the shroud for overlying the optical window and protecting the testing apparatus optics. The strip track has stabilizing members for holding the strip in testing position. The hood provides camming members for guiding the leading edge of an inserted strip into cooperative engagement with the stabilizing members for ensuring proper insertion of the strip.

Abstract: An improved electrochemical method for disassociating a biological binding partner from a corresponding second biological binding partner associated with a waveguide surface, the electrochemical method involving the application of an electrical potential to said waveguide surface (118), the improvement comprising: applying the electrical potential to the waveguide surface (118) as a square wave polarization function. Preferably, the waveguide surface is comprised of indium tin oxide. The biological binding partners are selected from the group consisting of antigen-antibody, avidin-biotin, enzyme-substrate, cell receptor-substrate/analog, antibody/anti-antibody, DNA, RNA, and fragments thereof. The antigen may be comprised of an epitope. The epitope is produced by a solid phase peptide synthesis performed on said waveguide surface (118).

Abstract: Methods for quantitatively measuring the amount of an analyte of interest in a fluid sample are disclosed. The methods involve providing a membrane having an application point, a detection zone, and a contact region, where the contact region is between the application point and the detection zone, and has test particles and internal control particles imbedded within it; contacting the application point with the fluid sample; maintaining the membrane under conditions sufficient to allow fluid to transport analyte by capillary action to the contact region, where the analyte binds to the test particles; further maintaining the membrane under conditions sufficient to allow fluid to transport analyte-bound test particles and internal control particles to the detection zone, where they interact with a detection reagent; and detecting the amount of test particles and the amount of internal control particles in the detection zone.

Abstract: The optical sensor contains an optical waveguide (1) with a substrate (104), waveguiding material (105), a cover medium (106) and a waveguide grating structure (101-103). By means of a light source (2), light can be emitted to the waveguide grating structure (101-103) from the substrate side and/or from the cover medium side. (101-103). With means of detection (11), at least two differing light proportions (7-10) radiated from the waveguide (1) can be detected. For carrying out a measurement, the waveguide can be immovably fixed relative to the light source (2) and the means of detection (11). The waveguide grating structure (101-103) itself consists of one or several waveguide grating structure units (101-103), which if so required can be equipped with (bio-)chemo-sensitive layers. The sensor permits the generation of absolute measuring signals.

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: The present invention relates to methods and compositions for the direct detection of analytes using color changes that occur in immobilized biopolymeric material in response to selective binding of analytes to their surface. In particular, the present invention provides methods and compositions related to the encapsulation of biopolymeric material into metal oxide glass using the sol-gel method.

Abstract: Disclosed are fluorescent energy transfer dyes which are capable of moving between a more stacked configuration to exhibit fluorescent quenching and a more spaced configuration to exhibit fluorescence can be conjugated to a peptide epitope for use in the detection of an unknown antibody in bulk solution. The resulting labeled peptide reagent can be used in an immunoassay procedure by placing it in bulk solution along with the unknown antibody to be detected. When the antibody binds to the peptide epitope, the pair of dyes carried by the peptide epitope will have their configuration altered from a stacked to an unstacked configuration and will exhibit a fluorescent increase in response thereto.

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: The present invention provides a method for detecting or predicting ischemic disorders in a subject by using as an indication the concentration of human lipocalin-type prostaglandin D synthase (hPGDS) in body fluid samples from the subject. More specifically, the method comprises comparing the hPGDS concentrations in the body fluid samples from a subject with the reference values established for a normal subject, thereby detecting or predicting the ischemic disorders.

Abstract: A test piece for use in biological analyses includes a plurality of different known specific binding substances disposed in predetermined positions on a substrate. The specific binding substances are disposed on a plurality of surfaces provided by the substrate and arranged in the direction of thickness of the substrate.

Abstract: Solid phase methods for the identification of an analyte in a biological medium, such as a body fluid, using bioluminescence are provided. A chip designed for performing the method and detecting the bioluminescence is also provided. Methods employing biomineralization for depositing silicon on a matrix support are also provided. A synthetic synapse is also provided.

Abstract: A test strip platform for a testing apparatus of the type using test strips, wherein the platform has a shroud defining a strip track for positioning an inserted strip over an optical aperture for making analytical determinations. The platform has a hood permanently mounted to the shroud for overlying the optical window and protecting the testing apparatus optics. The strip track has stabilizing members for holding the strip in testing position. The hood provides camming members for guiding the leading edge of an inserted strip into cooperative engagement with the stabilizing members for ensuring proper insertion of the strip.

Abstract: The invention provides a method for measuring the amount of analyte in a sample of biological fluid using a simple low sample volume reagent test strip with a built in metering system. The test strip may comprise a microtitration zone to prevent oversampling and an integrated capillary to prevent problems associated with short sampling and act as means of absorbing the fluid sample. The test strip comprises a wicking layer and a reaction matrix embossed layer in the form of a pillow assembled into a microtitration pocket formed in the strip. The test strip is used in single use applications such as the determination of the concentration of glucose in blood.