Abstract: An integrated biomolecule sensor comprising a plurality of optical fibers whose proximal ends are held together with the end-faces arranged substantially in the same plane and oriented substantially in the same direction and which have probe polymers with different base sequences bound to the core end-face at their distal ends. The method and apparatus for fabricating the integrated biomolecule sensor, and the method and apparatus for detecting biomolecules using the integrated biomolecule sensor are also disclosed. Researchers can make their own sensors best suited for individual requirements, and detect the presence of target biomolecules quickly, without need of expensive equipment.

Abstract: A device for detecting the presence of an antigen including (1) a cell having antibodies which are expressed on the surface of the cell and are specific for the antigen to be detected, where binding of the antigen to the antibodies results in an increase in calcium concentration in the cytosol of the cell, the cell further having a emitter molecule which, in response to the increased calcium concentration in the cytosol, emits a photon; (2) a liquid medium for receiving the antigen and in which the cell is immersed; and (3) an optical detector arranged for receiving the photon emitted from the cell.

Abstract: The invention relates to new systems, methods and products for analyzing polymers and in particular new systems, methods and products useful for obtaining sequence information from polymers. The invention has numerous advantages over prior art systems and methods used to obtain sequence-related information. Using the methods of the invention the entire human genome could be analyzed several orders of magnitude faster than could be accomplished using conventional technology. In addition to obtaining sequencing information for the entire genome, the systems, methods and products of the invention can be used to create comprehensive and multiple expression maps for developmental and disease processes. The ability to analyze an individual's genome and to generate multiple expression maps will greatly enhance the ability to determine the genetic basis of any phenotypic trait or disease process.

Abstract: Array units and methods are provided which have constructions to reduce or take advantage of Fresnel reflection. The array units may have a subtantially unreflective substrate. In one arrangement a transparent spacer layer is provided while in another an anti-reflective layer is present.

Abstract: A method and an apparatus for laser microdissection of specimen regions (23) of interest of a specimen (4) are described. In a first step, an incomplete cut line (25) enclosing the specimen region (23) of interest is generated by means of a laser beam (7). At the incomplete point of the cut line (25), there remains a web (26) which joins the specimen region (23) of interest to the surrounding specimen (4). In a second step, the web (26) is severed with a single laser pulse directed onto it, thereby completing the cut line. The specimen region (23) of interest is in that context detached from the specimen (4) and falls by the action of gravity into a collection vessel (19).

Abstract: A mold indicator having a piece of leather, a covering over at least a first portion of the piece of leather, at least a second portion of the piece of leather not covered by the covering exposable to an environment around the mold indicator. The mold indicator including the piece of leather is untanned. The mold indicator including the covering is a layer includes anti-mold agent.

Abstract: The present invention involves an optical assay device and method of use for the detection of an analyte of interest in a sample that conveniently allows control of the flow characteristics of the sample through the device without significant user intervention. The optical assay device includes a base having an absorbent material, and a member having an optically active test stack that is rotatably coupled to the base for rotation between a lowered position and a raised position. In the lowered position, the optically active test stack contacts the absorbent material for drawing the sample through the surface. In the raised position, the optically active test stack does not contact the absorbent material.

Abstract: A method and apparatus is provided for detection of volatile products from a sample using a transducer which changes voltage as a function of contact of the volatile products with the transducer to produce a gas signature of the volatile products and a spectrophotometer to analyze the volatile products to produce a spectral footprint of the volatile products. The apparatus and method are used to detect spoilage of a biological material, such as a food. The apparatus is also used to detect microorganisms and by comparing the gas signature and spectral footprint to a library of gas signatures and spectral footprints, the apparatus enables identification of the microorganisms and in particular identification of pathogenic microorganisms.

Abstract: A process for detecting an analyte which process comprises (a) contacting a sample suspected of containing said analyte with a containment means comprising a barrier which separates signal generating reagents from said sample, in the presence of an element which interacts specifically with said analyte, under conditions whereby interaction between the analyte and the said element results in activation of the signal generating reagents within the containment means on the side of the barrier opposite to the sample, and (b) detecting any signal generated and retained within the containment means from the sample side of the barrier. The process of the invention provides for sensitive detection of very small numbers of analyte materials using measurement techniques which include counting methods such as flow cytometry.

Abstract: A micro ELISA reader includes a housing, a tray longitudinally movably provided in the housing, a carrier transversally movably mounted on the tray, a light source board provided on the carrier, and a scanning assembly longitudinally movably mounted in the housing and above the light source board. The ELISA reader is integrally installed in a personal computer. During a testing, a microtiter plate is stably positioned in the carrier and between the light source board and the scanning assembly, and scanned by the scanning assembly.

Abstract: An immunoassay, e.g. ELISA, method and kit for determining (preferably quantitatively) an analyte adsorbed at a surface or present in a liquid sample, comprising binding the analyte to a solid phase, attaching a marker to the analyte, and detecting marker attached to the solid-phase. The invention proposes to use a combination of marker and detection (e.g. an enzyme-substrate combination) which is capable of producing a precipitate on a solid phase which carries the marker and to detect the binding of analyte to the solid phase by in-situ determining the change in surface mass of the solid phase due to the formation of the precipitate. Ellipsometry is an example of a technique suitable for determining the change of surface mass of the solid phase, which could be made of a silicon- or chromium-sputtered glass slide The invention shortens the assay time and/or improves the assay sensitivity, and allows to measure extremely low surface concentrations of analytes of interest.

Abstract: The measurement of the wavelength shifts in the reflectometric interference spectra of a porous semiconductor substrate such as silicon, make possible the highly sensitive detection, identification and quantification of small analyte molecules. The sensor of the subject invention is effective in detecting multiple layers of biomolecular interactions, termed “cascade sensing”, including sensitive detection of small molecule recognition events that take place relatively far from the semiconductor surface.

Abstract: The process is used for the screening of molecules from molecule libraries with regard to their individual binding behavior towards at least one given ligand. For this purpose the ligands labelled with a fluorescent dye are mixed with the molecule library which is in the form of a suspension. The mixture is plated out on a two-dimensional substrate (2) after the excess, unbound ligands have been washed out. Then the local fluorescence intensities on the substrate are electro-optically identified in a fluorescence microscope (5) and electronically discriminated in accordance with given selection criteria. The objects selected and localised in this way are then sequentially positioned exactly by a displacement, the coordinates of which are controlled by the image calculator, between the substrate (2) and a separation actuator (20, 21) and are spatially separated from the substrate (2) by the separation actuator (20, 21).

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: A surface plasmon resonance apparatus for detecting a soluble analyte (e.g. a protein) or a particulate analyte (e.g. a cell), the apparatus comprising: (a) a sensor block adapted to receive a sensor, said sensor, for example a sensor slide, having a metallized sensor surface capable of binding the analyte; (b) a light source capable of generating an evanescent wave at the sensor surface of a sensor slide on the sensor block; (c) a first detector capable of detecting light from the light source which is internally reflected from the sensor surface; and (d) a second detector (e.g. a video camera) capable of detecting light scattered or emitted from an analyte bound thereto. Optionally the apparatus further comprises a second light source for increasing the intensity of the light scattered or emitted from an analyte bound to the sensor surface, preferably, this is sited to such as to minimize the amount of light transmitted therefrom which is detected by the first detector.

Abstract: The invention provides methods for determining a characteristic of a tissue sample, such as a state of health, using spectral data and/or images obtained within an optimal period of time following the application of a chemical agent to the tissue sample. The invention provides methods of determining such optimal windows of time. Similarly, the invention provides methods of determining other criteria for triggering the acquisition of an optical signal for classifying the state of health of a region of a tissue sample.

Abstract: The invention relates to devices and methods for carrying out quantitative fluorescence immunoassays using evanescent field excitation. Light from at least one light source is directed onto the boundary between two media which have differing refractive indices. The light source emits practically monochromatic light with a wavelength suitable for exciting a marking substance. The light is directed onto a boundary surface disposed between an optically transparent base plate, the refractive index of which is greater than that of the material above the boundary surface, and a receiving region for the sample. The receiving region is covered with a covering plate on the side disposed opposite the base plate, there being arranged between the base plate and covering plate at least one functional layer. A detector for detecting the fluorescent light is disposed on the same side of the base plate as the light source.

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 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: A biosensor, sensor array, sensing method and sensing apparatus are provided in which individual cells or randomly mixed populations of cells, having unique response characteristics to chemical and biological materials, are deployed in a plurality of microwells formed at the distal end of individual fibers within a fiber optic array. The biosensor array utilizes an optically interrogatable encoding scheme for determining the identity and location of each cell type in the array and provides for simultaneous measurements of large numbers of individual cell responses to target analytes. The sensing method utilizes the unique ability of cell populations to respond to biologically significant compounds in a characteristic and detectable manner. The biosensor array and measurement method may be employed in the study of biologically active materials, in situ environmental monitoring, monitoring of a variety of bioprocesses, and for high throughput screening of large combinatorial chemical libraries.

Abstract: A device for the detection of electromagnetic radiation, wherein the device has (i) a photoactive layer of a semiconductor having a band gap of greater than 2.5 eV, (ii) a dye applied to the semiconductor, and (iii) a charge transport layer comprising a hole conductor material, where the hole conductor material is preferably solid and amorphous.

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: An optical assaying method and system having a movable sensor is described. In one aspect, the present invention is a sensing system having a rotating sensor disk coated with indicator dyes sensitized to a variety of substances. In this configuration the sensing system further includes a detector for sensing spectral changes in light received from one or more of the indicator dyes. In another aspect, the present invention is a sensing system having a surface plasmon resonance sensor disk having grooves extending radially from a center of the disk. In yet another aspect, the present invention is a sensing system including a diffraction anomaly sensor disk having a dielectric layer that varies in thickness. The present invention allows for construction of an inexpensive sensing system that is capable of easily detecting a variety of substances either in a sample or a surrounding environment.

Abstract: A device for rapidly collecting tissue samples from organisms serves as a reaction chamber. It includes a solvent used to extract the analyte, a filter, and optional bioconcentrators. The filtered suspension is irradiated with a predetermined wavelength and the emitted, scattered, or reflected photons transmitted to a detector that identifies and quantifies the analyte. The bioconcentrators may consist of antibodies and colloidal metal nanoparticles that enhance emission of Raman signal frequencies by analytes bound to the antibodies. Alternatively, the device may contain only the extraction solvent and a filter.

Abstract: A process challenge device tailored to mimic the resistance of a particular product-package combination to a particular biological inactivation, disinfection, or sterilization process. The device is used to challenge the process, thus providing a means to validate the efficacy of the process. In one embodiment, the process indicator includes a biological indicator organism stored on a carrier enclosed within a chamber formed by a barrier film material. The specific indicator organism and carrier substrate are chosen for their appropriateness for a given process. The materials comprising the barrier film material of the process challenge device are chosen for the materials' specific resistance to the given process. The process challenge device may also comprise a separate second chamber filled with an appropriate culture medium or enzyme substrate that is separated from the chamber containing the process indicator by a separation means, such as a valve, a clip, or a frangible separation.

Abstract: A tissue-based, deployable, standoff air quality sensor for detecting the presence of at least one chemical or biological warfare agent, includes: a cell containing entrapped photosynthetic tissue, the cell adapted for analyzing photosynthetic activity of the entrapped photosynthetic tissue; means for introducing an air sample into the cell and contacting the air sample with the entrapped photosynthetic tissue; a fluorometer in operable relationship with the cell for measuring photosynthetic activity of the entrapped photosynthetic tissue; and transmitting means for transmitting analytical data generated by the fluorometer relating to the presence of at least one chemical or biological warfare agent in the air sample, the sensor adapted for deployment into a selected area.

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: 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 fermentation apparatus is constructed to produce a known and repeatable amount of unpoisoned fermentation product using multiple fermentation vessels. To facilitate further processing compatible with other product processing steps, the fermentation apparatus has an array of sample vessels arranged in a container frame. The container frame is configured to hold the sample vessels during fermentation and to transport the vessel array to or from another processing station. Corresponding to the number of sample vessels in the sample vessel array, a cannula array is configured such that each cannula may be placed inside a sample vessel. The cannula array is attached to a gas distributor that delivers oxygen and/or one or more other gases from a gas source through the cannula into the sample vessel.

Abstract: A sensor for the detection of tetrameric multivalent neuraminidase within a sample is disclosed, where a positive detection indicates the presence of a target virus within the sample. Also disclosed is a trifunctional composition of matter including a trifunctional linker moiety with groups bonded thereto including (a) an alkyl chain adapted for attachment to a substrate, (b) a fluorescent moiety capable of generating a fluorescent signal, and (c) a recognition moiety having a spacer group of a defined length thereon, the recognition moiety capable of binding with tetrameric multivalent neuraminidase.

Abstract: A method of measuring the enzymatic activity of a luciferase includes contacting a luminogenic protein, such as a luciferase, with a protected luminophore to form a composition; and detecting light produced from the composition. The protected luminophore provides increased stability and improved signal-to-background ratios relative to the corresponding unmodified coelenterazine.

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 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: 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: 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: 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: 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: A composition is disclosed that comprises a mixture of polypeptides of opposite charge and an excipient selected from the group consisting of arginine, lysine, glutamic acid, sodium dodecyl sulfate, beta-hydroxy cyclodextrin, and beta-cyclodextrin sulfobutyl ether.

Abstract: A method is disclosed for detecting the presence of a difference between two related nucleic acid sequences. In the method a complex is formed comprising both strands of each sequence. Each member of at least one pair of non-complementary strands within the complex have labels. The association of the labels as part of the complex is determined as an indication of the presence of a difference between the two related sequences. The complex generally comprises a Holliday junction. In one aspect a medium suspected of containing said two related nucleic acid sequences is treated to provide partial duplexes having non-complementary tailed portions at one end. The double stranded portions of the partial duplexes are identical except for said difference.

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: The invention relates to the addition of dyes to aerobically curable adhesive compositions based on free-radically polymerizable compounds. The dyes serve as user-friendly indicators for monitoring the oxygen intake required to trigger the polymerization. The indicator dyes are especially suitable for aerobically adhesive compositions which contain activator systems for forming peroxides upon contact with air. Suitable dyes and indicators are those whose color change in aqueous solution lies within a pH range from 3.0 to 6.5.

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: Disclosed is a method for removing polynucleotide from the skin. This polynucleotide can be used to detect dermatitis and distinguish an irritant reaction from an allergic reaction by characterizing the polynucleotide according to the polypeptide which it encodes. Additionally, provided are methods for non-invasive isolation of samples from the skin as well as kits for use in the methods provided herein.

Abstract: Microfluidic devices and systems having enhanced detection sensitivity, particularly for use in non-fluorogenic detection methods, e.g., absorbance. The systems typically employ planar microfluidic devices that include one or more channel networks that are parallel to the major plane of the device, e.g., the predominant plane of the planar structure, and a detection channel segment that is substantially orthogonal to that plane. The detection system is directed along the length of the detection channel segment using a detection orientation that is consistent with conventional microfluidic systems.

Abstract: Sensors for detecting microorganisms in gases, liquids, and aerosols are provided which include molecular receptors to interact with the microorganisms, polymeric membranes containing luminescent reagents, optional non-drying membrane additives, an optical substrate as a sensor support, an optional conformable optical substrate or rotating film to refresh the sensor chemistry, and means for detecting the signal from the sensor. Optical sign can be enhanced by immobilizing biocidal compounds in the sensing membrane, immobilizing metal colloids in the sensing membrane, or immobilizing sol-gel coated colloidal particles in the sensing membrane.

Abstract: Improvements in calorimetric assays, surfaces for arraying microcolonies and instrument hardware for screening mutagenized enzymes and proteins in a solid phase format are presented. These improvements permit new enzyme activities to be screened. New filter membrane materials and formats for arraying the microcolonies provide higher throughput, better solvent resistance and ease of handling. Modifications to the instrument heating and illumination systems provide improved temperature control and a more compact, folded light path.