Abstract: The invention is directed to a method and device for simultaneously testing a sample for the presence, absence, and/or amounts of one or more of a plurality of selected analytes. The invention includes, in one aspect, a device for detecting or quantitating a plurality of different analytes in a liquid sample. Each chamber may include an analyte-specific reagent effective to react with a selected analyte that may be present in the sample, and detection means for detecting the signal. Also disclosed are methods utilizing the device.

Abstract: A method of screening solution conditions suitable for the crystallization of macromolecules with a picogram to a microgram of protein using picoliter or nanoliter volumes is provided. A preferred method comprises preparing a plurality of recipe solutions in milliliter volumes, aspirating protein and recipe solutions, respectively, from a plurality of wells, and dispensing the protein and recipe solutions into a plurality of wells, covering the combined protein and recipe solutions with oil, and maintaining the solution wells until crystallization or precipitation occur therein.

Abstract: The invention concerns a method for the detection of an analyte in a sample using analyte-specific conjugates which have at least one heterologous group for an analyte-independent binding to a control zone. The present invention additionally provides new conjugates and reagent kits.

Abstract: Methods, articles, and kits for obtaining elevated concentrations of a substance from a sample that has become bound, for example by providing a positive test result in an immunoassay or other binding assay. The concentrated substance is optionally subjected to further processing or analysis, for example to confirm the identity of the substance, such as a pathogenic organism in a food sample.

Abstract: The invention is directed to a method and device for simultaneously testing a sample for the presence, absence, and/or amounts of one or more a plurality of selected analytes. The invention includes, in one aspect, a device for detecting or quantitating a plurality of different analytes in a liquid sample. The device includes a substrate which defines a sample-distribution network having (i) a sample inlet, (ii) one or more detection chambers, and (iii) channel means providing a dead-end fluid connection between each of the chambers and the inlet. Each chamber may include an analyte-specific reagent effective to react with a selected analyte that may be present in the sample, and detection means for detecting the signal. Also disclosed are methods utilizing the device.

Abstract: Use of calibrant in extraction phase is described for quantification of components of interest in samples in laboratory application as well as in on-site monitoring. This approach is particularly useful for in-vivo investigation of living systems.

Abstract: A test device and method for determining the presence or absence of an analyte in a fluid sample, the test device including a support bearing a mark thereon, and a matrix defining an axial flow path. In operation, an observation area in the test device becomes transparent, thereby allowing the user to view a mark that is present on a support that is disposed beneath the observation area. Typically, the mark on the underlying support is configured as a minus (?) sign. In the absence of analyte in the sample, the test device presents a negative result as a minus (?) signal. In the presence of analyte in the sample, however, the mark operates in concert with a perpendicular test line on the observation area to present a positive result as a plus (+) signal that is visible to the user.

Abstract: The invention is directed to a method and device for simultaneously testing a sample for the presence, absence, and/or amounts of one or more a plurality of selected analytes. The invention includes, in one aspect, a device for detecting or quantitating a plurality of different analytes in a liquid sample. The device includes a substrate which defines a sample-distribution network having (i) a sample inlet, (ii) one or more detection chambers, and (iii) channel means providing a dead-end fluid connection between each of the chambers and the inlet. Each chamber may include an analyte-specific reagent effective to react with a selected analyte that may be present in the sample, and detection means for detecting the signal. Also disclosed are methods utilizing the device.

Abstract: A test device and method for determining the presence or absence of one or more analytes in a fluid sample, the test device including a support or member bearing a mark thereon, and a matrix or member containing a capture zone. In operation, an observation area in the test device becomes transparent, thereby allowing the user to view a mark that is present on a support that is disposed beneath the observation area. Typically, the mark on the underlying support is configured as a minus (?) sign. In the absence of analyte in the sample, the test device presents a negative result as a minus (?) signal. In the presence of analyte in the sample, however, the mark operates in concert with a perpendicular test line on the observation area to present a positive result as a plus (+) signal that is visible to the user.

Abstract: The present invention relates mainly to reaction vessels, to sets of such vessels for automatic immunological assay apparatuses, to automatic immunological assay apparatuses making use of such sets of vessels, and to a method implementing sets of such vessels. According to the present invention, photometric detection is implemented of the luminescence of a reaction mixture found in a reaction vessel, the apparatus and/or the vessel guaranteeing light-tightness so as to prevent entry of external light falsifying the measurement. Advantageously, sets of vessels in accordance with the present invention are made out of a material that is opaque. The present invention is particularly applicable to detecting the presence of a chemical or a biological substance in a sample. The present invention applies mainly to medical analysis and research.

Abstract: The present invention is a method for selectively removing objects from a surface utilizing a probe. The probe is scanned over the surface utilizing a greater and greater relative amount of force so that a certain number of the objects are removed from the surface. The force required to remove the objects from the surface can be calculated utilizing Hook's law and the spring constant of the probe. After removal of the objects that have a relatively weaker binding affinity with the surface, the remaining objects can be harvested, characterized, and subjected to further study.

Abstract: Separation apparatus and method for separating magnetic and/or magnetically-labeled particles from a test medium. Test medium within a reaction chamber is caused to flow past a collecting surface, and a high-gradient magnetic field is applied to the surface to capture magnetically responsive particles in the test medium. The particles are deflected toward the collection surface by baffles, a spinner, or a sprayer, or are funneled past the surface by a plunger operable to be displaced into close proximity to the surface to provide a narrow flow path for the particle-laden test medium. The particles normally suspended in the medium are separated out of suspension by adhesion to the collection surface. The particles may be resuspended by removal of the surface from the high-gradient field, or removal of the high-gradient field from the surface. The collection surface is a thin-walled non-magnetic material having a plurality of magnetic pole faces positioned therearound.

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: This invention provides a novel Cryptosporidium parvum protein disulfide isomerase polypeptide, and nucleic acids that encode this polypeptide. The invention also provides methods, reagents, and kits that are useful for diagnosing infection by Cryptosporidium parvum. The methods are based on the discovery of binding agents, including recombinant polyclonal antibodies, that bind to the protein disulfide isomerase polypeptide of C. parvum.

Abstract: A nucleic acid-bound polypeptide produced by binding a nucleic acid to a polypeptide, a method of producing the nucleic acid-bound polypeptide, and applications of the nucleic acid-bound polypeptide, including immunoassays for an antigen or antibody, such as an agglutination immunoassay are provided.

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 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 invention concerns an analytical test element for the determination of an analyte in a liquid containing an inert carrier, a detection element and a channel capable of capillary liquid transport which has a sample application opening at one end and a vent opening at the other end of the channel capable of capillary liquid transport, wherein the channel capable of capillary liquid transport is formed at least partially by the carrier and the detection element and extends in the direction of capillary transport from the sample application opening at least to the edge of the detection test element that is nearest to the vent opening and wherein a notch is located in one of the surfaces forming the channel capable of capillary liquid transport at the edge of the test element forming the sample application opening so that one side of the edge of the test element forming the sample application opening is at least partially discontinuous and the surface opposite to the notch is exposed.

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 a more efficient and faster way to prepare tissue samples for sectioning. More particularly, in accordance with the present invention, a tissue sample is embedded in a porous embedding media in a desired orientation, processed, and sectioned all while being held in the porous embedding media. The post-tissue processing step of manual embedding in paraffin is eliminated from the process.

Abstract: The invention provides methods and devices for detecting the presence of one or more target analytes in a sample employing a channel having affixed therein one or more binding partners for each target analyte. Assays are carried out by transporting the sample through the channel to each successive binding partner so that target analyte present in said sample binds to the corresponding binding partner. The sample is then transported beyond the binding partner(s), followed by detection of any target analyte bound to each binding partner. In one embodiment, binding efficiency is increased by the use of segmented transport, wherein a first bolus or bubble of a fluid that is immiscible with the sample precedes the sample during transport and a second bolus or bubble of a fluid that is immiscible with the sample follows the sample. Many configurations are possible for the device of the invention.

Abstract: A method to determine the presence or absence of Streptococcus Group A antigen in a sample, comprising the following steps: extracting the antigen from the sample in an assay chamber with two or less extraction reagents, wherein the two reagents may be added to the assay chamber in no particular sequence; introducing a lateral flow immunochromatographic assay device into the extraction reagents containing the extracted antigen without further addition of reagents or manipulation of the sample; forming an antigen-indicator labeling reagent complex; and determining the presence or absence of the antigen in the sample by the presence or absence of a signal formed by the binding of the antigen-indicator labeling reagent complex to an indicator capture reagent specific for said antigen-indicator labeling reagent complex.

Abstract: Methods and apparatus for evanescent light fluoroimmunoassays are disclosed. The apparatus employs a planar waveguide with an integral semicylindrical lens, and has multi-analyte features and calibration features, along with improved evanescent field intensity. A preferred embodiment of the biosensor and assay method has patches of capture molecules, each specific for a different analyte disposed adjacently within a single reservoir. The capture molecules are immobilized to the patches on the waveguide surface by site-specific coupling of thiol groups on the capture molecules to photo-affinity crosslinkers, which in turn are coupled to the waveguide surface or to a nonspecific binding-resistant coating on the surface. The patches of different antibodies are produced by selectively irradiating a portion of the waveguide surface during the process of coupling the photo-affinity crosslinkers, the selective irradiation involving a mask, a laser light source, or the like.

Abstract: Simultaneous forward and reverse blood group testing is described using both a visual detection system and a fluorescent based labeling and detection system. Forward and reverse tests could be performed separately, but A and B agglutinates can be detected and discriminated simultaneously.

Abstract: A process is described, and also the system for its embodiment, for the determination of pollution by MTBE in the soil and in the overlying atmosphere. An example is described relating to the monitoring of underground fuel tanks for autotraction containing an oxygenated additive.

Abstract: The present invention provides methods and apparatus for sequencing, fingerprinting and mapping biological macromolecules, typically biological polymers. The methods make use of a plurality of sequence specific recognition reagents which can also be used for classification of biological samples, and to characterize their sources.

Abstract: A system for the rapid characterization of multi-analyte fluids, in one embodiment, includes a light source, a sensor array, and a detector. The sensor array is formed from a supporting member into which a plurality of cavities may be formed. A series of chemically sensitive particles are, in one embodiment positioned within the cavities. The particles may be configured to produce a signal when a receptor coupled to the particle interacts with the analyte. Using pattern recognition techniques, the analytes within a multi-analyte fluid may be characterized.

Abstract: A method for multiplexed detection and quantification of analytes by reacting them with probe molecules attached to specific and identifiable carriers. These carriers can be of different size, shape, color, and composition. Different probe molecules are attached to different types of carriers prior to analysis. After the reaction takes place, the carriers can be automatically analyzed. This invention obviates cumbersome instruments used for the deposition of probe molecules in geometrically defined arrays. In the present invention, the analytes are identified by their association with the defined carrier, and not (or not only) by their position. Moreover, the use of carriers provides a more homogenous and reproducible representation for probe molecules and reaction products than two-dimensional imprinted arrays or DNA chips.

Abstract: The invention relates to an optical system for determining the distribution, environment, or activity of fluorescently labeled reporter molecules in cells for the purpose of screening large numbers of compounds for specific biological activity. The invention involves providing cells containing fluorescent reporter molecules in an array of locations and scanning numerous cells in each location with a fluorescent microscope, converting the optical information into digital data, and utilizing the digital data to determine the distribution, environment or activity of the fluorescently labeled reporter molecules in the cells. The array of locations may be an industry standard 96 well or 384 well microtiter plate or a microplate which is a microplate having a cells in a micropaterned array of locations. The invention includes apparatus and computerized method for processing, displaying and storing the data.

Abstract: An improved microfabricated apparatus for conducting a multiplicity of individual and simultaneous binding reactions is described. The apparatus comprises a substrate on which are located discrete and isolated sites for binding reactions. The apparatus is characterized by discrete and isolated regions that extend through said substrate and terminate on a second surface thereof such that when a test sample is applied to the substrate, it is capable of penetrating through each such region during the course of said binding reaction. The apparatus is especially useful for sequencing by hybridization of DNA molecules.

Abstract: A method of measuring the physical and chemical properties of tissue or cells and a device for the same is provided, with which the physical and chemical environment of the tissue or cells can be changed arbitrarily corresponding to experimental necessities. The device comprises a system 40 for keeping the physical and chemical environment surrounding the biological tissue or cells constant, a system 50 for arbitrarily changing the physical and chemical environment, observation systems 10 and 20 for observing the physical and chemical properties of the tissue or cells, and a system 30 for comparing the change of the physical and chemical properties of the tissue or cells before and after changing the physical and chemical environment. The observation system 10 is a potential measurement device for measuring the electrophysiological properties of the tissue or cells.

Abstract: The present invention relates to a device for binding molecules, molecular groups, molecular parts and/or cells contained in a liquid to target structures, the device having at least one object holder with at least one target structure firmly held therein and which contacts at least one duct made of at least one material. One aperture of the duct is a liquid inlet aperture, and a second aperture is a liquid outlet aperture. At least one object holder thermostat is used for cooling the object holder.

Abstract: A test device and method for determining the presence or absence of an analyte in a fluid sample, the test device including a support bearing a mark thereon, and a matrix defining an axial flow path. In operation, an observation area in the test device becomes transparent, thereby allowing the user to view a mark that is present on a support that is disposed beneath the observation area. Typically, the mark on the underlying support is configured as a minus (?) sign. In the absence of analyte in the sample, the test device presents a negative result as a minus (?) signal. In the presence of analyte in the sample, however, the mark operates in concert with a perpendicular test line on the observation area to present a positive result as a plus (+) signal that is visible to the user.

Abstract: A bead dispenser device useful for supplying, one at a time, beads for heterogenous immunoassay, including an inner chamber having a return spring integrally formed to the inner chamber. The bead device also includes a plunger housed within a plunger chamber. The plunger includes a bead holding member and a notch. The return spring communicates with the notch of the plunger and biases the plunger in a resting position. In the resting position, the bead holding member is aligned with a bead receiving channel formed partly in the base of the inner chamber. When the plunger is depressed, the bead residing in the bead holding member is transported to a bead exit opening for dispensing therefrom. In this position, the return spring is also displaced inward to an inner portion of the inner chamber and is capable of agitating and contacting the beads located within the inner chamber.

Abstract: The invention is based on the discovery of reduced valency carbohydrate binding ligands (CBLs) that can be used to to detect or quantitate (i.e., evaluate) carbohydrates in a sample. CBLs can be used with fluorescence resonance energy transfer (FRET) to evaluate free carbohydrates or those within a carbohydrate containing compound.

Abstract: This invention discloses a method and composition for detecting the presence of class specific antibodies reactive with analytes such as bacteria, allergens, autoimmune antigens, viral proteins, and carbohydrates by lateral flow techniques. In one embodiment of the invention, a test sample obtained from bodily fluids reacts with a gold labeled antigen. The resulting complex travels across the membrane, and along the lateral flow strip. Red colored lines formed in specific locations along the test strip indicate the presence of class specific antibodies in the test specimen. In another embodiment of the invention, the lateral flow assay serves as an immunochromatographic screening test for the detection of allergen-specific IgE antibodies in human serum. Test sample reacts with gold labeled anti-IgE antibody. The resulting complex travels across the membrane where immobilized allergens capture the allergen specific IgE complex.

Abstract: The invention provides methods and devices for detecting the presence of one or more target analytes in a sample employing a channel having affixed therein one or more binding partners for each target analyte. Assays are carried out by transporting the sample through the channel to each successive binding partner so that target analyte present in said sample binds to the corresponding binding partner. The sample is then transported beyond the binding partner(s), followed by detection of any target analyte bound to each binding partner. In one embodiment, binding efficiency is increased by the use of segmented transport, wherein a first bolus or bubble of a fluid that is immiscible with the sample precedes the sample during transport and a second bolus or bubble of a fluid that is immiscible with the sample follows the sample. Many configurations are possible for the device of the invention.

Abstract: Detection apparatus for use in the detection of the presence of a selected pathogen in a sample are disclosed. Such apparatus include: a substrate with a detection region on a surface thereof, the detection region having microstructures including grooves formed therein that will align liquid crystal material in contact therewith, the width and depth of the grooves being in the range of 10 &mgr;m or less; a blocking layer on the surface of the detection region of the substrate that does not disrupt the alignment of liquid crystal material in contact therewith, the blocking layer blocking nonspecific adsorption of pathogens to the surface; and a binding agent on the surface of the detection region of the substrate, the binding agent specifically binding the selected pathogen.

Abstract: An immunological test kit suitable for the rapid detection of ciguatoxin and related low molecular weight lipid polyether marine toxins in fish tissues in the field, home or laboratory. The test procedure utilizes a synthetic membrane laminated onto one end of a solid plastic stick, which is immersed into alcohol with a piece of fish tissue. The membrane is then removed and dried thoroughly, then placed in the suspension of mixed colored beads coated with anti-ciguatoxin. The membrane is then rinsed in water and the intensity of the color compared with a standard range of colors formed (0-3+). The color intensity is proportional to the concentration of toxin in the piece of tissue. The kit includes the synthetic membrane on a plastic stick, a suspension of mixed colored beads coated with anti-ciguatoxin antibody, testing instruments, and a supply of solvent.

Abstract: A predictive test for rheumatoid arthritis comprises the detection of antibodies to collagen in a biological sample from a patient by contacting the biological sample with an antigen comprising the CB10 peptide of mammalian type II collagen, or an antibody-binding fragment or variant thereof, for a time and under conditions for an antibody-antigen complex to form, and detecting the antibody-antigen complex, for example by immunoassay. A diagnostic test kit is also disclosed.

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: Novel peptides which are epitopes of the human 60 kDa heat shock protein (hsp60) may be used for the diagnosis and treatment of insulin-dependent diabetes mellitus (IDDM). Pharmaceutical compositions containing such peptides and kits for use in diagnosis of IDDM are also disclosed.

Abstract: The present invention is a method and an apparatus to provide a dynamic matrix system for synthesizing a plurality of chemical compounds simultaneously, i.e. in parallel, and to synthesize a series of plurality of simultaneously synthesized chemical compounds sequentially, i.e. in series. The apparatus includes a base support structure, a physical chemistry teabag support structure, a plurality of physical chemistry teabags and a fixed-reactant/liquid reactant mixture shifting (changing) mechanism. The base support structure has a plurality of reaction vessels arranged in at least a two dimensional predetermined array. The physical chemistry teabag support structure is adapted to hold and support a plurality of physical chemistry teabags arranged in at least a two dimensional predetermined teabag array, at least partially coinciding with the base support structure reaction vessel array. The teabags have at least one predetermined fixed reactant thereon.

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: A method and apparatus for collecting a fluid specimen, locally analyzing the specimen to qualitatively detect specified chemical components at concentrations above threshold levels, and providing machine readable test results for facilitating data collection and reporting. The apparatus includes an assaying device comprised of a cup for collecting a fluid specimen and a cap carrying at least one test strip for visually reacting to one or more specified chemical components in the specimen. The cap also carries an aliquot delivery mechanism for forcing an aliquot of the fluid specimen onto the test strip. The assaying device is preferably configured to interact with a reader device capable of reading the reaction of the test strip to produce a data output.

Abstract: Apparatus and methods are disclosed which facilitate immobilization of magnetically labelled particulate entities, e.g., cells, preferably in a defined pattern, on a collection surface via binding between specific binding pair members, as an aid to particle analysis.

Abstract: An immunochromatographic assay employing superparamagnetic particles to lable the target analytes. An opaque cover prevents misinterpretive readings in field situations and provides a protective surface on the porous membrane. Additional features include separability of the test strip from any backing or housing which is configured to support the strip, and that quantitative measurements of the target analytes are easily and accurately made by means of an electromagnetic reader device.

Abstract: A method is disclosed for obtaining and/or immunologically detecting an analyte contained in a gas phase by immunologically binding the analyte to a binding partner thereof contained in a gas- and liquid-permeable first carrier matrix. Said method is characterized in that a) the analyte-containing gas phase is brought into contact with the first carrier matrix (immune adsorber), b) the analyte is bound to the first binding partner which is contained in the first matrix and not bound to the matrix, and c) the complex of analyte and first binding partner and the free first binding partner are eluted from the first matrix, d) the eluted complex or the free first binding partner is determined as a measure for the amount of analyte present.

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 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.