Abstract: A system for performing chemical analyses includes at least two analyzers and at least one peripheral device capable of serving either analyzer. A control system is coupled to the analyzers and to the peripheral device and selectively commands the peripheral device to serve one or the other of the analyzers depending upon the analyses requested for each analyzer and the analytical method applied. A control system providing sharing of peripheral devices in such a system is also provided, as is a method for performing chemical analyses wherein a peripheral device is shared by analyzers. The system permits simultaneous and asynchronous analysis for a variety of analytes while reducing the physical space occupied by the system and the idle time of both the analyzers and the peripheral devices.

Abstract: A system and method of determining absence or presence of an illicit substance in a flowing mixture of requisite reagents by agglutination or lack thereof. A plurality of photodetectors are positioned over an illuminated read area oblique to a path of the flowing mixture. Signal samples of each of the detectors are processed individually. Successive samples are processed over a period time to detect differences or edges between relatively clear liquid and relatively opaque clusters in the flowing mixture. The illicit substance is determined in accordance with the number of variations in signal samples for a predetermined number of detectors.

Abstract: New devices and kits for solid-phase immuno-assays comprising a solid porous support, preferably in the form of a sheet, where antigens or immuno-globulins or both of them are bound by direct application in any suitable geometry, e.g. as an assay of dots or lines. Such porous supports are suitable for effecting an unlimited number of antibody-antigen reactions simultaneously and in one operation.

Abstract: An automated, continuous and random access analytical system, having apparatus and methodology capable of simultaneously performing multiple assays of liquid samples using different assay methodologies, and providing continuous and random access while performing a plurality of different assays on the same or different samples during the same time period, is disclosed. A method is also disclosed of operating an automated continuous and random access analytical system capable of simultaneously effecting multiple assays of a plurality of liquid samples wherein scheduling of various assays of the plurality of liquid samples is followed by creating a unit dose disposable and separately transferring a first liquid sample and reagents to a reaction vessel without initiation of an assay reaction sequence, followed by physical transfer of the unit dose disposable to a processing workstation, whereby a mixture of the unit dose disposable reagents and sample are achieved during incubation.

Abstract: The present invention provides chromatographic assay devices that can perform multiple assays simultaneously in the same test strip, as well as methods for their use. One of the assays can be an immunological assay to detect an antigen, such as human chorionic gonadotropin, while another assay can be a serological assay to detect an antibody, such as anti-rubella antibody. An assay device according to the present invention can comprise: (1) a first opposable component including at least one chromatographic medium having a specific binding partner to the first analyte and a specific binding partner to the second analyte immobilized thereto in separate, discrete, non-overlapping zones; and (2) a second opposable component including an absorber.

Abstract: Methods of glycosylation analysis are described in which a sample containing one or more specific oligosaccharide(s) (the analyte) is contacted with a surface on which is immobilized a glycosidase specific for the analyte and/or a specific binding partner for a product of the action of a glycosidase on the analyte. The surface may be the active surface of a biosensor, e.g., a biosensor based on the principle of frustrated total reflection.

Abstract: A magnetic separator for isolating magnetically-labeled substances of interest, such as immunological agents, from a non-magnetic test medium using a method of high gradient magnetic separation. The target substance is contacted with microscopic magnetic particles having a receptor for binding with the target substance. The test medium containing the magnetic particles is held in a non-magnetic container and placed into a gap within an arrangement of magnets for causing the magnetic particles to adhere to selected locations upon the interior wall of the container. The quantity of magnetic particles may be controlled to cause the magnetic particles collected upon the interior wall to form a monolayer. The magnets are arranged upon a yoke which may provide linear, surrounding multipolar, or partially surrounding multipolar configurations of magnetic pole faces about the gap.

Abstract: A support for biological molecules comprising a porous inorganic matrix and particles of a water-insoluble polymer, and a biologically active support comprising a porous inorganic matrix and particles of a water-insoluble polymer "sensitized" by biological molecules. The supports are prepared by bringing the matrix into contact with an aqueous dispersion of optionally "sensitized" polymer particles, and the use of such supports in biological application.

Abstract: An affinity column antibody purification method using a synthetic hCG analyte-analog insolubilized on a support material. The immobilized hCG analyte-analogs are peptide sequences which duplicate or mimic the determinants formed by the amino acid residues of the C-terminus peptide sequence or portions or variants thereof. The antibodies produced according to the present invention are useful in immunoassays for hCG.

Abstract: The present invention relates to an apparatus for performing a fluoroimmunoassay, the apparatus comprising an excitation light source, a fluorescence detector, an optical fiber for an excitation light from the excitation light source to which an antigen or antibody is bound, and a spectroscope, in which the mentioned antigen or antibody is bound to an outgoing end surface of the optical fiber for the excitation light. In the apparatus the spectroscope is constructed so that it introduces the excitation light emitted from the excitation light source to a incident end surface of the optical fiber for the excitation light and introduces a fluorescence emitted from a fluorescence-labeled antibody or antigen which forms an immunological complex with the antigen or antibody to the fluorescence detector. In the apparatus the outgoing end surface of the optical fiber for the excitation light has a transmittance for the excitation light from the excitation light source.

Abstract: The present invention relates to an apparatus for conducting a variety of assays that are responsive to a change in the viscosity of a sample fluid and relates to methods of conducting such assays. In particular, the present invention is related to the use of a cartridge for conducting one or more coagulation assays or, conversely, fibrinolysis assays. The disclosed device enjoys simplicity and is adaptable to the point-of-care clinical diagnostic area, including use in accident sites, emergency rooms, surgery or intensive care units.

Abstract: A method and apparatus for preparation of a substrate containing a plurality of sequences. Photoremovable groups are attached to a surface of a substrate. Selected regions of the substrate are exposed to light so as to activate the selected areas. A monomer, also containing a photoremovable group, is provided to the substrate to bind at the selected areas. The process is repeated using a variety of monomers such as amino acids until sequences of a desired length are obtained. Detection methods and apparatus are also disclosed.

Abstract: An reaction vessel utilizes a sample carrier composed of a magnetic core and a surface coating effective to support sample of protein or peptide. The sample carrier is floated magnetically and positioned within a reaction chamber. Edman reagent is applied to the sample to effect amino acid sequence analysis of protein or peptide from amino-terminal. By such construction, reaction efficiency is increased to produce sequentially thiazolinon amino-acid derivatives to thereby increase number of identified remaining amino acids, thereby enabling microanalysis of sample.

Abstract: A method for simultaneously detecting a plurality of target polynucleotides in a sample on a single reaction chip and a method for separating a plurality of target polynucleotides are provided. On the reaction chip are arranged a plurality of independent cells for capturing different target polynucleotides. Different probes are immobilized onto the individual cells, and labeled probes detect the cells where the target polynucleotides are captured, thereby analyzing the species of the captured target polynucleotides. Also, the individual cells function as electrodes to elute the captured target polynucleotides therethrough, thereby separating a plurality of the target polynucleotides.

Abstract: In a diagnostic apparatus system, a one piece porous substrate is provided in a container. The substrate serves both to extract an antigen in or on a top layer thereof with the remainder of the substrate serving as a reservoir. The pores in the top surface of the substrate are microscopic for entrapment of microspheres carrying antibodies. A target antigen in a test sample attaches to the antibodies when the test sample is poured through the top layer. The pores in all but the top layer of the substrate have a much greater pore size to comprise tile reservoir portion of the substrate.

Abstract: Apparatus, and process, for extracting organic fluids and solids specimens from weighed amounts of semi-solids and solids samples for collection, concentration and transfer to an analytic unit. The organic specimen is picked up by a probe assembly from a single compartment septum-sealed vial by heating and slurrying the sample, contacting with a gas; and then transferring the organic specimen with the gas to a collection device, e.g., a syringe or adsorbent trap. The specimen is then transported to an analytical instrument for analysis.

Abstract: Devices and methods are provided for the clinical analysis of a sperm sample. The devices include a solid substrate, typically on the order of a few millimeters thick and approximately 0.2 to 2.0 centimeters square, microfabricated to define a sample inlet port and a mesoscale flow channel extending from the inlet port. In one embodiment, a sperm sample is applied to the inlet port, and the competitive migration of the sperm sample through the mesoscale flow channel is detected to serve as an indicator of sperm motility. In another embodiment, the substrate of the device is microfabricated with a sperm inlet port, an egg nesting chamber, and an elongate mesoscale flow channel communicating between the egg nesting chamber and the inlet port. In this embodiment, a sperm sample is applied to the inlet port, and the sperm in the sample are permitted to competitively migrate from the inlet port through the channel to the egg nesting chamber, where in vitro fertilization occurs.

Abstract: On a slab-like board formed of a transparent material is closely attached a wedge-shaped transparent cover member provided with a recess in a central inner portion, thereby to form a clearance. The height of the clearance between the recess and the board is configured to decrease continuously or in steps. When an immunological active substance such as a monoclonal antibody is caused to sensitize carrier particles F, and a reagent having the carrier particles F dispersed into a liquid medium mainly composed of the water is mixed with a specimen, the reaction will occur in which the flocculate is formed from plural carrier particles. When this reaction liquid is poured into the clearance through the opening, the reaction liquid penetrates in the direction having a narrower vertical spacing due to surface tension. A single carrier particle unflocculated can move deep within the recess because it is small in diameter, but the flocculate G is trapped on its way and can not move because of its size.

Abstract: The invention addresses an analysis element for the determination of an analyte according to the principle of a heterogeneous immunoassay. Said analysis element is made of a chromatographic porous carrier material and has a reaction zone, at least two detection zones and absorptive zones following said detection zones. The reaction zone contains analyte-specific and labelled binding partners which are present in a number of soluble compartments which are close together, but nevertheless spatially separated. The detection zones are adjacent to the reaction zones and contain an immobilized binding reagent for one of the binding partners present in the reaction zone. At least one detection zone contains a binding reagent for the analyte-specific unlabelled binding partner.

Abstract: The present invention relates generally to test articles and assays for the detection of analytes in biological fluid samples. More particularly, the present invention relates to test articles an assays which employ dyed microorganisms as visual labels to detect suspected analytes.

Abstract: Methods of performing an assay for biomolecules and solid supports for use in such assays are disclosed. An activated polymeric material is used as a solid support for binding biomolecules. In a preferred form, the support is made of a generally hydrophobic, nonporous polymer which has been activated by treatment with solvents or by mechanical means to enhance the binding characteristics of the support. The support can be made of a copolymer, such as a copolymer of polystyrene and polybutadiene. Detection of bound biomolecules is preferably performed by means of staining reactions and gray level scanning. Emulsifying agents, such as detergents, can be applied to the surface of the support to substantially inhibit additional materials from being bound to the support.

Abstract: The present invention relates to an apparatus for determining the presence or absence of a target analyte in a liquid sample, comprising:(i) a container capable of accommodating the liquid sample and having a transparent portion; and(ii) an insertion member which is capable of being inserted into the container comprising;a porous member which has a main surface and a reverse surface and which has on the main surface a substance capable of specifically binding to the target analyte; andan absorbent bonded to the reverse surface of the porous member;the porous member being supported in the insertion member whereby, when the insertion member is inserted into the container, the main surface can be observed from the outside of the container through the transparent portion of the vessel and the liquid sample is absorbed into the absorbent through the porous member.According to the analyzer of the present invention, the presence or absence of a target analyte in a sample can be easily determined.

Abstract: An ion mobility spectrometer for detecting substances such as narcotics and explosives, has inlets for a sample gas and a drift gas. The gas can be ambient air, bottled air, or another gas source. To ensure accuracy and prevent drifting of analyte peaks, the air is dried. A two stage dryer is provided comprising a first dryer, preferably a dryer which chills the air and removes water by condensation. This removes the bulk of the water. The second dryer includes a suitable absorbent, and reduces the water content to around 1-10 .mu.g/L, i.e. a level which will not substantially affect the performance of the IMS apparatus. The first dryer substantially reduces the load on the second dryer, and enables an extended period of use before the absorbent material in the second dryer either needs to be replaced or regenerated. The increased stability of calibrant and analyte peak positions allows detection windows to be narrowed, resulting in significantly lower false alarm rates.

Abstract: A technique for the synthesis of arrays of diverse polymers such as polypeptides and nucleic acids. The technique beneficially utilizes solid-phase chemistry techniques. Preferred embodiments utilize photolabile protecting groups, and photolithography. The technique forms polymers with monomer sequences and locations determined by the order of addition of monomers and the activation patterns formed on the substrate.

Abstract: A method is provided, in one embodiment, for the determination of an analyte in a biological fluid sample in the presence of a substance interfering with an assay for the analyte. This embodiment is implemented by using antibodies to cause the selective immunoreaction of at least one of the analyte or the interfering substance and then conducting an assay for the analyte in at least one of the immunoreactants or the non-reactants. Another embodiment provides a disposable reaction device to implement the method. The invention is applicable to the detection of a wide variety of analytes, including cholesterol in a targeted lipoprotein class in the presence of cholesterol in another class; to targeted isozymes of enzymes such as creatine kinase, lactate dehydrogenase, amylase, and alkaline or acid phosphatases in the presence of other isozymes; as well as to targeted immunoglobulins in the presence of non-targeted immunoglobulins.

Abstract: A sample solution is dripped on an injection region with a pipette. The sample solution immediately spreads in a reaction region by a capillary phenomenon. The sample solution is left for a predetermined period of time to bind a biological associated material in the sample solution with a specific affinity material bound on the inner surface of the reaction region. After the reaction, the outer surface portion of a support member is pushed against a reaction vessel main body to deform the support member, thereby bringing the sample solution into contact with a water absorbent member at a removal region. The sample solution is absorbed by the water absorbent member and is removed from the reaction region. A cleaning solution is dripped on the injection region in an appropriate amount to perform B/F separation and is allowed to spread in the reaction region. The cleaning solution is absorbed and removed by the water absorbent member. The biological associated material bound to the reaction region is assayed.

Abstract: This invention relates to an improved assay device and assay for detecting or quantitating the presence or absence of a substance in a sample. The device has multiple layers comprising a permeable layer (a) having a capture reagent attached to less than the entire membrane, a selectively permeable layer (b) which does not allow assay reagents to pass through (b) and an absorbent layer (c). Layer (b) is in communication with layers (a) and (c). Layer (b) has at least one hole extending therethrough and the hole or holes are directly below the capture reagent in layer (a). The area of the hole or the combined area of the holes is less than the area covered by the capture reagent. This invention also relates to a method of reducing background color development in an absorbent layer of an assay device.

Abstract: This invention relates to a method of determining the amount of test analyte in a sample using internal calibration comprising mixing a sample with a predetermined amount of a calibrator analyte foreign to the sample and with a comparable behavior in an assay to that of the test analyte, contacting the mixture with a solid support containing, each in a separate area, a regent for binding the test and calibrator analytes, respectively, contacting the solid support with a mixture of labelled reagents for binding the test and calibrator analytes, respectively, and determining the amount of test analyte in the sample by comparing the levels of labelled reagent bound to the test and calibrator analytes.

Abstract: A method and device for forming large arrays of polymers on a substrate (401). According to a preferred aspect of the invention, the substrate is contacted by a channel block (407) having channels (409) therein. Selected reagents are flowed through the channels, the substrate is rotated by a rotating stage (403), and the process is repeated to form arrays of polymers on the substrate. The method may be combined with light-directed methodolgies.

Abstract: The invention provides a method for supplying an enzyme substrate to a membrane-based, enzyme-linked reaction, comprising providing an open pore, high liquid retention capacity material impregnated with a predetermined amount of a substrate for the enzyme; and contacting the material with a membrane containing the enzyme-linked reaction under conditions which permit diffusion of the enzyme substrate to sites on the membrane containing the enzyme linked reaction.

Abstract: An analysis element for the determination of an analyte in a liquid sample, especially for medicinal uses. A carrier layer (2) contains, in a reagent domain (4), a reagent applied in a defined pattern by an ink-jet process. The pattern comprises several sets (A, B, C) of compartments (11-20), the compartments (e.g. 11, 13, 15, 17, 19) of the same set (e.g. A) having the same chemical composition, the compartments (11, 13, 15, 17, 19 or 12, 16, 20) of different sets (A or B) containing different reagents and the compartments of different sets being arranged in alteration so that the compartments containing different reagents are close together but nevertheless spatially separated.

Abstract: A sensor based on the technique of surface plasmon resonance (SPR) comprises an SPR device, a source of electromagnetic radiation from which radiation can be directed onto the device, and a detector to measure the intensity of radiation reflected from the SPR device. The electromagnetic radiation directed onto the SPR device contains both Transverse Electric-polarized and Transverse Electric-polarized components. A polarization analyzer is interposed between the device and the detector such that, at angles away from resonance, little or no light reaches the detector. The sensor is particularly useful in the qualitative and/or quantitative determination of biological, biochemical or chemical analytes.

Abstract: The present invention is an apparatus and method for performing a coagulation time test on a sample of blood wherein the blood is deposited in a fluid reservoir and disposable cuvette. Within the cuvette is formed a capillary conduit have at least one restricted region. The cuvette is inserted into a testing machine which engages the cuvette and draws blood from the fluid reservoir into the capillary conduit. The blood is then caused to reciprocally move within the capillary conduit whereby the blood is forced to traverse the restricted region. The testing machine measures the time required each time the blood is caused to traverse the restrict region. When a measured time is a predetermined percentage longer than an immediately preceding time, coagulation is considered to have occured and the overall coagulation time is displayed to the operator.

Abstract: The present invention relates to an integrated analytical system which includes a plurality of remote laboratories and a central monitoring station. The remote laboratories include a specimen analysis member and a plurality of peripheral devices. The central monitoring station includes a computer for controlling predetermined functions of the peripheral devices. A local area network provides communication between each of the remote laboratories and the central monitoring station. A computer interface provides bi-directional communication between analytical instruments, robots and peripheral devices and a computer. The system employs a robot which is responsive to computer commands and capable of performing mechanical functions.The mechanical functions include manipulating an analytical instrument, transporting the specimens to be analyzed through a variety of locations, and the manipulation of the container in which the specimen is housed.

Abstract: There are described a device and method for doing confined reactions such as PCR amplification and detection, wherein solids (e.g., beads) used to obtain separation between bound and "free" label reagents, are transferred from region to region, specifically through a wash liquid so as to wash off the "free" label reagent from the solids. Separate chambers have dividers that are overcome by piercing or by liquification, to create passageways for the transfer of the solids. The passageways remain contained within the device.

Abstract: An automated system for sampling and testing a fluid specimen using an analysis station. The fluid specimen is collected in a flexible container having an access port. A piercing element pierces the access port and is withdrawn, allowing the fluid specimen to drain from the container. Subsequently, the container can be resealed.

Abstract: A sample analyzer for analyzing the characteristics of a plurality of samples. The analyzer includes a movable sample support for holding samples arranged in a first plurality of holders in a sequence for movement in a first direction. An indexing drive for the sample support advances the sample support in the first direction in a set of one or more increments, wherein one increment in the set is a net amount equal to a second plurality of holders greater than one holder and less than the first plurality such that the second plurality is relatively prime with respect to the first plurality.

Abstract: The invention relates to a device for use in optical methods of assay. The device comprises an optical structure comprising a dielectric substrate (2) and a thin film waveguide (5), between which is interposed a buffer layer (4). The waveguide carries a layer (10) of reagent suitable for a desired assay. The invention also relates to methods of using the device in an assay.

Abstract: A method for quantifying glucose concentration in blood, body fluids, and other samples within, below and above the normal physiological range, which relies on non-radiative fluorescence resonance energy transfer, as well as devices useful in quantifying blood glucose concentration using the present method.

Abstract: A diagnostic microbiological testing apparatus and method includes at least one test tray including a plurality of reaction chambers, a light source disposed proximate to the test tray for directing light, at an excitation wavelength of a fluorescence emitting agent contained within the reaction chambers, at the test tray, a filter for passing therethrough only light generated by a fluorescence emitting reaction resulting from the interaction of the fluorescence emitting agent and a sample, and an imaging mechanism for detecting only the light generated by the fluorescence emitting reaction at the emission wavelength simultaneously from the plurality of reaction chambers.

Abstract: An evanescent wave sensor and method for use in analyzing one or more media, the sensor including a waveguide having first and second wave propagating surfaces. The waveguide propagates an input signal along the waveguide between the first and second surfaces. The first surface receives a first radiation signal which indicates the presence of a first analyte, and the second surface receives a second radiation signal representing one or both of a second analyte and a reference. The first and second surfaces can both be contacted with a single medium, or with two separate media, and one or more output signals can be detected.

Abstract: A new apparatus and method for immunoassays. A gold sol bead is held in a funnel member. First antibodies are associated with the gold sol bead. When the sample contacts the gold sol it dissolves the bead. A second antibody is impregnated on an immunosorbent surface. When the dissolved gold sol passes this surface, any antigen already reacted with the first antibody present reacts with the second antibody forming a gold: first antibody: antigen: second antibody: immunosorbent complex. The gold sol acts as the visible label.

Abstract: In determining the effectiveness of parameters on cells, after treatment of the cells with one or more selected parameters, the results of the treatment can be quickly determined by measuring the number n.sub.0 of cells having a predetermined cell form, subsequently mechanically stressing the cells for a sufficient period of time t to change the cell form substantially, thereafter again measuring the number n of cells having the predetermined cell form, and determining the cell viability .tau.defined by .tau.=t/1n(n.sub.0 /n).

Abstract: This invention uses the evanescent wave detection of particles to distinguish bound from free in an analyte-binding assay. Illumination below the critical angle is employed, and a beveled window is used to eliminate bulk fluorescence from the emitted evanescent wave liquid. The sample is held in a non-rigid film cuvette.

Abstract: Devices and methods are provided for the clinical analysis of a sperm sample. The devices comprise a solid substrate, typically on the order of a few millimeters thick and approximately 0.2 to 2.0 centimeters square, microfabricated to define a sample inlet port and a mesoscale flow channel extending from the inlet port. In one embodiment, a sperm sample is applied to the inlet port, and the competitive migration of the sperm sample through the mesoscale flow channel is detected to serve as an indicator of sperm motility. In another embodiment, the substrate of the device is microfabricated with a sperm inlet port, an egg nesting chamber, and an elongate mesoscale flow channel communicating between the egg nesting chamber and the inlet port. In this embodiment, a sperm sample is applied to the inlet port, and the sperm in the sample are permitted to competitively migrate from the inlet port through the channel to the egg nesting chamber, where in vitro fertilization occurs.

Abstract: A diagnostic test kit is disclosed for assessing whether patient chest pain is cardiac in origin and for differentiating between unstable angina and myocardial infarction at early onset of patient chest pain. The test kit comprises a receptacle for receiving and retaining a sample of blood or serum of the patient and at least three monoclonal or polyclonal antibodies suspended on a carrier. Each antibody is complementary to a different protein released by the heart muscle during early stages of a myocardial infarction and has corresponding reagents which are independently responsive to each antibody reacting the complementary protein. The combined response of reagents indicates the diagnostic condition of the patient.

Abstract: A method for DNA sequencing, and particularly for sequencing of the entire human genome. Different base-specific reactions are utilized to use different sets of DNA fragments from a piece of DNA of unknown sequence. Each of the different sets of DNA fragments has a common origin and terminates at a particular base along the unknown sequence. The molecular weight of the DNA fragments in each of the different sets is detected by a matrix assisted laser absorption mass spectrometer to determine the sequence of the different bases in the DNA. The methods and apparatus of the present invention provide a relatively simple and low cost technique which may be automated to sequence thousands of gene bases per hour, and eliminates the tedious and time consuming gel electrophoresis separation technique conventionally used to determine the masses of DNA fragments.

Abstract: An automated method of using a system for sampling and testing a fluid specimen including an analysis station comprising collecting the fluid specimen in a flexible container having an access port, piercing a housing of the access port, withdrawing the piercing element and allowing the fluid specimen to drain from the container.

Abstract: A device and process for detecting the presence of organic molecular analytes in a fluid comprising a first binding component having a predetermined first affinity for specifically reversibly binding an analyte, a molecular conjugate of the analyte with a signal generating molecule that generates a detectable signal, and a second binding component having a predetermined second affinity for reversibly binding the signal generating molecule. In the presence of analyte, a fluid conducting system allows competitive binding of the analyte with the molecular conjugate and causes displacement of the conjugate and conducts the displaced conjugate to the second binding component. The signal generating molecule generates a detectable signal distinguishing binding thereof at the first or second binding components thereby indicating the presence of the analyte in the fluid.

Abstract: The present invention provides a carrier for coating with immunologically-active material, wherein it consists of an injection molded synthetic resin with a content of adjuvant and additional materials of less than 1% by weight. The present invention also provides a carrier coated with immunologically-active material, wherein the carrier consists of synthetic resin with a content of adjuvant and additional materials of less than 1% by weight.