Abstract: The present invention provides a method for reducing undesirable light emission from a sample using at least one photon producing agent and at least one photon reducing agent (e.g. dye-based photon reducing agents). The present invention further provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one collisional quencher. The present invention also provides a method for reducing undesirable light emission from a sample (e.g., a biochemical or cellular sample) with at least one photon producing agent and at least one quencher, such as an electronic quencher. The present invention further provides a method of determining bound and free analyte in a sample using at least one photon reducing agent. The present invention also provides a method of screening test chemicals in fluorescent assays using photon reducing agents.

Abstract: A solid phase extraction plate includes a unitary tray having a plurality of spaced-apart discrete upstanding chambers molded therein with each chamber having a top opening and a bottom nozzle with downwardly tapering sidewalls extending between the top opening and the bottom nozzle. A plurality of solid phase extraction disks are provided and one secured in each of the plurality of chambers without the use of frits or retainer rings utilizing instead tapered sidewalls of the chamber for enabling a press fit of the disks therein.

Abstract: The invention concerns a solid-phase determination method and equipment and an adapter for use in these. In the method a sample is allowed to react with a separating reagent bound to the outer surface of a separate solid phase body, whereafter the body is removed from the vessel and is taken to a measurement vessel, if required through one or several intermediate step vessels. At least one vessel contains a medium needed in a determination step to be performed therein when the phase body is brought into this vessel. The invention is especially suitable for use in automatic immunodetermination systems.

Abstract: Systems and methods for processing membrane flow-through assays to provide more rapid testing. The systems include a plate for receiving a cartridge having a membrane which, for example, can be a membrane with antigens or antibodies fixed thereon. The agents can be pipetted onto the membrane and the systems can be activated to agitate the cartridge to evenly distribute the agents over the membrane, and a vacuum source can apply negative pressure to one side of the membrane to draw the agent therethrough.

Abstract: Provided are a magnetic particle separation assembly and method for separating a magnetically responsive complex from a non-magnetic test media in which the magnetically responsive complex is suspended. The assembly comprises an invertible rack for holding specimen containers and a magnetic support member for supporting the rack. The magnetic support member has a base and a planar member bisecting the base and extending upwardly therefrom. The planar vertical member has a plurality of magnets embedded therein. The magnets are disposed in a substantially horizontal orientation parallel to the base and spaced from the base. The invertible rack has a slot therethrough dimensioned to accept the planar vertical member of the magnetic support member. In one position, at least one container of a particular size is positioned within the rack so as to be adjacent to the magnetic support member in final assembly such that the magnetically responsive complex is separated from the non-magnetic media.

Abstract: Disclosed is a high throughput compatible assay that is useful for the identification of specific antagonists of TRAF-receptor interactions. The modular flexibility of the assay makes it possible to introduce simple modifications in order to measure the interaction of any TNF receptor cytoplasmic domain (or TRAF-binding protein) with any of the six TRAF proteins, TRAF1, TRAF2, TRAF3, TRAF4, TRAF5 and TRAF6.

Abstract: Methods of detecting and quantifying genomic nucleic acid molecule sequences are provided using the simultaneous amplification of a plurality of discrete nanoliter-sized samples. A miniaturized closed assembly is also provided for carrying out amplification of a nucleic acid molecule by polymerase chain reaction in multiple nanoliter-sized samples. Methods of filling miniaturized sample chambers are also provided as are methods for determining the number of template molecules in a sample by conducting replicate nucleic acid sequence amplification reactions on a set of terminally diluted samples and counting the number of positive amplification reactions. The methods can be used to detect a single starting nucleic acid target molecule.

Abstract: Method and apparatus for enabling resuspension wash and magnetic localization of sample components bound to particles with magnetic properties in reaction vessels during separation and wash for enhanced chemiluminescent signal generation in biomedical assays. The assays involve moving reaction vessels past magnets that partially localize the particles prior to passing a reduced strength magnet where washing occurs, with or without resuspension, after separating out the unbound particles and liquid. The band of particles is subsequently resuspended in acid for chemiluminescent purposes. A variety of magnet configurations are employed to realize the reduced strength magnet. Reduced strength magnets adjacent the full width magnets prevent the band of magnetic particles from becoming split. The localized particles enable more efficient resuspension by reagent.

Abstract: A method of determining the concentration of an analyte in a sample, said method comprising bringing said analyte in contact with an indicator zone comprising a concentration gradient of a mobile binding member; and bringing said mobile binding member gradient into operable contact with a test zone comprising a fixed binding member, wherein a detectable signal that indicates the concentration of said analyte is produced.

Abstract: A body 300 having a cavity 310 for mounting a substrate 120 fabricated with probe sequences at known locations according to the methods disclosed in U.S. Pat. No. 5,143,854 and PCT WO 92/10092 or others, is provided. The cavity includes inlets 350 and 360 for introducing selected fluids into the cavity to contact the probes. Accordingly, a commercially feasible device for use in high throughput assay systems is provided.

Abstract: A resin composition comprising a poly(phenylene sulfide) resin and .alpha.-alumina, wherein the composition comprises (A) 15 to 45 wt. % of a poly(phenylene sulfide) resin having a melt viscosity of 5 to 100 Pa.multidot.s as measured at 310.degree. C. and a shear rate of 1200/sec, and (B) 85 to 55 wt. % of .alpha.-alumina which contains .alpha.-alumina composed of .alpha.-crystals having an average particle size of at least 5 .mu.m in a proportion of at least 40 wt. %.

Abstract: A method of indirect agglutination immunoassay includes, allowing particles of a reagent for immunoassay to precipitate in bottoms of at least one well, inclining the well at a specified angle to form a precipitation pattern due to a flow of the particles in the bottom of the well due to a flow of the particles, relatively moving the well and a sensor in the direction of substantially vertical to a flow direction of the formed precipitation pattern, measuring the lengths of the formed precipitation pattern at a plurality of sections within the scope of the well, and judging the occurrence of an immunoreaction based on the values of the measured length of the precipitation patterns.

Abstract: A suspension of inert particles is prepared in an aqueous solution, to which an antibody or an antigen and a carrier-bound antigen or antibody, respectively, are added in any desired order. After centrifuging, the positive, weakly positive, or negative reaction can easily be recognized on the basis of a simple pattern.

Abstract: A lysis chamber of an assay device capable of producing lysis of cells in a sample fluid such as whole blood, said chamber comprising a surface which contacts the sample fluid when the sample fluid is placed into the assay device; and a lytic material immobilized on the surface, whereby cells of the sample fluid are lysed when they contact the lytic material. The chamber can delimit a capillary space, and lytic material can be saponin or a detergent. Methods employing devices comprising such chambers can assay for whole blood amounts of cyclosporin or hemoglobin A1c.

Abstract: A multi-slide assembly includes various components that alone or in combination facilitate testing of test samples with minimal manipulation of assay components. Moreover, the various device components permit centrifugation, culturing and analysis of each test sample to be performed in the same assembly. A frame retains a plurality of reaction vessel assemblies between a pair of opposing channels that are configured to slidably receive the opposing ends of each reaction vessel assembly. A strip cap seals the openings in each reaction vessel using cap members having sealing rings circumscribing the external walls thereof to form compression seals with internal walls of the reaction vessels. Furthermore, in a method of making a multi-well slide assembly, an ultrasonic welding process removably bonds a plurality of wells to a slide plate to provide an adequate seal therebetween during centrifugation, yet still enable separation thereof by an operator.

Abstract: A base plate is made of an insulating material, and comprised of a flat surface and a connector part connected therewith. A plurality of wells are vertically and transversely arranged on the surface of the base plate at regular intervals respectively, and the respective wells are provided with individual electrode patterns reaching the connector part from bottoms thereof through the surface of the base plate. The connector part is connected to an external high-voltage application part.

Abstract: A high-throughput light detection instrument and method are described. Confocal optics structure enables exclusive light detection from a sensed volume in a composition.

Abstract: A filtration apparatus for extracting particles from a fluid sample is provided. The filtration apparatus comprises a filtration well plate which forms one or more filtration wells. Each filtration well has a proximal chamber into which the fluid sample may be deposited and a distal channel into which a filter is fitted. Each filter comprises a plurality of vertically oriented cylindrical micro fibers defining a set of vertically oriented linear pores. Upon application of a sufficient downward force to the fluid sample, the fluid sample is driven into the filter and the particles are expelled from a lower end of the filter.

Abstract: Automated assays for detecting and measuring ion channel and cell surface receptor activity and for identifying compounds that modulate or potentiate such activity are provided. Among the assays are fluorescent indicator-based assays that use cells containing effective levels of a fluorescent indicator that is responsive to changes in ion concentration. Activation of the ion channels or receptors is initiated in the automated measurement apparatus by injection into one or more predetermined cell-containing wells of a reagent which is a known or possible activator or inhibitor of the ion channels or receptors of interest. The resulting activity of the ion channels or receptors, which causes changes in ion concentration in the cytoplasm, is determined by measurement of fluorescence intensity changes of the indicator in response to an excitation wavelength.

Abstract: A process is provided for the detection and identification of human antibody types which are specific for antigens such as platelet glycoproteins and Human Leukocyte Antigen (HLA). The process aids in detecting and identifying antibody types from a patient sample which are specific for a plurality of known glycoprotein types attached to a solid support, each glycoprotein type unique from each other and separated from each other.

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

Abstract: The invention provides exemplary testing devices, systems, and methods for evaluating the permeation of various chemicals through different types of cells. In one exemplary embodiment, a testing device is provided which comprises a base member and a top member having a plurality of wells which are aligned when the top member is secured to the base member. A membrane sheet which includes at least one layer of cells grown on the sheet is placed between the base member and the top member prior to assembly. Test samples are placed into the wells in the top member and samples are removed from the top and bottom wells at a later time and tested to determine the amount of test sample which permeated through the cells.

Abstract: A method to produce arrays of compounds for concurrent testing is described. Two formats are described using porous rods or porous sheet materials. In one format the compounds of the array are immobilized to porous rod elements. In the second format the compounds are immobilized as lines on a sheet of porous material. In both cases, a bundle is formed by radial compression of the rods or spiral wrapping of the sheet. A sheath is applied to the bundle and arrays are cut as slabs. Each synthesis or application step to create an array element is used to fabricate multiple arrays. Relatively high density arrays can be produced with current printing technologies. The method is particularly suited to mass production of arrays.

Abstract: A chromatographic assay device for use with immunoassays allows rapid and convenient assays of analytes of biological interest, and permits extractions to be carried out in situ, avoiding the use of separate extraction vessels. The device has a wide dynamic range and avoids interference from particulates or colored components. In one form, the device comprises: (1) a first opposable component comprising a sample preparation means adapted to receive a sample to be assayed; and (2) a second opposable component comprising a chromatographic medium. The first and second opposable components can be brought into opposition so as to cause the sample preparation means to apply the sample to be tested to the chromatographic medium. Preferably, the analyte is detected with a visually detectable label. Other variations of the device vary the arrangement of components to provide optimal chromatography for a variety of analytes, as well as to permit bidirectional chromatography.

Abstract: Methods and apparatus for the preparation and use of a substrate having an array of diverse materials in predefined regions thereon. A substrate having an array of diverse materials thereon is generally prepared by delivering components of materials to predefined regions on a substrate, and simultaneously reacting the components to form at least two materials. Materials which can be prepared using the methods and apparatus of the present invention include, for example, covalent network solids, ionic solids and molecular solids. More particularly, materials which can be prepared using the methods and apparatus of the present invention include, for example, inorganic materials, intermetallic materials, metal alloys, ceramic materials, organic materials, organometallic materials, non-biological organic polymers, composite materials (e.g., inorganic composites, organic composites, or combinations thereof), etc.

Abstract: A urine sample is analyzed for urine chemistry, formed bodies, and rare event evidence, all in a single sample container and under low power magnification. The sample container includes a urine sample receiving chamber which is connected to a urine chemistry chamber, to a formed body isolation chamber, and to a rare events detection chamber, so that the urine can flow from the receiving chamber to the other three chambers. The container may also include a sterile chamber for receiving an auxiliary portion of the urine which may be used for further analysis by the clinician if necessary. The chemistry chamber contains a miniaturized urine dip stick which is scanned by an optical scanning instrument for color emissions. The formed body isolation chamber can be precoated with one or more stains, and is formed with a plurality of different through plane thicknesses whereby smaller formed bodies will be isolated in the smaller thickness regions of the chamber which the larger formed bodies cannot enter.

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 slide having a portion thereof provided with transparent adhesive which adheres to a test sample. The slide and adhesive may be transparent. Specific types of infection and particularly fungal infections can be detected in the test sample using immunotest-methods. In a special embodiment the adhesive slide is fashioned with a peripheral lip or well to contain a test sample and a reagent.

Abstract: The present invention relates to a device for determining an analyte in a fluid sample in an assay. The device comprises a lid having a plurality of elements and a membrane. The elements have openings which allow passage of fluid to the membrane. The membrane is supported by the lid and covers the openings of the elements. The undersurface of the membrane is in contact with a porous wick which contains a first zone which includes binder attached to a particulate label and a second zone containing salt. The wick extends downward from the membrane and is in contact with the fluid sample.

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: A method for assaying a substance is provided in which an optical image is obtained from spots of light emitted from a chemiluminescent material capable of undergoing a luminescent reaction. The method comprises: (a) a step of distributing solid particles on the surface of a support, the solid particles having a diameter of not more than 100 .mu.

Abstract: The present invention provides novel processes for the large scale preparation of arrays of polymer sequences wherein each array includes a plurality of different, positionally distinct polymer sequences having known monomer sequences. The methods of the invention combine high throughput process steps with high resolution photolithographic techniques in the manufacture of polymer arrays.

Abstract: The method of base sequence determination according to the present invention ensures an effective determination of a long DNA base sequence, by providing simultaneous determination of base sequences of two or more positions of the long DNA or base sequences of two or more DNAs, using the DNA probe chip which classifies and retains the DNA oligomers having various sequences, and using fluorophorelabeled primers which have the same sequencies as the oligomers in the chip and are labeled by various fluorophores, then followed by the extension of the determined base length by re-selection of the primers complementary to the sequence thus determined.

Abstract: An assay plate for detecting the presence of a mobile reactant that binds to a immobilized reactant and the methods of making and using the same. An assay plate according to the present invention includes a substrate and at least one dried aliquot of the immobilized reactant, the immobilized reactant being bound to the surface of the substrate. The immobilized reactant binds the mobile reactant when a solution containing the mobile reactant is brought into contact with the immobilized reactant. The mobile and immobilized reactants may be any pair of biological compounds that have a specific affinity for one another. For example the reactants may be nucleic acids or antibody-antigen pairs. The preferred embodiment of an assay plate according to the present invention includes a plurality of assay spots, each spot having a different immobilized reactant or concentration thereof.

Abstract: Methods and apparatus are employed for determining interactions between different components, of the same or different type of composition. The apparatus provides for arrays of samples in tracks, where light emitting labels are excited and emitted light detected. Headers are provided for defining sites, so that particular interactions can be rapidly detected. Particularly, disks having circular tracks with headers defining sites on the tracks, so that positive signals can be interpreted in relation to the information provided by the header. Various modifications can be made, such as preprepared segments which may then be attached to the disk for assaying.

Abstract: A cartridge is provided to present a biological sample for analysis by an imaging instrument. The cartridge of the invention utilizes a series of channels, capillaries, reservoirs and stop junctions to precisely move a sample, reagent and diluent through the cartridge as a function of the sum of capillary, gravitational and low centrifugal forces. The operator applies a precise amount of sample to the cartridge; therefore, the cartridge fluidics need not meter the sample prior to dilution. A practical and cost effective cartridge and assay process is disclosed which overcomes many of the limitations of the prior art. Such a cartridge is especially useful with fixed volume assays which permit low centrifugal accelerations to move the fluids within the cartridge.

Abstract: The invention provides for multi-well plates with greater than 864 wells that comprise a layer of cycloolefin having low fluorescence and high transmittance. These multi-well plates are particularly well suited for fluorescence measurements.

Abstract: A solid phase extraction plate includes a unitary tray having a plurality of spaced-apart discrete upstanding chambers molded therein with each chamber having a top opening and a bottom nozzle with downwardly tapering sidewalls extending between the top opening and the bottom nozzle. A plurality of solid phase extraction disks are provided and one secured in each of the plurality of chambers without the use of frits or retainer rings utilizing instead tapered sidewalls of the chamber for enabling a press fit of the disks therein.

Abstract: A method for fractionating and sequencing DNA via affinity interaction is provided comprising contacting cleaved DNA to a first array of oligonucleotide molecules to facilitate hybridization between said cleaved DNA and the molecules; extracting the hybridized DNA from the molecules; contacting said extracted hybridized DNA with a second array of oligonucleotide molecules, wherein the oligonucleotide molecules in the second array have specified base sequences that are complementary to said extracted hybridized DNA; and attaching labeled DNA to the second array of oligonucleotide molecules, wherein the labeled re-hybridized DNA have sequences that are complementary to the oligomers.

Abstract: A method and apparatus for identifying molecular structures within a sample substance using an array having a plurality of test sites upon which the sample substance is applied. Each test site includes a probe formed therein to bond with an associated target molecular structure. An electrical signal is applied to the test site and the electrical properties of the test sites are detected to determine which probes have bonded to an associated target molecular structure.

Abstract: The present invention describes a multiple sample container for use in a method and apparatus for detecting microorganisms in a culture container. The container includes a block having a plurality of through holes for dividing the sample into a plurality of partial samples. Each partial sample has its own head space and its own sensor. The spacial array of partial samples is read out by a CCD camera and split into partial sample to generate a spacial array that results in a substantial reduction in the time to detection.

Abstract: Method and apparatus for enabling resuspension wash and magnetic localization of sample components bound to particles with magnetic properties in reaction vessels during separation and wash for enhanced chemiluminescent signal generation in biomedical assays. The assays involve moving reaction vessels past magnetic arrays that partially localized the particles prior to passing a gap where washing occurs, with or without resuspension, after separating out the unbound components and liquid. The band of particles is further localized by a focusing magnet at the end of the array prior to dosing the vessel with acid for chemiluminescent purposes. A block of soft magnetic material is employed in place of a magnet in the gap to minimize magnetic strength at the gap. Trimmed magnets adjacent the gap cause left, then right, particle shifting that localizes the magnetizable particles. The gap enables improved resuspension by wash, whereas the localized particles enable more efficient resuspension by reagent.

Abstract: Multiple chemical reactions are performed in a plurality of reaction vessels mounted in inlets in a manifold valve block. The manifold valve block is connected to a channel block which is utilized in conjunction with a solvent delivery system as part of the reaction cycle. The solvent fluid is drained from the reaction vessels when valves in the manifold valve block are opened while applying a vacuum thereto. Optionally, a thermal block may be utilized in conjunction with the manifold valve block and the channel block to facilitate the reaction. Upon completion of the reactant cycle, the manifold valve block is disconnected from the channel block and connected to a cleavage block assembly which contains vials for collecting reaction products. The cleavage product is drained from the reaction vessels through the manifold valve block into the vials upon opening the valves in the manifold valve block and applying a vacuum to the channel block.

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: A suspension of inert particles is prepared in an aqueous solution, to which an antibody or an antigen and a carrier-bound antigen or antibody, respectively, are needed in any desired order. After centrifuging, the positive, weakly positive, or negative reaction can easily be recognized on the basis of a simple pattern.

Abstract: Laboratory vessels are coated on an operational surface thereof with a hydrophobic coating polymer or reactive monomer to form a coating having an exposed surface populated with 30% by area or more terminal trifluoromethyl groups. Laboratory vessels coated with such coating solutions are provided having extremely low surface energies and high resistance to solvent attack. Methods of forming hydrophobic coatings on laboratory vessels are also provided and include methods of forming exposed coating surfaces having populations of from about 30% by area to 100% by area trifluoromethyl groups. The hydrophobic coatings may be prepared from solutions, suspensions or powdered materials containing a fluoroalkyl ethylenically unsaturated monomer substantially free of any crosslinking, having from about 3 to about 20 carbon atoms, and containing at least one terminal trifluoromethyl group, or containing a polymerization product of such a monomer.

Abstract: The invention provides a plate having a plurality uniformly sized reaction cells formed in its upper surface, wherein the density of the reaction cells is at least about 10 cells per cm.sup.2. Preferably, the area of each of the openings of the reaction cells is no more than about 55% of the area defined by the multiplication product of (1) the pitch between reaction cells in separate rows and (2) the pitch between reaction cells in separate columns.

Abstract: This Invention relates to a fertility analysis and reproductive health system that is applicable to both female and male mammals. In particular the Invention is a portable, handheld, integrated unit which can be manufactured out of plastic. The unit can be disposable for hygienic purposes, or cleaned or sterilized for repeated use as desired. The present Invention has numerous aspects.

Abstract: The present invention provides methods for determining the concentration of analytes in liquid samples in which the amount of binding agent having binding sites specific for a given analyte in the liquid sample is immobilized in a test zone on a solid support, the binding agent being divided into an array of spatially separated locations in the test zone. The concentration of the analyte is obtained by back-titrating the occupied binding agent with a developing agent having a marker and integrating the signal from each location in the array. The present invention also provides a method for determining a value representative of a fraction of binding sites of the binding agent which are occupied by the analyte, comprising immobilizing the specific binding agent on a solid support, wherein the specific binding agent used for the fractional occupancy is present in an amount less than 0.

Abstract: The invention relates to a biochemical sensor including a substrate on which yeast cells are deposited which are capable of capturing one type of molecules (M) and of producing a chemical entity (P) at the outcome of the capture; it also includes means for detecting the entity (P). The yeast cells employed are yeast cells obtained by genetic manipulation, in which the capture sites have been adapted to the type of molecules (M).