Abstract: There is described a positive calibrator/control composition for use in assays for the detection of antibodies to infectious disease agents. The composition includes a composite antibody of a nonspecific IgM immunoglobulin moiety covalently linked to a specific, non-IgM antibody moiety. Also described is an assay method which utilizes the positive calibrator or control composition.

Abstract: There is described an assay system for the assessment of unoccupied specific ligand binding sites on proteins in biological fluids. The assay is carried out with a multilayer assay element and is based on the principle of equilibrium distribution in which a ligand distributes itself between unoccupied sites on the proteins and the remainder of the element. The ligand can be labeled with a detectable moiety or it may be unlabeled and detected through the use of another detectable species. In one embodiment the assay format is utilized to estimate the number of sites on thyroxine binding globulin (TBG) which are not occupied by thyroxine (T4) or triiodothyronine (T3).

Abstract: An automated analytical instrument for conducting assays for components of interest in fluid samples. The instrument includes a rotably mounted supply unit or segment adapted to hold a plurality of foil-sealed magazines containing assay modules, a testing system for assaying a fluid sample for a component of interest using an assay module, an assay module transport assembly for transporting an assay module from a magazine in the supply unit to the testing system, and a microprocessor for controlling the operation of the automated analytical instrument.

Abstract: A method for determining the amount of an analyte in a sample fluid utilizing an assay element which comprises at least one reagent layer. The assay method includes the steps of optically reading a signal producing species, e.g., a fluorescent label, a first time prior to depositing the sample fluid on the assay element and a second time, at the same wavelength and in the same location within the assay element after the sample fluid has been applied to the assay element and the sample analyte has interacted with the reagent(s) present in the assay element. The first, or dry, reading is corrected for relative humidity and/or temperature variations.

Abstract: A compound represented by the formula ##STR1## wherein X is a spacer group. The compound is useful for conjugating a compound having an alcohol group or an amine group to a compound having a thiol group. The compound can be used to conjugate a biologically active group such as an antigen to a protein such as an enzyme to provide an enzyme-labeled antigen for use in enzyme-amplified immunoassay methods for analytes or metabolites in sample fluids. The compound can also be used to immobilize a material such as a protein to a solid support.

Abstract: A multilayer diagnostic assay element wherein glyoxyl agarose, an aldehyde group - derivatized agarose, is utilized in one or more layers of the element. In a preferred embodiment the glyoxyl agarose is used to immobilize biological species such as a protein in a layer of the element.

Abstract: An assay cartridge suitable for use with automated analytical instruments which include a conveyor such as a carousel. The cartridge is configured with ledges extending outwardly from sides thereof, preferably at the bottom of the cartridge. The conveyor includes berths for receiving the cartridges, each berth being formed as a depressed region within a top surface of the conveyor and bounded by a floor at the bottom of the berth and opposed sidewalls and an end wall extending upwardly from the floor. The sidewalls are preferably parallel to each other. An open end of the berth, opposite the end wall serves as a port through which the cartridge is inserted and extracted from the berth. Each of the sidewalls of the berth is provided with a shoulder which extends inwardly towards a center line of the berth, and upon insertion of the cartridge, extends over the ledges of the cartridge to serve as a guide. The guide includes grooves formed between the shoulders and the floor.

Abstract: A temperature controlled chamber for an analytical instrument which includes a circular conveyor for transporting assay cartridges, the chamber enclosing the outer peripheral part of the conveyor on which the assay cartridges reside. The temperature controlled chamber has a bottom wall of polymeric material located beneath the conveyor, an outer wall of polymeric material extending upward above the conveyor, a metallic top wall and a metallic inner wall which extends downward to the upper surface of the conveyor. Thermal control, including rapid thermal response to compensate for temperature perturbations induced by periodic introduction of assay cartridges which are at a temperature less than that of the chamber, is accomplished by heating elements located above and below the conveyor. The heating elements are pulsed by an electrical circuit at a rate substantially faster than the rate of introduction of new assay cartridges.

Abstract: An assay cartridge suitable for use with automated analytical instruments which include a conveyor such as a carousel. The cartridge is configured with ledges extending cutwardly from sides thereof, preferably at the bottom of the cartridge. The conveyor incudes berths for receiving the cartridges, each berth being formed as a depressed region within a top surface of the conveyor and bounded by a floor at the bottom of the berth and opposed sidewalls and an end wall extending upwardly from the floor. The sidewalls are preferably parallel to each other. An open end of the berth, opposite the end wall serves as a port through which the cartridge is inserted and extracted from the berth. Each of the sidewalls of the berth is provided with a shoulder which extends inwardly towards a center line of the berth, and upon insertion of the cartridge, extends over the ledges of the cartridge to serve as a guide. The guide includes grooves formed between the shoulders and the floor.

Abstract: A method for determining the amount of an analyte in a sample fluid utilizes a multilayer assay element which comprises at least one reagent layer and a light-blocking layer. The assay method includes the steps of optically reading a signal producing species, e.g. a fluorescent label, a first time before the sample fluid is applied to the assay element and a second time, at the same wavelength and in the same location within the assay element, after the sample fluid has been applied to the assay element and the sample analyte has interacted with the reagent(s) present in the assay element. The ratio of the two signals is taken and compared with that for known amounts of the analyte to determine the amount of analyte in the sample fluid.

Abstract: There is described an assay element suitable for use in an automated analytical test instrument for assaying a fluid sample. The element includes a thin porous member possessing a high degree of capillarity such as a fibrous mesh pad supported within a guide defined by surfaces contiguous the porous member. The dimensions of the porous member and its degree of capillarity are such as to provide for capillary transport of fluid through the member. A fluid dispenser and a fluid collecting chamber are disposed contiguous to opposed ends of the porous member. The fluid dispenser is formed as a well with a port at the bottom of the well, the port being contiguous the porous member and having a ridge extending along a perimeter of the port. The ridge protrudes into the porous member a distance sufficient for entraining fluid present in the well to propagate within the member rather than along an interface between a surface of the member and guide surfaces which hold it in place.

Abstract: There is described an analytical isntrument for the analysis of fluids such as biological fluids. The instrument includes a fluid dispensing system having a pipette for dispensing fluid test samples and test reagents to assay cartridges. An optical detection system provides a light beam which intercepts a downward travel path of the pipette prior to its reaching the dispense position. Measurement of the intensity of the light beam in conjunction with the position of the pipette enables a controller to indicate the presence or absence of a pipette tip. In addition, interception of the light beam by the pipette initiates a final approach sequence for the pipette to the dispense position above an assay cartridge by a predetermined increment of travel.

Abstract: A method of calibrating pipette position in an automated assay instrument employing a conveyor for holding assay cartridges and a transport for transporting a pipette between various locations is accomplished by alignment of a pipette stem with targets located at various locations within the system. Two targets are located on a tray having a plurality of reservoirs for holding liquid, and one target is located on a dummy cartridge carried by the conveyor. An indicator having a spring-loaded tab is used in conjunction with a pipette stem modified by inclusion of a circumferential slot for receiving the spring loaded tab. The stem is inserted into the indicator and locked therein, with limited sliding being provided by movement of the tab within confines of the slot. Alignment marks are provided on both the stem and the indicator to permit visual alignment of the stem relative to a target upon abutment of the indicator with the target.