Abstract: A method for amplification and detection of a low copy target nucleic acid includes coamplification of a high copy target nucleic acid. After a number of conventional amplification cycles which include a denaturation step, several cycles are carried out during which the denatured products are renatured for a brief period of time. This intermediate step in later cycles of the amplification process reduces the effective concentration of the high copy target nucleic acid available for amplification in later cycles, thereby making more DNA polymerase available for amplification of the low copy target nucleic acid.

Abstract: A method and kit are disclosed for recalibrating a factory-prepared relationship between concentration and expected signal R.sub.exp produced by an analyzer. The method and kit use two or three calibrators at the field to obtain an actual signal R.sub.act for the two calibrators C.sub.low and C.sub.high, for example, and these two actual signals are used to create a ratio of R.sub.actlow /R.sub.explow and R.sub.acthigh /R.sub.exphigh. The first of these is used to correct the expected signals for concentrations below the lower calibrator concentration, and the second is used to correct expected signals for concentrations above the higher calibrator concentration, producing pseudosignals PS.sub.low and PS.sub.high. A straight-line relationship is applied between the corrected PS.sub.low and PS.sub.high, and that relationship is used for concentrations between C.sub.low and C.sub.high.

Abstract: A wide bandwidth slope detector has a comparator with first and second time constant circuits coupled to first and second inputs thereof. Where one time constant is on the order of three times the other, the comparator will change state in response to the slopes of an input analog signal coupled to the time constant circuit. Feedback can be provided by a fixed resistor or by a tracking circuit. A smoothing or clipping circuit can be used to pre-process the input analog signals to eliminate noise therefrom. A bar code reading system combines first and second clipping circuits to smooth the highs and lows of the input signal, coupled to a slope detector. The tracking circuit can be used to provide a symmetrical hysteresis characteristic.

Abstract: A labeled carbamazepine analogue is described comprising:(A) a label, of the type used in immunoassays, having an amine or sulfhydryl group such as horseradish peroxidase;(B) a carbamazepine nucleus; and(C) a linking chain linking the carboxamide group of the carbamazepine nucleus to the label, said linking chain having about 4 to about 40 atoms consisting of:(1) C.sub.2 to C.sub.6 alkylene groups; and(2) 5 to 7 membered heterocyclic ring groups, each group being joined into the linking group through chemical groups selected from(a) esters,(b) amides(c) heteroatoms selected from --O--, --S--, and --NR--; wherein R represents hydrogen or C.sub.1 to C.sub.6 alkyl; and(d) carbonyl.The new labeled analogues are useful in immunoassay elements and processes for detection of carbamazepine drugs, for example, in body fluids.

Abstract: This invention provides a rapid and highly effective method for extracting nucleic acids from cells or virions without the use of proteolytic enzymes. Extraction is accomplished within a few minutes using a lysing composition comprising a buffer, a source of a DNA polymerase cofactor, a stabilizer and at least one nonionic surfactant which will release nucleic acids from cytoplasmic and nuclear membranes of cells or virions. The resulting mixture is heated to boiling for up to fifteen minutes, and the nucleic acids are recovered for amplification using polymerase chain reaction. No proteolytic enzyme is used in the extraction process.

Abstract: An ion-junction fibrous bridge and a potentiometric test element incorporating the same, wherein the fibers extending generally along the center-line between two liquid access apertures in the bridge, are readily capable of conducting aqueous liquid through the bridge, and fibers extending at an angle of at least 20 .degree. from said center-line are not readily capable of conducting aqueous liquid.

Abstract: There is disclosed a slide test element and method of assay that allows for detection of analytes in biological liquids without the use of any detection reagents. The method uses NIR spectroscopy and a test element comprising a support, and a substantially constant light-path defining layer comprising a diffusely-reflecting material that is a) sufficiently porous in all directions as to allow a liquid to spread uniformly in all directions, and b) homogeneously reflects at least 95% of NIR radiation.

Abstract: A wide bandwidth slope detector has a comparator with first and second time constant circulars coupled to first and second inputs thereof. Where one time constant is on the order of three times the other, the comparator will change state in response to the slopes of an input analog signal coupled to the time constant circuit. Feedback can be provided by a fixed resistor or by a tracking circuit. A smoothing or clipping circuit can be used to pre-process the input analog signals to eliminate noise therefrom. A bar code reading system combines first and second clipping circuits to smooth the highs and lows of the input signal, coupled to a slope detector. The tracking circuit can be used to provide a symmetrical hysteresis characteristic.

Abstract: A wide bandwidth slope detector has a comparator with first and second time constant circuits coupled to first and second inputs thereof. Where one time constant is on the order of three times the other, the comparator will change state in response to the slopes of an input analog signal coupled to the time constant circuit. Feedback can be provided by a fixed resistor or by a tracking circuit. A smoothing or clipping circuit can be used to pre-process the input analog signals to eliminate noise therefrom. A bar code reading system combines first and second clipping circuits to smooth the highs and lows of the input signal, coupled to a slope detector. The tracking circuit can be used to provide a symmetrical hysteresis characteristic.

Abstract: The invention is directed to an immunoassay for a thyronine derivative comprising:A. contacting a liquid sample, containing a thyronine derivative, with a labeled thyronine hapten analogue of the derivative in the presence of antibodies for the thyronine derivative under conditions that promote the formation of antibody-thyronine immunocomplexes; andB. determining the bound or unbound quantity of the thyronine derivative in the liquid; characterized in that the labeled thyronine derivative comprises:(i) a label, of the type used in immunoassays, having an amine or sulfhydyl group;(ii) a thyronine nucleus and(iii) a linking chain linking the label to the thyronine nucleus.

Abstract: A wide bandwidth slope detector has a comparator with first and second time constant circuits coupled to first and second inputs thereof. Where one time constant is on the order of three times the other, the comparator will change state in response to the slopes of an input analog signal coupled to the time constant circuit. Feedback can be provided by a fixed resistor or by a tracking circuit. A smoothing or clipping circuit can be used to pre-process the input analog signals to eliminate noise therefrom. A bar code reading system combines first and second clipping circuits to smooth the highs and lows of the input signal, coupled to a slope detector. The tracking circuit can be used to provide a symmetrical hysteresis characteristic.

Abstract: A method for verifying the effectiveness of a washing operation on a clinical dry chemistry slide element in which wash liquid is dispensed onto the surface of the slide element and then detection devices are used to verify the effectiveness of the wash by making an initial detection at an on center site followed by making a second detection at a second and off-center radial position. A comparison of the two readings provides verification of the wash. In addition, rate measurements can be made at each of the read positions to measure the effectiveness of the wash and to verify sample application for immunological assays.

Abstract: There is disclosed a slide test element and method of assay that allows for detection of analytes in biological liquids without the use of any detection reagents. The method uses NIR spectroscopy and a test element comprising a support, and a substantially constant light-path defining layer comprising a diffusely-reflecting material that is a) sufficiently porous in all directions as to allow a liquid to spread uniformly in all directions, and b) homogeneously reflects at least 95% of NIR radiation.

Abstract: An incubator assembly useful in a clinical analyzer having at least two incubators, each having a rotationally driven rotor assembly having a plurality of slide element holding stations, which incubators are stacked one above the other to define a substantially vertical arrangement. In a preferred embodiment, in which the incubators are of varying size, the smaller rotor assembly is horizontally offset so that the outside diameter of each rotor assembly is coincident in one location, preferably an input station, so that slide elements can be loaded into and removed more conveniently from either rotor assembly.

Abstract: Weakly basic ethylenically unsaturated polymerizable monomers and polymers have been prepared. The monomers are represented by the structure (I): ##STR1## wherein R is hydrogen or methyl, and R.sup.1 is alkylene of 1 to 3 carbon atoms. The resulting polymers are water-soluble and cationic at acidic pH, but water-insoluble and neutral in charge at basic pH. The polymers are useful for precipitating nucleic acids.

Abstract: Apparatus and a method for automatically transferring by pushing and pulling a reagent module onto and off of a rotor of modules. A surface of the module and the transfer mechanism are cooperatively shaped with a loose-fitting tongue and arcuate groove, both the tongue and groove having a curved extension along an arc concentric with the axis of rotation of the rotor, such that modules mounted on the rotor can be rotated off the transfer mechanism by sliding the tongue relative to the groove in a rotational direction. An additional groove is provided at an angle to said arcuate groove, along which the tongue or arcuate groove, whichever is on the transfer mechanism, reciprocates to push or pull a module into or out of the rotor.

Abstract: A dry immunoassay analytical element, for assaying a ligand, comprising a support bearing:(a) a labeled ligand zone;(b) a spreading zone; and(c) a receptor zone containing a fixed concentration of an immobilized receptor for the ligand and the labeled ligand and the receptor is covalently bonded to polymeric beads having a diameter in the range of 0.1 to 5 .mu.m;characterized in that the element contains a compound containing a vanadium IV (V.sup.+4) ion and the zones can be in the same or separate layers.

Abstract: A nucleic acid test article can be used to detect a targeted nucleic acid found in a specimen. The test article includes a substrate having two opposing surfaces and a water-insoluble nucleic acid probe attached in a distinct zone of one of the surfaces. The probe is prepared from a water-insoluble particle to which is covalently attached an oligonucleotide which is complementary to the targeted nucleic acid. Substantially none of the probe is embedded within the surface of the substrate. Particularly useful test articles have a multiplicity of water-insoluble probes located in distinct zones on one of the substrate surfaces. These probes are useful for the detection of a multiplicity of targeted nucleic acids, particularly after amplification by polymerase chain reaction.

Abstract: A stack of plastic articles and a process of forming the stack are disclosed. Preferably the stack is of heat-fusible plastic slide elements for use in a diagnostic analyzer, the elements being temporarily and non-destructively fused together so that the stack can be used free of a cartridge.In another embodiment, the stack can be of any plastic article temporarily fused to adjacent elements, one side edge of each element bearing a colorant and another bearing no colorant, so that a bar code for the stack is inherently formed simply by rotating each element to project outwardly the colored side edge or the side edge lacking colorant, prior to fusing the elements together.