Miles Laboratories, Inc.

Mast Immunosystems, Inc.

John F Burd

Robert T Buckler

Robert J Carrico

Thomas M Li

Robert C Boguslaski

Jeffrey L Benovic

Raphael C Wong

Christopher R Brown

Vincent A Marinkovich

John W Dyminski

Stephan G Thompson

Robert C Bocuslaski

Keith W Higgins

An attenuator is included in a reagent medium of a luminescent specific-binding assay to suppress undesirable extraneous light. In one such assay, an analyte in a sample is reacted with a specific binding partner attached to a solid surface, forming an immobilized pair at the surface. One member of the immobilized pair is then allowed to react with a specific binding partner previously conjugated with one component of a luminescent reaction system, and the remaining components are provided in the reagent medium. The resulting light emitted in the luminescent reaction is recorded on photographic film or other photodetector as a measure of the presence and quantity of the analyte in the sample. The reagent medium containing the remaining luminescent reaction system components also includes an attenuator, preferably a dye, which absorbs light over a range of wavelengths including that of the light emitted in the luminescent reaction, the attenuator being present in an amount sufficient to suppress the extraneous light observed adjacent the solid surface in the absence of the attenuator. Reduction of such extraneous light sharpens the recorded luminescent image, thereby allowing a more precise analysis of the light intensity, and additionally reduces the occurrence of false positive images in the assay. In another embodiment, the attenuator preferentially absorbs light emitted in remote portions of a reaction volume so that only light emitted from proximal portions reaches a measurement means. Reactions otherwise requiring a separation step may thereby be conducted homogeneously.

Attenuator to suppress extraneous light in luminescent specific-binding

A luminescent substrate preparation having a concentration of catalytic inhibitors of less than about 100 ppm. The preparation is obtained by heating commercial grade luminol in a basic solution, crystallizing the luminol and separating the luminol crystals from the boiled solution. The heating, crystallization and separation steps are preferably repeated sequentially at least four times, with the starting material for each sequence after the first being the luminol preparation produced in the previous sequence. The luminol preparation has an enhanced pattern of activity, in that light output is substantially constant over a period of at least about one hour, with the intensity of light emitted by the preparation being at least about ten times that of commercially available luminol. Because of these enhanced characteristics, the luminol preparation is particularly adapted for use as a tag in specific binding assays where the concentration of analyte to be detected is low.

Luminescent substrate preparation and its use in specific binding assays

Immunogens for preparing antibodies against the drug lidocaine and related compounds, labeled conjugates, synthetic intermediates, and the use of such antibodies and labeled conjugates in immunoassays for determining lidocaine and such related compounds. The immunogens comprise lidocaine or an analog thereof coupled through one of the aromatic methyl groups to a conventional immunogenic carrier. The antibodies and labeled conjugates are particularly useful in homogeneous nonradioisotopic immunoassays for measuring lidocaine or its analogs in biological fluids such as serum.

Immunogens, antibodies, labeled conjugates, and related derivatives for

Immunoassay method and reagent means for determining theophylline in biological fluids such as serum. The antibody employed in the method is prepared from an immunogen comprising theophylline coupled at its 9-position to an immunogenic carrier material.

#3B theophylline immunoassay employing 9-theophylline reagents

Theophylline immunogens, antibodies prepared therefrom, labeled theophylline conjugates, synthetic intermediates, and the use of such antibodies and labeled conjugates in immunoassays for determining theophylline. The immunogens comprise theophylline coupled at its 9-position to an immunogenic carrier material. Likewise, the labeled conjugates and synthetic intermediates are 9-position derivatives of theophylline or synthetic precursors thereof. The antibody and labeled reagents are particularly useful in homogeneous nonradioisotopic immunoassays for measuring theophylline in biological fluids such as serum.

Theophylline immunogens, antibodies, labeled conjugates, and related

Intermediates in the preparation of 9-position derivatives of theophylline useful in synthesizing theophylline immunogens and labeled conjugates. The labeled conjugates and the antibodies produced against the immunogens are particularly useful in homogeneous nonradioisotopic immunoassay for measuring theophylline in biological fluids such as serum.

6-[N-(.omega.-Carboxyalkyl)amino]-1,3-dimethyl-5-formamidouracils

An improved specific binding assay method and reagent for determining a ligand in a liquid medium employing, as an enzyme-cleavable substrate label, a residue having the formula:

Beta-galactosyl-umbelliferone-labeled hapten conjugates

.beta.-Galactosyl-umbelliferone-labeled protein and polypeptide

A homogeneous specific binding assay method and reagent means for determining a ligand, such as a hapten, antigen or antibody, in, or the ligand binding capacity of, a liquid medium employing a labeled conjugate which upon enzymatic cleavage produces a detectable indicator product. The improvement comprises employing as the label component in the labeled conjugate, a residue having the formula:

Homogeneous specific binding assay employing an intramolecularly

Reagents for use in binding assays, particularly immunoassays, to determine valproic acid in liquid media such as serum. Such reagents include antibody to valproic acid and .beta.-galactosyl-umbelliferone-valproic acid conjugates. Also provided are compounds used to prepare such reagents, including valproic acid immunogen conjugates and intermediates in the synthesis of such immunogen conjugates and .beta.-galactosyl-umbelliferone-labeled conjugates.

.beta.Galactosyl-umbelliferone valproic acid conjugates

Specific binding assay employing an enzyme-cleavable substrate as label

Title compounds of the formula: ##STR1## wherein R is hydroxy substituted lower alkyl. The compounds have advantageous water solubility and spectral characteristics for use as instrument calibrators for certain homogeneous fluorescent immunoassays.

N-(hydroxyalkyl)-7-hydroxycoumarin-3-carboxamides

Valproic acid immunogen conjugates and antibodies thereto

.beta.-Galactosyl-umbelliferone labeled aminoglycoside antibiotics, e.g., gentamicin, useful in homogeneous and heterogeneous specific binding assays for such antibiotics in liquid media such as serum. Also provided are a .beta.-galactosyl-umbelliferone-carboxylic acid and salts thereof which are intermediates in a method of preparing the labeled antibiotics.

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Elkhart, IN, United States of America

John F Burd