Miles Laboratories, Inc.

Miles Inc.

Bert Walter

Alfred C Greenquist

Steven C Charlton

Patricia A Rupchock

Richard J Tyhach

Joel M Blatt

Mary Ellen Warchal-Windham

Thomas M Li

Mary E Warchal

An analytical method and test composition for determining whether an analyte is present in a test sample at a predetermined concentration level by measuring or observing a preselected level of indicator response, e.g., color generation. A subtractive reaction is carried out on the test sample prior to the indicator reaction in order to stoichiometrically and specifically consume a predetermined amount of analyte. The resulting indicator reaction generates the preselected level of indicator response only if the analyte is present at the predetermined concentration level or greater. The subtractive reaction is enzymatically specific for the analyte in the reaction mixture and the amount of analyte consumed can be closely controlled by the amount of a regulating coreactant present at initiation. The method enables the determination of analyte without the need for standards or comparators, e.g., color charts, and therefore is self-indicating. In another embodiment, there is provided a method and test composition for improving an otherwise suboptimal assay response due to oversaturation of the response, e.g., color, generated by an indicator reaction.

Self-indicating analysis employing stoichiometric chemical subtraction

A method of making a multilayer analytical test element comprises providing layers at least one of which is responsive to detect a ligand in a liquid sample, or to detect the ligand binding capacity of the sample, and at least one other layer that is fusible when subjected to sonic energy, arranging the layers one on top of the other together to form a composite blank of layers, subjecting the composite to ultrasonic or laser energy to cut the composite to the desired dimension of the test element and to simultaneously weld the layers at the edges thereof, said energy softening and fusing the fusible layer to thereby bond the layers together.

Multilayer analytical element and method of making, using ultrasonic or

A homogeneous specific binding assay device, a method for its preparation, and a method for its use in determining a ligand, such as antigen, hapten, or antibody, in, or the ligand binding capacity of, a liquid sample. The test device comprises a solid carrier member, such as a fibrous web matrix, e.g., paper, or a polymeric film or gel, incorporated with reagents for a homogeneous specific binding assay system which produces a detectable response, usually an electromagnetic radiation signal, that is a function of the presence or amount of the ligand in or the ligand binding capacity of the sample. Useful homogeneous specific binding assay systems include those involving enzyme substrate labels, enzyme prosthetic group labels, and enzyme labels. The detectable response preferably is a luminescent, fluorescent, spectrophotometric, or colorimetric response, which is measurable by visual observation or instrument means.

Multilayer homogeneous specific binding assay device

A homogeneous specific binding assay element, a method for its preparation, and a method for its use in determining a ligand in or the ligand binding capacity of a liquid sample. The test element comprises a solid carrier incorporated with reagents for a homogeneous specific binding assay system which produces a detectable response, usually an electromagnetic radiation signal, that is a function of the presence or amount of the ligand in or the ligand binding capacity of the sample. Also a method for preparing a homogeneous specific binding assay element for determining a ligand in or the ligand binding capacity of a liquid sample by incorporating a carrier with a composition which includes a label conjugate, comprising a label component coupled to a ligand moiety or a specific binding analog thereof, and a reagent reactive with the label conjugate, which method comprises (a) incorporating the carrier with the reagent reactive with the label conjugate in a first liquid and drying the carrier; and then (b) incorporating the carrier of (a) with the label conjugate in a liquid effective to prevent reaction with the reagent reactive with the label conjugate prior to contact of the element with the sample and drying the carrier.

Preparing homogeneous specific binding assay element to avoid premature

A homogeneous specific binding assay device, a method for its preparation, and a method for its use in determining a ligand, such as antigen, hapten, or antibody, in a liquid sample. The test device comprises a solid carrier member, such as a fibrous web matrix, e.g., paper, or a polymeric film or gel, incorporated with reagents for a homogeneous specific binding assay system which produces a detectable response, usually an electromagnetic radiation signal, that is a function of the presence or amount of the ligand in the sample. For example, disclosed is a test device for determining a ligand in a liquid sample, comprising (a) a reagent composition including a complex of (i) a labeled conjugate comprising a label component coupled to said ligand or a specific binding analog thereof, and (ii) a specific binding partner for said ligand, said label providing a detectable response, or interacting with a detectant system to provide a detectable response, which is different when the labeled conjugate is bound by said binding partner compared to when it is not so bound, whereby the detectable response is a function of the presence of the ligand in the sample, and (b) a carrier incorporated with said complex. Useful homogeneous specific binding assay systems include those involving enzyme substrate labels, enzyme prosthetic group labels, and enzyme labels. The detectable response preferably is a luminescent, fluorescent, spectrophotometric, or colorimetric response, which is measurable by visual observation or instrument means.

Homogeneous specific binding assay device and preformed complex method

A multilayer analytical element for detecting a ligand in or the ligand binding capacity of a liquid sample of the type having a reagent layer incorporating reagents which are responsive to the ligand in or the ligand binding capacity of the sample to give a detectable response, a radiation diffusing and blocking layer, and a support layer, the improvement wherein the radiation diffusing and blocking layer is (a) interposed between the reagent layer and the support layer; (b) impermeable to the ligand, reagents of the reagent layer, and products of their interreaction; and (c) inert to the ligand, reagents of the reagent layer, and products of their interreaction.

Multilayer analytical element having an impermeable radiation diffusing

Test means, such as a composition, a test device, method of making the test device and process for determining glucose in a body fluid sample are disclosed. More particularly, the contemplated test means comprises glucose oxidase, a peroxidatively active substance, such as peroxidase, and a 3,3',5,5'-tetraalkylbenzidine indicator in an amount sufficient rapidly to produce upon contact of the test means with a predetermined amount of a glucose containing sample, a stable colored reaction product. The preferred benzidine indicator is 3,3',5,5'-tetramethylbenzidine.

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South Bend, IN, United States of America

Bert Walter