Abstract: A method for separation of erythrocytes from whole blood by diluting the whole blood with saline and introducing low concentrations of soluble salts of trivalent cations into the diluted blood sample.
Abstract: A conductive sensor and its use in a diagnostic assay are disclosed. The miniaturized conductive sensor, utilizing a conducting polymer, is used in a diagnostic device to determine the presence or concentration of a predetermined analyte in a liquid test sample, wherein the predetermined analyte, like glucose, is assayed by an oxidase interaction. The interaction between the oxidase and a small amount of the predetermined analyte in the test sample generates, either directly or indirectly, a dopant compound in a reaction zone of the conductive sensor. The dopant compound then migrates to the detection zone of the conductive sensor of the diagnostic device to oxidize the conducting polymer and convert the conducting polymer from an insulating form to a conducting form. The resulting increase in conductivity of the conducting polymer is measured, then the conductivity increase is correlated to the concentration of the predetermined analyte in the test sample.
Type:
Grant
Filed:
November 18, 1991
Date of Patent:
April 13, 1993
Assignee:
Miles Inc.
Inventors:
Matthew K. Musho, J. Oakey Noell, Pius H. Tse
Abstract: 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.
Type:
Grant
Filed:
August 21, 1992
Date of Patent:
April 6, 1993
Assignee:
Miles Inc.
Inventors:
Joel M. Blatt, Steven C. Charlton, Bert Walter, Mary E. Warchal
Abstract: Chromogenic merocyanine enzyme substrate compounds of the general formula: ##STR1## where Y is an enzymatically-cleavable group such as a radical of a sugar, carboxylic acid, amino acid, peptide, phosphoric acid, or sulfuric acid; A and B represent residues that complete 5- or 6-membered ring systems; R.sup.1 is substituted or unsubstituted alkyl; R.sup.2 and R.sup.3, independently, are hydrogen or lower alkyl; m, n, and p, which can be different, are integers from 0 through 3 provided that m+n+p must be at least 2; and X is an appropriate counterion (anion).
Abstract: Chromogenic enzyme substrate compounds comprising a dibenz[b,e] [1,4]oxazepinone or dibenzo[b,e] [1,4]thiazepinone nucleus having an enzyme-cleavable group such as a radical of a sugar, carboxylic acid, amino acid, peptide, phosphoric acid, or sulfuric acid. The substrate compounds are, in general, highly soluble in aqueous media and only slightly colored, and produce, upon enzyme cleavage, a chromogen exhibiting a large change in absorbance and a pKa below 7. Such substrates find use as indicators for the determination of enzyme analytes and enzymes used as markers in a variety of assays, including immunoassays.
Abstract: An assay for the detection of a peroxidatively active substance in a test sample. The assay employs a phenylenediamine and a naphthol which, under the conditions of the assay, couple to form a chromogen thereby indicating the presence of the analyte. The assay is carried out at a pH of from 10 to 14 since false positives due to ascorbate interference are minimized in highly alkaline media.
Abstract: A procedure for detecting proteins in fluids (particularly body fluids) which involves contacting such fluid with a composition comprising copper in a form capable of forming a copper/protein complex, a peroxide and a redox indicator which provides a detectable response when oxidized, together with an ionizable phosphate containing compound to prevent interference with the redox indicator from substances present in the fluid.
Abstract: Disclosed is a diagnostic test device which comprises a fluid permeable structural support member having on one side thereof a layer of a macroporous membrane comprising polyethyleneimine impregnated with iodate ion and on the other side of the support member having a layer of a microporous membrane having dispersed therein a chromogenic indicator capable of providing a colored response upon being oxidized.The intensity of the colored response is less subject to ascorbate interference due to the activity of the iodate ion.
Type:
Grant
Filed:
April 30, 1991
Date of Patent:
November 3, 1992
Assignee:
Miles Inc.
Inventors:
Karlheinz Hildenbrand, Herbert Hugl, Rolf Dhein
Abstract: Disclosed is an improved method for preparing a particulate citric acid or an alkali metal or alkaline earth metal salt thereof. The method involves spray granulating citric acid or a salt thereof from its partially purified fermentation broth to form granules which are freer flowing and less inclined to fracture than is citric acid or its salts prepared by crystallization techniques which properties render the material prepared by the present method suitable for handling in bulk.
Type:
Grant
Filed:
November 15, 1991
Date of Patent:
September 22, 1992
Assignee:
Haarmann & Beimer
Inventors:
Helmut A. Mothes, Bhalchandra H. Patwardhan, Theo G. Schroeder, David J. Solow
Abstract: General classes of 2-thiazolyl tetrazolium salt compounds have been found to be characterized by a reflectance spectrum exhibiting an extended plateau above about 600-650 nm. Such compounds are useful as chromogenic indicators for reducing substances such as NADH. The reflectance plateau confers improved accuracy to analytical assays, particularly for the determination of analytes of medical diagnostic significance, in which a colorimetric response on a reagent carrier matrix is measured by reflectance.
Type:
Grant
Filed:
September 19, 1990
Date of Patent:
June 30, 1992
Assignee:
Miles Inc.
Inventors:
Robert P. Hatch, Jurgen Kocher, Nan-Horng Lin, Scott Ruetten, Klaus Wehling
Abstract: Chromogenic merocyanine enzyme substrate compounds of the general formula: ##STR1## where Y is an enzymatically-cleavable group such as a radical of a sugar, carboxylic acid, amino acid, peptide, phosphoric acid, or sulfuric acid; A and B represent residues that complete 5- or 6-membered ring systems; R.sup.1 is substituted or unsubstituted alkyl; R.sup.2 and R.sup.3, independently, are hydrogen or lower alkyl; m, n, and p, which can be different, are integers from 0 through 3 provided that m+n+p must be at least 2; and X is an appropriate counterion (anion).
Abstract: A new and improved method and apparatus are provided for non-invasive monitoring of changes in blood glucose concentration in a tissue specimen and particularly in an individual. The method uses acoustic velocity measurements for monitoring the effect of glucose concentration upon the density and adiabatic compressibility of the serum.In a preferred embodiment, the acoustic velocity measurements are made through the earlobe of a subject by means of an acoustic probe or monitor which includes a transducer for transmitting and receiving ultrasonic energy pulses to and from the blood flowing in the subject's earlobe and a reflector for facilitating reflection of the acoustic pulses from the blood. The probe is designed in such a way that when properly affixed to an ear, the transducer is positioned flush against the anterior portion of an earlobe while the reflector is positioned flush against the interior portion of the earlobe.
Type:
Grant
Filed:
May 2, 1990
Date of Patent:
June 9, 1992
Assignee:
Miles Inc.
Inventors:
Graham H. Thomas, Roger M. Watson, J. Oakey Noell
Abstract: Chromogenic enzyme substrate compounds comprising a dibenz[b,e][1,4]oxazepinone or dibenzo[b,e][1,4]thiazepinone nucleus having an enzyme-cleavable group such as a radical of a sugar, carboxylic acid, amino acid, peptide, phosphoric acid, or sulfuric acid. The substrate compounds are, in general, highly soluble in aqueous media and only slightly colored, and produce, upon enzyme cleavage, a chromogen exhibiting a large change in absorbance and a pKa below 7. Such substrates find use as indicators for the determination of enzyme analytes and enzymes used as markers in a variety of assays, including immunoassays.
Abstract: Disclosed is an improved method for preparing a particulate citric acid or an alkali metal alkaline earth metal salt thereof. The method involves spray granulating citric acid or a salt thereof from its partially purified fermentation broth to form granules which are freer flowing and less inclined to fracture than is citric acid or its salts prepared by crystallization techniques which properties render the material prepared by the present method suitable for handling in bulk.
Type:
Grant
Filed:
April 29, 1991
Date of Patent:
April 14, 1992
Assignee:
Haarmann & Reimer
Inventors:
Helmut A. Mothes, Bhalchandra H. Patwardhan, Theo G. Schroeder, David J. Solow
Abstract: Optical indicator chalcogen (selenide or sulfide) compounds responsive to oxidants, e.g., hydrogen peroxide, and a method for using such indicators. Upon oxidation the resulting intermediate undergoes spontaneous elimination of the chalcogen residue to yield a signal compound which provides an optical signal such as fluorescence. Preferred fluorogenic indicator compounds are 3-chalcogen-3,4-dihydrocoumarin derivatives and 3-chalcogen-3,4-dihydro-2-quinolone derivatives. Such indicator compounds provide highly fluorescent products upon oxidation by hydrogen peroxide and are useful in analytical systems which generate hydrogen peroxide in response to the analyte under determination.
Abstract: The present invention relates to a number of innovative electrophilic substitution reactions involving 2,5-dithienylpyrrole (2,5-DTP). More specifically, these reactions are used in the synthesis of monomers for preparing functionalized conducting organic polymers.The electrophilic substitution reactions in this invention are accomplished under conditions not requiring the use of N-1 pyrrole blocking groups to direct reaction at the pyrrole C-3 position. This is because the steric bulk of the 2,5-dithienyl groups prevent N-acylation and therefore direct reactions with electrophiles at the pyrrole C-3 position.The reaction conditions chosen have also demonstrated a greater regioselectivity towards functionalization at the pyrrole 3-position than the basic reaction conditions suggested in the prior art. This result may be explained by an activation of the pyrrole 3-position towards electrophilic substitution. This is attributed to an electron donating resonance contribution of the 2,5 thienyl groups.