US3001915A - Diagnostic composition - Google Patents

Diagnostic composition Download PDF

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Publication number
US3001915A
US3001915A US702819A US70281957A US3001915A US 3001915 A US3001915 A US 3001915A US 702819 A US702819 A US 702819A US 70281957 A US70281957 A US 70281957A US 3001915 A US3001915 A US 3001915A
Authority
US
United States
Prior art keywords
test
glucose
barrier
solution
indicator
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
US702819A
Other languages
English (en)
Inventor
Dale E Fonner
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Corp
Original Assignee
Miles Laboratories Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to NL233808D priority Critical patent/NL233808A/xx
Priority to IT599130D priority patent/IT599130A/it
Priority to BE573475D priority patent/BE573475A/xx
Application filed by Miles Laboratories Inc filed Critical Miles Laboratories Inc
Priority to US702819A priority patent/US3001915A/en
Priority to FR1213963D priority patent/FR1213963A/fr
Priority to CH6671458A priority patent/CH384251A/de
Priority to GB40012/58A priority patent/GB867192A/en
Application granted granted Critical
Publication of US3001915A publication Critical patent/US3001915A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/64—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving ketones
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/54—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving glucose or galactose
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/52—Use of compounds or compositions for colorimetric, spectrophotometric or fluorometric investigation, e.g. use of reagent paper and including single- and multilayer analytical elements
    • G01N33/521—Single-layer analytical elements
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/84—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving inorganic compounds or pH

Definitions

  • This invention relates to a diagnostic composition.
  • the invention relates to a diagnostic composition for detecting conditions of abnormality in biological fluids.
  • the invention relates to a diagnostic composition for body fluids which represents a combination of two or more tests performed in a single operation.
  • the instant invention has as its object the description of a combination diagnostic composition whereby two or more tests may be made on a biological fluid simultaneously.
  • a further object of the invention is to furnish to those interested in diagnoses a test indicator capable of performing a plurality of tests upon a biological fluid with a single motion.
  • the diagnostic composition to which this invention is directed comprises a bibulous carrier which is impregnated at separate portions thereof with a reagent material which will indicate the presence or absence of a different abnormality of a biological fluid.
  • a reagent material which will indicate the presence or absence of a different abnormality of a biological fluid.
  • the bibulous carrier is preferably in the form of a stick or strip of a material which is ca pable of being saturated with a solution of the reagent material. strips of filter paper, for example, or other bibulous material which comprises a mass or complex of cellulose fibers may be used.
  • the preferred embodiment of this invention contemplates a strip of bibulous material which may be held by the fingers on one hand and dipped into the biological fluid so as to immerse the test portions thereof in said fluid
  • any other physical embodiment such as a continuous roll or strip of the bibulous carrier may be used.
  • each test portion be separated from the other by means of a barrier.
  • This barrier may be formed by impregnating a portion of the bibulous carrier between the separate test portions with a solution of a material which is impervious to water. The solvent then evaporates leaving the barrier. It is essential that the barrier be present throughout the cross sectional area of the bibulous carrier. That is to say, the barrier portion must be suificient to completely prevent the co-minglinig of the various reagents used in the separate test portions.
  • a solvent must be chosen which will completely dissolve the water im pervious material and leave a fluid film or layer of such material throughout the barrier portion. It is preferred,
  • the solvent chosen must be one in which the waterimpervious material is sufficiently soluble and which evap crates at a uniformly rapid rate so as to leave the desired complete barrier.
  • Operable solvents include acetone, methylethylketone, the various hydrocarbon solvents such as benzene, petroleum naphtha, petroleum ether, and the like.
  • the preferred material used for preparing the barrier portion is a 5% solution of ethyl cellulose in acetone to which there is added 50 rug/liter of a coloring agent such as D&C Yellow #11.
  • compositions of this -invention comprise multiple testing devices for determining abnormalities in biological fluids.
  • the combination diagnostic may be so prepared to test, by a single operation, a biological fluid for the presence or absence of glucose, albumin, ketone bodies "and hydrogen ion concentrations or any combination of two or more of these.
  • the surface active agent was Tween- 81, a polyoxyethylene substituted sorbitan mono-oleate.
  • the gelatin was dissolved in 150 ml. of water and mixed with a solution of the sodium citrate and citric acid in 150 ml. of water.
  • the o-tolidine and the FD&C Red #3 (disodium salt of 9-o-carboxyphenyl-6-hydroxy-2,4,5,7-tetraiodo-3-isoxanthone) was dissolved in the ethanol, and this solution added to the gelatin-butter solution. The two solutions were then mixed and stirred. This final solution was used to impregnate the desired portion of the bibulous carrier and the impregnated carrier was dried.
  • This indicator when contacted with a biological fluid containing as little as 0.05 glucose gave a blue color. A solution containing no glucose resulted in no color formation whatsoever.
  • the glucose indicator may comprise an enzyme which has oxidase activity for glucose plus a material which undergoes a color reaction in the presence of a product which is formed when said enzyme is contacted with glucose.
  • reagent materials useful for indicating the presence or absence of glucose may be used.
  • any other buffer composition capable of buifering from a pH of 2 to 8, preferably 4 to 8, may be used.
  • o-tolidine other color forming materials such as benzidine and the salts thereof, guaiacols, orcinol, pyrogallol gallic acid, leuco dyes such as leucomalachite, leucophenolphthalein and the like may be used.
  • the preferred glucose indicator contemplates a glucose oxidase, peroxidase, and a color forming substance oxidizable by hydrogen peroxide in the presence of said peroxidase, particularly o-tolidine.
  • tetrabromphenol blue In addition to the tetrabromphenol blue, other indicator materials which exhibit protein error may be used. These indicators will, in a solvent containing protein, by their color indicate a higher pH value for such solution than is actually the case. The extent to which the characteristic color change point of the indicator is shifted is some indication of the amount of protein in the solution.
  • tetrabromphenol blue the ethyl ester of tetrabromophenolphthalein, brom cresol green, dimethylaminoazobenzene and Congo red may be used.
  • the preferred composition is selected so as to lower the pH of the carrier and the dye to a pH slightly below the pH value at which the dye characteristically undergoes its color change.
  • the preferred composition therefore comprises a dye which exhibits protein error, and a fluid acid reacting material effective to buffer the carrier and said dye at a point adjacent to, but on the acid side of, the pH at which the color change of said dye normally occurs.
  • the sodium nitroprusside was then dissolved in water and added with stirring to the cooled solution. This final solution was used to impregnate the desired portion of the bibulous carrier. The impregnated carrier is dried. When contacted with a biological fluid containing 0.005% of acetoacetic acid, a lavender color was formed in 30 seconds. No color change was observed in the absence of acetoacetic acid.
  • the preferred embodiment of the invention contemplates a ketone body indicator which comprises a water soluble nitroprusside, a diacid phosphate, a monoacid phosphate, and aminoacetic acid, said constituents being so adjusted as to have, in solution, a pH within the range of from 6.5 to 7.5.
  • the barrier portion of the bibulous carrier is prepared by impregnating a portion of the bibulous carrier with a material which is impervious to water in such a fashion as to prevent co-mingling of the various reagent materials described above during use, that is to say, when all of the test portions are simultaneously contacted with a biological fluid under test.
  • the various materials which exhibit the desired properties, solubility in a suitable carrier medium or solvent, and imperviousness to water include the various cellulose esters such as methyl, ethyl, and propyl cellulose, cellulose nitrate, cellulose acid phthalate, polystyrene,
  • Example Strips of a bibulous carrier approximately 2 inches long and one quarter of an inch wide were immersed in the glucose indicator described above so that the indicator impregnated the lower one half inch of the strip.
  • the strips were then dried at room temperature.
  • a barrier portion was then prepared by impregnating a one eighth inch area of the strip immediately above the glucose indicator portion with a 5% solution of ethyl cellulose in acetone containing 5-0 ing/liter of D&C Yellow #11 (2-(2-qninolyl)-1,3-indandione).
  • D&C Yellow #11 (2-(2-qninolyl)-1,3-indandione
  • the strip After drying the strip, the next one half inch was impregnated with the ketone body indicator and dried again. Then a third one eighth inch barrier portion was prepared and the next one half inch of the strip was impregnated with the pH indicator.
  • the impregnations were carried out by means of hypodermic needles, and when finished, the strip comprises a diagnostic composition for testing biological fluids for glucose, albumin, ketone bodies and hydrogen ion concentrations reading from bottom to top.
  • a sample of urine of pH 7 and containing 0.05% glucose, 0.1% albumin, and 0.005% acetoacetic acid was tested by immersing the strip in the urine so as to completely cover the test portions. The glucose portion turned blue, the albumin test portion green, the ketone body test portion lavender, and the pH indicating portion, a yellow-green within 30 seconds.
  • Diagnostic compositions for various combinations of the reagent materials described above were prepared and checked with a test solution.
  • the solution used was a normal urine of pH 7.0 which was made up to contain 0.05% glucose, 0.1% albumin, and 0.005% aminoacetic acid. Results obtained are set out in the table below.
  • the reagent strips in accordance with the instant invention may be prepared by a multiple operation which involves impregnating a roll of bibulous carrier with continuous lines of the barrier material and of each of the indicating compositions. After drying the roll is then cut into separate test strips.
  • a multiple operation which involves impregnating a roll of bibulous carrier with continuous lines of the barrier material and of each of the indicating compositions. After drying the roll is then cut into separate test strips.
  • G glucose
  • A albumin
  • K ketone bodies.
  • a test indicator for biological fluids which comprises a bibulous strip having at least two test portions separately impregnated with a reagent material capable of detecting abnormality of said biological fluid, each test portion being separated from the other by a barrier portion to prevent co-mingling of said reagent material when contacted by said biological fluid, said barrier portion having been formed by dissolving in a solvent therefor a barrier material selected from the group consisting of ethyl cellulose, polystyrene, rosin and paraffin, impregnating said bibulous strip with said dissolved material so that said material completely saturates the cross-sectional area of said bibulous strip and removing said solvent from said impregnated bibulous strip.
  • test indicator for biological fluids wherein said solvent is acetone and wherein said barrier material is ethyl cellulose.
  • a test indicator for biological fluids according to claim 1, wherein said barrier portion contains a coloring amount of 2-(2-quinolyl)-1,3-indandione.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Hematology (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Urology & Nephrology (AREA)
  • Biotechnology (AREA)
  • Biochemistry (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Analytical Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Organic Chemistry (AREA)
  • Cell Biology (AREA)
  • Food Science & Technology (AREA)
  • General Physics & Mathematics (AREA)
  • Pathology (AREA)
  • Wood Science & Technology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Zoology (AREA)
  • Biophysics (AREA)
  • Emergency Medicine (AREA)
  • Inorganic Chemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Investigating Or Analysing Biological Materials (AREA)
US702819A 1957-12-16 1957-12-16 Diagnostic composition Expired - Lifetime US3001915A (en)

Priority Applications (7)

Application Number Priority Date Filing Date Title
NL233808D NL233808A (is") 1957-12-16
IT599130D IT599130A (is") 1957-12-16
BE573475D BE573475A (is") 1957-12-16
US702819A US3001915A (en) 1957-12-16 1957-12-16 Diagnostic composition
FR1213963D FR1213963A (fr) 1957-12-16 1958-11-27 Composition de diagnostic
CH6671458A CH384251A (de) 1957-12-16 1958-11-28 Diagnostisches Mittel
GB40012/58A GB867192A (en) 1957-12-16 1958-12-11 Diagnostic compositions

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US702819A US3001915A (en) 1957-12-16 1957-12-16 Diagnostic composition

Publications (1)

Publication Number Publication Date
US3001915A true US3001915A (en) 1961-09-26

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ID=24822735

Family Applications (1)

Application Number Title Priority Date Filing Date
US702819A Expired - Lifetime US3001915A (en) 1957-12-16 1957-12-16 Diagnostic composition

Country Status (7)

Country Link
US (1) US3001915A (is")
BE (1) BE573475A (is")
CH (1) CH384251A (is")
FR (1) FR1213963A (is")
GB (1) GB867192A (is")
IT (1) IT599130A (is")
NL (1) NL233808A (is")

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3066081A (en) * 1961-05-05 1962-11-27 Edward S Rorem Means for detecting galactose
US3123443A (en) * 1960-04-18 1964-03-03 Composition for diagnosing glucose
US3127281A (en) * 1964-03-31 Means and method of making multi-test indicator
US3149054A (en) * 1962-04-09 1964-09-15 Dundee Lab Inc Bacteria determination method
US3232710A (en) * 1951-01-28 1966-02-01 Boehringer & Soehne Gmbh Indicator and method for manufacturing the same
US4225557A (en) * 1977-07-01 1980-09-30 Rohm Gmbh Packaged diagnostic test strip
US4274832A (en) * 1979-02-12 1981-06-23 Eastman Kodak Company Analytical element and method for analysis of multiple analytes
EP0036543A1 (en) * 1980-03-20 1981-09-30 Miles Laboratories, Inc. Improved method and device for the semiquantitative determination of glucose in aqueous fluids and method of preparing the device
US4551306A (en) * 1983-05-20 1985-11-05 Miles Laboratories, Inc. Sealed reagent matrix
US4622207A (en) * 1984-12-14 1986-11-11 Miles Laboratories, Inc. Reagent test device having sealed matrix boundaries
US4983416A (en) * 1985-02-04 1991-01-08 Propper Manufacturing Co., Inc. Manufacturing method for an occult fecal blood test slide
EP1211512A3 (en) * 2000-11-30 2002-11-06 Serim Research Corporation Test strip for determining dialysate composition
EP1318397A1 (en) * 2001-12-05 2003-06-11 Lifescan, Inc. Test strips having a plurality of reaction zones and methods for using and manufacturing the same
US6583722B2 (en) 2000-12-12 2003-06-24 Kimberly-Clark Worldwide, Inc. Wetness signaling device
US6603403B2 (en) 2000-12-12 2003-08-05 Kimberly-Clark Worldwide, Inc. Remote, wetness signaling system

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NL296257A (is") * 1962-08-06
US4336330A (en) * 1980-12-15 1982-06-22 Miles Laboratories, Inc. Device for detecting glucose concentration
US5764355A (en) * 1996-01-12 1998-06-09 Gagnon; David R. Spectroscopic sample holder

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2129754A (en) * 1937-08-12 1938-09-13 Carl Schleicher & Schull Co In Test paper
US2606102A (en) * 1946-12-03 1952-08-05 Allied Chem & Dye Corp Test strips for detecting low concentrations of chlorine in air

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2129754A (en) * 1937-08-12 1938-09-13 Carl Schleicher & Schull Co In Test paper
US2606102A (en) * 1946-12-03 1952-08-05 Allied Chem & Dye Corp Test strips for detecting low concentrations of chlorine in air

Cited By (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3127281A (en) * 1964-03-31 Means and method of making multi-test indicator
US3232710A (en) * 1951-01-28 1966-02-01 Boehringer & Soehne Gmbh Indicator and method for manufacturing the same
US3123443A (en) * 1960-04-18 1964-03-03 Composition for diagnosing glucose
US3066081A (en) * 1961-05-05 1962-11-27 Edward S Rorem Means for detecting galactose
US3149054A (en) * 1962-04-09 1964-09-15 Dundee Lab Inc Bacteria determination method
US4225557A (en) * 1977-07-01 1980-09-30 Rohm Gmbh Packaged diagnostic test strip
US4274832A (en) * 1979-02-12 1981-06-23 Eastman Kodak Company Analytical element and method for analysis of multiple analytes
EP0036543A1 (en) * 1980-03-20 1981-09-30 Miles Laboratories, Inc. Improved method and device for the semiquantitative determination of glucose in aqueous fluids and method of preparing the device
US4551306A (en) * 1983-05-20 1985-11-05 Miles Laboratories, Inc. Sealed reagent matrix
US4622207A (en) * 1984-12-14 1986-11-11 Miles Laboratories, Inc. Reagent test device having sealed matrix boundaries
US4983416A (en) * 1985-02-04 1991-01-08 Propper Manufacturing Co., Inc. Manufacturing method for an occult fecal blood test slide
EP1211512A3 (en) * 2000-11-30 2002-11-06 Serim Research Corporation Test strip for determining dialysate composition
US6583722B2 (en) 2000-12-12 2003-06-24 Kimberly-Clark Worldwide, Inc. Wetness signaling device
US6603403B2 (en) 2000-12-12 2003-08-05 Kimberly-Clark Worldwide, Inc. Remote, wetness signaling system
EP1318397A1 (en) * 2001-12-05 2003-06-11 Lifescan, Inc. Test strips having a plurality of reaction zones and methods for using and manufacturing the same
US6723500B2 (en) 2001-12-05 2004-04-20 Lifescan, Inc. Test strips having reaction zones and channels defined by a thermally transferred hydrophobic barrier
SG120900A1 (en) * 2001-12-05 2006-04-26 Lifescan Inc Test strips having a plurality of reaction zones and methods for using and manufacturing the same

Also Published As

Publication number Publication date
NL233808A (is")
FR1213963A (fr) 1960-04-05
GB867192A (en) 1961-05-03
BE573475A (is")
IT599130A (is")
CH384251A (de) 1964-11-15

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