US3252762A - Stabilized occult blood diagnostic - Google Patents

Stabilized occult blood diagnostic Download PDF

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Publication number
US3252762A
US3252762A US107646A US10764661A US3252762A US 3252762 A US3252762 A US 3252762A US 107646 A US107646 A US 107646A US 10764661 A US10764661 A US 10764661A US 3252762 A US3252762 A US 3252762A
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United States
Prior art keywords
hydroperoxide
blood
dialdehyde
organic
encapsulated
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
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US107646A
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English (en)
Inventor
Jr Ernest C Adams
Norman R Novak
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Bayer Corp
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Miles Laboratories Inc
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Publication date
Priority to NL277911D priority Critical patent/NL277911A/xx
Application filed by Miles Laboratories Inc filed Critical Miles Laboratories Inc
Priority to US107646A priority patent/US3252762A/en
Priority to GB14043/62A priority patent/GB981955A/en
Priority to CH524662A priority patent/CH427353A/de
Priority to FR896360A priority patent/FR1321267A/fr
Priority to DEM52734A priority patent/DE1265453B/de
Priority to DK200362AA priority patent/DK103213C/da
Priority to BE617211A priority patent/BE617211A/fr
Application granted granted Critical
Publication of US3252762A publication Critical patent/US3252762A/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

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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
    • G01N33/72—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood pigments, e.g. haemoglobin, bilirubin or other porphyrins; involving occult blood
    • G01N33/721—Haemoglobin
    • G01N33/725—Haemoglobin using peroxidative activity
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
    • Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y10S436/00—Chemistry: analytical and immunological testing
    • Y10S436/904—Oxidation - reduction indicators

Definitions

  • This invention relates to a composition which has utility in the detection of blood.
  • the invention relates to compositions which are suitable for use in the qualitative detection and quantitative estimation of blood in body fluids such as urine, vomitus, gastric content, cerebral spinal fluids and in feces. More particularly, the invention relates to blood testing compositions wherein one component of the test is encapsulated by means of a novel encapsulating material.
  • occult blood in body fluids and feces has become an invaluable aid to the medical practitioner in the diagnosis of a great number of disorders.
  • Blood is found in the gastric contents and in vomitus in conditions associated with erosion of the mucous membranes in ulcers and incarcinomas.
  • the regular and frequent occurrence of occult blood is suggestive of gastro-intestinal cancer, gastric or duodenal ulcers or hemorrhoids.
  • the hemorrhage is often so slight that it is not possible to detect blood by microscopic identification of the erythrocytes (red blood cells) and a sensitive and specific chemical test for occult blood becomes invaluable.
  • hematuria or blood pigment (hemoglobinuria) is found in typhus, scurvy, purpura, pyemia, nephritis, renal calculi, as the result of a burn covering a large part of the body, as a result of the action of various hemolytic toxins and the like.
  • the instant inventive concept is based on the catalytic activity of the prosthetic groups present in blood.
  • These catalytically active substances identified in hemoglobin, belong to the general class of hemoproteins, conjugate proteins all of which have the same prosthetic groups, iron protoporphyrin or heme.
  • This prosthetic group has the ability to catalyze the transfer of oxygen from an oxygen source to an acceptor which in turn becomes oxidized. If the acceptor is a dye precursor, colorless until it becomes oxidized and colored in its oxidized form, then the presence of the catalytic activity is indicated by color formation.
  • the composition of this invention comprises an indicator or dye precursor plus an oxygen source.
  • the transfor of oxygen from the oxygen source to the acceptor or dye precursor will occur and the indicator will become oxidized and colored.
  • the presence of color is an indication of the presence of blood.
  • the rapidity of the color change and the depth or density of the color, when compared to a set'of standards, is a means of the quantitative estimation of the blood present.
  • the instant invention is directed to an improvement over the prior art techniques of testing for blood, particularly occult blood in body fluids and in'other substances. It has now been found that an improved test composition results when one of a group of organic hydroperoxides having pronounced sensitivity in the indicator reaction above described is encapsulated or entrapped within a colloidal material such as gelatin, which has been hardened by fixing with a dialdehyde polysaccharide which is efiective for this purpose, and combined in this form along with a suitable indicator and buffering means.
  • hydroperoxides As pointed out above, a certain group of organic hydroperoxides has been found to have the pronounced sensitivity which is required for the indicator reaction to be utilized in the diagnostic compositions of this invention.
  • the hydroperoxides consist of a group of materials including cumene hydroperoxide, diisopropylbenzene hydroperoxide, paramenthane hydroperoxide, and 2,5-dimethylhexane 2,5-dihydroperoxide to mention the most significant members of this group.
  • Other organic hydroperoxides of similar structure may likewise be used if desired.
  • a novel encapsulating material for the organic hydroperoxides may be comprised of various protein or polysaccharide materials such as gelatin, algin, carrageenin, casein, albumin or other materials of this nature. These various protein or polysaccharide materials are applied to the test compositions and then hardened by means of a fixing process, which involves treating with a dialdehyde polysaccharide which is effective for this purpose.
  • emulsifying agent such as acacia mucilage
  • emulsifying agents include polyvinyl alcohol, gum arabic, carboxy vinyl polymer and the like.
  • a surfactant or wetting agent such as dioctyl sodium sulfosuccinate may also be used.
  • the emulsifying agent serves to lower the surface tension of the oily organic hydroperoxide and forms a film around each individual oil droplet.
  • the surfactant if used, assists in this regard.
  • the resulting primary emulsion is buffered by means of an appropriate buffer such as a mixture of sodium citrate and citric acid.
  • the butter is first mixed with the material which is to form the encapsulation for the organic hydroperoxide such as gelatin before addition to the hydroperoxide emulsion.
  • the material which is to form the encapsulation for the organic hydroperoxide such as gelatin
  • various materials may be used for the encapsulation as pointed out above.
  • An aqueous dispersion of a dialdehyde polysaccharide, such as dialdehyde starch, is next added to serve as a fixing agent for the encapsulating material.
  • the encapsulation material which is present in the film around the oily organic hydroperoxide droplets is thereby fixed by the dialdehyde polysaccharide resulting in a more stable preparation.
  • This composition is then buffered and may be applied O hydroperoxide and is the preferred buffer for this purpose, there may be used any other suitable buffer material, such as, for example, a tartrate, phosphate, phthalate, acetate or other buffer.
  • suitable buffer material such as, for example, a tartrate, phosphate, phthalate, acetate or other buffer.
  • the preferred range of hydrogen ion concentration to which the composition is buffered is from about pH 4 to pH 7.
  • Dialdehyde polysaccharides of which dialdehyde starch is an example, may be prepared by the well known oxidation of polysaccharides with periodic acid. This preparation is illustrated by the conversion of starch to dialdehyde starch using periodic acid as the oxidizing agent in accordance with the following equation CIHQOH O H H jg H104 011 H L
  • the dialdehyde polysaccharides to be used in this process may be the dialdehyde derivatives'of any polysaccharide such as corn, wheat, tapioca or potato starches, celluloses, dextrans, algins, inulin or others.
  • the dialdehyde derivatives of starch known generically as dialdehyde starch, are the best known and most often used. However, where it is desired to have derivatives of other polysaccharides, these may also be used.
  • dialdehyde polysaccharides which are from about 50% to 100% oxidized, that is, those wherein 50 to 100 of the original anhydroglucose units have been converted to dialdehyde units, such as by periodate oxidation.
  • the dialdehyde polysaccharide is used in the form of an aqueous dispersion, which may be readily prepared by adding the dialdehyde polysaccharide in the desired concentration, usually from about 0.25% to about 1.5%, to tap water or to a buffer solution and then mixing the aqueous dispersion until a relatively homogeneous dispersion is obtained.
  • the dialdehyde polvsaccharide may be used in whatever concentration is required to satisfactorily harden the encapsuating material to provide the desired stability features of the instant invention. The precise concentration to be used will be pointed out more particularly hereafter.
  • orthotolidine is the preferred indicator for the diagnostic compositions of this invention
  • various other indicator materials may be used so long as they satisfy the requirements pointed out above, namely that they undergo a color change in the presence of an oxygen source and the blood for which the unknown material is being tested.
  • Such indicators comprise a variety of organic materials, principally those of the aniline and phenol derivatives.
  • orthotolidine o-toluidine, p-toluidine, o-phenylenediamine, N,N-dimethylp-phenylenediamine, N,N-diethyl-p-phenylenediamine, benzidine, p-anisidine, di-anisidine, o-cresol, m-cresol, p-cresol, a-naphthol, 8- naphthol, catechol, guaiacol and pyrogallol.
  • compositions of this invention may be incorporated in any of various diagnostic media, it has been found that incorporating these compositions upon discs or strips of paper produces the most useful and most satisfactory diagnostics.
  • sticks of bibulous material such as rigid paper sticks, have been found to be eminently satisfactory for this purpose.
  • compositions of the diagnostic materials provided by this invention may vary within fairly wide limits in accordance with the general teachings set forth above, it has been found that particularly useful compositions can be provided by using the various ingredients within the ranges set forth in the table below, which is an illustration of the types of compositions which may be used in this invention rather than a limitation of the total entire useful range to the precise concentrations set forth.
  • Emulsifying agent (60% w./-v.), ml -100 Organic hydroperoxide, ml. 2.5-10 Surfactant for hydroperoxide emulsion, ml. 0-2 Buffer I, ml. 25-50 Encapsulating material, g 0.7-3.5 Dialdehyde polysaccharide (1% w./v.), ml. 0.4-3
  • the citrate buifer was then mixed with 0.7 g. of gelatin and 50 ml. of the buffergelatin mixture was added to the primary emulsion and mixed well. Next was added 1 ml. of a 1% dispersion of dialdehyde starch with thorough mixing. A 5% solution of sodium lauryl sulfate was then added to the mixture in an amount of 12 ml. The resulting composition was then homogenized by means of a hand homogenizer and 50 ml. of a buifer solution prepared as above using 500 ml. of water, 163 g. of sodium citrate and 37 g. of citric acid was added with mixing.
  • the finished emulsion was then applied to paper strips by dipping and the impregnated paper strips were then dried in an oven at C. to C. for 24 hours. Finally, 320 mg. of orthotolidine was dissolved in 16 ml. of choloroform and applied to the dried paper strips by dipping. The excess chloroform was evaporated from the strips by means of mild heat. These strips were then tested on various urine samples and showed positive on samples containing one part blood in 30,000 parts urine.
  • Example II To a 1,000 ml. lbeaker was added 500 ml. of acacia mucilage, prepared by adding 500 ml. of boiling water to 200 g. of acacia, and 25 ml. of cumene hydroperoxide. These ingredients were mixed with a Lightning mixer for minutes at a rheostat setting of 70-80. In another beaker 1,500 ml. of boiling water was added to a mixture of 163 g. of sodium citrate and 37 g. of citric acid. Upon cooling 3.5 g. of gelatin was dissolved in the citrate buffer and the mixture was added to the beaker containing the acacia mucilage and cumene hydroperoxide. Next there was added 5 ml.
  • dialdehyde starch 1% w./v. dispersion of dialdehyde starch.
  • the dialdehyde. starch was allowed to mix with the'other ingredients and then 50 ml. of sodium lauryl sulfate was added and mixing continued for 5 minutes at a rheostat setting of 60.
  • the resulting emulsion was passed through a Manton-Gaul-in homogenizer for 5 minutes at 2,000 lb. pressure.
  • To the homogenized mixture was added 250 ml. of a citrate buifer which had previously been prepared by adding 500 m1. of boiling water to a mixture of 163 g. of sodium citrate and 37 g. of citric acid and mixing continued.
  • the emulsion was then applied to paper strips by dipping and the impregnated strips were placed in a kiln at 160 F. for 16 hours. Finally, the strips were dipped into a chloroform solution of orthotolidine which had been prepared by dissolving 1.28 g. of orthotolidinc in 64 ml. of chloroform and the excess chloroform allowed to evaporate by use of the kiln. These strips were then tested in various urine samples and were shown to be sensitive to one part of blood in 25,000 parts of urine.
  • vthe invention relates to novel diagnostic compositions for the detection of occult blood in various fluids, which include an organic hydroperoxide encapsulated in a polysaccharide or protein material which has been hardened or fixed by treatment with dialdehyde polysaccharide buffered at a pH of from pH 4 to pH 7 and an indicator material which is capable of undergoing a color change by virtue of oxygen transfer between the aforementioned organic hydroperoxide and the indicator in the presence of blood.
  • These compositions are particularly useful for incorporation in diagnostic discs or sticks.
  • a test composition in dry solid form for the detection of blood which comprises an encapsulated organic hydroperoxide selected from the group consisting of cumene hydroperoxide, diisopropylbenzene hydroperoxide, paramenthane hydroperoxide, and 2,5-dimethy1hexane 2,5-dihydroperoxide, an indicator capable of accepting a catalytic transfer of oxygen from the hydroperoxide by means of the prosthetic group of hemoglobin and be coming oxidized with an accompanying color change, a buffer maintaining the pH of material being tested to one within the range of about from pH 4 to pH 7, said organic hydroperoxide being encapsulated by means of a dialdehyde polysaccharide fixed gelatin.
  • an encapsulated organic hydroperoxide selected from the group consisting of cumene hydroperoxide, diisopropylbenzene hydroperoxide, paramenthane hydroperoxide, and 2,5-dimethy1hexane 2,5-dihydroperoxid
  • dialdehyde polysaccharide is dialdehyde starch.
  • a device according to claim 5 wherein the organic hydroperoxide is cumene hydroperoxide.
  • a test composition in dry solid form for the detection of blood which comprises an encapsulated organic hydroperoxide selected from the group consisting of cumene hydroperoxide, diisopropyI-benzene hydroperoxide, para-menthane hydroperoxide and 2,5-dimethyl hexane 2,5-dihydroperoxide, an indicator capable of accepting a catalytic transfer of oxygen from the hydroperoxide by means of the phosthetic group of hemoglobin and becoming oxidized with an accompanying color change, a buifer maintaining the pH of the test composition within the range of about from pH 4 to pH 7, said organic hydroperoxide being encapsulated by means of a dialdehyde polysaccharide fixed gelatin and as a surfactant, sodium lauryl sulfate.
  • an encapsulated organic hydroperoxide selected from the group consisting of cumene hydroperoxide, diisopropyI-benzene hydroperoxide, para-menthane hydroperoxide and 2,5
  • dialdehyde polysaccharide is dialdehyde starch.
  • a composition according to claim 9 wherein the organic hydroperoxide is cumene hydroperoxide.
  • a composition according to claim 9 wherein the indicator material is orthotolidine.
  • a device in dry solid form for the detection of blood which comprises a bibulous carrier and incorporated therewith, an encapsulated cumene hydroperoxide and orthotolidine, said cumene hydroperoxide being encapsulated by means of a dialdehyde polysaccharide fixed gelatin.
  • a process for the preparation of a test composition for the detection of blood which comprises mixing an organic hydroperoxide selected from the group consisting of cumene hydroperoxide, diiso propylbenzene hydroperoxide, paramenthane hydroperoxide and 2,5-dimethylhexane 2,5-dihydroperoxide with an emulsifying agentto form a primary emulsion,
  • a process according to claim 14 wherein the emulsifying agent is gum arabic.
  • a process according to claim 14 wherein the organic hydroperoxide is cumene hydroperoxide.
  • a process according to claim 14 wherein the surfactant is sodium lauryl sulfate.
  • dialdehyde polysaccharide is dialdehyde starch.

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Hematology (AREA)
  • Engineering & Computer Science (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Chemical & Material Sciences (AREA)
  • Immunology (AREA)
  • Urology & Nephrology (AREA)
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  • Food Science & Technology (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Pathology (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
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US107646A 1961-05-04 1961-05-04 Stabilized occult blood diagnostic Expired - Lifetime US3252762A (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
NL277911D NL277911A (en, 2012) 1961-05-04
US107646A US3252762A (en) 1961-05-04 1961-05-04 Stabilized occult blood diagnostic
GB14043/62A GB981955A (en) 1961-05-04 1962-04-11 Improvements in or relating to diagnostic compositions
CH524662A CH427353A (de) 1961-05-04 1962-05-02 Stabilisierte Mischung zum Nachweis von Blut
FR896360A FR1321267A (fr) 1961-05-04 1962-05-03 Composition de diagnostic pour déceler le sang
DEM52734A DE1265453B (de) 1961-05-04 1962-05-03 Zum Nachweis von Blut bestimmtes diagnostisches Mittel
DK200362AA DK103213C (da) 1961-05-04 1962-05-03 Middel til påvisning af blod.
BE617211A BE617211A (fr) 1961-05-04 1962-05-03 Composition de diagnostic pour déceler le sang

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BE (1) BE617211A (en, 2012)
CH (1) CH427353A (en, 2012)
DE (1) DE1265453B (en, 2012)
DK (1) DK103213C (en, 2012)
GB (1) GB981955A (en, 2012)
NL (1) NL277911A (en, 2012)

Cited By (31)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3290117A (en) * 1963-06-24 1966-12-06 Miles Lab Occult blood diagnostic composition with color enhancing agent
US3853471A (en) * 1972-07-18 1974-12-10 Boehringer Mannheim Gmbh Diagnostic composition for the detection of peroxidatively active substances in body fluids
US3945798A (en) * 1973-05-24 1976-03-23 Eastman Kodak Company Formaldehyde test element and method of use
US3975162A (en) * 1974-03-13 1976-08-17 Marine Colloids, Inc. Applying reagent to medium and device therefor
US4017261A (en) * 1974-10-16 1977-04-12 Lachema, Narodni Podnik Biological diagnostic test strip and method of producing same
US4063894A (en) * 1975-11-21 1977-12-20 Shionogi & Co., Ltd. Test strip for the detection of occult blood in excreta
US4071317A (en) * 1977-03-14 1978-01-31 Miles Laboratories, Inc. Test composition and device for determining peroxidatively active substances and process for preparing same
US4071321A (en) * 1977-03-14 1978-01-31 Miles Laboratories, Inc. Test composition and device for determining peroxidatively active substances
US4071318A (en) * 1977-03-14 1978-01-31 Miles Laboratories, Inc. Test composition and device for determining peroxidatively active substances
US4175923A (en) * 1978-06-26 1979-11-27 Friend William G Method and apparatus for occult blood testing in the home
US4329317A (en) * 1981-01-29 1982-05-11 Smithkline Instruments, Inc. Method of stabilizing a specimen slide for occult blood testing
US4382064A (en) * 1981-01-29 1983-05-03 Smithkline Instruments, Inc. Specimen slide for occult blood testing
US4447542A (en) * 1983-04-04 1984-05-08 Miles Laboratories, Inc. Analytical test composition, device and method for the determination of peroxidatively active substances
EP0130520A1 (en) * 1983-06-29 1985-01-09 Miles Laboratories, Inc. Stabilized test composition, device and method for the determination of peroxidatively active substances
US4526869A (en) * 1980-09-24 1985-07-02 Regents Of The University Of Minnesota Method for quantitatively determining the concentration of hemoglobin in a biological sample
US4615982A (en) * 1984-12-11 1986-10-07 Lawrence Paul J Fecal occult blood test
WO1987001460A1 (en) * 1985-08-30 1987-03-12 Terje Silsand Test device for determination of blood in faeces
US4676950A (en) * 1984-02-03 1987-06-30 Foster Research Corporation Indicator and test device for detecting occult blood
US4818702A (en) * 1986-06-02 1989-04-04 Litmus Concepts, Inc. Fecal occult blood test reagent
US4895798A (en) * 1987-11-13 1990-01-23 Miles, Inc. Test devices for determination of occult blood
US4956300A (en) * 1982-01-05 1990-09-11 Helena Laboratories Corporation Aid for determining the presence of occult blood, method of making the aid, and method of using the aid
US5081040A (en) * 1987-06-29 1992-01-14 Helena Laboratories Corporation Composition and kit for testing for occult blood in human and animal excretions, fluids, or tissue matrixes
US5196167A (en) * 1989-04-04 1993-03-23 Helena Laboratories Corporation Fecal occult blood test product with positive and negative controls
US5217874A (en) * 1989-04-04 1993-06-08 Helena Laboratories Corporation Fecal occult blood test product with positive and negative controls
US5273888A (en) * 1984-01-16 1993-12-28 Helena Laboratories Corporation Chemical test kit and method for determining the presence of blood in a specimen and for verifying the effectiveness of the chemicals
US5702913A (en) * 1983-12-21 1997-12-30 Helena Laboratories Corporation Chromgen-reagent test system
US20020136436A1 (en) * 2001-02-23 2002-09-26 Schrier Wayne H. Devices and methods for reading and interpreting guaiac-based occult blood tests
EP1337830A2 (en) * 2000-12-01 2003-08-27 Auburn University Use of acacia gum (arabic gum) to isolate and preserve biological material
US20060172332A1 (en) * 2000-12-01 2006-08-03 Vodyanoy Vitaly J Use of protective natural polymers to isolate and preserve biological material
WO2012150453A1 (en) 2011-05-05 2012-11-08 Diagnodus Limited Device and method for non-invasive collection of colorectal mucocellular layer and disease detection
WO2019190787A1 (en) * 2018-03-27 2019-10-03 Exact Sciences Corporation Method for stabilizing hemoglobin and reagents for performing the same

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3311887A1 (de) * 1983-03-31 1984-12-20 Byk-Mallinckrodt Chemische Produkte Gmbh, 6057 Dietzenbach Verfahren zur bestimmung der peroxidase-aktivitaet durch endverduennungstitration und mittel zur durchfuehrung des verfahrens
DE3925938C1 (en, 2012) * 1989-08-03 1990-04-12 Geb. Sehl Claudia 1000 Berlin De Keck

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US3043782A (en) * 1958-12-22 1962-07-10 Upjohn Co Process for preparing a more impermeable coating by liquid-liquid phase separation
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US2290436A (en) * 1940-09-26 1942-07-21 Miles Lab Diagnostic composition and method
US2754289A (en) * 1952-02-29 1956-07-10 Shell Dev Process for polymerizing unsaturated compounds by conducting droplets through an aqueous medium with control of pressure fluctuations
US2800458A (en) * 1953-06-30 1957-07-23 Ncr Co Oil-containing microscopic capsules and method of making them
US2799660A (en) * 1954-04-15 1957-07-16 Miles Lab Blood test composition and method
US2953454A (en) * 1957-04-23 1960-09-20 Ncr Co Phototropic data storage capsules and base coated therewith
US2986453A (en) * 1957-11-13 1961-05-30 Miles Lab Diagnostic compositions
US2886445A (en) * 1958-12-08 1959-05-12 Gen Foods Corp Process for making chewing gum and product
US3043782A (en) * 1958-12-22 1962-07-10 Upjohn Co Process for preparing a more impermeable coating by liquid-liquid phase separation
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US3057723A (en) * 1959-06-24 1962-10-09 Eastman Kodak Co Hardening of gelatin with oxystarch
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Cited By (40)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3290117A (en) * 1963-06-24 1966-12-06 Miles Lab Occult blood diagnostic composition with color enhancing agent
US3853471A (en) * 1972-07-18 1974-12-10 Boehringer Mannheim Gmbh Diagnostic composition for the detection of peroxidatively active substances in body fluids
US3945798A (en) * 1973-05-24 1976-03-23 Eastman Kodak Company Formaldehyde test element and method of use
US3975162A (en) * 1974-03-13 1976-08-17 Marine Colloids, Inc. Applying reagent to medium and device therefor
US4017261A (en) * 1974-10-16 1977-04-12 Lachema, Narodni Podnik Biological diagnostic test strip and method of producing same
US4063894A (en) * 1975-11-21 1977-12-20 Shionogi & Co., Ltd. Test strip for the detection of occult blood in excreta
US4071317A (en) * 1977-03-14 1978-01-31 Miles Laboratories, Inc. Test composition and device for determining peroxidatively active substances and process for preparing same
US4071321A (en) * 1977-03-14 1978-01-31 Miles Laboratories, Inc. Test composition and device for determining peroxidatively active substances
US4071318A (en) * 1977-03-14 1978-01-31 Miles Laboratories, Inc. Test composition and device for determining peroxidatively active substances
US4175923A (en) * 1978-06-26 1979-11-27 Friend William G Method and apparatus for occult blood testing in the home
US4526869A (en) * 1980-09-24 1985-07-02 Regents Of The University Of Minnesota Method for quantitatively determining the concentration of hemoglobin in a biological sample
US4329317A (en) * 1981-01-29 1982-05-11 Smithkline Instruments, Inc. Method of stabilizing a specimen slide for occult blood testing
US4382064A (en) * 1981-01-29 1983-05-03 Smithkline Instruments, Inc. Specimen slide for occult blood testing
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GB981955A (en) 1965-02-03
CH427353A (de) 1966-12-31
NL277911A (en, 2012)
DK103213C (da) 1965-11-29
DE1265453B (de) 1968-04-04
BE617211A (fr) 1962-08-31

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