US3359072A - Method of making and using diagnostic aid for determination of albumin in biological fluids - Google Patents
Method of making and using diagnostic aid for determination of albumin in biological fluids Download PDFInfo
- Publication number
- US3359072A US3359072A US333178A US33317863A US3359072A US 3359072 A US3359072 A US 3359072A US 333178 A US333178 A US 333178A US 33317863 A US33317863 A US 33317863A US 3359072 A US3359072 A US 3359072A
- Authority
- US
- United States
- Prior art keywords
- albumin
- paper
- test
- solution
- acid
- 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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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
- G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
Definitions
- This diagnostic aid comprises a paper sheet having a wettable surface prepared by first impregnating the paper with a solution of an acid buffer, drying the buffer impregnated sheet, thereafter impregnating the dried sheet with a solution of an indicator dye exhibiting the so-called protein error, the solution of acid buffer having a pH below 7 but being so constituted as to maintain the indicator dye on the alkaline side of the acid-to-base color change point thereof and thereafter finally drying this twice impregnated sheet.
- test papers are characterized by an increased sensitivity and can be employed for the determination of albumin in biological fluids such as urine Where the concentration of the albumin is as low as 0.005%.
- the color of the paper strip undergoes a change in color, the same cor responding to the concentration of albumin in the biological fluid i.e., the strips which are pale yellow in color on immersion into an albumin containing fluid, take on strong blue colorations, the color intensity being a measure of the albumin concentration.
- This invention relates to new articles of manufacture and to new methods of manufacturing the same. More particularly, the invention relates to a diagnostic aid for use in carrying out relatively rapid determinations for the presence of albumin in biological fluids.
- albumin in biological fluids, as for instance urine, spinal fluid, etc. is of critical importance to the physician in making a diagnosis in kidney disease, circulatory disturbances, arteriosclerosis, hypertonia, diabetes, brain and spinal cord damage, etc.
- Methods for the detection of albumin are known, as for example, methods based on the su1fo-salicylic acid test, acetic acid-heat test, nitric acid ring test, and picric acid test. All of the aforesaid methods are based on precipitation reactions and cannot be carried out without a certain minimum amount of laboratory equipment. Therefore, these methods do not lend themselves for use as rapid diagnostic procedures.
- Test papers meet the requirement of providing a means for making rapid, on the spot determinations of this type.
- a color reaction suitable for use in the analytical detection of alubumin has been described by Feigl et al. (Mikrochim. Acta 2/1937, page 107).
- the reaction in volved is based on the so-called protein error exhibited by certain indicators: If the pH value of a reagent solution is held below the characteristic acid-to-base color change of the indicator, upon the addition of albumin, a color change occurs which is independent of the pH 3,359,072 Patented Dec. 19, 1967 value and which is due to the content of albumin in the solution; the color intensity varying directly with the concentration of alubumin.
- Feigl developed the afore-mentioned albumin detection procedure for use as a spot reaction test (wet), in connection with which he used as reagent a potassium salt of tetrabromo-phenolphthaleinethyl ester and acetic acid.
- the acetic acid must be replaced by a non-volatile acid.
- an acid buffer substance such as, for example, citrate buffer.
- albumin testing strips obtained in this manner, are not entirely satisfactory in that the differences in color between the negaitve and positive albumin reactions in albumin concentration ranges of below 0.1% are very slight.
- a positive test produces a more or less strongly yellowish green color, and the negative test is greenish yellow and is of a darker coloration than the dry test strip.
- the sensitivity of these test papers leaves much to be desired (detection limit about 0.03-0.01% of albumin).
- the absorbent carrier or test paper strip is impregnated with a solution which contains the buffer substance together with the color producing agent.
- This invention has an object a simple and practical method for producing a diagnostic aid for use in the determination of albumin in urine in concentrations as low as 0.005%.
- a further object of the invention is a simple and practical method for producing a diagnostic aid for use in the determination of alubumin in urine concentrations as low as 0.005% which determinations can be carried out rapidly without the use of laboratory equipment and by untrained personnel as routine matters.
- a still further object of the invention is a simple and practical method for producing a diagnostic aid comprising a test paper for use in the determination of albumin in urine in concentrations as low as 0.005% which determination can be carried out rapidly without the use of laboratory equipment and by untrained personnel as routine matters.
- a still further object of the present invention is a method for this purpose applicable to the treatment of preformed test paper strips.
- test papers for the determination of albumin in urine having a considerably increased sensitivity can be obtained by impregnating a test paper with a buffering solution having a pH of below 7 and thereafter impregnating the test paper with a chemical reagent capable of changing color in the presence of albumin, the gradation of color changes being a measure of the albumin content.
- the test papers obtained in this way are colored a pale yellow and on immersion into an albumin-containing fluid take on strong blue colorations, the gradation of color (i.e. color intensity) being a measure of the albumin concentration, the colors produced being clearly distinct from the yellow coloration of a negative test.
- the test strips prepared in accordance with the invention it is possible to positively detect 3 0.005% of albumin and even lower albumin concentrations being capable of measurement.
- the color of the paper strip does not change in either neutral or in an alkaline fluid.
- the test strip of the invention comprising a diagnostic aid for the determination of albumin in biological fluids is composed of a reagent capable of changing color to indicate the presence of protein, an acid buffering substance, and an absorbent carrier, which has been prepared by impregnating the absorbent carrier, first with an acid butter solution, and subsequently with a solution of the color producing chemical reagent.
- any indicator dye which exhibits the so-called protein error that is demonstrating the presence of albumin by a color change in the acid pH range, in particular tetra-bromo-phenolphthalein-ethyl ester and -butyl ester, as well as tetra-bromo-benzaurine.
- a suitable solvent for the indicator Most advantageously a readily volatile solvent should be used in order that the test strips dry quickly following the impregnation. If the indicator is dissolved in methanol or acetone, this solution then being used to impregnate a paper strip which has already been impregnated with the buffering agent, the test paper obtained will demonstrate numerous blue spots.
- a halogenated hydrocarbon Most suitable for this purpose are, for example, chloroform or carbon tetrachloride.
- a particularly suitable solvent is methylene chloride.
- any buffering system which can be adjusted to a pH of below 7.0 can be used and preferably a citrate buffer, i.e., an aqueous solution of citric acid and tertiary sodium citrate.
- a citrate buffer i.e., an aqueous solution of citric acid and tertiary sodium citrate.
- the optimum pH value lies at about 5.0.
- the preparation of the diagnostic acid according to the invention takes place otherwise in the conventional manner.
- the absorbent carrier as for example, filter paper
- a buffer solution is firstly impregnated with a buffer solution, and thereafter is dried immediately.
- the butter solution one of the usual surface-active agents, as for example, sodium lauryl sulfate or polyoxyethylene sorbitan monolaurate.
- the filter paper is then treated with the indicator solution, dried, and cut to size.
- the albumin test strips obtained in this manner can be used as such or sealed within synthetic foils as described in patent application Ser. No. 262,827 issued to US. Patent 3,232,710. In the latter case, it has been found advantageous to seal together the test paper with a second, unimpregnated paper strip as a result of which a more uni form coloration of the test strip is assured;
- composition of the indicator solution Tetra bromo phenolphthalein ethyl ester mg 40 Methylene chloride ml.
- Ad 100 Filter paper (Schleicher & Schiill No. 2316) is impregnated first with a buffer solution as above set out by running such a paper band through a bath of the impregnating solution and thereafter drying the paper in the open air. Then, the dried paper is impregnated for a second time, but using the indicator solution as above set out and thereafter Once more air dried. The dried paper is formed into rolls and the rolls are cross-cut to the desired width of 5 mm.
- the test strips thereby obtained are colored pale yellow and do not change their color on being moistened with albumin-free normal urine.
- the presence of albumin in the urine produces a more or less visible blue coloration in the test paper, the color intensity being used to grade the albumin content. In this manner the presence of albumin in urine can be clearly detected even when the same is present in concentrations of 0.005%.
- the albumin test strips as set out above are sealed between sheets of water insoluble plastic and preferably employing in that connection a plastic coated paper instead of one of the plastic covering whereby there is provided an opaque background for the test strip.
- a plastic coated paper instead of one of the plastic covering whereby there is provided an opaque background for the test strip.
- test paper is sealed between a white colored and a transparent polyethylene coated polyterephthalic acid ester foil substantially as follows: the test paper strips having a width of about 5 mm. are placed between two synthetic plastic foils having a width of about 30 cm. and sealed therein by passing the same between two rollers one or both of which are heated. The plastic synthetic foils are thereby welded together and the paper strip is welded on one or both sides to the plastic sheet by the hot contact. Shallow grooves provided on the rollers assure that the portions of the plastic sheets adjacent the strips of paper are firmly welded together. The synthetic plastic bands with the paper strips sealed therein are cut cross-wise to form the test paper strips.
- any other buffering system adjusted to a pH of below 7 may be used, f.i. malonic acid-malonate buffer, boric acidborate buffer or tartaric acid-tartrate buffer.
- Suitable indicator dyes are also tetra-bromo-phenolphthalein-butyl ester, tetra-bromo-benzaurine, bromo-phenol-blue, tetrabromo-phenol-blue, bromo cresol green, thymol blue, alizarine or methyl violet.
- indicator dyes may be dissolved in Water, methanol, ethanol, acetone, methylene chloride, chloroform or carbon tetrachloride.
- sodium lauryl sulfate also polyoxyethylene sorbitane monolaurate can be used as surface-active agent which is to be added to the buffer solution.
- Analytical test paper for the detection of albumin in biological fluids comprising a substantially plane paper sheet, having a wettable surface prepared by first impregnating said paper sheet with a solution of an acid buffer, drying said buffer impregnated sheet and thereafter impregnating said sheet with a solution of an indicator dye exhibiting the so-called protein error, said solution of acid buffer having a pH value below 7 and regulated for maintaining the indicator dye at a pH on the alkaline side of the acid-to-base color change point thereof, and thereafter drying the thusly impregnated sheet.
- said indicator dye is a member selected from the group consisting of tetra-bromo-phenolphthalein ethyl ester, tetra-bromophenolphthalein butyl ester and tetra-bromo-benzaurine.
- the method of producing an analytical test paper for detection of albumin in biological fluids which comprises forming an assembly of a substantially plane paper sheet having a wettable surface which has been impregnated with an acid buffer solution, thereafter dried, said buffer impregnated sheet thereafter being impregnated with a solution of an indicator dye exhibiting the so-called protein error, said solution of acid buffer having a pH value below 7 and regulated for maintaining the indicator dye at a pH on the alkaline side of the acid-to-base color change point thereof and drying the doubly impregnated sheet, said test paper thereafter being included between a superposed upper and lower sheet of a water insoluble plastic and subjecting the assembly to increased pressure and temperature to there-by bond the plastic sheets together along their longitudinal edge portions.
- a method of carrying out an analytical test for the presence of albumin in biological fluids which com rises immersing an analytical test paper comprising a substantially plane paper sheet having a wettable surface which has been impregnated with an acid buffer solution, thereafter dried and then impregnated with a solution of an indicator dye exhibiting the so-called protein error, said solution of acid buffer having a pH value below 7 and regulated for maintaining the indicator dye at a pH on the alkaline side of the acid-to-base color change point thereof, and thereafter drying the thusly impregnated sheet, into a liquid to be tested whereby said liquid to be tested is drawn upwardly and is spread over said paper surface and examining said test paper for visual evidence of the presence of albumin in said liquid.
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- Life Sciences & Earth Sciences (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Food Science & Technology (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DEB70383A DE1253934B (de) | 1963-01-18 | 1963-01-18 | Verfahren zur Herstellung eines Diagnostiziermittels zur Bestimmung von Eiweiss in biologischen Fluessigkeiten |
Publications (1)
Publication Number | Publication Date |
---|---|
US3359072A true US3359072A (en) | 1967-12-19 |
Family
ID=6976648
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
US333178A Expired - Lifetime US3359072A (en) | 1963-01-18 | 1963-12-24 | Method of making and using diagnostic aid for determination of albumin in biological fluids |
Country Status (9)
Country | Link |
---|---|
US (1) | US3359072A (fr) |
AT (1) | AT246929B (fr) |
BE (1) | BE642648A (fr) |
CH (1) | CH425277A (fr) |
DE (1) | DE1253934B (fr) |
DK (1) | DK104864C (fr) |
GB (1) | GB997644A (fr) |
LU (1) | LU45228A1 (fr) |
NL (1) | NL301192A (fr) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3533749A (en) * | 1967-09-12 | 1970-10-13 | Warner Lambert Pharmaceutical | Method for the determination of total albumin |
US3678151A (en) * | 1969-07-25 | 1972-07-18 | Gugol Clini Tex Inc | Biological staining method |
US4013416A (en) * | 1975-03-12 | 1977-03-22 | Boehringer Mannheim G.M.B.H. | Diagnostic means for the detection of protein in body fluids |
US4568647A (en) * | 1983-10-11 | 1986-02-04 | Eastman Kodak Company | Method and element for albumin assay |
US5194390A (en) * | 1988-07-05 | 1993-03-16 | Miles Inc. | Composition for the assay of albumin |
US5910421A (en) * | 1995-12-21 | 1999-06-08 | University Of Florida | Rapid diagnostic method for distinguishing allergies and infections |
US20020137117A1 (en) * | 1995-12-21 | 2002-09-26 | Parker Small | Rapid diagnostic method for distinguishing allergies and infections and nasal secretion collection unit |
US20070148716A1 (en) * | 2005-12-27 | 2007-06-28 | Gorres Geoffrey H | Device for monitoring a patient for a urinary tract infection |
WO2018230842A1 (fr) * | 2017-06-14 | 2018-12-20 | 주식회사 청도제약 | Procédé de mesure du stress oxydatif dans un fluide corporel humain |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2897058A (en) * | 1957-05-08 | 1959-07-28 | Galat Alexander | Albumin detecting method and means |
GB840362A (en) * | 1957-11-13 | 1960-07-06 | Miles Lab | Diagnostic composition for determining albumin |
US3011874A (en) * | 1959-03-13 | 1961-12-05 | Marshall E Deutsch | Indicator strip and method of testing |
-
0
- NL NL301192D patent/NL301192A/xx unknown
-
1963
- 1963-01-18 DE DEB70383A patent/DE1253934B/de active Pending
- 1963-12-24 US US333178A patent/US3359072A/en not_active Expired - Lifetime
-
1964
- 1964-01-15 CH CH39664A patent/CH425277A/de unknown
- 1964-01-16 LU LU45228A patent/LU45228A1/xx unknown
- 1964-01-16 DK DK22064AA patent/DK104864C/da active
- 1964-01-17 AT AT36464A patent/AT246929B/de active
- 1964-01-17 BE BE642648A patent/BE642648A/xx unknown
- 1964-01-17 GB GB2163/64A patent/GB997644A/en not_active Expired
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2897058A (en) * | 1957-05-08 | 1959-07-28 | Galat Alexander | Albumin detecting method and means |
GB840362A (en) * | 1957-11-13 | 1960-07-06 | Miles Lab | Diagnostic composition for determining albumin |
US3011874A (en) * | 1959-03-13 | 1961-12-05 | Marshall E Deutsch | Indicator strip and method of testing |
Cited By (17)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3533749A (en) * | 1967-09-12 | 1970-10-13 | Warner Lambert Pharmaceutical | Method for the determination of total albumin |
US3678151A (en) * | 1969-07-25 | 1972-07-18 | Gugol Clini Tex Inc | Biological staining method |
US4013416A (en) * | 1975-03-12 | 1977-03-22 | Boehringer Mannheim G.M.B.H. | Diagnostic means for the detection of protein in body fluids |
US4568647A (en) * | 1983-10-11 | 1986-02-04 | Eastman Kodak Company | Method and element for albumin assay |
US5194390A (en) * | 1988-07-05 | 1993-03-16 | Miles Inc. | Composition for the assay of albumin |
US5910421A (en) * | 1995-12-21 | 1999-06-08 | University Of Florida | Rapid diagnostic method for distinguishing allergies and infections |
US20020137117A1 (en) * | 1995-12-21 | 2002-09-26 | Parker Small | Rapid diagnostic method for distinguishing allergies and infections and nasal secretion collection unit |
US6764849B2 (en) | 1995-12-21 | 2004-07-20 | Univeristy Of Florida | Rapid diagnostic method for distinguishing allergies and infections and nasal secretion collection unit |
US6855491B2 (en) | 1995-12-21 | 2005-02-15 | University Of Florida | Device for rapidly diagnosing upper respiratory conditions |
US6967084B2 (en) | 1995-12-21 | 2005-11-22 | University Of Flordia | Kit for rapidly diagnosing upper respiratory conditions |
US20070148716A1 (en) * | 2005-12-27 | 2007-06-28 | Gorres Geoffrey H | Device for monitoring a patient for a urinary tract infection |
US7727206B2 (en) | 2005-12-27 | 2010-06-01 | Gorres Geoffrey H | Device for monitoring a patient for a urinary tract infection |
US20100274156A1 (en) * | 2005-12-27 | 2010-10-28 | Gorres Geoffrey H | Device for Monitoring a Patient for a Urinary Tract Infection |
US8343122B2 (en) | 2005-12-27 | 2013-01-01 | Geoffrey H Gorres | Device for monitoring a patient for a urinary tract infection |
WO2018230842A1 (fr) * | 2017-06-14 | 2018-12-20 | 주식회사 청도제약 | Procédé de mesure du stress oxydatif dans un fluide corporel humain |
CN109804249A (zh) * | 2017-06-14 | 2019-05-24 | 清滔制药株式会社 | 用于测定人体体液氧化应激的方法 |
US11385220B2 (en) | 2017-06-14 | 2022-07-12 | Chungdo Pharm. Co., Ltd | Methods for measuring oxidative stress in human body fluids |
Also Published As
Publication number | Publication date |
---|---|
NL301192A (fr) | |
GB997644A (en) | 1965-07-07 |
DK104864C (da) | 1966-07-11 |
DE1253934B (de) | 1967-11-09 |
AT246929B (de) | 1966-05-10 |
LU45228A1 (fr) | 1964-03-16 |
CH425277A (de) | 1966-11-30 |
BE642648A (fr) | 1964-07-17 |
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