US3212855A - Diagnostic device - Google Patents
Diagnostic device Download PDFInfo
- Publication number
- US3212855A US3212855A US214867A US21486762A US3212855A US 3212855 A US3212855 A US 3212855A US 214867 A US214867 A US 214867A US 21486762 A US21486762 A US 21486762A US 3212855 A US3212855 A US 3212855A
- Authority
- US
- United States
- Prior art keywords
- solution
- copolymers
- nitroprusside
- amino acid
- ethanol
- 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
Links
- 239000000243 solution Substances 0.000 claims description 32
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 24
- 150000002576 ketones Chemical class 0.000 claims description 20
- 238000000034 method Methods 0.000 claims description 19
- 238000012360 testing method Methods 0.000 claims description 19
- YEESUBCSWGVPCE-UHFFFAOYSA-N azanylidyneoxidanium iron(2+) pentacyanide Chemical compound [Fe++].[C-]#N.[C-]#N.[C-]#N.[C-]#N.[C-]#N.N#[O+] YEESUBCSWGVPCE-UHFFFAOYSA-N 0.000 claims description 16
- 229920001577 copolymer Polymers 0.000 claims description 16
- 229960002460 nitroprusside Drugs 0.000 claims description 16
- 150000001413 amino acids Chemical class 0.000 claims description 12
- 238000001035 drying Methods 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- 238000001514 detection method Methods 0.000 claims description 7
- 230000008569 process Effects 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 239000003960 organic solvent Substances 0.000 claims description 6
- 239000002202 Polyethylene glycol Substances 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 150000001340 alkali metals Chemical class 0.000 claims description 4
- 210000001124 body fluid Anatomy 0.000 claims description 4
- 239000010839 body fluid Substances 0.000 claims description 4
- 229920001223 polyethylene glycol Polymers 0.000 claims description 4
- 229920002689 polyvinyl acetate Polymers 0.000 claims description 4
- 239000011118 polyvinyl acetate Substances 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 4
- 229920006243 acrylic copolymer Polymers 0.000 claims description 3
- 239000007864 aqueous solution Substances 0.000 claims description 3
- UPBDXRPQPOWRKR-UHFFFAOYSA-N furan-2,5-dione;methoxyethene Chemical compound COC=C.O=C1OC(=O)C=C1 UPBDXRPQPOWRKR-UHFFFAOYSA-N 0.000 claims description 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
- 239000000203 mixture Substances 0.000 description 41
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 28
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 14
- 239000004471 Glycine Substances 0.000 description 14
- -1 aliphatic amino acid Chemical class 0.000 description 13
- 235000001014 amino acid Nutrition 0.000 description 13
- XEYBHCRIKKKOSS-UHFFFAOYSA-N disodium;azanylidyneoxidanium;iron(2+);pentacyanide Chemical compound [Na+].[Na+].[Fe+2].N#[C-].N#[C-].N#[C-].N#[C-].N#[C-].[O+]#N XEYBHCRIKKKOSS-UHFFFAOYSA-N 0.000 description 13
- 229940083618 sodium nitroprusside Drugs 0.000 description 13
- 238000009472 formulation Methods 0.000 description 11
- 239000012153 distilled water Substances 0.000 description 10
- 210000002700 urine Anatomy 0.000 description 9
- 229910019142 PO4 Inorganic materials 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 235000021317 phosphate Nutrition 0.000 description 8
- 239000010452 phosphate Substances 0.000 description 8
- 239000001488 sodium phosphate Substances 0.000 description 8
- 239000003599 detergent Substances 0.000 description 7
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 7
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 7
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- 239000000443 aerosol Substances 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 5
- BNIILDVGGAEEIG-UHFFFAOYSA-L disodium hydrogen phosphate Chemical class [Na+].[Na+].OP([O-])([O-])=O BNIILDVGGAEEIG-UHFFFAOYSA-L 0.000 description 5
- 239000004615 ingredient Substances 0.000 description 5
- 230000003647 oxidation Effects 0.000 description 5
- 238000007254 oxidation reaction Methods 0.000 description 5
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical class [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 5
- WGIMXKDCVCTHGW-UHFFFAOYSA-N 2-(2-hydroxyethoxy)ethyl dodecanoate Chemical compound CCCCCCCCCCCC(=O)OCCOCCO WGIMXKDCVCTHGW-UHFFFAOYSA-N 0.000 description 4
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
- 208000007976 Ketosis Diseases 0.000 description 4
- 150000001412 amines Chemical class 0.000 description 4
- 239000000872 buffer Substances 0.000 description 4
- 238000006243 chemical reaction Methods 0.000 description 4
- 235000019800 disodium phosphate Nutrition 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 3
- 230000002159 abnormal effect Effects 0.000 description 3
- 235000004279 alanine Nutrition 0.000 description 3
- 150000001414 amino alcohols Chemical class 0.000 description 3
- 238000002405 diagnostic procedure Methods 0.000 description 3
- 229910000397 disodium phosphate Inorganic materials 0.000 description 3
- 239000003925 fat Substances 0.000 description 3
- 235000019197 fats Nutrition 0.000 description 3
- FPYJFEHAWHCUMM-UHFFFAOYSA-N maleic anhydride Chemical compound O=C1OC(=O)C=C1 FPYJFEHAWHCUMM-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000002609 medium Substances 0.000 description 3
- XJRBAMWJDBPFIM-UHFFFAOYSA-N methyl vinyl ether Chemical compound COC=C XJRBAMWJDBPFIM-UHFFFAOYSA-N 0.000 description 3
- 235000019801 trisodium phosphate Nutrition 0.000 description 3
- 229910000406 trisodium phosphate Inorganic materials 0.000 description 3
- WDJHALXBUFZDSR-UHFFFAOYSA-N Acetoacetic acid Natural products CC(=O)CC(O)=O WDJHALXBUFZDSR-UHFFFAOYSA-N 0.000 description 2
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 2
- 206010023388 Ketonuria Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 230000003139 buffering effect Effects 0.000 description 2
- 235000014121 butter Nutrition 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- WOWBFOBYOAGEEA-UHFFFAOYSA-N diafenthiuron Chemical compound CC(C)C1=C(NC(=S)NC(C)(C)C)C(C(C)C)=CC(OC=2C=CC=CC=2)=C1 WOWBFOBYOAGEEA-UHFFFAOYSA-N 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 238000005470 impregnation Methods 0.000 description 2
- 230000006872 improvement Effects 0.000 description 2
- 230000004140 ketosis Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 230000004060 metabolic process Effects 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 235000019448 polyvinylpyrrolidone-vinyl acetate copolymer Nutrition 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 235000011008 sodium phosphates Nutrition 0.000 description 2
- 159000000000 sodium salts Chemical class 0.000 description 2
- 238000010998 test method Methods 0.000 description 2
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 2
- 239000000080 wetting agent Substances 0.000 description 2
- ADNXYZUJPHVRPJ-UHFFFAOYSA-N 1-ethenylpyrrolidin-2-one;styrene Chemical compound C=CN1CCCC1=O.C=CC1=CC=CC=C1 ADNXYZUJPHVRPJ-UHFFFAOYSA-N 0.000 description 1
- OZIZXEZZMVXSMQ-UHFFFAOYSA-N 3-oxobutanoic acid Chemical compound CC(=O)CC(O)=O.CC(=O)CC(O)=O OZIZXEZZMVXSMQ-UHFFFAOYSA-N 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 201000007848 Arts syndrome Diseases 0.000 description 1
- KCXVZYZYPLLWCC-UHFFFAOYSA-N EDTA Chemical compound OC(=O)CN(CC(O)=O)CCN(CC(O)=O)CC(O)=O KCXVZYZYPLLWCC-UHFFFAOYSA-N 0.000 description 1
- 239000001856 Ethyl cellulose Substances 0.000 description 1
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 229910020335 Na3 PO4.12H2 O Inorganic materials 0.000 description 1
- XTXRWKRVRITETP-UHFFFAOYSA-N Vinyl acetate Chemical compound CC(=O)OC=C XTXRWKRVRITETP-UHFFFAOYSA-N 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- NIXOWILDQLNWCW-UHFFFAOYSA-N acrylic acid group Chemical group C(C=C)(=O)O NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 230000004888 barrier function Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 150000001642 boronic acid derivatives Chemical class 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 239000001569 carbon dioxide Substances 0.000 description 1
- 229910002092 carbon dioxide Inorganic materials 0.000 description 1
- 150000004649 carbonic acid derivatives Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 150000001860 citric acid derivatives Chemical class 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 230000002939 deleterious effect Effects 0.000 description 1
- 230000002542 deteriorative effect Effects 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 235000014113 dietary fatty acids Nutrition 0.000 description 1
- 238000009792 diffusion process Methods 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 229920001249 ethyl cellulose Polymers 0.000 description 1
- 235000019325 ethyl cellulose Nutrition 0.000 description 1
- 229940116333 ethyl lactate Drugs 0.000 description 1
- 229940071106 ethylenediaminetetraacetate Drugs 0.000 description 1
- 239000000194 fatty acid Substances 0.000 description 1
- 229930195729 fatty acid Natural products 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000035876 healing Effects 0.000 description 1
- 238000010348 incorporation Methods 0.000 description 1
- 239000013067 intermediate product Substances 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- VUZPPFZMUPKLLV-UHFFFAOYSA-N methane;hydrate Chemical compound C.O VUZPPFZMUPKLLV-UHFFFAOYSA-N 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000007530 organic bases Chemical class 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 150000003014 phosphoric acid esters Chemical class 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- 150000008163 sugars Chemical class 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 239000002023 wood Substances 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01S—RADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
- G01S15/00—Systems using the reflection or reradiation of acoustic waves, e.g. sonar systems
- G01S15/87—Combinations of sonar systems
-
- 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
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01S—RADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
- G01S15/00—Systems using the reflection or reradiation of acoustic waves, e.g. sonar systems
- G01S15/02—Systems using the reflection or reradiation of acoustic waves, e.g. sonar systems using reflection of acoustic waves
- G01S15/06—Systems determining the position data of a target
- G01S15/08—Systems for measuring distance only
- G01S15/10—Systems for measuring distance only using transmission of interrupted, pulse-modulated waves
- G01S15/101—Particularities of the measurement of distance
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01S—RADIO DIRECTION-FINDING; RADIO NAVIGATION; DETERMINING DISTANCE OR VELOCITY BY USE OF RADIO WAVES; LOCATING OR PRESENCE-DETECTING BY USE OF THE REFLECTION OR RERADIATION OF RADIO WAVES; ANALOGOUS ARRANGEMENTS USING OTHER WAVES
- G01S7/00—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00
- G01S7/52—Details of systems according to groups G01S13/00, G01S15/00, G01S17/00 of systems according to group G01S15/00
- G01S7/56—Display arrangements
-
- 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
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/20—Oxygen containing
- Y10T436/200833—Carbonyl, ether, aldehyde or ketone containing
Definitions
- This invention relates to an improved diagnostic composition and to a method for its preparation.
- this invention is concerned with a diagnostic test useful in qualitative detection and quantitative determination of ketone bodies in body fluids, especially acetoacetic acid (beta-ketobutyric acid) in urine.
- this invention is concerned with a diagnostic test reagent composition which is incorporated upon a bibulous carrier.
- the fats utilized by the body normally undergo complete oxidation with formation of carbon dioxide and water. Since the fatty acid molecules have long chains of carbon atoms, it is theorized that a large number of intermediate products are formed during the oxidation and under normal circumstances these are rapidly further oxidized. Findings in the field of fat metabolism suggest that during the course of oxidation of the fatty acid chain the carbon atoms are split off in pairs, or in other words, oxidation takes place at the ,B-carbon atom. In certain abnormal physical conditions the oxidation of fat is incomplete and certain products such as acetoacetic acid appear in the urine. These substances are called ketone bodies and their appearance creates a condition which is called ketosis.
- Ketosis occurs typically in diabetes mellitus, but it also occurs as a result of other abnormal conditions, e.g., fasting, hyperpituitary activity, etc. Under these abnormal conditions ketone bodies tend to accumulate in the blood and, because the rental threshold for them is low, they appear in the urine.
- the healing arts have long recognized the usefulness of tests for ketone bodies in the urine, hence it is considered extremely desirable to provide a simple and economical test for the qualitative and quantitative determination of ketone bodies in the urine which may be advantageously used by the laboratory technician as well as the physician.
- reagents and techniques have been used or proposed in the past for the detection of ketone bodies in urine.
- a number of such reagents and techniques have involved the use of a water soluble nitroprusside as a reactive ingredient or agent.
- the nitroprusside reaction is carried out in the present of ammonia in order to develop particular colorations (see, for example, U.S. Patent 2,186,902 to Fortune).
- An improvement over the Fortune-type formulation is disclosed in US. Patent 2,509,140 to Alfred H. Free, and assigned to the assignee of the present application' This patent discloses formulations for the detection of ketone bodies in urine which contain water soluble nitroprusside, an aliphatic amino acid and an alkaline material.
- a diagnostic composition which is particularly adapted for the detection of ketone bodies in urine without evolution of ammonia.
- the prior art teaches the use of a water soluble nitroprusside, an aliphatic amino acid and an alkaline phosphate buffer as essential ingredients of a test for ketone bodies and teaches the preparation of such diagnostic compositions in the form of bibulous strips or sticks and a method of preparing same.
- test compositions in the form of bibulous strips or sticks are highly preferred for the reason that such provide the diagnostician with a simple dip and read test.
- Such simple dip and read tests provide many advantages over prior known liquid or tabletted reagent compositions from the standpoint of absence of cumbersome equipment, ease and simplicity of test procedure, ease of disposal of test devices and rapidity of test procedure, to mention a few of the advantages.
- an improved composition for a ketone diagnostic in stick form which is tremendously stable, and resistant to the deteriorative effects of moisture and the alkaline sodium phosphates.
- an improved method for preparing an improved diagnostic in strip or stick form comprising a two-step procedure which involves initially treating the bibulous carrier with 3, an aqueous phosphate-containing formulation and, secondly, impregnating the thusly treated carrier with a novel formulation comprising sodium nitroprusside and an organic film-forming polymer.
- the first step of the preparation may be carried out well ahead of the second step, i.e., the carrier impregnated with the phosphate-containing composition may be prepared and stored for periods of time prior to impregnation with the second formulation.
- the initial treating formulation comprises a bufier, providing a pH range of about 8 10, and an amino acid.
- buffering systems useful in the compositions of this invention are triand disodium phosphates, borates, citrates, carbonates, ethylene diamine tetraacetate (sodium salt), etc.
- any water soluble amino acid may be used in the compositions of this invention, in the preferred embodiment the amino acid is selected from the group of glycine and alanine.
- the second treatment formulation comprises alkali metal nitroprusside, an organic film-forming compound and an organic solvent.
- the organic film-forming compounds called for in the compositions of this invention may be any organic film-forming compound which is soluble in the commonly used organic solvents, does not exhibit strong buffering capacity, and has a pH on the acid side, for example, polyvinylpyrrolidone-vinyl acetate copolymers; vinyl pyrrolidone-styrene copolymers; water solutions of acrylic copolymers; coploymers of methyl vinyl ether and maleic anhydride; polyethylene glycol; polyvinyl acetate; and interpolymers of methyl vinyl ether and maleic anhydride.
- organic solvents found suitable for use in the compositions and method of this invention are dimethyl sulfoxide, methanol, ethanol and dimethyl formamide and mixtures thereof.
- diluent substances as chloroform, carbon tetrachloride, benzene, etc. and a wetting agent, for example, aerosol, diglycol laurate and organic phosphate esters of anionic detergents in ethanol which are known commercially as Gafac RE610 and Gafac RESIO, and mixtures thereof.
- the diluent substances are useful to reduce hygroscopicity of the testing reagents, while the wetting agent aids in producing an even diffusion of color on the diagnostic stick.
- Solution B 8 grams of sodium nitroprusside were measured into a one liter volumetric flask. To this was added 65 ml. of polyvinylpyrrolidone/vinyl acetate copolymer and 185 ml. of anhydrous ethanol and the solution mixed thoroughly. 380 ml. of dimethyl sulfoxide were then added to the mixture with stirring until the nitroprusside was solubilized. 350 ml. of chloroform, 17 ml. of a 10% anionic detergent (organic phosphate ester) in anhydrous ethanol were then added to the solution.
- anionic detergent organic phosphate ester
- PREPARATION OF REAGENT STRIPS Bibulous sticks that is, absorbent paper out into narrow strips having dimensions of about 3" x /s" x 0.029, imprinted with a water impervious barrier portion of about from the tip were dipped into impregnating Solution A, followed by drying in a drying tunnel at a temperature of about 100 C., for 13 minutes. After drying, the strips were similarly dipped into Solution B and dried at about C. for 11 minutes in a forced draft oven. The finished impregnated strips are light buff in color.
- an impregnated strip prepared as described above is dipped in the liquid specimen to be tested.
- the test strip When contacted with a fluid specimen containing ketone bodies, the test strip will give a positive color reaction.
- the color resulting on the strip is then compared with a precalibrated color chart for determination of the quantitative amount of ketone bodies contained on the specimen tested.
- the color developed on the strips in the presence of ketone bodies varies in intensity according to the amount of ketone bodies present in the specimen, i.e., from very light purple indicating the presence of 10-20 mg. percent of ketonebodies to a very dark purple indicating over mg. percent.
- a positive color reaction will de velop within 15 to 30 seconds in the presence of ketone bodies.
- a process for the preparation of a test device for the detection of ketone bodies in body fluids which comprises:
- polymeric substance selected from the group consisting of polyvinylpyrrolidone-vinyl acetate copolymers, methyl vinyl ether-maleic anhydride copolymers, polyethylene glycol, polyvinyl acetate, methyl vinyl ether-maleic anhydride interpolymers, vinyl pyrrolidone-styrene copolymers and water soluble acrylic copolymers; and
- amino acid is selected from the group consisting of glycine and alanine.
- a process as in claim 1 wherein the buffer is a mixture of disodium phosphate and trisodium phosphate.
- a process as in claim 1 wherein the solvent is selected from the group consisting of dimethyl sulfoxide, methanol, ethanol, dimethyl formamide and mixtures thereof.
- a test device for the detection of ketone bodies in body fluids prepared by a process which comprises:
Description
United States Patent 3,212,855 DIAGNOSTIC DEVICE Ray Mast, John Rebar, Jr., and Joseph Fraser, Elkhart, Ind., assignors to Miles Laboratories, Inc., Elkhart, Ind., a corporation of Indiana N0 Drawing. Filed Aug. 6, 1962, Ser. No. 214,867 7 Claims. (Cl. 23253) This invention relates to an improved diagnostic composition and to a method for its preparation. In particular, this invention is concerned with a diagnostic test useful in qualitative detection and quantitative determination of ketone bodies in body fluids, especially acetoacetic acid (beta-ketobutyric acid) in urine. More particularly, this invention is concerned with a diagnostic test reagent composition which is incorporated upon a bibulous carrier.
The fats utilized by the body normally undergo complete oxidation with formation of carbon dioxide and water. Since the fatty acid molecules have long chains of carbon atoms, it is theorized that a large number of intermediate products are formed during the oxidation and under normal circumstances these are rapidly further oxidized. Findings in the field of fat metabolism suggest that during the course of oxidation of the fatty acid chain the carbon atoms are split off in pairs, or in other words, oxidation takes place at the ,B-carbon atom. In certain abnormal physical conditions the oxidation of fat is incomplete and certain products such as acetoacetic acid appear in the urine. These substances are called ketone bodies and their appearance creates a condition which is called ketosis. Ketosis occurs typically in diabetes mellitus, but it also occurs as a result of other abnormal conditions, e.g., fasting, hyperpituitary activity, etc. Under these abnormal conditions ketone bodies tend to accumulate in the blood and, because the rental threshold for them is low, they appear in the urine. The healing arts have long recognized the usefulness of tests for ketone bodies in the urine, hence it is considered extremely desirable to provide a simple and economical test for the qualitative and quantitative determination of ketone bodies in the urine which may be advantageously used by the laboratory technician as well as the physician.
A variety of reagents and techniques have been used or proposed in the past for the detection of ketone bodies in urine. A number of such reagents and techniques have involved the use of a water soluble nitroprusside as a reactive ingredient or agent. In one particular reagent formulation, the nitroprusside reaction is carried out in the present of ammonia in order to develop particular colorations (see, for example, U.S. Patent 2,186,902 to Fortune). An improvement over the Fortune-type formulation is disclosed in US. Patent 2,509,140 to Alfred H. Free, and assigned to the assignee of the present application' This patent discloses formulations for the detection of ketone bodies in urine which contain water soluble nitroprusside, an aliphatic amino acid and an alkaline material. It was found, according to the patent, that when a soluble nitroprusside is present in alkaline solution with an aliphatic amino acid, e.g., glycine, a diagnostic composition is provided which is particularly adapted for the detection of ketone bodies in urine without evolution of ammonia.
An improvement of the foregoing test composition is described and claimed in U.S. Patent 2,577,978, issued December 11, 1951, to Nicholls and Fonner and assigned to the assignee of the present application. It was discovered by these patentees that incorporation of lactose or similar sugars into the diagnostic composition of US. Patent 2,509,140 greatly enchanced the utility and reliability of the diagnostic composition.
3,212,855 Patented Oct. 19, 1965 'ice A still further improved test composition is described in US. Patent 2,990,253, issued June 27, 1961, to Robert R. Smeby and assigned to the assignee of the present application, which provides a test composition in the form of bibulous strips or sticks. However, because of the instability of nitroprusside in an aqueous alkaline medium, the nitroprusside must be kept separated not only during the impregnation of the carrier but until such time as the test is ready for use. A method was discovered by the patentee of US. 2,990,253 of achieving the necessary separation, which separation was etfected by first ap plying the nitroprusside to the carrier in an acidic, aqueous medium thus preserving the stability of the compound and, after drying, dipping the carrier into a nonaqueous solution of organic bases such as various amines or aminoalcohols to achieve the necessary alkalinity.
The volatility and hygroscopicity of the amine constituents of the prior art formulations, however, are undesirable features of that test. Further, the selection of amines or aminoalcohols or mixtures thereof is rendered difiicult in that all amines and aminoalcohols are not operable. In addition, in all of the prior compositions and methods, it has been difiicult if not substantially impossible to protect the nitroprusside ingredients from the deleterious effects of moisture and alkaline sodium phosphates during storage.
\Vhile the foregoing discussed patents have contributed greatly to the advancement of the art of diagnosing for ketonuria and other disturbances of metabolism evidenced by the presence of ketone bodies in the urine and the advances made have been worthwhile, none have completely solved the problem of the instability of sodium nitroprusside in an aqueous alkaline medium. Nitroprusside is stable only at a pH below 7 and is operable only in an alkaline medium at a pH over 8. In other words, most of the nitroprusside is destroyed so that no perceptible reaction with acetoacetic acid can be obtained under those circumstances. The commercial diagnostic methods made available in accordance with the disclosures thereof have, however, aided the physicians and clinicians in the diagnoses and control of the causes of ketonuria.
To summarize, the prior art teaches the use of a water soluble nitroprusside, an aliphatic amino acid and an alkaline phosphate buffer as essential ingredients of a test for ketone bodies and teaches the preparation of such diagnostic compositions in the form of bibulous strips or sticks and a method of preparing same.
From a commercial point of view the test compositions in the form of bibulous strips or sticks are highly preferred for the reason that such provide the diagnostician with a simple dip and read test. Such simple dip and read tests provide many advantages over prior known liquid or tabletted reagent compositions from the standpoint of absence of cumbersome equipment, ease and simplicity of test procedure, ease of disposal of test devices and rapidity of test procedure, to mention a few of the advantages.
In accordance with this invention, we have discovered an improved diagnostic composition and method of preparing such ketone diagnostic composition in strip or stick form which successfully overcomes the hereinabove enumerated disadvantages of the prior known compositions.
More specifically, we have discovered an improved composition for a ketone diagnostic in stick form which is tremendously stable, and resistant to the deteriorative effects of moisture and the alkaline sodium phosphates. In addition, we have discovered an improved method for preparing an improved diagnostic in strip or stick form comprising a two-step procedure which involves initially treating the bibulous carrier with 3, an aqueous phosphate-containing formulation and, secondly, impregnating the thusly treated carrier with a novel formulation comprising sodium nitroprusside and an organic film-forming polymer.
Among the numerous advantages provided by this invention, one is that the first step of the preparation may be carried out well ahead of the second step, i.e., the carrier impregnated with the phosphate-containing composition may be prepared and stored for periods of time prior to impregnation with the second formulation.
Broadly, the initial treating formulation comprises a bufier, providing a pH range of about 8 10, and an amino acid. By way of example of buffering systems useful in the compositions of this invention are triand disodium phosphates, borates, citrates, carbonates, ethylene diamine tetraacetate (sodium salt), etc. While any water soluble amino acid may be used in the compositions of this invention, in the preferred embodiment the amino acid is selected from the group of glycine and alanine.
The second treatment formulation comprises alkali metal nitroprusside, an organic film-forming compound and an organic solvent. The organic film-forming compounds called for in the compositions of this invention may be any organic film-forming compound which is soluble in the commonly used organic solvents, does not exhibit strong buffering capacity, and has a pH on the acid side, for example, polyvinylpyrrolidone-vinyl acetate copolymers; vinyl pyrrolidone-styrene copolymers; water solutions of acrylic copolymers; coploymers of methyl vinyl ether and maleic anhydride; polyethylene glycol; polyvinyl acetate; and interpolymers of methyl vinyl ether and maleic anhydride. From an economic standpoint and ease of handling, however, copolymers of polyvinylpyrrolidone-vinyl acetate are preferred. It is readily seen that the selection of an organic filmforming compound meeting the requirements of this invention is dictated solely by economic considerations.
Among the organic solvents found suitable for use in the compositions and method of this invention are dimethyl sulfoxide, methanol, ethanol and dimethyl formamide and mixtures thereof. In addition to the foregoing ingredients, we have found that it is desirable but not essential to include such diluent substances as chloroform, carbon tetrachloride, benzene, etc. and a wetting agent, for example, aerosol, diglycol laurate and organic phosphate esters of anionic detergents in ethanol which are known commercially as Gafac RE610 and Gafac RESIO, and mixtures thereof. The diluent substances are useful to reduce hygroscopicity of the testing reagents, while the wetting agent aids in producing an even diffusion of color on the diagnostic stick.
The following examples will illustrate the improved diagnostic composition of the present invention, the scope of the invention not, however, being limited to the specific details of these examples:
Example ].Frmulati0n of the impregnating solutions Na PO .12H O g 210 Disodium phosphate, anhydrous g 90 Glycine g 187 Distilled water to ml 1000 Sodium nitroprusside, anhydrous g 8 Polyvinyl pyrrolidone/ vinyl acetate copolymer (50% in ethanol) ml 65 Dimethyl sulfoxide ml 380 Anhydrous ethanol ml 185 Chloroform ml 350 Organic phosphate ester of anionic detergent ml 17 PREPARATION OF IMPREGNATING SOLUTIONS Solution A.-210 grams of trisodium phosphate, 90
grams of disodium phosphate and 187 grams of glycine were mixed together in the dry state. 750 ml. of boiling hot distilled water were added to the dry mixture and stirred until solution occurred.
Solution B.8 grams of sodium nitroprusside were measured into a one liter volumetric flask. To this was added 65 ml. of polyvinylpyrrolidone/vinyl acetate copolymer and 185 ml. of anhydrous ethanol and the solution mixed thoroughly. 380 ml. of dimethyl sulfoxide were then added to the mixture with stirring until the nitroprusside was solubilized. 350 ml. of chloroform, 17 ml. of a 10% anionic detergent (organic phosphate ester) in anhydrous ethanol were then added to the solution.
PREPARATION OF REAGENT STRIPS Bibulous sticks, that is, absorbent paper out into narrow strips having dimensions of about 3" x /s" x 0.029, imprinted with a water impervious barrier portion of about from the tip were dipped into impregnating Solution A, followed by drying in a drying tunnel at a temperature of about 100 C., for 13 minutes. After drying, the strips were similarly dipped into Solution B and dried at about C. for 11 minutes in a forced draft oven. The finished impregnated strips are light buff in color.
In preparing the formulations for use in the diagnostic strips of this invention, We have found the optimum ranges of essential ingredients to be about 0.525 grams sodium nitroprusside; ll.7585.0 grams amino acid; l8.8940.0 grams buffer, comprising trisodium phosphate in the range of about 13.2657.0 grams and a range of about 5.6282.5 grams disodium phosphate; and 4.1202.5 grams organic film-forming material.
The following examples are illustrative of other formulations prepared in accordance with this invention:
Example 2 Solution A:
Na HPO anhydrous gm 58.4 Glycine gm 20.0 Distilled water ml 180.0 Solution B:
Sodium nitroprusside gm 1.0 Anhydrous methanol ml 100.0 Diglycol laurate ml 1.0 Polyvinylpyrrolidone/vinyl acetate copolymer (50% in ethanol) ml 20.0
Example 3 Solution A:
Sodium borate gm 5.0 Glycine gm 10.0 Distilled water ml 100.0 Solution B:
Sodium nitroprusside gm 0.5 Anhydrous methanol ml 9.0 Anhydrous ethanol ml 40.0 Polyvinylpyrrolidone/ vinyl acetate copolymer (50% in ethanol) ml 3.0 Diglycol laurate ml 2.0
Example 4 Solution A:
Glycine gm 25.0 Na CO gm 30.0 Distilled water ml 100.0 Solution B:
Sodium nitroprusside gm 0.5 Anhydrous methanol ml 9.0 Anhydrous ethanol ml 40.0 Polyvinylpyrrolidone/vinyl acetate copolymer (50% in ethanol) ml 3.0 Diglycol laurate ml 2.0
Example 5 Solution A:
Glycine gm E t h y l e n e diamine tetraacetate (sodium salt) "gm" Distilled water ml Solution B:
Sodium nitroprusside gm Polyvinylpyrrolidone/vinyl acetate copolyrner (50% in ethanol) ml Anhydrous ethanol ml Dimethylsulfoxide ml Chloroform ml Aerosol (25 in ethanol ml Organic phosphate ester of anionic detergent in ethanol ml Example 6 Solution A:
Glycine gm N33P04.12H2O gl'I1 Na HPO anhydrous gm Distilled water ml Solution B:
Sodium nitroprusside gm Anhydrous ethanol ml Dimethylsulfoxide ml Chloroform ml Polyvinyl acetate ml Organic phosphate ester of anionic detergent (10%) in ethanol ml Aerosol (25%) in ethanol ml Example 7 Solution A:
Glycine "gm-.. Na3PO4.12H2O gm Na HPO anhydrous gm Distilled Water ml Solution B:
Sodium nitroprusside gm Anhydrous ethanol ml Dimethylsulfoxide ml Chloroform ml Organic phosphate ester of anionic detergent (10%) in ethanol ml Aerosol (25%) in ethanol ml Interpolymer of methyl vinyl ether and maleic anhydride gm Example 8 Solution A:
Glycine gm N33PO4-12H2O grn Nag-IP0 anhydrous gm Distilled water ml Solution 13:
Sodium nitroprusside gm Anhydrous methanol ml Aerosol (25%) in ethanol ml Ethyl cellulose gm Anhydrous ethanol ml Example 9 Solution A:
Glycine --gm Na PO .12I-I O gm NilgHPO gm Distilled water ml Solution B:
Sodium nitroprusside gm Polyvinylpyrrolidone/vinyl acetate copolymer ml Anhydrous ethanol gm Ethyl lactate ml Chloroform ml Organic phosphate ester of anionic detergent (10%) in ethanol ml Aerosol (25%) in ethanol ml The preparation of the impregnating solutions and reagent strips based on the foregoing Examples 2 through 9 are carried out in the manner described in Example 1.
In use, an impregnated strip prepared as described above is dipped in the liquid specimen to be tested. When contacted with a fluid specimen containing ketone bodies, the test strip will give a positive color reaction. The color resulting on the strip is then compared with a precalibrated color chart for determination of the quantitative amount of ketone bodies contained on the specimen tested. The color developed on the strips in the presence of ketone bodies varies in intensity according to the amount of ketone bodies present in the specimen, i.e., from very light purple indicating the presence of 10-20 mg. percent of ketonebodies to a very dark purple indicating over mg. percent. Utilizing the diagnostic strips of this invention, a positive color reaction will de velop within 15 to 30 seconds in the presence of ketone bodies.
It is to be understood that other bibulous materials, e.g., small sticks of wood, etc., as well as other methods for applying the impregnating solutions to the test strips and for drying the thus impregnated strips may also be employed.
It is obvious that certain changes may be made in the above compositions and methods without departing from the spirit and scope of the invention and it is intended that all matter contained in the foregoing description shall be interpreted as illustrative and not in a limiting sense. It is also understood that other modifications may be made Without departing from the spirit and scope of the appended claims.
We claim:
1. A process for the preparation of a test device for the detection of ketone bodies in body fluids which comprises:
(A) impregnating a bibulous carrier with an aqueous solution of a buffer providing a pH range of from about 8 to about 10 and a water soluble amino acid,
(B) drying the impregnated bibulous carrier;
(C) further impregnating the bibulous carrier in the area previously impregnated with the buffer and amino acid with a solution, in an organic solvent, of
(1) an alkali metal nitroprusside, and
(2) a polymeric substance selected from the group consisting of polyvinylpyrrolidone-vinyl acetate copolymers, methyl vinyl ether-maleic anhydride copolymers, polyethylene glycol, polyvinyl acetate, methyl vinyl ether-maleic anhydride interpolymers, vinyl pyrrolidone-styrene copolymers and water soluble acrylic copolymers; and
(D) removing the solvent from the further impregnated bibulous carrier.
2. A process as in claim 1 wherein the amino acid is selected from the group consisting of glycine and alanine.
3. A process as in claim 1 wherein the buffer is a mixture of disodium phosphate and trisodium phosphate.
4. A process as in claim 1 wherein the solvent is selected from the group consisting of dimethyl sulfoxide, methanol, ethanol, dimethyl formamide and mixtures thereof.
5. A process as in claim 1 wherein the organic filmforming polymeric substance has a pH on the acid side.
6. A test device for the detection of ketone bodies in body fluids prepared by a process which comprises:
(A) impregnating a bibulous carrier with an aqueous solution of a butter providing a pH range of from about 8 to about 10 and a water soluble amino acid;
(B) drying the impregnated bibulous carrier;
(C) further impregnating the bibulous carrier in the area previously impregnated With the butter and amino acid with a solution, in an organic solvent, of
(1) an alkali metal nitroprusside, and
7 8 (2) a polymeric substance selected from the References Cited by the Examiner group consisting of polyvinylpyrrolidone-vinyl UNITED STATES PATENTS acetate copolymers, methyl vinyl ether-maleic anhydride copolymers, polyethylene glycol, poly- 2186902 1/40 Fortunevinyl acetate, methyl vinyl ether-maleic anhy- 5 2229155 1/41 Wenker 23253 dride interpolymers, vinyl pyrrolidone-styrene 250914O 5/50 l 23 230 copolymers and water soluble acrylic copoly- 2577978 12/51 Nlchons et 23 230 mars; and, 2,990,253 6/61 Smeby 23-253 (D) removing the solvent from the further impreg- 3092465 6/63 Adams et 23253 nated bibulous carrier. 10 FOREIGN PATENTS 7. A test device as in claim 6 wherein the amino acid 867192 5/61 Great Britain is selected from the group consisting of glycine and alanine. MORRIS O. WOLK, Primary Examiner.
Claims (1)
1. A PROCESS FOR THE PREPARATION OF A TEST DEVICE FOR THE DETECTION OF KETONE BODIES IN BODY FLUIDS WHICH COM PRISES: (A) IMPREGNATING A BIBULOUS CARRIER WITH AN AQUEOUS SOLUTION OF A BUFFER PROVIDING A PH RANGE OF FROM ABOUT 8 TO ABOUT 10 AND A WATER SOLUBLE AMINO ACID, (B) DRYING THE IMPREGNATED BIBULOUS CARRIER; (C) FURTHER IMPREGNATING THE BIBULOUS CARRIER IN THE AREA PREVIOUSLY IMPREGNATED WITH THE BUFFER AND AMINO ACID WITH A SOLUTION, IN AN ORGANIC SOLVENT, OF (1) AN ALKALI METAL NITROPRUSSIDE, AND (2) A POLYMERIC SUBSTANCE SELECTED FROM THE GROUP CONSISTING OF POLYVINYLPYRROLIDONE-VINYL ACETATE COPOLYMERS, METHYL VINYL ETHER-MALEIC ANHYDRIDE COPOLYMERS, POLYETHYLENE GLYCOL, POLYVINYL ACETATE, METHYL VINYL ETHER-MALEIC ANHYDRIDE INTERPOLYMERS, VINYL PYRROLIDONE-STYRENE COPOLYMERS AND WATER SOLUBLE ACRYLIC COPOLYMERS; AND (D) REMOVING THE SOLVENT FROM THE FURTHER IMPREGNATED BIBULOUS CARRIER.
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BE635883D BE635883A (en) | 1962-08-06 | ||
NL296257D NL296257A (en) | 1962-08-06 | ||
US118933A US3212055A (en) | 1961-06-22 | 1961-06-22 | Distance measuring system |
US214867A US3212855A (en) | 1962-08-06 | 1962-08-06 | Diagnostic device |
GB30171/63A GB1012542A (en) | 1962-08-06 | 1963-07-30 | Diagnositc composition |
DEM57708A DE1256920B (en) | 1962-08-06 | 1963-08-01 | Test indicator for the detection of ketone compounds in body fluids and process for its preparation |
DK371863AA DK115733B (en) | 1962-08-06 | 1963-08-02 | Method for preparing a diagnostic composition. |
SE8616/63A SE310433B (en) | 1962-08-06 | 1963-08-05 | |
FR943952A FR1366340A (en) | 1962-08-06 | 1963-08-06 | Diagnostic composition |
CH972963A CH439804A (en) | 1962-08-06 | 1963-08-06 | Diagnostic reagent |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
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US214867A US3212855A (en) | 1962-08-06 | 1962-08-06 | Diagnostic device |
Publications (1)
Publication Number | Publication Date |
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US3212855A true US3212855A (en) | 1965-10-19 |
Family
ID=22800720
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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US214867A Expired - Lifetime US3212855A (en) | 1961-06-22 | 1962-08-06 | Diagnostic device |
Country Status (8)
Country | Link |
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US (1) | US3212855A (en) |
BE (1) | BE635883A (en) |
CH (1) | CH439804A (en) |
DE (1) | DE1256920B (en) |
DK (1) | DK115733B (en) |
GB (1) | GB1012542A (en) |
NL (1) | NL296257A (en) |
SE (1) | SE310433B (en) |
Cited By (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3507269A (en) * | 1965-04-26 | 1970-04-21 | Homer H Berry | Clinical diagnostic device for halitosis |
US3880590A (en) * | 1973-11-08 | 1975-04-29 | Shionogi & Co | Test strip for ketone bodies |
US4097240A (en) * | 1976-02-11 | 1978-06-27 | Riedel-De Haen Aktiengesellschaft | Process for the production of a diagnostic agent for the detection of ketones |
FR2398307A1 (en) * | 1977-07-23 | 1979-02-16 | Riedel De Haen Ag | DIAGNOSIS AGENT FOR DETECTION OF KETONIC BODIES IN LIQUIDS |
US4147514A (en) * | 1977-11-21 | 1979-04-03 | Miles Laboratories, Inc. | Test means and method for detecting ketone bodies |
US4172049A (en) * | 1977-05-13 | 1979-10-23 | Behringwerke Aktiengesellschaft | Control-solution for diagnostic detection methods for substances contained in the urine |
FR2434393A1 (en) * | 1978-06-15 | 1980-03-21 | Miles Lab | DEVICE AND METHOD FOR DETERMINING THE UREA CONTENT OF LIQUIDS |
US4215995A (en) * | 1979-05-15 | 1980-08-05 | Miles Laboratories, Inc. | Test means and assay for determining the urea content of fluids |
US4283491A (en) * | 1977-09-06 | 1981-08-11 | Eastman Kodak Company | Analytical elements with improved reagent stability |
US4356149A (en) * | 1979-07-02 | 1982-10-26 | Fuji Photo Film Co., Ltd. | Multi-layer chemical analytical materials |
US4388271A (en) * | 1980-01-10 | 1983-06-14 | Rohm Gmbh | Rapid diagnostic agents |
US4405721A (en) * | 1980-03-22 | 1983-09-20 | Behringwerke Aktiengesellschaft | Diagnostic agent for the detection of ketone bodies |
EP0279069A2 (en) * | 1986-12-22 | 1988-08-24 | Abbott Laboratories | Method and device for ketone measurement |
US4970172A (en) * | 1986-12-22 | 1990-11-13 | Abbott Laboratories | Method and device for ketone measurements |
US6583722B2 (en) | 2000-12-12 | 2003-06-24 | Kimberly-Clark Worldwide, Inc. | Wetness signaling device |
US6586195B1 (en) | 2001-11-19 | 2003-07-01 | R.E. Davis Chemical Corporation | Method of detecting sugars |
US6603403B2 (en) | 2000-12-12 | 2003-08-05 | Kimberly-Clark Worldwide, Inc. | Remote, wetness signaling system |
US6762035B1 (en) | 2002-02-04 | 2004-07-13 | Surendra K. Gupta | Method and test strips for the measurement of fat loss during weight loss programs |
US20060144588A1 (en) * | 2004-10-22 | 2006-07-06 | Core Laboratories Lp | Method for determining tracer concentration in oil and gas production fluids |
WO2014126995A1 (en) | 2013-02-14 | 2014-08-21 | Siemens Healthcare Diagnostics Inc. | Reduction of false positive on reagent test devices |
US9606103B2 (en) | 2011-12-16 | 2017-03-28 | Siemens Healthcare Diagnostics Inc. | Waste ramp for reagent cards |
EP3301433A1 (en) | 2012-03-09 | 2018-04-04 | Siemens Healthcare Diagnostics Inc. | Calibration method for reagent card analyzers |
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DE2436598C2 (en) * | 1974-07-30 | 1983-04-07 | Boehringer Mannheim Gmbh, 6800 Mannheim | Stable test strip for the detection of ingredients in liquids |
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- BE BE635883D patent/BE635883A/xx unknown
- NL NL296257D patent/NL296257A/xx unknown
-
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- 1962-08-06 US US214867A patent/US3212855A/en not_active Expired - Lifetime
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1963
- 1963-07-30 GB GB30171/63A patent/GB1012542A/en not_active Expired
- 1963-08-01 DE DEM57708A patent/DE1256920B/en active Pending
- 1963-08-02 DK DK371863AA patent/DK115733B/en unknown
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Cited By (30)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3507269A (en) * | 1965-04-26 | 1970-04-21 | Homer H Berry | Clinical diagnostic device for halitosis |
US3880590A (en) * | 1973-11-08 | 1975-04-29 | Shionogi & Co | Test strip for ketone bodies |
US4097240A (en) * | 1976-02-11 | 1978-06-27 | Riedel-De Haen Aktiengesellschaft | Process for the production of a diagnostic agent for the detection of ketones |
US4172049A (en) * | 1977-05-13 | 1979-10-23 | Behringwerke Aktiengesellschaft | Control-solution for diagnostic detection methods for substances contained in the urine |
US4184850A (en) * | 1977-07-23 | 1980-01-22 | Behringwerke Aktiengesellschaft | Diagnostic agent for the detection of ketone bodies in fluids and process for its manufacture |
FR2398307A1 (en) * | 1977-07-23 | 1979-02-16 | Riedel De Haen Ag | DIAGNOSIS AGENT FOR DETECTION OF KETONIC BODIES IN LIQUIDS |
US4283491A (en) * | 1977-09-06 | 1981-08-11 | Eastman Kodak Company | Analytical elements with improved reagent stability |
US4147514A (en) * | 1977-11-21 | 1979-04-03 | Miles Laboratories, Inc. | Test means and method for detecting ketone bodies |
FR2434393A1 (en) * | 1978-06-15 | 1980-03-21 | Miles Lab | DEVICE AND METHOD FOR DETERMINING THE UREA CONTENT OF LIQUIDS |
US4215995A (en) * | 1979-05-15 | 1980-08-05 | Miles Laboratories, Inc. | Test means and assay for determining the urea content of fluids |
US4356149A (en) * | 1979-07-02 | 1982-10-26 | Fuji Photo Film Co., Ltd. | Multi-layer chemical analytical materials |
US4388271A (en) * | 1980-01-10 | 1983-06-14 | Rohm Gmbh | Rapid diagnostic agents |
US4405721A (en) * | 1980-03-22 | 1983-09-20 | Behringwerke Aktiengesellschaft | Diagnostic agent for the detection of ketone bodies |
EP0279069A3 (en) * | 1986-12-22 | 1990-01-17 | Abbott Laboratories | Method and device for ketone measurement |
EP0279069A2 (en) * | 1986-12-22 | 1988-08-24 | Abbott Laboratories | Method and device for ketone measurement |
US4970172A (en) * | 1986-12-22 | 1990-11-13 | Abbott Laboratories | Method and device for ketone measurements |
US5071769A (en) * | 1986-12-22 | 1991-12-10 | Abbott Laboratories | Method and device for ketone measurement |
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 |
US6586195B1 (en) | 2001-11-19 | 2003-07-01 | R.E. Davis Chemical Corporation | Method of detecting sugars |
US6762035B1 (en) | 2002-02-04 | 2004-07-13 | Surendra K. Gupta | Method and test strips for the measurement of fat loss during weight loss programs |
US7347260B2 (en) | 2004-10-22 | 2008-03-25 | Core Laboratories Lp, A Delaware Limited Partnership | Method for determining tracer concentration in oil and gas production fluids |
US20060144588A1 (en) * | 2004-10-22 | 2006-07-06 | Core Laboratories Lp | Method for determining tracer concentration in oil and gas production fluids |
US9606103B2 (en) | 2011-12-16 | 2017-03-28 | Siemens Healthcare Diagnostics Inc. | Waste ramp for reagent cards |
US10444221B2 (en) | 2011-12-16 | 2019-10-15 | Siemens Healthcare Diagnostics Inc. | Method of transferring a reagent card from a card travel surface of an automated analyzer to a waste receptacle |
US11187694B2 (en) | 2011-12-16 | 2021-11-30 | Siemens Healthcare Diagnostics Inc. | Method for assembling an automated analyzer, waste ramp, and waste receptacle for reagent cards |
EP3301433A1 (en) | 2012-03-09 | 2018-04-04 | Siemens Healthcare Diagnostics Inc. | Calibration method for reagent card analyzers |
US11035799B2 (en) | 2012-03-09 | 2021-06-15 | Siemens Healthcare Diagnostics Inc. | Calibration method for reagent card analyzers |
WO2014126995A1 (en) | 2013-02-14 | 2014-08-21 | Siemens Healthcare Diagnostics Inc. | Reduction of false positive on reagent test devices |
US9612249B2 (en) | 2013-02-14 | 2017-04-04 | Siemens Healthcare Diagnostics Inc. | Reduction of false positive on reagent test devices |
Also Published As
Publication number | Publication date |
---|---|
BE635883A (en) | |
CH439804A (en) | 1967-07-15 |
DE1256920B (en) | 1967-12-21 |
GB1012542A (en) | 1965-12-08 |
SE310433B (en) | 1969-04-28 |
NL296257A (en) | |
DK115733B (en) | 1969-11-03 |
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