US3659104A - Method of measuring serum thyroxine - Google Patents
Method of measuring serum thyroxine Download PDFInfo
- Publication number
- US3659104A US3659104A US51005A US3659104DA US3659104A US 3659104 A US3659104 A US 3659104A US 51005 A US51005 A US 51005A US 3659104D A US3659104D A US 3659104DA US 3659104 A US3659104 A US 3659104A
- Authority
- US
- United States
- Prior art keywords
- column
- serum
- thyroxine
- gel
- iodine
- 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
- 238000000034 method Methods 0.000 title claims abstract description 27
- 210000002966 serum Anatomy 0.000 title claims abstract description 23
- XUIIKFGFIJCVMT-UHFFFAOYSA-N thyroxine-binding globulin Natural products IC1=CC(CC([NH3+])C([O-])=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-UHFFFAOYSA-N 0.000 title claims abstract description 21
- XUIIKFGFIJCVMT-GFCCVEGCSA-N D-thyroxine Chemical compound IC1=CC(C[C@@H](N)C(O)=O)=CC(I)=C1OC1=CC(I)=C(O)C(I)=C1 XUIIKFGFIJCVMT-GFCCVEGCSA-N 0.000 title claims abstract description 20
- 229940034208 thyroxine Drugs 0.000 title claims abstract description 20
- 230000002285 radioactive effect Effects 0.000 claims description 11
- 239000012670 alkaline solution Substances 0.000 claims description 6
- 230000000717 retained effect Effects 0.000 claims description 6
- 239000007982 barbital buffer Substances 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 5
- 238000010828 elution Methods 0.000 claims description 4
- 102000002572 Alpha-Globulins Human genes 0.000 claims 1
- 108010068307 Alpha-Globulins Proteins 0.000 claims 1
- 229920005654 Sephadex Polymers 0.000 abstract description 15
- 238000004458 analytical method Methods 0.000 abstract description 8
- 239000012507 Sephadex™ Substances 0.000 abstract description 7
- 108010017384 Blood Proteins Proteins 0.000 abstract description 5
- 102000004506 Blood Proteins Human genes 0.000 abstract description 5
- 238000010790 dilution Methods 0.000 abstract description 2
- 239000012895 dilution Substances 0.000 abstract description 2
- 238000000338 in vitro Methods 0.000 abstract description 2
- 239000000499 gel Substances 0.000 description 17
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 14
- 235000013675 iodine Nutrition 0.000 description 14
- 239000011230 binding agent Substances 0.000 description 13
- 229910052740 iodine Inorganic materials 0.000 description 13
- 239000011630 iodine Substances 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- 210000001685 thyroid gland Anatomy 0.000 description 9
- 239000000243 solution Substances 0.000 description 8
- 230000000694 effects Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- FTOAOBMCPZCFFF-UHFFFAOYSA-N 5,5-diethylbarbituric acid Chemical compound CCC1(CC)C(=O)NC(=O)NC1=O FTOAOBMCPZCFFF-UHFFFAOYSA-N 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- 102000004169 proteins and genes Human genes 0.000 description 6
- 108090000623 proteins and genes Proteins 0.000 description 6
- 238000003556 assay Methods 0.000 description 4
- 230000014759 maintenance of location Effects 0.000 description 4
- 238000012360 testing method Methods 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 229960002319 barbital Drugs 0.000 description 3
- 230000037323 metabolic rate Effects 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- -1 polyethylene Polymers 0.000 description 3
- 229920000573 polyethylene Polymers 0.000 description 3
- 239000011347 resin Substances 0.000 description 3
- 229920005989 resin Polymers 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 2
- 102000009027 Albumins Human genes 0.000 description 2
- 108010088751 Albumins Proteins 0.000 description 2
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 2
- 239000003957 anion exchange resin Substances 0.000 description 2
- 230000002860 competitive effect Effects 0.000 description 2
- 239000003599 detergent Substances 0.000 description 2
- 230000003054 hormonal effect Effects 0.000 description 2
- 229940088597 hormone Drugs 0.000 description 2
- 239000005556 hormone Substances 0.000 description 2
- 208000003532 hypothyroidism Diseases 0.000 description 2
- 239000003456 ion exchange resin Substances 0.000 description 2
- 229920003303 ion-exchange polymer Polymers 0.000 description 2
- 239000004033 plastic Substances 0.000 description 2
- 229920003023 plastic Polymers 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- VSWSDTLXDWESGZ-AWEZNQCLSA-N (2s)-3-[4-(4-hydroxyphenoxy)phenyl]-2-(iodoamino)propanoic acid Chemical class C1=CC(C[C@@H](C(=O)O)NI)=CC=C1OC1=CC=C(O)C=C1 VSWSDTLXDWESGZ-AWEZNQCLSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 102000014914 Carrier Proteins Human genes 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 206010018498 Goitre Diseases 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 206010020850 Hyperthyroidism Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 206010028665 Myxoedema Diseases 0.000 description 1
- 102000007584 Prealbumin Human genes 0.000 description 1
- 108010071690 Prealbumin Proteins 0.000 description 1
- 102000002248 Thyroxine-Binding Globulin Human genes 0.000 description 1
- 108010000259 Thyroxine-Binding Globulin Proteins 0.000 description 1
- 102000009488 Thyroxine-Binding Proteins Human genes 0.000 description 1
- 108010048889 Thyroxine-Binding Proteins Proteins 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000008351 acetate buffer Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 239000000908 ammonium hydroxide Substances 0.000 description 1
- 108091008324 binding proteins Proteins 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 239000012888 bovine serum Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000000969 carrier Substances 0.000 description 1
- 238000005119 centrifugation Methods 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 239000000356 contaminant Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 239000012153 distilled water Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 108010074605 gamma-Globulins Proteins 0.000 description 1
- 201000003872 goiter Diseases 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 230000002989 hypothyroidism Effects 0.000 description 1
- 150000002497 iodine compounds Chemical class 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- ZLVYMPOQNJTFSG-QMMMGPOBSA-N monoiodotyrosine Chemical compound OC(=O)[C@@H](NI)CC1=CC=C(O)C=C1 ZLVYMPOQNJTFSG-QMMMGPOBSA-N 0.000 description 1
- 208000003786 myxedema Diseases 0.000 description 1
- 150000005527 organic iodine compounds Chemical class 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 239000000700 radioactive tracer Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 238000012546 transfer Methods 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
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
- G01N33/74—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving hormones or other non-cytokine intercellular protein regulatory factors such as growth factors, including receptors to hormones and growth factors
- G01N33/78—Thyroid gland hormones, e.g. T3, T4, TBH, TBG or their receptors
-
- 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
- Y10S436/804—Radioisotope, e.g. radioimmunoassay
-
- 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
- Y10S436/825—Pretreatment for removal of interfering factors from sample
-
- 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
- Y10S436/826—Additives, e.g. buffers, diluents, preservatives
Definitions
- Thyroxine which is released in response to nervous or hormonal stimuli.
- Thyroxine enters the circulatory system and acts either directly upon the cell or indirectly upon other hormonal systems.
- Abnormal activity of the thyroid is a common malady in humans. In hypothyroidism, the body has decreased thyroid activity which is manifest by such diseases as cretinism and myxedema. Hyperthyroidism is a state of excessive thyroid activity in which one becomes nervous, develops an increased pulse rate and sometimes goiter.
- Thyroid deficiency was associated with a reduced metabolic rate as early as 1895 and several systems based on basal metabolic rate were devised for estimating thyroid activity. However, such systems were not reliable, so more direct and precise methods were sought.
- iodine was discovered in thyroid extract but the relationship between blood iodine level and thyroid function was not firmly established until I933. This led to the use of protein-bound iodine as a means of estimating thyroid function, and by 1955 the FBI test was standard for checking thyroid activity. It soon became apparent that this test was influenced by the administration of other iodine containing compounds to the patient.
- BEI butanol-extractable iodine
- T-4 analysis occurred in 1959 when Galton et al., Biochem. J. 72, 310 (1959) liberated T-4 from serum protein by hydrolysis and separated it from other iodine compounds by passage through a resin column. Later, Pileggi et al., J. Clin. Endocr. Met. 21, 1272 (1961) developed this column chromatographic procedure into a clinically usable method.
- U.S. Pat. No. 3,471,553 set forth still another column chromatography T-4 assay in which an anionexchange resin is adjusted to an alkaline pH of about 12 to dissociate the thyroxine from its albumin and globulin carriers.
- the diluted serum solution is then poured onto the resin wherein proteins, amino acids, thyroxine, iodotyrosine and inorganic iodine are adsorbed.
- Successive washes with acetate buffer isopropyl alcohol and acetic acid remove serum proteins, iodothyronines and some organic iodine compounds.
- Further treatment of the resin with 50 percent acetic acid at a pH of 2 quantitatively removes T-4.
- the present invention for determining T4 is based on the competitive protein binding principle which is a modified form of saturation analysis.
- the T-4 to be determined is mixed with a detenninate sample of T-4 labeled with a trace amount of radioactive isotope.
- a binding agent is added which will bind a definite number of molecules. Since the binding agent cannot distinguish between the labeled and unlabeled molecules, they compete with each other on an equal basis for the binding sites. These molecules are uniformly mixed so that the binding agent will bind them in the same ratio as that existing in the free or unbound state.
- the ratio becomes smaller and fewer labeled molecules are bound by the binding agent, leaving more of the labeled molecules in the free state.
- the crosslinked dextran gel column acts as the secondary binding agent for the unbound or free T-4, whereas the primary binding agent is a thyroxine (T-4) binding protein.
- T-4 thyroxine
- a measured amount of serum is mixed with some T-4 labeled with radioactive iodine on top of the column. Both the column and T4 mixture are at pHl2 to 13. At this pH, the T-4 binding serum proteins such as prealbumin, albumin and thyroxine binding globulin are completely dissociated from T4. As the mixture flows down the column, the T-4 is bound by the dextran gel. The serum proteins are washed away with a barbital buficr at a pH of 8.6 which automatically adjusts the pH of the column to that of the buffer.
- the pH is such that the transfer of the T-4 from the column to the primary binding agent is facilitated.
- the primary binding agent dissolved in barbital buffer is then added. Equilibrium is quickly established between the two binding agents and the primary binder is washed away carrying a portion of the T-4 with it.
- the dextran gels employed in the column are crosslinked with various amounts of epichlorohydrin as described in U.S. Pat. No. 3,042,667 and have a water regain of from I to 5 grams per gram of dry gel product.
- Such gels are produced commercially by Pharmacia of Uppsala, Sweden and sold under the trade name of Sephadex in various molecular weight ranges and sieve sizes.
- Sephadex G-lO has a water regain of one gram per gram of dry gel
- Sephadex G-l5 has a water regain of 1.5 grams per gram of dry gel
- Sephadex 6-25 has a water regain of 2.5 grams per gram of dry gel
- Sephadex G50 has a water regain of 5 grams per gram of dry gel.
- Sephadex G-25 is preferred.
- the dextran gel column employed in this invention is prepared by suspending 500 grams of dry gel in two liters of distilled water and allowing it to hydrate overnight. Fines are removed by slurrying the gel in 0.1 N sodium hydroxide for about 5 minutes, allowing it to settle for 15 minutes and then drawing off the supernatant by suction. The process is repeated three times and the gel is suspended in 4,400 milliliters of 0.1 N sodium hydroxide. Four milliliters of this suspension is placed in a six milliliter plastic syringe barrel having a diameter of 13 millimeters and a length of 66 millimeters.
- Each barrel is prefitted with a bottom closure means, for example, a removable cap, and a detergent treated sintered polyethylene retaining disc about l.5 millimeters thick and having a diameter of 13 millimeters is pressed coaxially to the bottom of the plastic barrel.
- a bottom closure means for example, a removable cap
- a detergent treated sintered polyethylene retaining disc about l.5 millimeters thick and having a diameter of 13 millimeters is pressed coaxially to the bottom of the plastic barrel.
- the suspension is stirred and permitted to settle free of air bubbles after which another detergent-treated sintered polyethylene disc, like the first-mentioned disc, is inserted into the syringe barrel and pushed coaxially into firm contact with the gel.
- About 1.5 milliliters of sodium hydroxide solution remains above the upper disc.
- the upper end of the syringe is closed with a new polyethylene cap. This procedure provides a column containing about 450 milligrams of gel.
- the T-4 test herein contemplated is performed by utilizing the gel column thus prepared as follows:
- the gel column can be made alkaline by potassium hydroxide or ammonium hydroxide if desired.
- Human a-globulin can be replaced with an equivalent amount of human serum, bovine serum or bovine gamma globulin as the primary binding agent.
- Aqueous alkaline solutions buffered to a pH of from 8 to 10 with sodium phosphate or tris (hydroxymethyl) amino methane can be used at concentrations from 0.01. to 0.2 molar, but an aqueous barbital solution is preferred, since it facilitates better quantitation when used to dissolve the human a-globulin or other binding agents.
- Another variation of the present invention involves determining the radioactivity of the solutions before addition to the gel column and after elution therefrom rather than determining the radioactivity of the column itself. Percent retention is then determined by a difference calculation. However, for the sake of efficiency, it is preferable to determine the radioactivity of the column before and after elution.
- Assays for T-4 by the column methods of the prior art should not be confused with the present method which involves saturation analysis using a radioactive tracer.
- a column was utilized only to separate contaminating iodines prior to analysis of iodine. In certain cases, this was done by using an ion exchange resin column at an alkaline pH, and iodine analysis was performed on the T-4 recovered from the column by measuring the effect of iodine on the ceric-arsenious acid reaction.
- the saturation analysis method herein disclosed is a direct determination of thyroxine, rather than the indirect measurement of thyroxine as iodine.
- a process for the in vitro determination of thyroxine in serum comprising:
- aqueous alkaline solution is a barbital buffer having a pH of 8.6.
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Endocrinology (AREA)
- Biomedical Technology (AREA)
- Chemical & Material Sciences (AREA)
- Urology & Nephrology (AREA)
- Hematology (AREA)
- Immunology (AREA)
- Microbiology (AREA)
- Cell Biology (AREA)
- Biotechnology (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 |
|---|---|---|---|
| US5100570A | 1970-06-29 | 1970-06-29 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US3659104A true US3659104A (en) | 1972-04-25 |
Family
ID=21968790
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US51005A Expired - Lifetime US3659104A (en) | 1970-06-29 | 1970-06-29 | Method of measuring serum thyroxine |
Country Status (11)
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3753655A (en) * | 1971-11-09 | 1973-08-21 | B Schreiber | Process for isolation and separation of thyroid hormones |
| US3816076A (en) * | 1971-06-15 | 1974-06-11 | Merck Patent Gmbh | Process for the determination of thyroxine |
| US3911096A (en) * | 1972-06-23 | 1975-10-07 | Professional Staff Ass Of The | Radioimmunoassay for measurement of thyroxine (T{HD 4{B ) and triiodothyonine (T{HD 3{B ) in blood serum |
| US3918909A (en) * | 1971-09-21 | 1975-11-11 | Philips Corp | Apparatus for performing saturation analyses |
| US3929410A (en) * | 1970-11-09 | 1975-12-30 | Benjamin Schloss | Analytical process |
| US3941564A (en) * | 1973-09-13 | 1976-03-02 | Miles Laboratories, Inc. | Method for assessing thyroid function |
| US3947564A (en) * | 1973-05-29 | 1976-03-30 | Bio-Rad Laboratories | Radioactive determination of serum thyroxine |
| US3961894A (en) * | 1973-04-24 | 1976-06-08 | Yissum Research Development Company | Test for determination of triiodothyronine |
| DE2806860A1 (de) * | 1977-03-10 | 1978-09-14 | Lepetit Spa | Verfahren zur bestimmung der konzentration der freien fraktion eines hormons in einer biologischen fluessigkeit |
| US4170454A (en) * | 1978-03-30 | 1979-10-09 | Union Carbide Corporation | Process for the preparation of a solid-phase radioimmunoassay support and use thereof |
| US4225576A (en) * | 1978-11-20 | 1980-09-30 | Miles Laboratories, Inc. | Combined radioimmunoassay for triiodothyronine and thyroxine |
| US4230797A (en) * | 1975-04-28 | 1980-10-28 | Miles Laboratories, Inc. | Heterogenous specific binding assay employing a coenzyme as label |
| US4318980A (en) * | 1978-04-10 | 1982-03-09 | Miles Laboratories, Inc. | Heterogenous specific binding assay employing a cycling reactant as label |
| US4492751A (en) * | 1978-04-10 | 1985-01-08 | Miles Laboratories, Inc. | Heterogenous specific binding assay employing an enzyme substrate as label |
| USRE32098E (en) * | 1972-06-23 | 1986-03-25 | Research And Education Institute, Inc. | Radioimmunoassay for measurement of thyroxine (T4) and triiodothyronine (T3) in blood serum |
| US5217903A (en) * | 1990-05-15 | 1993-06-08 | Trustees Of Boston University | Measuring connective tissue breakdown products in body fluids |
| KR20020065698A (ko) * | 2001-02-07 | 2002-08-14 | 주식회사 바이오라인 | 방사면역측정법을 이용한 갑상선 호르몬 측정키트 |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4301139A (en) * | 1979-06-21 | 1981-11-17 | Ames-Yissum Ltd. | Multilayer column chromatography specific binding assay method, test device and test kit |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3451777A (en) * | 1965-08-20 | 1969-06-24 | Walter Di Giulio | Method and apparatus for determining the thyroid hormone content of blood |
| US3507618A (en) * | 1964-11-27 | 1970-04-21 | Squibb & Sons Inc | Apparatus and method for determining thyroid function |
-
1970
- 1970-06-29 US US51005A patent/US3659104A/en not_active Expired - Lifetime
-
1971
- 1971-05-26 ZA ZA713408A patent/ZA713408B/xx unknown
- 1971-06-14 IL IL37046A patent/IL37046A/xx unknown
- 1971-06-22 HU HUII65A patent/HU166424B/hu unknown
- 1971-06-26 ES ES392664A patent/ES392664A1/es not_active Expired
- 1971-06-28 SE SE7108334A patent/SE392346B/xx unknown
- 1971-06-28 FR FR7123530A patent/FR2100008A5/fr not_active Expired
- 1971-06-28 JP JP4640271A patent/JPS5331399B1/ja active Pending
- 1971-06-28 GB GB3027671A patent/GB1351836A/en not_active Expired
- 1971-06-28 CA CA116,818A patent/CA955159A/en not_active Expired
- 1971-06-28 DE DE2132112A patent/DE2132112C3/de not_active Expired
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3507618A (en) * | 1964-11-27 | 1970-04-21 | Squibb & Sons Inc | Apparatus and method for determining thyroid function |
| US3451777A (en) * | 1965-08-20 | 1969-06-24 | Walter Di Giulio | Method and apparatus for determining the thyroid hormone content of blood |
Cited By (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3929410A (en) * | 1970-11-09 | 1975-12-30 | Benjamin Schloss | Analytical process |
| US3816076A (en) * | 1971-06-15 | 1974-06-11 | Merck Patent Gmbh | Process for the determination of thyroxine |
| US3918909A (en) * | 1971-09-21 | 1975-11-11 | Philips Corp | Apparatus for performing saturation analyses |
| US3753655A (en) * | 1971-11-09 | 1973-08-21 | B Schreiber | Process for isolation and separation of thyroid hormones |
| US3911096A (en) * | 1972-06-23 | 1975-10-07 | Professional Staff Ass Of The | Radioimmunoassay for measurement of thyroxine (T{HD 4{B ) and triiodothyonine (T{HD 3{B ) in blood serum |
| USRE32098E (en) * | 1972-06-23 | 1986-03-25 | Research And Education Institute, Inc. | Radioimmunoassay for measurement of thyroxine (T4) and triiodothyronine (T3) in blood serum |
| US3961894A (en) * | 1973-04-24 | 1976-06-08 | Yissum Research Development Company | Test for determination of triiodothyronine |
| US3947564A (en) * | 1973-05-29 | 1976-03-30 | Bio-Rad Laboratories | Radioactive determination of serum thyroxine |
| US3941564A (en) * | 1973-09-13 | 1976-03-02 | Miles Laboratories, Inc. | Method for assessing thyroid function |
| US4230797A (en) * | 1975-04-28 | 1980-10-28 | Miles Laboratories, Inc. | Heterogenous specific binding assay employing a coenzyme as label |
| DE2806860A1 (de) * | 1977-03-10 | 1978-09-14 | Lepetit Spa | Verfahren zur bestimmung der konzentration der freien fraktion eines hormons in einer biologischen fluessigkeit |
| US4170454A (en) * | 1978-03-30 | 1979-10-09 | Union Carbide Corporation | Process for the preparation of a solid-phase radioimmunoassay support and use thereof |
| US4318980A (en) * | 1978-04-10 | 1982-03-09 | Miles Laboratories, Inc. | Heterogenous specific binding assay employing a cycling reactant as label |
| US4492751A (en) * | 1978-04-10 | 1985-01-08 | Miles Laboratories, Inc. | Heterogenous specific binding assay employing an enzyme substrate as label |
| US4225576A (en) * | 1978-11-20 | 1980-09-30 | Miles Laboratories, Inc. | Combined radioimmunoassay for triiodothyronine and thyroxine |
| US5217903A (en) * | 1990-05-15 | 1993-06-08 | Trustees Of Boston University | Measuring connective tissue breakdown products in body fluids |
| KR20020065698A (ko) * | 2001-02-07 | 2002-08-14 | 주식회사 바이오라인 | 방사면역측정법을 이용한 갑상선 호르몬 측정키트 |
Also Published As
| Publication number | Publication date |
|---|---|
| DE2132112A1 (de) | 1972-01-27 |
| GB1351836A (en) | 1974-05-01 |
| ZA713408B (en) | 1972-01-26 |
| ES392664A1 (es) | 1973-08-01 |
| CA955159A (en) | 1974-09-24 |
| IL37046A (en) | 1974-05-16 |
| DE2132112C3 (de) | 1974-09-19 |
| SE392346B (sv) | 1977-03-21 |
| HU166424B (enrdf_load_stackoverflow) | 1975-03-28 |
| FR2100008A5 (enrdf_load_stackoverflow) | 1972-03-17 |
| JPS5331399B1 (enrdf_load_stackoverflow) | 1978-09-02 |
| DE2132112B2 (de) | 1974-02-21 |
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