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US4005187A Expired / Lapsed US ⏱️ 0.0 years remaining

Diagnostic test method

Assignee: Data Diagnostic Corp
•
Filing: 1974-06-03
•
Granted: 1977-01-25
•
Expires: 1994-06-03
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Abstract

Abstract A method of measuring a diagnostically significant component in a fluid test sample in which the desired component is selectively adsorbed by a solid adsorbent formed, in situ, in the sample, the amount of the component then being determined by a suitable technique such as, for example, radioassaying. In a preferred embodiment, the invention is directed to thyroid function testing in which the in situ formed solid adsorbent is used to selectively adsorb the free thyroid hormone in the test serum, the amount of thyroid hormone and/or the unsaturated binding capacity of thyroid hormone binding protein being determined by radioassaying methods employing radioisotope labeled thyroid hormone as a tracer.

Inventors

  • 👤 Gustave F. Kilthau
  • 👤 Diana R. Loftin

Bibliographic Details

Application Number —
Jurisdiction US
Data Source google_patents
Last Synchronized 2026-11-08 14:02
CPC Classifications
G; G01; G01N; G01N33/00; G01N33/48; G01N33/50; G01N33/74; G01N33/78; G01N30/00; Y; Y10; Y10S; Y10S436/00; Y10S436/804; Y10S436/825; Y10S436/826

Claims Analysis

Total Claims: 61
Claim 1
Independent Claim 65 words
A method of isolating a diagnostically significant component in a test fluid mixture comprising contacting at least 2 solutes in said test fluid mixture, which solutes react to form in situ a solid absorbent, said solid absorbent formed of material other than said diagnostically significant component and being of a nature so as to selectively adsorb at least a portion of said diagnostically significant component.
Claim 2
Independent Claim 65 words
A method of isolating a diagnostically significant component in a test fluid mixture comprising contacting at least 2 solutes in said test fluid mixture, which solutes react to form in situ a solid absorbent, said solid absorbent formed of material other than said diagnostically significant component and being of a nature so as to selectively adsorb at least a portion of said diagnostically significant component.
Claim 3
Dependent Claim 32 words
The method of claim 1 further including the step of separating said solid adsorbent and the adsorbed portion of said diagnostically significant component from the resulting test fluid mixture of claim 1.
Claim 4
Dependent Claim 38 words
The method of claim 2 including the step of assaying the separated solid adsorbent and said adsorbed portion of said diagnostically significant component to determine the amount of said diagnostically significant component present in said test fluid mixture.
Claim 5
Dependent Claim 33 words
The method of claim 2 including the step of assaying said resulting test fluid mixture from claim 2 to determine the amount of said diagnostically significant component present in said test fluid mixture.
Claim 6
Dependent Claim 59 words
The method of claim 1 wherein the contacting step to effect the in situ formation of said solid adsorbent is accomplished by the addition to said test fluid mixture of a solution containing a first solute which reacts in said test fluid mixture with a second solute originally present in said test fluid mixture to form said solid adsorbent.
Claim 7
Dependent Claim 59 words
The method of claim 1 wherein the contacting step to effect the in situ formation of said solid adsorbent is accomplished by adding to said test fluid mixture a first solution containing a first solute and a second solution containing a second solute, said first and second solutes reacting in said test fluid mixture to form said solid adsorbent.
Claim 8
Dependent Claim 15 words
The method of claim 5 wherein said first solute comprises a water soluble inorganic compound.
Claim 9
Dependent Claim 15 words
The method of claim 7 wherein said second solute comprises a water soluble inorganic compound.
Claim 10
Dependent Claim 16 words
The method of claim 6 wherein said first and second solutes comprise water soluble inorganic compounds.
Claim 11
Dependent Claim 16 words
The method of claim 1 wherein said diagnostically significant component comprises a biologically produced endogenous component.
Claim 12
Dependent Claim 29 words
The method of claim 1 wherein said test fluid mixture contains an endogenous biological product and said diagnostically significant component comprises an exogenous material present in said biological product.
Claim 13
Dependent Claim 155 words
In a method for determining thyroid function wherein a measured amount of radioisotope labeled thyroid hormone is added to a test fluid containing an unknown amount of said thyroid hormone and an unknown amount of thyroid hormone binding protein to determine the level of binding capacity of said thyroid hormone binding protein by radioassaying of either said free labeled hormone or said labeled hormone which binds to said thyroid hormone binding protein, the improvement comprising: 1. contacting at least two solutes in said test fluid containing said measured amount of said radioactive labeled thyroid hormone, which solutes react to form in situ a solid adsorbent, said solid adsorbent formed of material other than said thyroid hormone or said thyroid hormone binding protein and being of a nature so as to selectively adsorb free thyroid hormone, and 2. separating said solid adsorbent containing the adsorbed thyroid hormone from the resulting test fluid prior to said radioassaying.
Claim 14
Dependent Claim 155 words
In a method for determining thyroid function wherein a measured amount of radioisotope labeled thyroid hormone is added to a test fluid containing an unknown amount of said thyroid hormone and an unknown amount of thyroid hormone binding protein to determine the level of binding capacity of said thyroid hormone binding protein by radioassaying of either said free labeled hormone or said labeled hormone which binds to said thyroid hormone binding protein, the improvement comprising: 1. contacting at least two solutes in said test fluid containing said measured amount of said radioactive labeled thyroid hormone, which solutes react to form in situ a solid adsorbent, said solid adsorbent formed of material other than said thyroid hormone or said thyroid hormone binding protein and being of a nature so as to selectively adsorb free thyroid hormone, and 2. separating said solid adsorbent containing the adsorbed thyroid hormone from the resulting test fluid prior to said radioassaying.
Claim 15
Dependent Claim 57 words
The method of claim 12 wherein the contacting step to effect the in situ formation of said solid adsorbent is accomplished by adding to said test fluid a first solution containing a first solute and a second solution containing a second solute, said first and second solutes reacting in said test fluid to form said solid adsorbent.
Claim 16
Dependent Claim 18 words
The method of claim 13 wherein said first solute and said second solute comprise water soluble inorganic compounds.
Claim 17
Dependent Claim 70 words
The method of claim 13 wherein said first solute is a water soluble substance selected from the class consisting of carboxylic acids, salts of carboxylic acids, carbonates, phosphates, hydroxides, silicates, aluminates, sulphates, and mixtures thereof and said second solute is selected from the class consisting of water soluble salts of the metallic elements of Groups IIa, IIIa, IVa, Ib, IIb, IVb and VIII of the Periodic Table and mixtures thereof.
Claim 18
Dependent Claim 81 words
The method of claim 13 wherein said first solute comprises a water soluble salt of a metallic element of Groups IIa, IIIa, IVa, Ib, IIb, IVb and VIII of the Periodic Table and said second solute comprises a water soluble salt of a metallic element of Groups IIa, IIIa, IVa, Ib, IIb, IVb and VIII of the Periodic Table, the anion of one of said solutes reacting with the cation of the other of said solutes to form said solid adsorbent.
Claim 19
Dependent Claim 14 words
The method of claim 13 wherein said first solute comprises an alkali metal carbonate.
Claim 20
Dependent Claim 13 words
The method of claim 17 wherein said alkali metal carbonate comprises sodium carbonate.
Claim 21
Dependent Claim 15 words
The method of claim 13 wherein said second solute comprises an alkaline earth metal chloride.
Claim 22
Dependent Claim 14 words
The method of claim 19 wherein said alkaline earth metal chloride comprises calcium chloride.
Claim 23
Dependent Claim 13 words
The method of claim 12 wherein said radioassaying is accomplished by scintillation counting.
Claim 24
Independent Claim 143 words
A method of determining the amount of thyroid hormone binding capacity in a test fluid containing an unknown amount of said thyroid hormone and an unknown amount of thyroid hormone binding protein comprising: 1. adding to said test fluid a measured amount of radioisotope labeled thyroid hormone, 2. contacting at least two solutes in said test fluid containing said measured amount of said radioactive labeled thyroid hormone, which solutes react to form in situ a solid adsorbent, said solid adsorbent formed of material other than said thyroid hormone or said thyroid hormone binding protein and being of a nature so as to selectively adsorb free thyroid hormone, 3. separating said solid adsorbent containing the adsorbed thyroid hormone from the resulting test fluid, 4. radioassaying either the radioisotope labeled hormone on said solid adsorbent or said bound radioisotope labeled hormone in said resulting solution.
Claim 25
Independent Claim 143 words
A method of determining the amount of thyroid hormone binding capacity in a test fluid containing an unknown amount of said thyroid hormone and an unknown amount of thyroid hormone binding protein comprising: 1. adding to said test fluid a measured amount of radioisotope labeled thyroid hormone, 2. contacting at least two solutes in said test fluid containing said measured amount of said radioactive labeled thyroid hormone, which solutes react to form in situ a solid adsorbent, said solid adsorbent formed of material other than said thyroid hormone or said thyroid hormone binding protein and being of a nature so as to selectively adsorb free thyroid hormone, 3. separating said solid adsorbent containing the adsorbed thyroid hormone from the resulting test fluid, 4. radioassaying either the radioisotope labeled hormone on said solid adsorbent or said bound radioisotope labeled hormone in said resulting solution.
Claim 26
Dependent Claim 57 words
The method of claim 22 wherein the contacting step to effect the in situ formation of said solid adsorbent is accomplished by adding to said test fluid a first solution containing a first solute and a second solution containing a second solute, said first and second solutes reacting in said test fluid to form said solid adsorbent.
Claim 27
Dependent Claim 18 words
The method of claim 23 wherein said first solute and said second solute comprise water soluble inorganic compounds.
Claim 28
Dependent Claim 70 words
The method of claim 23 wherein said first solute is a water soluble substance selected from the class consisting of carboxylic acids, salts of carboxylic acids, carbonates, phosphates, hydroxides, silicates, aluminates, sulphates, and mixtures thereof and said second solute is selected from the class consisting of water soluble salts of the metallic element of Groups IIa, IIIa, IVa, Ib, IIb, IVb and VIII of the Periodic Table and mixtures thereof.
Claim 29
Dependent Claim 81 words
The method of claim 23 wherein said first solute comprises a water soluble salt of a metallic element of Groups IIa, IIIa, IVa, Ib, IIb, IVb and VIII of the Periodic Table and said second solute comprises a water soluble salt of a metallic element of Groups IIa, IIIa, IVa, Ib, IIb, IVb and VIII of the Periodic Table, the anion of one of said solutes reacting with the cation of the other of said solutes to form said solid adsorbent.
Claim 30
Dependent Claim 12 words
The method of claim 23 wherein said first solute comprises sodium carbonate.
Claim 31
Dependent Claim 12 words
The method of claim 23 wherein said first solute comprises potassium phosphate.
Claim 32
Dependent Claim 12 words
The method of claim 23 wherein said second solute comprises calcium chloride.
Claim 33
Dependent Claim 13 words
The method of claim 22 wherein said radioassaying is accomplished by scintillation counting.
Claim 34
Independent Claim 98 words
A method of isolating thyroid hormone in a test fluid containing said thyroid hormone and thyroid hormone binding protein comprising: 1. admixing sufficient acid or base with said test sample to free said thyroid hormone from said thyroid hormone binding protein, and 2. contacting at least two solutes in said test fluid containing said acid or said base, which solutes react to form in situ a solid adsorbent, said solid adsorbent formed of material other than said thyroid hormone or said thyroid hormone binding protein and being of a nature so as to selectively adsorb free thyroid hormone.
Claim 35
Independent Claim 98 words
A method of isolating thyroid hormone in a test fluid containing said thyroid hormone and thyroid hormone binding protein comprising: 1. admixing sufficient acid or base with said test sample to free said thyroid hormone from said thyroid hormone binding protein, and 2. contacting at least two solutes in said test fluid containing said acid or said base, which solutes react to form in situ a solid adsorbent, said solid adsorbent formed of material other than said thyroid hormone or said thyroid hormone binding protein and being of a nature so as to selectively adsorb free thyroid hormone.
Claim 36
Dependent Claim 24 words
The method of claim 31 further including separating said solid adsorbent containing the adsorbed free thyroid hormone from the resulting mixture of step 2.
Claim 37
Dependent Claim 35 words
The method of claim 32 wherein said test sample is admixed with acid, the amount of acid added being sufficient so as to result in a pH range of from about 1 to about 4.
Claim 38
Dependent Claim 36 words
The method of claim 32 wherein said test sample is admixed with base, the amount of said base added being sufficient so as to result in a pH range of from about 12 to about 14.
Claim 39
Dependent Claim 57 words
The method of claim 32 wherein the contacting step to effect the in situ formation of said solid adsorbent is accomplished by adding to said test fluid a first solution containing a first solute and a second solution containing a second solute, said first and second solutes reacting in said test fluid to form said solid adsorbent.
Claim 40
Dependent Claim 18 words
The method of claim 35 wherein said first solute and said second solute comprise water soluble inorganic compounds.
Claim 41
Dependent Claim 70 words
The method of claim 35 wherein said first solute is a water soluble substance selected from the class consisting of carboxylic acids, salts of carboxylic acids, carbonates, phosphates, hydroxides, silicates, aluminates, sulphates and mixtures thereof and said second solute is selected from the class consisting of water soluble salts of the metallic elements of Groups IIa, IIIa, IVa, Ib, IIb, IVb and VIII of the Periodic Table and mixtures thereof.
Claim 42
Independent Claim 217 words
A method of measuring thyroid hormone in a fluid test sample containing said thyroid hormone and thyroid hormone binding protein comprising: 1. acidifying said fluid test sample to effect separation of said thyroid hormone from said thyroid hormone binding protein, 2. admixing said acidified fluid test sample with a solid sorbent material to effect selective separation of the free thyroid hormone, 3. separating said solid sorbent material containing the adsorbed thyroid hormone from the remainder of said acidified fluid test sample, 4. admixing said solid sorbent material containing said thyroid hormone with an elution liquid to form an elution mixture having a pH sufficiently high enough to effect elution of said thyroid hormone from said solid sorbent, 5. admixing said elution mixture with thyroid hormone binding globulin and a radioactive isotope labeled thyroid hormone, 6. contacting at least two solutes in said elution mixture containing said thyroid binding globulin and said radioactive isotope labeled thyroid hormone, which solutes react to form in situ a solid adsorbent, said adsorbent formed of material other than said thyroid binding globulin or said thyroid hormone and being of a nature so as to selectively adsorb free thyroid hormone, and 7. radioassaying either said labeled thyroid hormone adsorbed by said solid adsorbent or the remaining labeled thyroid hormone in said elution mixture.
Claim 43
Independent Claim 217 words
A method of measuring thyroid hormone in a fluid test sample containing said thyroid hormone and thyroid hormone binding protein comprising: 1. acidifying said fluid test sample to effect separation of said thyroid hormone from said thyroid hormone binding protein, 2. admixing said acidified fluid test sample with a solid sorbent material to effect selective separation of the free thyroid hormone, 3. separating said solid sorbent material containing the adsorbed thyroid hormone from the remainder of said acidified fluid test sample, 4. admixing said solid sorbent material containing said thyroid hormone with an elution liquid to form an elution mixture having a pH sufficiently high enough to effect elution of said thyroid hormone from said solid sorbent, 5. admixing said elution mixture with thyroid hormone binding globulin and a radioactive isotope labeled thyroid hormone, 6. contacting at least two solutes in said elution mixture containing said thyroid binding globulin and said radioactive isotope labeled thyroid hormone, which solutes react to form in situ a solid adsorbent, said adsorbent formed of material other than said thyroid binding globulin or said thyroid hormone and being of a nature so as to selectively adsorb free thyroid hormone, and 7. radioassaying either said labeled thyroid hormone adsorbed by said solid adsorbent or the remaining labeled thyroid hormone in said elution mixture.
Claim 44
Dependent Claim 12 words
The method of claim 38 wherein said solid sorbent material comprises bentonite.
Claim 45
Dependent Claim 28 words
The method of claim 38 wherein said acidifying is sufficient to adjust the pH of said test fluid to a range of from about 1 to about 3.
Claim 46
Dependent Claim 19 words
The method of claim 38 wherein said pH sufficient to effect elution is from about 8.5 to about 11.
Claim 47
Dependent Claim 57 words
The method of claim 38 wherein the contacting step to effect the in situ formation of said solid adsorbent is accomplished by adding to said test fluid a first solution containing a first solute and a second solution containing a second solute, said first and second solutes reacting in said test fluid to form said solid adsorbent.
Claim 48
Dependent Claim 18 words
The method of claim 42 wherein said first solute and said second solute comprise water soluble inorganic compounds.
Claim 49
Dependent Claim 70 words
The method of claim 42 wherein said first solute is a water soluble substance selected from the class consisting of carboxylic acids, salts of carboxylic acids, carbonates, phosphates, hydroxides, silicates, aluminates, sulphates, and mixtures thereof and said second solute is selected from the class consisting of water soluble salts of the metallic elements of Groups IIa, IIIa, IVa, Ib, IIb, IVb and VIII of the Periodic Table and mixtures thereof.
Claim 50
Dependent Claim 14 words
The method of claim 43 wherein said first solute comprises an alkali metal carbonate.
Claim 51
Dependent Claim 12 words
The method of claim 45 wherein said first solute comprises sodium carbonate.
Claim 52
Dependent Claim 15 words
The method of claim 43 wherein said second solute comprises an alkaline earth metal chloride.
Claim 53
Dependent Claim 12 words
The method of claim 44 wherein said second solute comprises calcium chloride.
Claim 54
Dependent Claim 24 words
The method of claim 42 wherein said first solution containing said first solute is added to said fluid test sample with said elution liquid.
Claim 55
Dependent Claim 32 words
The method of claim 49 wherein said second solution containing said second solute is added to said elution mixture following addition of said thyroid hormone binding globulin and said labeled thyroid hormone.
Claim 56
Independent Claim 156 words
A method of measuring thyroxine in a fluid test sample containing thyroxine and thyroid hormone binding protein comprising: 1. liberating said thyroxine from said thyroid hormone binding protein, 2. separating the thyroxine from the resulting fluid test sample of step 1, 3. admixing the thyroxine from step 2 with a fluid containing thyroid hormone binding globulin and radioactive isotope labeled thyroxine, 4. equilibrating the resultant mixture from step 3, 5. contacting at least two solutes in the mixture from step 4, which soluter react to form in situ a solid adsorbent, said solid adsorbent formed of material other than said thyroid hormone binding globulin or said thyroxine and being of a nature so as to selectively adsorb free thyroxine, 6. separating said solid adsorbent material from the resulting mixture of step 5, and 7. radioassaying either the free labeled thyroxine on said solid adsorbent or said labeled thyroxine remaining in said resulting solution from step 6.
Claim 57
Independent Claim 156 words
A method of measuring thyroxine in a fluid test sample containing thyroxine and thyroid hormone binding protein comprising: 1. liberating said thyroxine from said thyroid hormone binding protein, 2. separating the thyroxine from the resulting fluid test sample of step 1, 3. admixing the thyroxine from step 2 with a fluid containing thyroid hormone binding globulin and radioactive isotope labeled thyroxine, 4. equilibrating the resultant mixture from step 3, 5. contacting at least two solutes in the mixture from step 4, which soluter react to form in situ a solid adsorbent, said solid adsorbent formed of material other than said thyroid hormone binding globulin or said thyroxine and being of a nature so as to selectively adsorb free thyroxine, 6. separating said solid adsorbent material from the resulting mixture of step 5, and 7. radioassaying either the free labeled thyroxine on said solid adsorbent or said labeled thyroxine remaining in said resulting solution from step 6.
Claim 58
Dependent Claim 51 words
A tracer dilution method of measuring thyroxine in a fluid test sample containing thyroxine and thyroid hormone binding protein comprising: 1. liberating said thyroxine from said thyroid hormone binding protein, 2. admixing a measured amount of radioisotope labeled thyroxine with the test fluid sample of step 1 containing the free thyroxine,
Claim 59
Dependent Claim 51 words
A tracer dilution method of measuring thyroxine in a fluid test sample containing thyroxine and thyroid hormone binding protein comprising: 1. liberating said thyroxine from said thyroid hormone binding protein, 2. admixing a measured amount of radioisotope labeled thyroxine with the test fluid sample of step 1 containing the free thyroxine,
Claim 60
Dependent Claim 78 words
contacting at least two solutes in the mixture from step 2, which solutes react to form in situ a solid adsorbent, said adsorbent formed of material other than said thyroxine and being of a nature so as to selectively adsorb free thyroxine, 4. separating said solid adsorbent containing the adsorbed free thyroxine from the resulting mixture of step 3, and 5. radioassaying either said labeled thyroxine adsorbed by said solid adsorbent or said labeled thyroxine remaining in solution.
Claim 61
Dependent Claim 78 words
contacting at least two solutes in the mixture from step 2, which solutes react to form in situ a solid adsorbent, said adsorbent formed of material other than said thyroxine and being of a nature so as to selectively adsorb free thyroxine, 4. separating said solid adsorbent containing the adsorbed free thyroxine from the resulting mixture of step 3, and 5. radioassaying either said labeled thyroxine adsorbed by said solid adsorbent or said labeled thyroxine remaining in solution.

References Cited (Backward Citations)

US3666854A Cited
US3793445A Cited
US3799740A Cited
US3776698A Cited

USPTO Annuity & Maintenance Windows

Annuity Stage Window Opens Payment Deadline Surcharge Period Until Estimated Fee Status
3.5 Years (Year 4) 1980-01-25 1980-07-26 1981-01-25 $2000.00 Window Closed / Lapsed
7.5 Years (Year 8) 1984-01-25 1984-07-26 1985-01-25 $3760.00 Window Closed / Lapsed
11.5 Years (Year 12) 1988-01-25 1988-07-26 1989-01-25 $7700.00 Window Closed / Lapsed

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