Reagent formulations for assaying biological specimens and methods of preparing and using same

• US 3,950,133 A
• Filed: 05/06/1974
• Issued: 04/13/1976
• Est. Priority Date: 10/20/1971
• Status: Expired due to Term

• Current Assignee: Mallinckrodt Incorporated (Mallinckrodt plc)
• Original Assignee: Mallinckrodt Incorporated (Mallinckrodt plc)
• Inventors: Chiang, Ching, Monte, Alexander A.
• Primary Examiner(s): Scovronek, Joseph
• Application Number:
  US05/467,550
• Time in Patent Office: 708 Days
• Field of Search: 23/230 B
• US Class Current: 436/66
• CPC Class Codes: C12Q 1/30 involving catalase
• CPC Class Codes: C12Q 1/32 involving dehydrogenase
• CPC Class Codes: C12Q 1/42 involving phosphatase
• CPC Class Codes: C12Q 1/52 involving transaminase
• CPC Class Codes: C12Q 1/54 involving glucose or galactose
• CPC Class Codes: C12Q 1/58 involving urea or urease
• CPC Class Codes: C12Q 1/62 involving uric acid
• CPC Class Codes: G01N 33/50 Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing measuring or testing processes involving enzymes or microorganisms, compositions or test papers therefor; processes for forming such compositions, condition responsive control in microbiological or enzymological processes C12Q
• CPC Class Codes: G01N 33/68 involving proteins, peptides or amino acids involving lipoproteins G01N33/92
• CPC Class Codes: G01N 33/721 Haemoglobin
• CPC Class Codes: G01N 33/84 involving inorganic compounds or pH
• CPC Class Codes: Y10T 436/166666 of inorganic phosphorus compound in body fluid

Abstract

A solid, water-soluble substantially anhydrous, storage-stable reagent formulation for use in conducting a clinical diagnostic test on a biological specimen is provided. The reagent formulation comprises a mixture containing a reagent capable of participating in a test reaction to effect a measurable change in a test system; and a nitrogen bearing polyoxyalkylene nonionic surfactant. The surfactant has a structure corresponding to that obtained when ethylene diamine is reacted sequentially with propylene oxide and ethylene oxide in the presence of a catalyst. The polyoxypropylene chains of said surfactant have an average molecular weight of between about 750 and about 6750. Methods of preparing the reagent formulations and methods of using them to conduct clinical diagnostic tests are also provided.

Claims

1. In a method of conducting a clinical diagnostic test on a biological specimen wherein the specimen is mixed with a liquid reagent formulation to form a specimen/reagent system, the liquid reagent formulation containing a reagent capable of effecting a reaction which causes a measurable change in the specimen/reagent system, and a change in the system resulting from the reaction is measured, the improvement which comprises preparing the liquid reagent formulation by dissolving in water a granular, water-soluble, substantially anhydrous, storage-stable mixture containing the reagent and a nitrogen-containing polyoxyalkylene nonionic surfactant obtained by the sequential reaction of ethylenediamine with propylene oxide and ethylene oxide in the presence of a catalyst, the surfactant containing polyoxypropylene chains having an average molecular weight of between about 750 and about 6750 and polyoxyethylene chains constituting between about 10 and about 80 weight percent of the surfactant.

2. A method as set forth in claim 1 wherein the nitrogen-containing surfactant is solid and the polyoxypropylene chains thereof have an average molecular weight of less than about 4000.

3. A method as set forth in claim 2 wherein the polyoxypropylene chains of the surfactant have an average molecular weight of about 2750 and the weight percentage of the polyoxyethylene units thereof is about 70%.

4. In a method of assaying a biological specimen for hemoglobin utilizing a liquid reagent formulation containing potassium ferricyanide and potassium cyanide the improvement which comprises preparing the liquid reagent formulation by dissolving in water, a granular, water-soluble, substantially anhydrous, storage-stable reagent formulation containing potassium ferricyanide, potassium cyanide, sodium bicarbonate, mannitol and a nitrogen-containing polyoxyalkylene nonionic surfactant obtained by the sequential reaction of ethylenediamine with propylene oxide and ethylene oxide in the presence of a catalyst, the surfactant containing polyoxypropylene chains having an average molecular weight of between about 750 and about 6750 and polyoxyethylene chains constituting between about 10 and about 80 weight percent of the surfactant.

5. A method as set forth in claim 4 wherein the polyoxypropylene chains of the surfactant have an average molecular weight of about 2750 and the weight percentage of the polyoxyethylene units thereof is about 70%.

6. In a method of assaying a biological specimen for protein utilizing a liquid reagent formulation containing cupric tartrate the improvement which comprises preparing the liquid reagent formulation by dissolving in water a granular, water-soluble, substantially anhydrous, storage-stable reagent formulation contaning cupric tartrate, sodium tartrate, lithium hydroxide, a surfactant comprising polyoxyethylene ether alcohol and urea, and a nitrogen-containing polyoxyalkylene nonionic surfactant obtained by the sequential reaction of ethylene diamine with propylene oxide and ethylene oxide in the presence of a catalyst, the surfactant containing polyoxypropylene chains having an average molecular weight of between about 750 and about 6750 and polyoxyethylene chains constituting between about 10 and about 80 weight percent of the surfactant.

7. A method as set forth in claim 6 wherein the polyoxypropylene chains of the surfactant have an average molecular weight of about 2750 and the weight percentage of the polyoxyethylene units thereof is about 70%.

8. In a method of assaying a biological specimen for phosphorus utilizing a first liquid reagent formulation containing sodium molybdate and a second liquid reagent formulation containing ascorbic acid, the improvement which comprises preparing the first liquid reagent formulation by dissolving in water a granular, water-soluble, substantially anhydrous, storage-stable reagent formulation containing sodium molybdate, tris-(hydroxymethyl)-aminomethane, sodium lauryl sulfate and a nitrogen-containing polyoxyalkylene nonionic surfactant obtained by the sequential reaction of ethylenediamine with propylene oxide and ethylene oxide in the presence of a catalyst, the surfactant containing polyoxypropylene chains having an average molecular weight of between about 750 and about 6750 and polyoxyethylene chains constituting between about 10 and about 80 weight percent of the surfactant, and preparing the second liquid reagent formulation by dissolving in water a second granular, water-soluble, substantially anhydrous, storage-stable reagent formulation containing ascorbic acid, sulfamic acid, sodium lauryl sulfate, and the nitrogen-containing polyoxyalkylene nonionic surfactant.

9. A method as set forth in claim 8 wherein the polyoxypropylene chains of the surfactant have an average molecular weight of about 2750 and the weight percentage of the polyoxyethylene units thereof is about 70%.