Universal rinse reagent and method for use in hematological analyses of whole blood samples

• US 5,888,752 A
• Filed: 05/16/1995
• Issued: 03/30/1999
• Est. Priority Date: 05/16/1995
• Status: Expired due to Term

• Current Assignee: Siemens Healthcare Diagnostics Incorporated (Siemens AG)
• Original Assignee: Bayer Corporation (Bayer AG)
• Inventors: Shapiro, Phyllis, Malin, Michael J.
• Primary Examiner(s): Housel, James C.
• Assistant Examiner(s): GRUN, JAMES LESLIE
• Application Number:
  US08/442,363
• Time in Patent Office: 1,414 Days
• Field of Search: 435/7.24, 435/7.25, 435/962, 422/1, 436/546, 436/8, 436/63, 436/49, 252/106, 252/174.21-174.23, 424/78.17, 510/161
• US Class Current: 435/7.24
• CPC Class Codes: C11D 1/722 Ethers of polyoxyalkylene glycols having mixed oxyalkylene groups; Polyalkoxylated fatty alcohols or polyalkoxylated alkylaryl alcohols with mixed oxyalkylele groups C11D1/721 takes precedence
• CPC Class Codes: C11D 3/3707 Polyethers, e.g. polyalkyleneoxides
• CPC Class Codes: Y10S 435/962 Prevention or removal of interfering materials or reactants or other treatment to enhance results, e.g. determining or preventing nonspecific binding
• CPC Class Codes: Y10T 436/10 Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
• CPC Class Codes: Y10T 436/114998 with treatment or replacement of aspirator element [e.g., cleaning, etc.]

Abstract

The present invention provides a heretofore unknown use for a aqueous reagent composition that serves as a universal rinse for performing and/or improving a variety of hematological analyses on automated analyzers. The universal rinse reagent comprises a phosphate buffer to maintain the rinse solution pH at from about 7.0 to about 7.6; a nonhemolytic nonionic surfactant, such as a Pluronic® an alkali metal salt, such as NaCi; antimicrobial and anti-oxidant compounds; and has an osmolality of about 285 to 305 mOsmol/kg. The universal rinse reagent composition is highly suitable for use in the rinse phases or cycles of all types of blood cell analysis methods and processes performed on semi- and fully-automated systems. The invention allows the replacement of mutiple and specific rinse solutions with the disclosed universal rinse to obtain accurate and acceptable results, independent of the types of blood cell analyses that are performed. The universal rinse is most particularly useful for automated systems having intricate hardware and a number of different input and output channels. The universal rinse composition serves to economize, streamline, and simplify the design and operation of such systems.

Claims

1. A method for preventing blood sample and reagent mixture accumulation inside system hardware and in all cell flow channels and system components of a semi- or fully-automated hematology analyzer used in blood sample analysis, after a blood sample has been analyzed in the hematology analyzer and before analysis of another blood sample therein, comprising:

a) mixing an aqueous reagent composition comprising the following components to form a rinsing and cleansing reagent solution;

I) a nonionic nonhemolytic surfactant which is a block copolymer of polyoxyethylene and polyoxypropylene terminating in primary hydroxyl groups, wherein the weight percentage of polyoxyethylene is from about 20 to about 80 percent in a molecule of said surfactant, and the polyoxypropylene in said surfactant has a weight range of about 2000 to about 4000 g/mol; and

ii) a buffer or buffer mixture at a concentration effective for maintaining an approximately neutral pH of said reagent solution;

wherein said reagent solution rinses and removes unlysed cells, lysed cells and released intracellular contents thereof, and residual reagent components from all blood cell channels and system hardware of said hematology analyzer between blood sample analysis, thereby preventing sample carryover; and

b) rinsing and removing lysed blood cells, released contents thereof, unlysed blood cells and reagent mixture accumulation from all blood cell channels of said analyzer and inside all system hardware and components thereof by contacting all said blood cell channels, system hardware and components thereof with the rinsing and cleansing reagent solution of step a) after the analysis of blood sample in said analyzer, before the analysis of another blood sample.

2. The method according to claim 1, wherein, in said reagent composition of step (a), the nonionic nonhemolytic surfactant has a weight percentage of polyoxyethylene of from about 30 to about 70 percent in said surfactant molecule.

3. The method according to claim 1, wherein, in said reagent composition of step (a), the nonionic nonhemolytic surfactant has a weight percentage of polyoxyethylene of about 50 percent in said surfactant molecule.

4. The method according to claim 1, wherein, in said reagent composition of step (a), the nonionic nonhemolytic surfactant has an average molecular weight selected from the group consisting of about 4200, 4600, 4950, 5900, 5750 and 6500 g/mol.

5. The method according to claim 1, wherein said nonionic nonhomolytic surfactant has an average molecular weight of about 6500 and has a weight percentage of polyoxyethylene of about 50 percent.

6. The method according to claim 1, wherein said buffer or buffer mixture maintains a pH of said risen reagent solution at from about 7.0 to about 7.3.

7. The method according to claim 1, wherein said buffer or buffer mixture comprises Na₂ HPO₄, or a mixture thereof.

8. The method according to claim 1, wherein, in step (a), the buffer or buffer mixture maintains the pH of the rinse reagent solution at from about 6.8 to about 7.8.

9. The method according to claim 1, wherein said aqueous reagent composition of step a) further comprises an alkali metal chloride salt.

10. The method according to claim 9, where said alkali metal chloride salt is NaCl, KCl, or LiCl.

11. The method according to claim 10, wherein said alkali metal chloride salt is NaCl.

12. The method according to claim 1, wherein said aqueous reagent composition of said step a) further comprises an anti-microbial compound.

13. The method according to claim 12, wherein said anti-microbial compound is selected from the group consisting of 2-methyl-4-isothiazolin-3-one, 5-chloro-2-methyl-4-isothiazolin-3-one, N,N'"'"'-methylenebis (N'"'"'-(1-(hydroxymethyl)-2,5-dioxo-4-imidazolidinyl) urea, 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride, and 2-bromo-2-nitropropane-1,3-diol (C₃ H₆ BrNO₄).

14. The method according to claim 1, wherein said aqueous reagent composition of said step a) further comprises an anti-oxidant compound.

15. The method according to claim 14, wherein said anti-oxidant is selected from the group consisting of 3,3'"'"'-thiodiproprionic acid, 3,3'"'"'-dithioacetic acid, water-soluble vitamin E, butylated hydroxytoluene (BHT), 2, 6-di-tert-butyl-4-methylphenol, butylated hydroxyanisole (BHA), 2-tert-butyl-4-methoxyphenol, and ρ

-methoxyphenol.

16. The method according to claim 1, wherein said aqueous reagent composition of said step a) has an osmolality from about 285 m Osmol/kg to about 305 mOsmol/kg.

17. The method according to claim 1, wherein, in step (b), the blood cell channels rinsed by said reagent include red blood cell/platelet channel, reticulocyte channel, basophil channel, peroxidase channel and hemoglobin channel.

18. A method for removing blood sample and reagent mixtures from inside of system components of semi- and fully-automated hematology analyzers used in the analysis of blood samples, comprising rinsing the insides of said hematology analyzer components including all blood cell analysis channels within said analyzer with an aqueous rinse reagent composition at least once after performing said hematology analysis, said rinse composition comprising:

a nonionic nonhemolytic surfactant which is a block copolymer of polyoxyethylene and polyoxypropylene termination in primary hydroxyl groups, the weight percentage of said polyoxyethylene being from about 20 to about 80 percent in a molecule of said surfactant and a buffer or buffer mixture present at a concentration effective for maintaining an approximately neutral pH of the rinse composition.

19. The method according to claim 18, wherein, in said reagent composition of step (a), the nonionic nonhemolytic surfactant has a weight percentage of polyoxyethylene of from about 30 to about 70 percent in said surfactant molecule.

20. The method according to claim 18, wherein, in said reagent composition of step (a), the nonionic nonhemolytic surfactant has a weight percentage of polyoxyethylene of about 50 percent in said surfactant molecule.

21. The method according to claim 18, wherein, in said reagent composition of step (a), the nonionic nonhemolytic surfactant has an average molecular weight selected from the group consisting of about 4200, 4600, 4950, 5900, 5750 and 6500 g/mol.

22. The method according to claim 18, wherein said nonionic nonhemolytic surfactant has an average molecular weight of about 6500 and has a weight percentage of polyoxyethylene of about 50 percent.

23. The method according to claim 18, wherein the polyoxypropylene in the nonionic nonhemolytic surfactant has a weight range of about 2000 to about 4000 g/mol.

24. The method according to claim 18, wherein said rinse reagent composition further comprises a buffer or buffer mixture which maintains a pH of from about 6.8 to about 7.8.

25. The method according to claim 18, wherein said rinse reagent composition further comprises a buffer or buffer mixture which maintains a pH of from about 7.0 to about 7.3.

26. The method according to claim 20 or claim 25, wherein said buffer comprises Na₂ HPO₄, NaH₂ PO₄, or a mixture thereof.

27. The method according to claim 18, wherein said aqueous rinse reagent composition further comprises an alkali metal chloride salt.

28. The method according to claim 27, wherein said alkali metal chloride salt is NaCl, KCl, or LiCl.

29. The method according to claim 27, wherein said alkali metal chloride salt is NaCl.

30. The method according to claim 18, wherein said aqueous rinse reagent composition further comprises an anti-microbial compound.

31. The method according to claim 30, wherein said anti-microbial compound is selected from the group consisting of 2-methyl-4-isothiazolin-3-one, 5-chloro-2-methyl-4-isothiazolin-3-one, N,N'"'"'-methylenebis (N'"'"'-(1-(hydroxymethyl)-2,5-dioxo-4-imidazolidinyl) urea, 1-(3-chloroallyl)-3,5,7-triaza-1-azoniaadamantane chloride, and 2-bromo-2-nitropropane-1,3-diol (C₃ H₆ BrNO₄).

32. The method according to claim 18, wherein said aqueous rinse reagent composition further comprises an anti-oxidant compound.

33. The method according to claim 32, wherein said anti-oxidant is selected from the group consisting of 3,3'"'"'-thiodiproprionic acid, 3,3'"'"'-dithioacetic acid, water-soluble vitamin E, butylated hydroxytoluene (BHT), 2, 6-di-tert-butyl-4-methylphenol, butylated hydroxyanisole (BHA), 2-tert-butyl-4-methoxyphenol, and ρ

-methoxyphenol.

34. The method according to claim 18, wherein said aqueous rinse reagent composition has an osmolality from about 285 m Osmol/kg to about 305 mOsmol/kg.

35. The method according to claim 18, wherein the blood cell channels rinsed by said reagent include red blood cell/platelet channel, reticulocyte channel, basophil channel, peroxidase channel and hemoglobin channel.