WO1997019350A1 - A method and a rinse solution used in operating instruments analyzing protein-containing biological liquids - Google Patents
A method and a rinse solution used in operating instruments analyzing protein-containing biological liquids Download PDFInfo
- Publication number
- WO1997019350A1 WO1997019350A1 PCT/DK1996/000468 DK9600468W WO9719350A1 WO 1997019350 A1 WO1997019350 A1 WO 1997019350A1 DK 9600468 W DK9600468 W DK 9600468W WO 9719350 A1 WO9719350 A1 WO 9719350A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- rinse solution
- rinse
- blood
- instrument
- procedure
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 37
- 239000007788 liquid Substances 0.000 title claims abstract description 17
- 102000004169 proteins and genes Human genes 0.000 title claims abstract description 7
- 108090000623 proteins and genes Proteins 0.000 title claims abstract description 7
- 239000008280 blood Substances 0.000 claims abstract description 32
- 210000004369 blood Anatomy 0.000 claims abstract description 32
- 239000000126 substance Substances 0.000 claims abstract description 31
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 claims abstract description 24
- HTTJABKRGRZYRN-UHFFFAOYSA-N Heparin Chemical compound OC1C(NC(=O)C)C(O)OC(COS(O)(=O)=O)C1OC1C(OS(O)(=O)=O)C(O)C(OC2C(C(OS(O)(=O)=O)C(OC3C(C(O)C(O)C(O3)C(O)=O)OS(O)(=O)=O)C(CO)O2)NS(O)(=O)=O)C(C(O)=O)O1 HTTJABKRGRZYRN-UHFFFAOYSA-N 0.000 claims abstract description 12
- 229920000669 heparin Polymers 0.000 claims abstract description 12
- 229960002897 heparin Drugs 0.000 claims abstract description 11
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 10
- 238000004159 blood analysis Methods 0.000 claims description 9
- 150000003839 salts Chemical class 0.000 claims description 5
- 239000011780 sodium chloride Substances 0.000 claims description 5
- 230000002070 germicidal effect Effects 0.000 claims description 4
- 238000004458 analytical method Methods 0.000 claims description 3
- 239000000872 buffer Substances 0.000 claims description 3
- 101100536354 Drosophila melanogaster tant gene Proteins 0.000 claims 1
- 239000000243 solution Substances 0.000 description 30
- 239000006174 pH buffer Substances 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 4
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
- 239000000203 mixture Substances 0.000 description 4
- 239000000523 sample Substances 0.000 description 4
- 239000004094 surface-active agent Substances 0.000 description 4
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
- PUPZLCDOIYMWBV-UHFFFAOYSA-N (+/-)-1,3-Butanediol Chemical compound CC(O)CCO PUPZLCDOIYMWBV-UHFFFAOYSA-N 0.000 description 2
- HZAXFHJVJLSVMW-UHFFFAOYSA-N 2-Aminoethan-1-ol Chemical compound NCCO HZAXFHJVJLSVMW-UHFFFAOYSA-N 0.000 description 2
- YIWUKEYIRIRTPP-UHFFFAOYSA-N 2-ethylhexan-1-ol Chemical compound CCCCC(CC)CO YIWUKEYIRIRTPP-UHFFFAOYSA-N 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Chemical compound CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 102000004506 Blood Proteins Human genes 0.000 description 2
- 108010017384 Blood Proteins Proteins 0.000 description 2
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- 239000001110 calcium chloride Substances 0.000 description 2
- 229910001628 calcium chloride Inorganic materials 0.000 description 2
- SWXVUIWOUIDPGS-UHFFFAOYSA-N diacetone alcohol Chemical compound CC(=O)CC(C)(C)O SWXVUIWOUIDPGS-UHFFFAOYSA-N 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- HJOVHMDZYOCNQW-UHFFFAOYSA-N isophorone Chemical compound CC1=CC(=O)CC(C)(C)C1 HJOVHMDZYOCNQW-UHFFFAOYSA-N 0.000 description 2
- RLSSMJSEOOYNOY-UHFFFAOYSA-N m-cresol Chemical compound CC1=CC=CC(O)=C1 RLSSMJSEOOYNOY-UHFFFAOYSA-N 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RTBFRGCFXZNCOE-UHFFFAOYSA-N 1-methylsulfonylpiperidin-4-one Chemical compound CS(=O)(=O)N1CCC(=O)CC1 RTBFRGCFXZNCOE-UHFFFAOYSA-N 0.000 description 1
- IHPYMWDTONKSCO-UHFFFAOYSA-N 2,2'-piperazine-1,4-diylbisethanesulfonic acid Chemical compound OS(=O)(=O)CCN1CCN(CCS(O)(=O)=O)CC1 IHPYMWDTONKSCO-UHFFFAOYSA-N 0.000 description 1
- NUMXHEUHHRTBQT-AATRIKPKSA-N 2,4-dimethoxy-1-[(e)-2-nitroethenyl]benzene Chemical compound COC1=CC=C(\C=C\[N+]([O-])=O)C(OC)=C1 NUMXHEUHHRTBQT-AATRIKPKSA-N 0.000 description 1
- BEVWMRQFVUOPJT-UHFFFAOYSA-N 2,4-dimethyl-1,3-thiazole-5-carboxamide Chemical compound CC1=NC(C)=C(C(N)=O)S1 BEVWMRQFVUOPJT-UHFFFAOYSA-N 0.000 description 1
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 1
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 1
- AJTVSSFTXWNIRG-UHFFFAOYSA-N 2-[bis(2-hydroxyethyl)amino]ethanesulfonic acid Chemical compound OCC[NH+](CCO)CCS([O-])(=O)=O AJTVSSFTXWNIRG-UHFFFAOYSA-N 0.000 description 1
- POAOYUHQDCAZBD-UHFFFAOYSA-N 2-butoxyethanol Chemical compound CCCCOCCO POAOYUHQDCAZBD-UHFFFAOYSA-N 0.000 description 1
- ZNQVEEAIQZEUHB-UHFFFAOYSA-N 2-ethoxyethanol Chemical compound CCOCCO ZNQVEEAIQZEUHB-UHFFFAOYSA-N 0.000 description 1
- DUHQIGLHYXLKAE-UHFFFAOYSA-N 3,3-dimethylglutaric acid Chemical compound OC(=O)CC(C)(C)CC(O)=O DUHQIGLHYXLKAE-UHFFFAOYSA-N 0.000 description 1
- DVLFYONBTKHTER-UHFFFAOYSA-N 3-(N-morpholino)propanesulfonic acid Chemical compound OS(=O)(=O)CCCN1CCOCC1 DVLFYONBTKHTER-UHFFFAOYSA-N 0.000 description 1
- FMTLDVACNZDTQL-UHFFFAOYSA-N 5-ethyl-1,3-diazinane-2,4,6-trione Chemical compound CCC1C(=O)NC(=O)NC1=O FMTLDVACNZDTQL-UHFFFAOYSA-N 0.000 description 1
- 239000007992 BES buffer Substances 0.000 description 1
- ZNSMNVMLTJELDZ-UHFFFAOYSA-N Bis(2-chloroethyl)ether Chemical compound ClCCOCCCl ZNSMNVMLTJELDZ-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- OPFTUNCRGUEPRZ-QLFBSQMISA-N Cyclohexane Natural products CC(=C)[C@@H]1CC[C@@](C)(C=C)[C@H](C(C)=C)C1 OPFTUNCRGUEPRZ-QLFBSQMISA-N 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- 239000006173 Good's buffer Substances 0.000 description 1
- 239000007995 HEPES buffer Substances 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 239000007993 MOPS buffer Substances 0.000 description 1
- JOCBASBOOFNAJA-UHFFFAOYSA-N N-tris(hydroxymethyl)methyl-2-aminoethanesulfonic acid Chemical compound OCC(CO)(CO)NCCS(O)(=O)=O JOCBASBOOFNAJA-UHFFFAOYSA-N 0.000 description 1
- 239000007990 PIPES buffer Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 102000035195 Peptidases Human genes 0.000 description 1
- 108091005804 Peptidases Proteins 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 239000007994 TES buffer Substances 0.000 description 1
- UWHCKJMYHZGTIT-UHFFFAOYSA-N Tetraethylene glycol, Natural products OCCOCCOCCOCCO UWHCKJMYHZGTIT-UHFFFAOYSA-N 0.000 description 1
- 239000007983 Tris buffer Substances 0.000 description 1
- JFCQEDHGNNZCLN-UHFFFAOYSA-N anhydrous glutaric acid Natural products OC(=O)CCCC(O)=O JFCQEDHGNNZCLN-UHFFFAOYSA-N 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 150000007656 barbituric acids Chemical class 0.000 description 1
- 235000019437 butane-1,3-diol Nutrition 0.000 description 1
- 210000001217 buttock Anatomy 0.000 description 1
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 1
- SZXQTJUDPRGNJN-UHFFFAOYSA-N dipropylene glycol Chemical compound OCCCOCCCO SZXQTJUDPRGNJN-UHFFFAOYSA-N 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 229940031098 ethanolamine Drugs 0.000 description 1
- 239000007789 gas Substances 0.000 description 1
- ZFGMDIBRIDKWMY-PASTXAENSA-N heparin Chemical class CC(O)=N[C@@H]1[C@@H](O)[C@H](O)[C@@H](COS(O)(=O)=O)O[C@@H]1O[C@@H]1[C@@H](C(O)=O)O[C@@H](O[C@H]2[C@@H]([C@@H](OS(O)(=O)=O)[C@@H](O[C@@H]3[C@@H](OC(O)[C@H](OS(O)(=O)=O)[C@H]3O)C(O)=O)O[C@@H]2O)CS(O)(=O)=O)[C@H](O)[C@H]1O ZFGMDIBRIDKWMY-PASTXAENSA-N 0.000 description 1
- IIRDTKBZINWQAW-UHFFFAOYSA-N hexaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCO IIRDTKBZINWQAW-UHFFFAOYSA-N 0.000 description 1
- 125000002883 imidazolyl group Chemical group 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000002207 metabolite Substances 0.000 description 1
- GLZWNFNQMJAZGY-UHFFFAOYSA-N octaethylene glycol Chemical compound OCCOCCOCCOCCOCCOCCOCCOCCO GLZWNFNQMJAZGY-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- JLFNLZLINWHATN-UHFFFAOYSA-N pentaethylene glycol Chemical compound OCCOCCOCCOCCOCCO JLFNLZLINWHATN-UHFFFAOYSA-N 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 description 1
- RUOJZAUFBMNUDX-UHFFFAOYSA-N propylene carbonate Chemical compound CC1COC(=O)O1 RUOJZAUFBMNUDX-UHFFFAOYSA-N 0.000 description 1
- 210000002966 serum Anatomy 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- -1 tetrahy¬ drofuran Chemical compound 0.000 description 1
- ZIBGPFATKBEMQZ-UHFFFAOYSA-N triethylene glycol Chemical compound OCCOCCOCCO ZIBGPFATKBEMQZ-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
-
- C—CHEMISTRY; METALLURGY
- C11—ANIMAL OR VEGETABLE OILS, FATS, FATTY SUBSTANCES OR WAXES; FATTY ACIDS THEREFROM; DETERGENTS; CANDLES
- C11D—DETERGENT COMPOSITIONS; USE OF SINGLE SUBSTANCES AS DETERGENTS; SOAP OR SOAP-MAKING; RESIN SOAPS; RECOVERY OF GLYCEROL
- C11D3/00—Other compounding ingredients of detergent compositions covered in group C11D1/00
- C11D3/16—Organic compounds
- C11D3/38—Products with no well-defined composition, e.g. natural products
- C11D3/384—Animal products
-
- C11D2111/20—
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/10—Devices for transferring samples or any liquids to, in, or from, the analysis apparatus, e.g. suction devices, injection devices
- G01N35/1004—Cleaning sample transfer devices
Definitions
- the present invention relates to a method and a rinse solution used in operating instruments analyzing pro ⁇ tein-containing biological liquids.
- Instruments analyzing biological liquids are in wide- spread use. Thus, instruments for analyzing blood, se ⁇ rum or plasma in more or less automated form are indis ⁇ pensable in hospitals and laboratories where it is of importance to know the values of various blood para ⁇ meters, e.g. pH, pC0 2 , p0 2 , hemoglobin content, electro- lyte concentration, metabolite concentration, etc. and parameters derived therefrom, e.g. "standard bicarbon ⁇ ate”.
- Instruments for analysis of blood, serum or plasma typically operate with al ⁇ ternation between an analysis procedure in which a sam- pie is introduced into the instrument for determination of one or more parameters and an rinse procedure in which a rinse solution is passed through the instrument manually or automatically (instrument-driven) .
- the rinse solution is introduced, either the same way as the sample or, especially for automatic instruments, from a rinse solution reservoir connected to the in ⁇ strument.
- the normal duration of the rinse procedure is of the same order as the normal duration of each analy ⁇ sis procedure.
- a calibration procedure is performed during which the sensors of the instrument are calibrated against calibration liquids or gases followed by rinsing with rinse solution. The course of the rinse procedure and calibration procedure is usually determined by the programming of the instru- ment.
- a source of errors in the determination of blood para ⁇ meters is deposits of a substance on the detection ar ⁇ eas of the sensors, particularly deposits of proteins or protein-containing substances from blood samples analyzed in the instrument.
- the purpose of the invention is therefore to provide an improved method and rinse solution which can be used in operating various types of blood analysis instruments, including blood analysis instruments containing one or more enzyme sensors.
- the heparin is preferably present as a heparin salt, most preferably sodium heparin salt.
- concentration of heparin in the rinse solution is preferably in the range of 200 - 20000 IU/kg, and par ⁇ ticularly in the range of 500 - 10000 IU/kg, the most preferred concentration of heparin in the rinse solu ⁇ tion being 1000 IU/kg rinse solution.
- a blood dissolving substance desig ⁇ nates a substance capable of dissolving blood or desorbing/removing adsorbed blood proteins.
- the rinse solution also contains one or more salts of a concentration resulting in a ionic strength of the rinse solution of the same level as the ionic strength of blood.
- the salt is preferably sodium chloride.
- the rinse solution contains prefera- bly one or more germicides and one or more surfactants, e.g. KathonTM, GermalTM, TritonTM CF54 and TritonTM X-100.
- the rinse solution also contains a pH buffer and has a pH value in the range of 6 - 9.
- the preferred pH buffer is imidazole. Said buffer has i.a. the advantage of not causing interference on the glu ⁇ cose measurement on measuring instruments containing an amperometric glucose sensor.
- pH buffers are glutaric acid deriva ⁇ tives, e.g. 3, 3-dimethylglutaric acid; barbituric acid derivatives, e.g. ethyl barbituric acid; the so-called Good-buffers having a pK in the range of 6.5 - 9.5, e.g. BES, TES, HEPES, PIPES and MOPS; the tris-buffer (2-amino-2-hydroxymethyl-l, 3-propanediol) and the hy ⁇ drogen phosphate/monohydrogen phosphate buffer system, if said buffers are compatible with the sensors of the blood analysis instrument.
- glutaric acid deriva ⁇ tives e.g. 3, 3-dimethylglutaric acid
- barbituric acid derivatives e.g. ethyl barbituric acid
- the so-called Good-buffers having a pK in the range of 6.5 - 9.5 e.g. BES,
- a second aspect of the invention relates to a method having the features discussed in the introductory part of claim 1, wherein said method is characterized by the rinse procedure being performed with a rinse solution containing or consisting of a blood dissolving organic substance.
- the invention also relates to a rinse solution used in the method, said rinse so ⁇ lution being characterized by the rinse solution con ⁇ taining or consisting of a blood dissolving organic substance.
- the invention further com ⁇ prises the use of a rinse solution containing or con ⁇ sisting of a blood dissolving organic substance in an instrument-driven rinse procedure.
- the rinse solu ⁇ tion contains preferably salt of a concentration re ⁇ sulting in an ionic strength of the rinse solution of the same level as the ionic strength of blood. Also, it is preferred to add a pH buffer to the rinse solution selected among the pH buffers mentioned above, as it is preferred to add to the rinse solution one or more ger ⁇ macdes or surfactants, particularly the ones mentioned previously.
- the invention relates to the use of a liquid containing or consisting of a blood dissolving organic substance for rinsing an instrument analyzing protein-containing biological liquids; a method for rinsing an instrument with a liquid containing or con- sisting of a blood dissolving organic substance by a rinse procedure wherein the liquid is introduced into the instrument by the operator the same way as a sample through the normal sample inlet of the instrument; as well as a liquid for use in this rinse procedure, said liquid being characterized by containing or consisting of a blood dissolving substance.
- Preferred embodiments of said liquid are as described above in connection with the second aspect of the in- vention.
- the manual rinse procedure can replace or sup- plement the previously discussed instrument-driven rinse procedure.
- the blood dissolving organic sub- stance forms part of a rinse solution relating to the first aspect of the invention, i.e. a rinse solution containing heparin, or forms part of a rinse solution relating to the second aspect of the invention, i.e. a rinse solution containing or consisting of a blood dis- solving organic substance, but which does not contain an anticoagulant, or forms part of a liquid relating to the third aspect of the invention, in which the liquid is used in a manual rinse procedure, the maximum con ⁇ tent of the blood dissolving organic substance will be determined by the impact of the substance on the sen ⁇ sors of the instrument, whereas the minimum content, which is effective, is determined by means of experi ⁇ ments.
- the organic blood dissolving substance is selected preferably among diethylene glycol, ethylene glycol, glycerol and compositions thereof;
- other suitable substances are substances from the group consisting of 2-ethyl hexanol, cyclo- hexane, ethanol amine, dimethyl sulphoxide, formamide, gamma butyrol acetone, 1,3-butane diol, propylene gly ⁇ col, dimethyl formamide, dipropylene glycol, aniline, ethylene glycol monomethyl ether, propylene carbonate, m-cresol, ethanol, methanol, ethylene glycol monoethyl ether, dichlorodiethyl ether, cyclo hexanol, nitroben ⁇ zene, benzaldehyde, 1-butanol, acetophenone, diacetone alcohol, methylene dichloride, ethylene dichloride, ethylene glycol monobutyl ether, isophorone, tetrahy ⁇ drofuran, triethylene glycol, tetraethylene glycol,
- the most preferred concentration range is 30 ppm - 15000 ppm, more preferred 90 ppm - 1500 ppm, and especially preferred is 150 ppm;
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- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Wood Science & Technology (AREA)
- Organic Chemistry (AREA)
- Zoology (AREA)
- Engineering & Computer Science (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
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Abstract
In instruments analyzing protein-containing biological liquids, the instrument-driven rinse procedure is performed by a rinse solution containing heparin. Preferably the rinse solution also contains a blood dissolving organic substance, such as diethylene glycol. In a second aspect, the instrument-driven rinse procedure is performed by a rinse solution containing or consisting of a blood dissolving organic substance. In a third aspect, a substance containing or consisting of a blood dissolving organic substance is used in a manual rinse procedure for rinsing an instrument analyzing protein-containing biological liquids.
Description
A METHOD AND A RINSE SOLUTION USED IN OPERATING INSTRUMENTS ANALYZING PROTEIN-CONTAINING BIOLOGICAL LIQUIDS
The present invention relates to a method and a rinse solution used in operating instruments analyzing pro¬ tein-containing biological liquids.
Instruments analyzing biological liquids are in wide- spread use. Thus, instruments for analyzing blood, se¬ rum or plasma in more or less automated form are indis¬ pensable in hospitals and laboratories where it is of importance to know the values of various blood para¬ meters, e.g. pH, pC02, p02, hemoglobin content, electro- lyte concentration, metabolite concentration, etc. and parameters derived therefrom, e.g. "standard bicarbon¬ ate".
It is a must that said parameters are determined with great exactitude as an accurate and reliable determina¬ tion of blood parameters in certain clinical situations is of decisive importance. Therefore, it is necessary that these instruments show a high degree of accuracy and reliability.
Instruments for analysis of blood, serum or plasma (hereinafter termed "blood analysis instruments" or "instruments" for brevity) typically operate with al¬ ternation between an analysis procedure in which a sam- pie is introduced into the instrument for determination of one or more parameters and an rinse procedure in which a rinse solution is passed through the instrument manually or automatically (instrument-driven) . The rinse solution is introduced, either the same way as the sample or, especially for automatic instruments, from a rinse solution reservoir connected to the in¬ strument. The normal duration of the rinse procedure is of the same order as the normal duration of each analy¬ sis procedure. At suitable intervals, a calibration procedure is performed during which the sensors of the
instrument are calibrated against calibration liquids or gases followed by rinsing with rinse solution. The course of the rinse procedure and calibration procedure is usually determined by the programming of the instru- ment.
A source of errors in the determination of blood para¬ meters is deposits of a substance on the detection ar¬ eas of the sensors, particularly deposits of proteins or protein-containing substances from blood samples analyzed in the instrument.
It is known to remove deposits in blood analysis in¬ struments by means of rinse solutions containing a pro- teolytic enzyme, cf. e.g. the specification of US Pat¬ ent No. US 4867797.
However, it has appeared that said known rinse solu¬ tions cannot be used in certain types of blood analysis instruments as the rinse solutions influence the detec¬ tion area of the sensors, thus causing measuring er¬ rors. This situation exists in i.a. a blood analysis instrument containing an enzyme sensor for determina¬ tion of glucose.
The purpose of the invention is therefore to provide an improved method and rinse solution which can be used in operating various types of blood analysis instruments, including blood analysis instruments containing one or more enzyme sensors.
It has now been shown that a satisfactory rinsing of a blood analysis instrument is obtained by a method as set forth in the introductory part of claim 1, wherein the rinse procedure is performed by a rinse solution containing heparin.
The heparin is preferably present as a heparin salt, most preferably sodium heparin salt.
The concentration of heparin in the rinse solution is preferably in the range of 200 - 20000 IU/kg, and par¬ ticularly in the range of 500 - 10000 IU/kg, the most preferred concentration of heparin in the rinse solu¬ tion being 1000 IU/kg rinse solution.
It has been found that the presence of a blood dissolv¬ ing organic substance, e.g. diethylene glycol, in¬ creases the effect of the rinse solution.
In this context, a blood dissolving substance desig¬ nates a substance capable of dissolving blood or desorbing/removing adsorbed blood proteins.
Preferably, the rinse solution also contains one or more salts of a concentration resulting in a ionic strength of the rinse solution of the same level as the ionic strength of blood. The salt is preferably sodium chloride. Finally, the rinse solution contains prefera- bly one or more germicides and one or more surfactants, e.g. Kathon™, Germal™, Triton™ CF54 and Triton™ X-100.
Preferably, the rinse solution also contains a pH buffer and has a pH value in the range of 6 - 9. The preferred pH buffer is imidazole. Said buffer has i.a. the advantage of not causing interference on the glu¬ cose measurement on measuring instruments containing an amperometric glucose sensor.
Other suitable pH buffers are glutaric acid deriva¬ tives, e.g. 3, 3-dimethylglutaric acid; barbituric acid derivatives, e.g. ethyl barbituric acid; the so-called Good-buffers having a pK in the range of 6.5 - 9.5, e.g. BES, TES, HEPES, PIPES and MOPS; the tris-buffer (2-amino-2-hydroxymethyl-l, 3-propanediol) and the hy¬ drogen phosphate/monohydrogen phosphate buffer system, if said buffers are compatible with the sensors of the blood analysis instrument.
A second aspect of the invention relates to a method having the features discussed in the introductory part of claim 1, wherein said method is characterized by the rinse procedure being performed with a rinse solution containing or consisting of a blood dissolving organic substance. In this aspect, the invention also relates to a rinse solution used in the method, said rinse so¬ lution being characterized by the rinse solution con¬ taining or consisting of a blood dissolving organic substance. In this aspect, the invention further com¬ prises the use of a rinse solution containing or con¬ sisting of a blood dissolving organic substance in an instrument-driven rinse procedure.
In this second aspect of the invention, the rinse solu¬ tion contains preferably salt of a concentration re¬ sulting in an ionic strength of the rinse solution of the same level as the ionic strength of blood. Also, it is preferred to add a pH buffer to the rinse solution selected among the pH buffers mentioned above, as it is preferred to add to the rinse solution one or more ger¬ micides or surfactants, particularly the ones mentioned previously.
In a third aspect, the invention relates to the use of a liquid containing or consisting of a blood dissolving organic substance for rinsing an instrument analyzing protein-containing biological liquids; a method for rinsing an instrument with a liquid containing or con- sisting of a blood dissolving organic substance by a rinse procedure wherein the liquid is introduced into the instrument by the operator the same way as a sample through the normal sample inlet of the instrument; as well as a liquid for use in this rinse procedure, said liquid being characterized by containing or consisting of a blood dissolving substance.
Preferred embodiments of said liquid are as described above in connection with the second aspect of the in- vention. The manual rinse procedure can replace or sup-
plement the previously discussed instrument-driven rinse procedure.
Regardless of whether the blood dissolving organic sub- stance forms part of a rinse solution relating to the first aspect of the invention, i.e. a rinse solution containing heparin, or forms part of a rinse solution relating to the second aspect of the invention, i.e. a rinse solution containing or consisting of a blood dis- solving organic substance, but which does not contain an anticoagulant, or forms part of a liquid relating to the third aspect of the invention, in which the liquid is used in a manual rinse procedure, the maximum con¬ tent of the blood dissolving organic substance will be determined by the impact of the substance on the sen¬ sors of the instrument, whereas the minimum content, which is effective, is determined by means of experi¬ ments.
In all aspects of the invention, the following applies to the organic blood dissolving substance:
the organic blood dissolving substance is selected preferably among diethylene glycol, ethylene glycol, glycerol and compositions thereof;
provided compatibility with the sensors proper in the instrument, other suitable substances are substances from the group consisting of 2-ethyl hexanol, cyclo- hexane, ethanol amine, dimethyl sulphoxide, formamide, gamma butyrol acetone, 1,3-butane diol, propylene gly¬ col, dimethyl formamide, dipropylene glycol, aniline, ethylene glycol monomethyl ether, propylene carbonate, m-cresol, ethanol, methanol, ethylene glycol monoethyl ether, dichlorodiethyl ether, cyclo hexanol, nitroben¬ zene, benzaldehyde, 1-butanol, acetophenone, diacetone alcohol, methylene dichloride, ethylene dichloride, ethylene glycol monobutyl ether, isophorone, tetrahy¬ drofuran, triethylene glycol, tetraethylene glycol, pentaethylene glycol, hexaethylene glycol, heptaethyl-
ene glycol, octaethylene glycol, higher ethylene gly¬ cols and compositions of the substances mentioned.
for diethylene glycol the most preferred concentration range is 30 ppm - 15000 ppm, more preferred 90 ppm - 1500 ppm, and especially preferred is 150 ppm;
selection of other suitable blood dissolving substances can take place by comparing their so-called Hansen- parameters with the corresponding parameters for blood or blood proteins, cf. e.g. CRC Handbook of Solubility Parameters and Other Cohesion Parameters, 2nd Ed., CRC Press, 1991, p. 95.
The first aspect of the invention is illustrated by ex¬ ample 1 below:
Example 1
Preparation and composition of a heparin-containing rinse solution
To one kilo water are added the following substances in the amounts stated:
Substance Gram IU
Imidazole 0.78
Hydrochloric acid, IN 3.29
Sodium chloride 7.68
Sodium bicarbonate 0.01
Potassium chloride 0.30
Calcium chloride 0.18
Diethylene glycol 0.15
Sodium heparinate 1000
Surfactants and germicides are also added in the fol¬ lowing amounts:
Gram Triton™ CF54 0.065
Triton™ X-100 0.070
Germal™ II 0.250
Kathon™ 886 MV 0.100
The second aspect of the invention is illustrated by example 2 below:
Example 2
Preparation and composition of a rinse solution con¬ taining a blood dissolving organic substance
To one kilo water are added the following substances in the amounts stated:
Substance Gram
Imidazole 0. .78
Hydrochloric acid, IN 3. .29
Sodium chloride 7. .68
Sodium bicarbonate 0. .01
Potassium chloride 0. .30
Calcium chloride 0. .18
Diethylene glycol 0. .15
Surfactants and germicides are also added in the fol¬ lowing amounts:
Gram Triton™ CF54 0. .065 Triton™ X-100 0. .070 Germal™ II 0. .250 Kathon™ 886 MV 0. .100
Claims
1. A method used in operating instruments analyzing protein-containing biological liquids, said method comprising alternating between an analysis proce¬ dure in which a sample to be analyzed is intro¬ duced into the instrument and an instrument-driven rinse procedure in which the rinse solution is passed through the measuring chambers and conduits of the instrument, c h a r a c t e r i z e d in that the rinse procedure is performed by a rinse solution containing heparin.
2. A method according to claim 1, c h a r a c t e r i z e d in that the concentration of heparin is preferably 200 - 20000 IU/kg, more preferably 500 - 10000 IU/kg and especially approx. 1000 IU/kg.
3. A method according to claims 1-2, c h a r a c t e r i z e d in that the rinse solution contains a blood dissolv¬ ing organic substance, preferably diethylene gly- col.
4. A method according to claims 1-3, c h a r a c t e r i z e d in that the rinse solution contains a salt, prefera- bly sodium chloride, of a concentration resulting in a ionic strength of the rinse solution of the same level as the ionic strength of blood.
5. A method according to any of the previous claims, c h a r a c t e r i z e d in that the rinse solution comprises one or more ger¬ micides.
6. A rinse solution for use in the method according to claims 1-5, c h a r a c t e r i z e d in that the rinse solution contains heparin.
7. A rinse solution according to claim 6, c h a r a c t e r i z e d in that it further contains a blood dissolving or¬ ganic substance, preferably diethylene glycol.
8. A rinse solution according to claims 6-7, c h a r a c t e r i z e d in that the rinse solution further contains a pH- buffer, preferably imidazole.
9. A rinse solution according to claims 6-8, c h a r a c t e r i z e d in that the rinse solution further contains a surfac¬ tant and/or one or more germicides.
10. A rinse solution according to claims 6-9, c h a r a c t e r i z e d in that the rinse solution contains a salt, prefera¬ bly sodium chloride, of a concentration resulting in a ionic strength of the rinse solution of the same level as the ionic strength of blood.
11. Use of a rinse solution containing heparin in an instrument-driven rinse procedure in a blood analysis instrument.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
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DK1292/95 | 1995-11-17 | ||
DK129295 | 1995-11-17 |
Publications (1)
Publication Number | Publication Date |
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WO1997019350A1 true WO1997019350A1 (en) | 1997-05-29 |
Family
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Family Applications (1)
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PCT/DK1996/000468 WO1997019350A1 (en) | 1995-11-17 | 1996-11-14 | A method and a rinse solution used in operating instruments analyzing protein-containing biological liquids |
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Cited By (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9091677B2 (en) | 2010-08-09 | 2015-07-28 | Beckman Coulter, Inc. | Isotonic buffered composition and method that enables counting of cells |
CN105441225A (en) * | 2015-12-18 | 2016-03-30 | 杭州毕肯莱博生物科技有限公司 | Biological instrument pipeline cleaning liquid and preparation method thereof |
CN107034054A (en) * | 2017-04-01 | 2017-08-11 | 合肥迪安医学检验所有限公司 | A kind of biochemical instruments cuvette cleaning fluid |
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US4127111A (en) * | 1976-10-26 | 1978-11-28 | Drolet Roland A | Automatic blood sampling system and method |
US4867797A (en) * | 1979-02-23 | 1989-09-19 | Radiometer A/S | Method for cleaning instruments used for analyzing protein-containing biological liquids |
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1996
- 1996-11-14 WO PCT/DK1996/000468 patent/WO1997019350A1/en active Application Filing
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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US4127111A (en) * | 1976-10-26 | 1978-11-28 | Drolet Roland A | Automatic blood sampling system and method |
US4867797A (en) * | 1979-02-23 | 1989-09-19 | Radiometer A/S | Method for cleaning instruments used for analyzing protein-containing biological liquids |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US9091677B2 (en) | 2010-08-09 | 2015-07-28 | Beckman Coulter, Inc. | Isotonic buffered composition and method that enables counting of cells |
US9567622B2 (en) | 2010-08-09 | 2017-02-14 | Beckman Coulter, Inc. | Isotonic buffered composition and method that enables counting of cells |
CN105441225A (en) * | 2015-12-18 | 2016-03-30 | 杭州毕肯莱博生物科技有限公司 | Biological instrument pipeline cleaning liquid and preparation method thereof |
CN107034054A (en) * | 2017-04-01 | 2017-08-11 | 合肥迪安医学检验所有限公司 | A kind of biochemical instruments cuvette cleaning fluid |
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