CA1172945A - Blood gas control - Google Patents
Blood gas controlInfo
- Publication number
- CA1172945A CA1172945A CA000382066A CA382066A CA1172945A CA 1172945 A CA1172945 A CA 1172945A CA 000382066 A CA000382066 A CA 000382066A CA 382066 A CA382066 A CA 382066A CA 1172945 A CA1172945 A CA 1172945A
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- CA
- Canada
- Prior art keywords
- liquid
- product
- volume
- preservative
- compound material
- 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.)
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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
- G01N33/96—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving blood or serum control standard
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2496/00—Reference solutions for assays of biological material
- G01N2496/70—Blood gas control solutios containing dissolved oxygen, bicarbonate and the like
-
- 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
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/10—Composition for standardization, calibration, simulation, stabilization, preparation or preservation; processes of use in preparation for chemical testing
- Y10T436/102499—Blood gas standard or control
Abstract
Abstract of the Disclosure A blood gas control liquid comprises a stable oil-in-water emulsion that has an oxygen solubility coefficient of at least 10 ml 02 per 100 ml emul-sion and a viscosity of less than 10 centipoises. The emulsion includes water, 5-40 percent by volume of a water-insoluble non-protein compound material, 0.25-10 percent by volume of a nonionic surfactant, a pH buffering agent and a preservative agent which is substantially non-reactive with the pH buffering agent. A preferred blood gas control liquid has a density of about 1.08. The blood gas control liquid has a pH in the range of 7-8, a partial pressure of carbon dioxide in the range of 15-80 millimeters Hg, and a partial pressure of oxygen in the range of 20-600 mm Hg.
Description
' t72945 This invention relates to blood gas control liquids for quality control and/or calibration of blood gas analyzer equiprr.ent.
Blood gas analyzers are utilized to measure parameters of blood such as pH, partial pressure of carbon dioxide (expressed as pCO2), and partial pressure of oxygen (expressed as PO2). Such blood gas analyzers require frequent calibration and quality control checks to insure the analyzer is operating properly and accurately. In connection with such quality control and calibration procedures, it is convenient to use a prepared blood gas control liquid of constant, know composition to monitor the accuracy of such analyzers. For practical purposes, the blood gas control liquid should have long term physical and chemical stability, constant pH, pCO2, and PO2 levels, flow characteristics comparable to blood, and should be readily cleaned from and not otherwise complicate or irnpair analyzer accuracy. Commercially available, pre-pared aqueous blood gas control liquids adequately mimic blood for pH
and pCO2, but do not have adequate oxygen buffering capacity as they are unable to dissolve an adequate amount of oxygen. Such controls are therefore prone to inaccuracy in the presence of relatively small amounts of outside oxygen contamination, and also may falsely indicate certain
Blood gas analyzers are utilized to measure parameters of blood such as pH, partial pressure of carbon dioxide (expressed as pCO2), and partial pressure of oxygen (expressed as PO2). Such blood gas analyzers require frequent calibration and quality control checks to insure the analyzer is operating properly and accurately. In connection with such quality control and calibration procedures, it is convenient to use a prepared blood gas control liquid of constant, know composition to monitor the accuracy of such analyzers. For practical purposes, the blood gas control liquid should have long term physical and chemical stability, constant pH, pCO2, and PO2 levels, flow characteristics comparable to blood, and should be readily cleaned from and not otherwise complicate or irnpair analyzer accuracy. Commercially available, pre-pared aqueous blood gas control liquids adequately mimic blood for pH
and pCO2, but do not have adequate oxygen buffering capacity as they are unable to dissolve an adequate amount of oxygen. Such controls are therefore prone to inaccuracy in the presence of relatively small amounts of outside oxygen contamination, and also may falsely indicate certain
2~ types of instrument malfunctions.
Other blood gas control products have been proposed which are based on components of human blood (e.g., Louderback United States Patent No. 3,973,913) or components proposed for use as blood substitutes such as fluorocarbon and silicone compound emulsions (e.g., Sorenson et al.
United States Patent No. 4,163,734). One blood gas control product proposed by Sorenson et al. contains a perfluorotributylamine compound, an emulsifying agent to provide a stable suspension of the perfluorinated ! 172945 compound, a phosphate buffer system, and a bicarbonate ion-carbon dioxide buffer system. Sterilization, which is necessary for stability, is accomplished by means of radioactive irradiation. Such a control liquid has several undesirable limitations. A perfluorotributylamine-water ; emulsion with an oxygen solubility coefficient of ten requires a high fluorocarbon: water ratio (in excess of 20% fluorocarbon) which results in an undesirable viscosity that is much higher than that of blood. The emulsion leaves bubbles in the measuring chambers of blood gas analyzer equipment, creating cleaning difficulties and causing control-to-sample carry over. The specific surfactant described in Sorenson et al., like all polyol surfactants, must be used in an amount that further undesirably increases viscosity. Also the phosphate buffer system is conducive to growtil of aerobic bacteria, which impair P02 stability, and efforts to sterilize the product by means of radioactive irradiation are themselves detrimental to oxygen stability.
We have discovered a superior blood gas control liquid that includes a stable oil in water emulsion that has an oxygen solubility coefficient of at least 10 ml 2 per 100 ml emulsion and a viscosity in the range of blood (a viscosity of less than 10 centipoises). The emulsion includes water, a water insoluble non-protein organic compound, and a nonionic surfactant that is partially soluble in both the water and the oil phases. The control liquid also includes a pH buffering agent and a nlicrobial growth inhibiting agent that is substantially nonreactive with the buffering agent. Control liquids in accordance with the invention have emulsions of long term stability (at least six months without breaking), superior oxygen buffering capacity, good pH buffering and viscosity of less than ten centipoises.
t 17294~
Preferred control liquids are formulated to provide pH, pC02, and P02 values at three different levels ~acidosis, normal, and alkalosis) and include coloring agents that simulate, both visually and analytically, corresponding hemoglobin value ranges, the acidosis level liquid having the appearance of normal venous blood, the normal level liquid having the appearance of normal arterial blood, and the alkalosis level liquid have the appearance of a low hemoglobin, high PO2 blood~ and each of these control liquids providing distinctive hemoglobin values when measured with hemoglobin analyzers. The density (at 20C) of a preferred blood gas control liquid is less than 1.12. Microbial growth in the liquids is discouraged without the use of irradiation or expensive sterile fill procedures; the liquids do not foam or form bubbles to a significant degree; and they are easily cleaned out of blood gas measuring equipment.
Blood gas control liquids in accordance with the invention are preferrably supplied enclosed in gas-tight, sealed ampoules and contain know concentrations of dissolved carbon dioxide and oxygen. A preferred liquid includes a water-based emulsion containing a water-insoluble perfluorinated compound material, a fluorocarbon-based surfactant capable of emulsifying the perfluorinated compound material, a preservative in a concentration sufficient to inhibit microbial growth without interfering with the quality control functions of the liquid, and a pH buffering agent substantially non-reactive with said preservative.
According to the invention, the perfluorinated compound material must have a high enough oxygen solubility coefficient, and be present in sufficient quantity, to yield a blood gas control liquid having an effective oxygen solubility coefficient of at least 10 ml O2/100 ml of emulsion. Further, the perfluorinated compound material must have a high ! 172g45 enough oxygen solubility coefficient to allow it to be used in an amount which constitutes less than about ~0% of the liquid by volume, because larger volumetric amounts would raise viscosity to an unacceptable level.
To provide a margin of safety, the effective oxygen coefficient of the perfluorinated compound material used in the invention should be, at one atmosphere pressure, 25DC, and a volumetric proportion of 15%, at least 10 mL O2/100 mL emulsion.
A preferred perfluorinated compound material of the invention is manufactured by 3M Company under the designation "FC-77" and is a mixture of perfluoroalkanes and perfluorocyclic ethers. We have found that FC-77 may be advantageously used in combination with perfluorotributy-lamine, sold by 3M Company under the designation "FC-43" and/or with a dimethyl siloxane polymer that has a density of about 0.5 grams per milliliter, sold by ~ow-Corning under the designation "200 Fluid -1 centistoke" (hereinafter "200-1"). Oil in water emulsions of these materials have the oxygen solubility coefficients shown in Table I below.
Preferred fluorocarbon-based surfactants of the invention include fluoroalkylpoly (ethyleneoxy) ethanol, sold by D~Port Corporation under ~J the designation Zonyl FSN; fluoracylpolyoxyethylene, sold under the designation Lodyne S-107 by Ciba-Geigy; fluorinated acylpolyoxyethylene ethanol, sold under the designation FC-170-C by 3M Company; and Monflor 51, a polymer of about 20-25 units of polyethyleneoxide with between one and four tetrafluoroethylene groups at each end, sold by Imperial Chemical Industries Ltd.
: I ~72945 ., TABLE I
VOLUME SOLUBILITY IN ml 2 ml EMULSION
( at one atmosphere and 25C) % Oil in Water 10% 15% 20%
200-1 4.12% 4.78 5.44 FC 43 6.12 7.78 9.44 PC 77 8.12 10.78 13.44
Other blood gas control products have been proposed which are based on components of human blood (e.g., Louderback United States Patent No. 3,973,913) or components proposed for use as blood substitutes such as fluorocarbon and silicone compound emulsions (e.g., Sorenson et al.
United States Patent No. 4,163,734). One blood gas control product proposed by Sorenson et al. contains a perfluorotributylamine compound, an emulsifying agent to provide a stable suspension of the perfluorinated ! 172945 compound, a phosphate buffer system, and a bicarbonate ion-carbon dioxide buffer system. Sterilization, which is necessary for stability, is accomplished by means of radioactive irradiation. Such a control liquid has several undesirable limitations. A perfluorotributylamine-water ; emulsion with an oxygen solubility coefficient of ten requires a high fluorocarbon: water ratio (in excess of 20% fluorocarbon) which results in an undesirable viscosity that is much higher than that of blood. The emulsion leaves bubbles in the measuring chambers of blood gas analyzer equipment, creating cleaning difficulties and causing control-to-sample carry over. The specific surfactant described in Sorenson et al., like all polyol surfactants, must be used in an amount that further undesirably increases viscosity. Also the phosphate buffer system is conducive to growtil of aerobic bacteria, which impair P02 stability, and efforts to sterilize the product by means of radioactive irradiation are themselves detrimental to oxygen stability.
We have discovered a superior blood gas control liquid that includes a stable oil in water emulsion that has an oxygen solubility coefficient of at least 10 ml 2 per 100 ml emulsion and a viscosity in the range of blood (a viscosity of less than 10 centipoises). The emulsion includes water, a water insoluble non-protein organic compound, and a nonionic surfactant that is partially soluble in both the water and the oil phases. The control liquid also includes a pH buffering agent and a nlicrobial growth inhibiting agent that is substantially nonreactive with the buffering agent. Control liquids in accordance with the invention have emulsions of long term stability (at least six months without breaking), superior oxygen buffering capacity, good pH buffering and viscosity of less than ten centipoises.
t 17294~
Preferred control liquids are formulated to provide pH, pC02, and P02 values at three different levels ~acidosis, normal, and alkalosis) and include coloring agents that simulate, both visually and analytically, corresponding hemoglobin value ranges, the acidosis level liquid having the appearance of normal venous blood, the normal level liquid having the appearance of normal arterial blood, and the alkalosis level liquid have the appearance of a low hemoglobin, high PO2 blood~ and each of these control liquids providing distinctive hemoglobin values when measured with hemoglobin analyzers. The density (at 20C) of a preferred blood gas control liquid is less than 1.12. Microbial growth in the liquids is discouraged without the use of irradiation or expensive sterile fill procedures; the liquids do not foam or form bubbles to a significant degree; and they are easily cleaned out of blood gas measuring equipment.
Blood gas control liquids in accordance with the invention are preferrably supplied enclosed in gas-tight, sealed ampoules and contain know concentrations of dissolved carbon dioxide and oxygen. A preferred liquid includes a water-based emulsion containing a water-insoluble perfluorinated compound material, a fluorocarbon-based surfactant capable of emulsifying the perfluorinated compound material, a preservative in a concentration sufficient to inhibit microbial growth without interfering with the quality control functions of the liquid, and a pH buffering agent substantially non-reactive with said preservative.
According to the invention, the perfluorinated compound material must have a high enough oxygen solubility coefficient, and be present in sufficient quantity, to yield a blood gas control liquid having an effective oxygen solubility coefficient of at least 10 ml O2/100 ml of emulsion. Further, the perfluorinated compound material must have a high ! 172g45 enough oxygen solubility coefficient to allow it to be used in an amount which constitutes less than about ~0% of the liquid by volume, because larger volumetric amounts would raise viscosity to an unacceptable level.
To provide a margin of safety, the effective oxygen coefficient of the perfluorinated compound material used in the invention should be, at one atmosphere pressure, 25DC, and a volumetric proportion of 15%, at least 10 mL O2/100 mL emulsion.
A preferred perfluorinated compound material of the invention is manufactured by 3M Company under the designation "FC-77" and is a mixture of perfluoroalkanes and perfluorocyclic ethers. We have found that FC-77 may be advantageously used in combination with perfluorotributy-lamine, sold by 3M Company under the designation "FC-43" and/or with a dimethyl siloxane polymer that has a density of about 0.5 grams per milliliter, sold by ~ow-Corning under the designation "200 Fluid -1 centistoke" (hereinafter "200-1"). Oil in water emulsions of these materials have the oxygen solubility coefficients shown in Table I below.
Preferred fluorocarbon-based surfactants of the invention include fluoroalkylpoly (ethyleneoxy) ethanol, sold by D~Port Corporation under ~J the designation Zonyl FSN; fluoracylpolyoxyethylene, sold under the designation Lodyne S-107 by Ciba-Geigy; fluorinated acylpolyoxyethylene ethanol, sold under the designation FC-170-C by 3M Company; and Monflor 51, a polymer of about 20-25 units of polyethyleneoxide with between one and four tetrafluoroethylene groups at each end, sold by Imperial Chemical Industries Ltd.
: I ~72945 ., TABLE I
VOLUME SOLUBILITY IN ml 2 ml EMULSION
( at one atmosphere and 25C) % Oil in Water 10% 15% 20%
200-1 4.12% 4.78 5.44 FC 43 6.12 7.78 9.44 PC 77 8.12 10.78 13.44
3 FC 77 -1 FC 43 7.62 10.03 12.44 The buffering agent used in the invention is selected so that it is substantially non-reactive with the preservative being used. Because the preferred preservatives arethe aldehydes, and particularly formaldehyde and gluteraldehyde, the preferred buffering agents are those containing a tertiary amine; such buffering agents do not react with aldehydes, and also are relatively non-conducive to microbial growth. The preferred tertiary amine buffering agent for use with an aldehydic preservative is HEPES
(N-2-Hydroxyethyl-piperazine-N'-2-ethane sulfonic acid), its pK being centered in the appropriate physiological pH range. Another effective tertiary amine buffering agent for use with aldehydic preservatives is triethanolamine.
The blood gas control liquids are preferrably formulated to simulate three physiological levels of pH, pCO2, and PO2 values; and have coloring agents that simulate hemoglobin values and visual appearances of a range of blood conditions. A preferred blood gas control liquid has a density (at 20C) of about 1.08, facilitating its use in "open junction"
types of blood gas analyzers where mixing of the blood gas control liquid and the potassium chloride electrolyte would interfere with and produce inaccurate measurement.
A preferred embodiment of the invention has the following formulation:
~ l7294~j Compound Concentration ~`C-77 10.95% (v/v) FC-43 3.65% ~v/v) 200-1 19.8% (v/v) Fluoroaklyl poly(ethyleneoxy) ethanol(Zonyl FSN) 2.5% (v/v) II~P~S Buffer salts 32.8 mM
NaOH 30.50-35.23 mM
NaCl 26.32-48.99 mM
Formaldehyde 43.5 mM
The first step in the preparation of this liquid was to prepare the antibacterial/surfactant/water solution by mixing together 1250 grams of 40% Zonyl FSN and 120 mL of formaldehyde and bringing the solution up to 16.0 liters with distilled water. The 200-1 silicone oil is then poured into the hopper of a Gaulin Homogenizer (Model 15M) and the aqueous phase is added at the rate of 725 mL/minute. The mixture is homogenized at a pressure of 2500 psig and repeatedly passed through an ice path and recirculated to the hopper until all of the oil had been dripped into it.
'l'he pressure was then increased to 8000 psig and two discrete passes through the homogenizer are carried out to form a stable emulsion.
Next, an oil mixture was prepared by combining 2.20 L FC-77 with 0.73 L FC-43. The silicone emulsion was placed in the hopper of a Gaulin Homogenizer (Model 15M) and the fluorocarbon oil mixture was pumped into the hopper at the rate of 180 mL/min. while the liquid in the hopper was homogenized at a pressure of 2500 psig. The liquid was repeatedly passed through an ice bath and recirculated to the hopper until all of the oil had been dripped into it. At this point, the pressure was increased to 8000 psig and nine discrete passes through the homogenizer were carried out.
~( TrQc~ Q~
l 17~94~
A stable emulsion was formed by the ninth pass.
The emulsion was allowed to stand for 24 hours, and was then filtered through Whatman #3 filter paper using vacuum filtration with a Buchner funnel.
In a separate operation, buffers were prepared to be added to the emulsion. Three different buffers were made using HEPES, NaOH, and NaCl in different concentrations. After the buffers were added to the emulsions, each of the three emulsions was equilibrated with a different gas mixture, producing three different control liquids to be used under appropriate conditions. The three levels differed in pH, pCO2, and P02, the levels having been chosen to reflect pH and gas partial pressure of the blood of normal patients, patients suffering from alkemia, and those suffering from acidemia. The three levels were:
Acidosis Normal Alkalosis pH 7.15-7.25 7.34-7.41 7.55-7.65 PC02 65-75 mm Hg 40-47 mm Hg 18-24 mm Hg PO2 60-70 mm Hg 95-110 mm Hg 140-160 mm Hg The buffer formulations corresponding to the three levels were:
Acidosis Normal Alkalosis NaOH 30.50mM/L emulsion 33.91 mM/L 35.23 mM/L
HEPES 32.80 mM 32.80 mM/L 32.80 mM/L
NaCl 26.32 mM 48.99 mM/L 48.94 mM/L
The buffer formulations were added to the emulsion and each level was then given a distinctive color using the following dyes:
Acidosis Normal Alkalosis 1.667 g/L 1.25 g/L 0.781 g/L
Red #33 Red #33 Red #33 3.333 g/L 1.25 g/L 1.406 g/L
Yellow #5 Yellow #5 Yellow #5 0.01667 g/L
Blue #l ~ 1 729~ 5 T}le emulsions, containing dyes and dissolved buffer salts and having viscosities of about 8 centipoises (measured wi~h a Brookfield Viscometer at 60 rpm - spindle # 1), 2 solubility coefficients of about 12.5, and densities of about 1.08 (at 20C), were then placed in a container which was thermally controlled to 25~C + 0.5C. The appropriate e4uilibration gas mixture was then bubbled through each emulsion at the rate of 3 L/min. until the pH, P02, and PC02 reached equilibrium values, as determined by blood gas measuring equipment. The equilibration gas mixtures had the following compositions:
Acidosis Normal Alkalosis C2 6.7% 4.15 2.0 0 9.0% 14.0 21.5 N2 84.3% 81.85 76.5 After equilibration, glass ampoules which has been purged with the same gas equilibration mixture used for the emulsion were filled with 2 mL of the appropriate emulsion, up to below a hand-breakable line, and the ampoules heat-sealed.
The formulated control liquids, in their sealed ampoules, were used successfully to check the calibration of blood gas analyzers.
An ampoule containing the appropriate emulsion is opened and the control liquid is placed in the blood gas analyzer, which measures and registers the pl-l. PC02 and P02 of the emulsion. A reading outside of the pH and gas partial pressure ranges known to exist in the liquid indicates the need for re-calibration or repair of the analyzer.
The appearances and hemoglobin values of these formulated control liquids as set out in the following table:
' ~7294~
ABL 1 & 2 IL 282 Appearance Acidosis 17-22 g/dL 11-14 g~dL Normal venous blood Normal 14-18 8-12 Normal arterial blood Alkalosis 8-12 6-9 High pO~, low hemoglobin blood Another embodiment of the invention has the following formulation:
Compound Concentration FC-77 15~ (v/v) FC-43 5% (v/v3 Fluoroalkyl poly(ethyleneoxy) ethanol (Zonyl FSN*) 2~ (v/v) HEPES Buffer salts 40 mM
NaOH 38.7-42.57 mM
NaCl 85.47-89.29 mM
Formaldehyde 53 mM
The first step in the preparation of this liquid was to prepare the antibacterial/surfactant/water solution by mixing together 500 grams of 40~ Zonyl FSN* and 60 mL of formal-dehyde and bringing the solution up to 8.0 liters with distilled water. Next, an oil mixture was prepared by combining 1.5 L FC-77 with 0.5 L FC-43.
The aqueous solution was placed in the hopper of a Gaulin Homogenizer (Model 15M) and the oil mixture placed in a separatory funnel mounted above the hopper. Oil was dripped into the hopper at the rate of 100 mL/min. while the liquid in the hopper was homogenized at a pressure of 2500 psi. The liquid was repeatedly passed through an ice bath and recirculated to the hopper until all of the oil had been dripped into it.
At this point, the pressure was increased to 8000 psi and nine discrete passes through the homogenizer were carried out. A
*Trade Mark ' ! 7 2 9 4 ~
stable emulsion was formed by the ninth pass.
The emulsion was allowed to stand 24 hours, and was then filtered through Whatman #3 filter paper using vacuum filtration with a Buchner funnel.
9a 1 1729~1~
In a separate operation, buffer solutions were prepared to be added to the emulsion. Three different buffer solutions were made using HEPES, NaOH, and NaCl in different concentrations. After the buffer solutions were added to the emulsions, each of the three emulsions was equilibrated with a different gas mixture, producing three different control liquids to be used under appropriate conditions. The three levels differed in pll, pC02, and P02, the levels having been chosen to reflect p}i and gas partial pressure of the blood of normal patients, patients suffering from alkemia, and those suffering from acidemia.
The three levels were:
Acidosis Normal Alkalosis pll 7.15-7.25 7.34-7.41 7.55-7.65 PC02 65-75 mm Hg 40-47 mm llg 18-24 mm Hg PU2 60-70 mm Hg 95-110 mm Hg 140-160 mm Hg The buffer formulations corresponding to the three levels were:
. Acidosis Normal Alkalosis NaOH 38.7 mM/L Emulsion 40.62 mM/L 42.57 mM/L
HEPES 40.00 40.00 mM/L 40.00 mM/L
NaCl 89.29 mM 87.38 mM/L 85.43 mM/L
The buffer formulations were added to the emulsion and each level was then given a distinctive color using the following dyes:
Acidosis Normal Alkalosis 100 mg/l Yellow #5 100 mg/l 66.67 mg/l Amarath Amarath, 133.33 mg/l Yellow #5 The emulsions, containing dyes and dissolved buffer salts and having viscosities of about 4.5 centipoises, 2 solubility coefficients of about 12.4, and a density of about 1.15 (at 20C), were then placed in a container which was thermally controlled to 25aC + 0.5~C. The appropriate ! 17294~
equilibration gas mixture was then bubbled through each emulsion at the rate of 2 L/min. until the pH, PO2, and PCO2 reached equilibrium values, as determined by blood gas measuring equipment. The equilibration gas mixtures had the following compositions:
Acidosis Normal Alkalosis C~2 7 0% 4.17 1.98 2 9.5% 14.0 21.5 N2 83.5% 81.83 76.52 After equilibration, glass ampoules which has been purged with the same gas equilibration mixture used for the emulsion were filled with 1 mL of the appropriate emulsion, up to below a hand-breakable line, and the ampoules heat-sealed.
Another embodiment of the invention employs a ~ixture of perfluoroalkanes and perfluorocyclic ethers (FC-77) and a polymer of about 20-25 units of polyethyleneoxide with between one and four tetrafluoroethylene groups at each end (Monflor 51). Two liters of FC-77 were emulsified, as described above for the FC-77/FC-43 emulsion, with an ~antibacterial surfactant/water solution consisting of 150 g Monflor 51 (about 1.5% by volume of emulsion) and 60 ml formaldehyde brought up to 8.00 liters with distilled water. After all the FC-77 had been added, the emulsion was subjected to seven discrete passes through the Gaulin I-lomogenizer.
Because Monflor 51 often contains IIF as an impurity, the emulsions were neutralized with NaOH. After neutralization, buffers and dyes were added as described above for FC-77/FC-43, they were equilibrated with the appropriate gas mixtures~ and the emulsions placed in ampoules. The liquids had viscosities of about 5 centipoises, 2 solubility coefficients of about 13.5, and densities of about 1.15. In still another embodiment, ~ T~ k } !729~5 liquids with stable emulsions of about 15% FC-77, 15% 200-l silicone oil and Monflor 51 surfactant formulated and equilibrated as above described have densities of about 1.09, 2 solubility coefficients of about 12.5, and viscosities of less than lO centipoises.
The embodiments described above do not include added bicarbonate, but these emulsions nevertheless, owing to the gas equilibration step, effectively contain bicarbonate. Alternatively, it is of course possible to add bicarbonate, in appropriate amounts, along with HEPES.
The emulsions, in their sealed ampoules, were used successfully to check the calibration of blood gas analyzers. An ampoule containing the appropriate emulsion is opened and the control liquid is placed in the blood gas analyzer, which measures and registers the pH, PCO2 and PO2 of the emulsion. A reading outside of the pH and gas partial pressure ranges known to exist in the liquid indicates the need for re-calibration or repair of the analyzer.
While particular embodiments of the invention have been described, various modifications will be apparent to those skilled in the art, and it is not intended that the invention be limited to the disclosed embodiments or to details thereof and departures may be made therefrom within the spirit and scope of the invention.
(N-2-Hydroxyethyl-piperazine-N'-2-ethane sulfonic acid), its pK being centered in the appropriate physiological pH range. Another effective tertiary amine buffering agent for use with aldehydic preservatives is triethanolamine.
The blood gas control liquids are preferrably formulated to simulate three physiological levels of pH, pCO2, and PO2 values; and have coloring agents that simulate hemoglobin values and visual appearances of a range of blood conditions. A preferred blood gas control liquid has a density (at 20C) of about 1.08, facilitating its use in "open junction"
types of blood gas analyzers where mixing of the blood gas control liquid and the potassium chloride electrolyte would interfere with and produce inaccurate measurement.
A preferred embodiment of the invention has the following formulation:
~ l7294~j Compound Concentration ~`C-77 10.95% (v/v) FC-43 3.65% ~v/v) 200-1 19.8% (v/v) Fluoroaklyl poly(ethyleneoxy) ethanol(Zonyl FSN) 2.5% (v/v) II~P~S Buffer salts 32.8 mM
NaOH 30.50-35.23 mM
NaCl 26.32-48.99 mM
Formaldehyde 43.5 mM
The first step in the preparation of this liquid was to prepare the antibacterial/surfactant/water solution by mixing together 1250 grams of 40% Zonyl FSN and 120 mL of formaldehyde and bringing the solution up to 16.0 liters with distilled water. The 200-1 silicone oil is then poured into the hopper of a Gaulin Homogenizer (Model 15M) and the aqueous phase is added at the rate of 725 mL/minute. The mixture is homogenized at a pressure of 2500 psig and repeatedly passed through an ice path and recirculated to the hopper until all of the oil had been dripped into it.
'l'he pressure was then increased to 8000 psig and two discrete passes through the homogenizer are carried out to form a stable emulsion.
Next, an oil mixture was prepared by combining 2.20 L FC-77 with 0.73 L FC-43. The silicone emulsion was placed in the hopper of a Gaulin Homogenizer (Model 15M) and the fluorocarbon oil mixture was pumped into the hopper at the rate of 180 mL/min. while the liquid in the hopper was homogenized at a pressure of 2500 psig. The liquid was repeatedly passed through an ice bath and recirculated to the hopper until all of the oil had been dripped into it. At this point, the pressure was increased to 8000 psig and nine discrete passes through the homogenizer were carried out.
~( TrQc~ Q~
l 17~94~
A stable emulsion was formed by the ninth pass.
The emulsion was allowed to stand for 24 hours, and was then filtered through Whatman #3 filter paper using vacuum filtration with a Buchner funnel.
In a separate operation, buffers were prepared to be added to the emulsion. Three different buffers were made using HEPES, NaOH, and NaCl in different concentrations. After the buffers were added to the emulsions, each of the three emulsions was equilibrated with a different gas mixture, producing three different control liquids to be used under appropriate conditions. The three levels differed in pH, pCO2, and P02, the levels having been chosen to reflect pH and gas partial pressure of the blood of normal patients, patients suffering from alkemia, and those suffering from acidemia. The three levels were:
Acidosis Normal Alkalosis pH 7.15-7.25 7.34-7.41 7.55-7.65 PC02 65-75 mm Hg 40-47 mm Hg 18-24 mm Hg PO2 60-70 mm Hg 95-110 mm Hg 140-160 mm Hg The buffer formulations corresponding to the three levels were:
Acidosis Normal Alkalosis NaOH 30.50mM/L emulsion 33.91 mM/L 35.23 mM/L
HEPES 32.80 mM 32.80 mM/L 32.80 mM/L
NaCl 26.32 mM 48.99 mM/L 48.94 mM/L
The buffer formulations were added to the emulsion and each level was then given a distinctive color using the following dyes:
Acidosis Normal Alkalosis 1.667 g/L 1.25 g/L 0.781 g/L
Red #33 Red #33 Red #33 3.333 g/L 1.25 g/L 1.406 g/L
Yellow #5 Yellow #5 Yellow #5 0.01667 g/L
Blue #l ~ 1 729~ 5 T}le emulsions, containing dyes and dissolved buffer salts and having viscosities of about 8 centipoises (measured wi~h a Brookfield Viscometer at 60 rpm - spindle # 1), 2 solubility coefficients of about 12.5, and densities of about 1.08 (at 20C), were then placed in a container which was thermally controlled to 25~C + 0.5C. The appropriate e4uilibration gas mixture was then bubbled through each emulsion at the rate of 3 L/min. until the pH, P02, and PC02 reached equilibrium values, as determined by blood gas measuring equipment. The equilibration gas mixtures had the following compositions:
Acidosis Normal Alkalosis C2 6.7% 4.15 2.0 0 9.0% 14.0 21.5 N2 84.3% 81.85 76.5 After equilibration, glass ampoules which has been purged with the same gas equilibration mixture used for the emulsion were filled with 2 mL of the appropriate emulsion, up to below a hand-breakable line, and the ampoules heat-sealed.
The formulated control liquids, in their sealed ampoules, were used successfully to check the calibration of blood gas analyzers.
An ampoule containing the appropriate emulsion is opened and the control liquid is placed in the blood gas analyzer, which measures and registers the pl-l. PC02 and P02 of the emulsion. A reading outside of the pH and gas partial pressure ranges known to exist in the liquid indicates the need for re-calibration or repair of the analyzer.
The appearances and hemoglobin values of these formulated control liquids as set out in the following table:
' ~7294~
ABL 1 & 2 IL 282 Appearance Acidosis 17-22 g/dL 11-14 g~dL Normal venous blood Normal 14-18 8-12 Normal arterial blood Alkalosis 8-12 6-9 High pO~, low hemoglobin blood Another embodiment of the invention has the following formulation:
Compound Concentration FC-77 15~ (v/v) FC-43 5% (v/v3 Fluoroalkyl poly(ethyleneoxy) ethanol (Zonyl FSN*) 2~ (v/v) HEPES Buffer salts 40 mM
NaOH 38.7-42.57 mM
NaCl 85.47-89.29 mM
Formaldehyde 53 mM
The first step in the preparation of this liquid was to prepare the antibacterial/surfactant/water solution by mixing together 500 grams of 40~ Zonyl FSN* and 60 mL of formal-dehyde and bringing the solution up to 8.0 liters with distilled water. Next, an oil mixture was prepared by combining 1.5 L FC-77 with 0.5 L FC-43.
The aqueous solution was placed in the hopper of a Gaulin Homogenizer (Model 15M) and the oil mixture placed in a separatory funnel mounted above the hopper. Oil was dripped into the hopper at the rate of 100 mL/min. while the liquid in the hopper was homogenized at a pressure of 2500 psi. The liquid was repeatedly passed through an ice bath and recirculated to the hopper until all of the oil had been dripped into it.
At this point, the pressure was increased to 8000 psi and nine discrete passes through the homogenizer were carried out. A
*Trade Mark ' ! 7 2 9 4 ~
stable emulsion was formed by the ninth pass.
The emulsion was allowed to stand 24 hours, and was then filtered through Whatman #3 filter paper using vacuum filtration with a Buchner funnel.
9a 1 1729~1~
In a separate operation, buffer solutions were prepared to be added to the emulsion. Three different buffer solutions were made using HEPES, NaOH, and NaCl in different concentrations. After the buffer solutions were added to the emulsions, each of the three emulsions was equilibrated with a different gas mixture, producing three different control liquids to be used under appropriate conditions. The three levels differed in pll, pC02, and P02, the levels having been chosen to reflect p}i and gas partial pressure of the blood of normal patients, patients suffering from alkemia, and those suffering from acidemia.
The three levels were:
Acidosis Normal Alkalosis pll 7.15-7.25 7.34-7.41 7.55-7.65 PC02 65-75 mm Hg 40-47 mm llg 18-24 mm Hg PU2 60-70 mm Hg 95-110 mm Hg 140-160 mm Hg The buffer formulations corresponding to the three levels were:
. Acidosis Normal Alkalosis NaOH 38.7 mM/L Emulsion 40.62 mM/L 42.57 mM/L
HEPES 40.00 40.00 mM/L 40.00 mM/L
NaCl 89.29 mM 87.38 mM/L 85.43 mM/L
The buffer formulations were added to the emulsion and each level was then given a distinctive color using the following dyes:
Acidosis Normal Alkalosis 100 mg/l Yellow #5 100 mg/l 66.67 mg/l Amarath Amarath, 133.33 mg/l Yellow #5 The emulsions, containing dyes and dissolved buffer salts and having viscosities of about 4.5 centipoises, 2 solubility coefficients of about 12.4, and a density of about 1.15 (at 20C), were then placed in a container which was thermally controlled to 25aC + 0.5~C. The appropriate ! 17294~
equilibration gas mixture was then bubbled through each emulsion at the rate of 2 L/min. until the pH, PO2, and PCO2 reached equilibrium values, as determined by blood gas measuring equipment. The equilibration gas mixtures had the following compositions:
Acidosis Normal Alkalosis C~2 7 0% 4.17 1.98 2 9.5% 14.0 21.5 N2 83.5% 81.83 76.52 After equilibration, glass ampoules which has been purged with the same gas equilibration mixture used for the emulsion were filled with 1 mL of the appropriate emulsion, up to below a hand-breakable line, and the ampoules heat-sealed.
Another embodiment of the invention employs a ~ixture of perfluoroalkanes and perfluorocyclic ethers (FC-77) and a polymer of about 20-25 units of polyethyleneoxide with between one and four tetrafluoroethylene groups at each end (Monflor 51). Two liters of FC-77 were emulsified, as described above for the FC-77/FC-43 emulsion, with an ~antibacterial surfactant/water solution consisting of 150 g Monflor 51 (about 1.5% by volume of emulsion) and 60 ml formaldehyde brought up to 8.00 liters with distilled water. After all the FC-77 had been added, the emulsion was subjected to seven discrete passes through the Gaulin I-lomogenizer.
Because Monflor 51 often contains IIF as an impurity, the emulsions were neutralized with NaOH. After neutralization, buffers and dyes were added as described above for FC-77/FC-43, they were equilibrated with the appropriate gas mixtures~ and the emulsions placed in ampoules. The liquids had viscosities of about 5 centipoises, 2 solubility coefficients of about 13.5, and densities of about 1.15. In still another embodiment, ~ T~ k } !729~5 liquids with stable emulsions of about 15% FC-77, 15% 200-l silicone oil and Monflor 51 surfactant formulated and equilibrated as above described have densities of about 1.09, 2 solubility coefficients of about 12.5, and viscosities of less than lO centipoises.
The embodiments described above do not include added bicarbonate, but these emulsions nevertheless, owing to the gas equilibration step, effectively contain bicarbonate. Alternatively, it is of course possible to add bicarbonate, in appropriate amounts, along with HEPES.
The emulsions, in their sealed ampoules, were used successfully to check the calibration of blood gas analyzers. An ampoule containing the appropriate emulsion is opened and the control liquid is placed in the blood gas analyzer, which measures and registers the pH, PCO2 and PO2 of the emulsion. A reading outside of the pH and gas partial pressure ranges known to exist in the liquid indicates the need for re-calibration or repair of the analyzer.
While particular embodiments of the invention have been described, various modifications will be apparent to those skilled in the art, and it is not intended that the invention be limited to the disclosed embodiments or to details thereof and departures may be made therefrom within the spirit and scope of the invention.
Claims (27)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A blood gas control product comprising water, 5 - 40% by volume of a water-insoluble perfluorinated compound material, said per-fluorinated compound material having an oxygen solubility coefficient, at one atmosphere pressure, 25°C, and a volumetric proportion of 15%, of at least 10 ml O2 per 100 ml liquid, 0.25 - 10% by volume of a non-ionic fluorocarbon-based surfactant capable of emulsifying said perfluorinated compound material in said water, a pH buffering agent, and a preservative present in a concentration sufficient to inhibit microbial growth in said blood gas control liquid without impairing the quality control functions of said liquid, said preservative being substantially non-reactive with said buffering agent.
2. A blood gas control product comprising a sealed container and a liquid composition of matter in said container, said composition of matter comprising water, 5 - 40% by volume of a water-insoluble perfluor-inated compound material, said perfluorinated compound material having an oxygen solubility coefficient, at one atmosphere pressure, 25°C, and a volumetric proportion of 15%, of at least 10 ml O2 per 100 ml liquid, 0.25 - 10% by volume of a non-ionic fluorocarbon-based surfactant capable of emulsifying said perfluorinated compound material, a pH buffering agent, and a preservative present in a concentration sufficient to inhibit microbial growth in said blood gas control liquid without impairing the quality control functions of said liquid, said preservative being sub-stantially non-reactive with said buffering agent, said blood gas control liquid having a pH in the range of 7.0 to 8.0, a partial pressure of CO2 in the range of 15-80 mm Hg, and a partial pressure of O2 in the range of 20-600 mm Hg.
3. A blood gas control product comprising a stable oil-in-water emulsion that includes water, a water insoluble non-protein organic compound material, and a non-ionic surfactant that is partially soluble in both said water and said compound material, a pH buffering agent, and a preservative present in a concentration sufficient to inhibit microbial growth in said blood gas control liquid without impairing the quality control functions of said liquid, said preservative being substantially non-reactive with said buffering agent, said product having a viscosity of less than ten centipoises and an oxygen solubility coefficient, at one atmosphere pressure and 25°C, of at least 10 ml O2 per 100 ml liquid.
4. The product of claim 1, 2 or 3 and further including a coloring agent to give said blood gas control liquid the appearance of normal arterial blood, said liquid having a partial pressure of oxygen of about 100 mm Hg, a partial pressure of carbon dioxide of about 45 mm Hg, and a pH
of about 7.4.
of about 7.4.
5. The product of claim 1, 2 or 3 and further including a coloring agent to give said blood gas control liquid the appearance of normal venous blood, said liquid having a partial pressure of oxygen of about 65 mm Hg, a partial pressure of carbon dioxide of about 70 mm Hg, and a pH of about 7.2.
6. The product of claim 1, 2 or 3 and further including a coloring agent to give said blood gas control liquid the appearance of low hemoglobin, high pO2 blood, said liquid having a partial pressure of oxygen of about 150 mm Hg, a partial pressure of carbon dioxide of about 21 mm Hg, and a pH of about 7.6.
7. The product of claim 1, 2 or 3 wherein said preservative is an aldehyde, and said buffering agent includes a tertiary amine.
8. The product of claim 1, 2 or 3 wherein said preservative is formaldehyde, and said buffering agent includes a tertiary amine comprising HEPES.
9. The product of claim 1, 2 or 3 wherein said composition further includes a coloring agent selected from the class consisting of Red #33, Yellow #5, Blue #1 and Amarath, and mixtures thereof.
10. The product of claim 1 or 2 wherein the viscosity of said composition is less than ten centipoises.
11. The product of claim 1, 2 or 3 wherein the density of said composition is less than 1.12.
12. The product of claim 1 or 2 wherein the oxygen solubility coefficient of said product is at least 10 ml O2 per 100 ml liquid.
13, The product of claim 3 wherein said compound material includes a perfluorinated compound material that has an oxygen solubility co-efficient, at one atmosphere pressure, 25°C, and a volumetric proportion of 15%, of at least 10 ml O2 per ml liquid.
14. The product of claim 1, 2 or 13 wherein said composition contains less than 25% by volume of said perfluorinated compound material, less than 5% by volume of said surfactant, said preservative includes an aldehyde, said buffering agent includes a tertiary amine, a partial pressure of oxygen in the range of 50-80 mm Hg, and said composition further includes a coloring agent selected from the class consisting of Red #33, Yellow #5, Blue #1 and Amarath, and mixtures thereof.
15. The product of claim 13 wherein said perfluorinated compound material comprises a mixture of perfluoroalkanes, perfluorocyclic ethers, and perfluorotributylamine, and said non-ionic surfactant comprises fluoroalkylpoly(ethyleneoxy)ethanols.
16. The product of claim 1, 2 or 3 wherein said preservative is formaldehyde, said buffering agent includes a tertiary amine comprising HEPES, said perfluorinated compound material comprises a mixture of perfluoroalkanes, perfluorocyclic ethers and perfluorotributylamine, and said non-ionic surfactant comprises fluoroalkylpoly(ethyleneoxy) ethanols.
17. The product of claim 13 wherein said perfluorinated compound material comprises a mixture of perfluoroalkanes and perfluorocyclic ethers, and said non-ionic fluorocarbon-based surfactant comprises a polymer of about 20-25 units of polyethylene oxide with between one and four tetrafluoroethylene groups at each end.
18. The product of claim 1, 2 or 3 wherein said preservative is formaldehyde, said buffering agent includes a tertiary amine comprising HEPES, said perfluorinated compound material comprises a mixture of perfluoroalkanes and perfluorocyclic ethers, and said non-ionic fluoro-carbon-based surfactant comprises a polymer of about 20-25 units of polyethylene oxide with between one and four tetrafluoroethylene groups at each end.
19. The blood gas control product of claim 15 wherein said perfluoroalkanes and perfluorocyclic ethers together comprise about 15% by volume of said liquid, said perfluorotributyl amine comprises about 5% by volume of said liquid, said fluoroalkylpoly(etheleneoxy) ethanol comprises about 2% by volume of said liquid, said preservative is formaldehyde present in a concentration of about 53 mM, and said product further comprises at least one dye.
20. The product of claim 1, 2 or 3 wherein said preservative is formaldehyde, said buffering agent includes a tertiary amine comprising HEPES, said perfluorinated compound material comprises a mixture of perfluoroalkanes, perfluorocyclic ethers and perfluorotributylamine, said non-ionic surfactant comprises fluoroalkylpoly(ethyleneoxy)ethanols, said perfluoroalkanes and perfluorocyclic ethers together comprise about 15% by volume of said liquid, said perfluorotributyl amine comprises about 5% by volume of said liquid, said fluoroalkylpoly(etheleneoxy) ethanol comprises about 2% by volume of said liquid, said preservative is formaldehyde present in a concentration of about 53 mM, and said product further comprises at least one dye.
21. The blood gas control product of claim 15 wherein said perfluoroalkanes and perfluorocyclic ethers together comprise about 11% by volume of said liquid,said perfluorotributyl amine comprises about 3.6% by volume of said liquid, said fluoroalkylpoly(etheleneoxy)ethanol comprises about 2.5% by volume of said liquid, said preservative is formaldehyde present in a concentration of about 43 mM, and said product further comprises about 20% by volume of a silicone oil and at least one dye.
22. The product of claim 1, 2 or 3 wherein said preservative is formaldehyde, said buffering agent includes a tertiary amine comprising HEPES, said perfluorinated compound material comprises a mixture of perfluoroalkanes, perfluorocyclic ethers and perfluorotributylamine, said non-ionic surfactant comprises fluoroalkylpoly(etheleneoxy)ethanol, said perfluoroalkanes and perfluorocyclic ethers together comprise about 11% by volume of said liquid, said perfluorotributyl amine comprises about 3.6% by volume of said liquid, said fluoroalkylpoly(ethyleneoxy)ethanol comprises about 2.5% by volume of said liquid, said preservative is formaldehyde present in a concentration of about 43 mM, and said product further comprises about 20% by volume of a silicone oil and at least one dye.
23. The product of claim 1, 2 or 13 wherein said composition contains less than 25% by volume of said perfluorinated compound material, less than 5% by volume of said surfactant, said preservative includes an aldehyde, said buffering agent includes a tertiary amine, a partial pressure of oxygen in the range of 50-80 mm Hg, said composition further includes a coloring agent selected from the class consisting of Red #33, Yellow #5, Blue #1 and Amarath, and mixtures thereof, said perfluoroalkanes and perfluorocyclic ethers together comprise about 20% of said liquid, said non-ionic polymeric, fluorocarbon-based surfactant comprises about 2% of said liquid by volume, and said preservative is formaldehyde present in a concentration of about 53 mM, and said product further comprises at least one dye.
24. A blood gas control product comprising a sealed container and a liquid composition of matter in said container, said composition of matter comprising a stable oil-in-water emulsion that comprises water, 5-40% by volume of a water-insoluble perfluorinated compound material, said emulsion having an oxygen solubility coefficient, at one atmosphere pressure and 25°C, of at least 10 ml O2 per 100 ml liquid, and 0.25-10% by volume of a non-ionic fluorocarbon-based surfactant capable of emulsifying said perfluorinated compound material, a pH buffering agent, and a preservative present in a concentration sufficient to inhibit microbial growth in said blood gas control liquid without impairing the quality control functions of said liquid, said preservative being substantially non-reactive with said buffering agent, said blood gas control liquid having a viscosity of less than ten centipoises, a pH in the range of 7.0 to 8.0, a partial pressure of CO2 in the range of 15-80 mm Hg, and a partial pressure of O2 in the range of 20-600 mm Hg.
25. The product of claim 3 or 24 wherein the density of said composition is less than 1.12 and said emulsion further includes 15-25%
by volume of a silicone oil.
by volume of a silicone oil.
26. The product of claim 1, 2 or 13 wherein said composition contains less than 25% by volume of said perfluorinated compound material, less than 5% by volume of said surfactant, said preservative includes an aldehyde, said buffering agent includes a tertiary amine, a partial pressure of oxygen in the range of 90-115 mm Hg, and said composition further includes a coloring agent selected from the class consisting of Red #33, Yellow #5, Blue #1 and Amarath, and mixtures thereof.
27. The product of 1, 2 or 13 wherein said composition contains less than 25% by volume of said perfluorinated compound material, less than 5% by volume of said surfactant, said preservative includes an aldehyde, said buffering agent includes a tertiary amine, a partial pressure of oxygen in the range of 130-170 mm Hg, and said composition further includes a coloring agent selected from the class consisting of Red #33, Yellow #5, Blue #1 and Amarath, and mixtures thereof.
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US170,600 | 1980-07-21 | ||
US06/170,600 US4299728A (en) | 1980-07-21 | 1980-07-21 | Blood gas control |
US241,600 | 1981-03-09 | ||
US06/241,600 US4369127A (en) | 1980-07-21 | 1981-03-09 | Blood gas control |
Publications (1)
Publication Number | Publication Date |
---|---|
CA1172945A true CA1172945A (en) | 1984-08-21 |
Family
ID=26866264
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA000382066A Expired CA1172945A (en) | 1980-07-21 | 1981-07-20 | Blood gas control |
Country Status (8)
Country | Link |
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US (1) | US4369127A (en) |
AU (1) | AU551459B2 (en) |
CA (1) | CA1172945A (en) |
DE (1) | DE3129033C2 (en) |
DK (1) | DK164674C (en) |
FR (1) | FR2487073A1 (en) |
GB (1) | GB2080525B (en) |
NL (1) | NL8103453A (en) |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5077036A (en) * | 1986-01-14 | 1991-12-31 | Alliance Pharmaceutical Corp. | Biocompatible stable fluorocarbon emulsions for contrast enhancement and oxygen transport comprising 40-125% wt./volume fluorocarbon combined with a phospholipid |
US4927623A (en) * | 1986-01-14 | 1990-05-22 | Alliance Pharmaceutical Corp. | Dissolution of gas in a fluorocarbon liquid |
US4865698A (en) * | 1986-03-17 | 1989-09-12 | Fuji Photo Film Co., Ltd. | Reference solution for measuring ionic activity |
US4753888A (en) * | 1986-04-09 | 1988-06-28 | Bionostics, Inc. | Multiple control standard for blood analysis |
US4843013A (en) * | 1986-04-09 | 1989-06-27 | Bionostics, Incorporated | Multiple control standard for blood analysis |
US4722904A (en) * | 1986-12-18 | 1988-02-02 | Fisher Scientific Company | Thermodynamically-stable aqueous perfluorocarbon microemulsion useful as blood gas control or calibrator |
US5422278A (en) * | 1987-11-17 | 1995-06-06 | Dade International Inc. | Blood gas/electrolyte calibrator and quality controls |
US4945062A (en) * | 1988-06-15 | 1990-07-31 | Bionostics Incorporated | Control for blood gas/calcium analysis instrumentation |
IT1226839B (en) * | 1988-08-10 | 1991-02-19 | Instrumentation Lab S P A M | METHOD AND APPARATUS TO PRODUCE A CALIBRATION SUBSTANCE IN LIQUID PHASE HAVING A PREDETERMINED PARTIAL PRESSURE OF 02 AND C02 SUITABLE FOR THE CALIBRATION OF ANALYTICAL INSTRUMENTS OF THE BLOOD-TYPE ANALYZERS. |
US4960708A (en) * | 1988-10-13 | 1990-10-02 | Baxter International Inc. | Pressurized packaged reference liquid for blood gas analysis |
AU4044189A (en) * | 1989-07-05 | 1991-01-17 | Alliance Pharmaceutical Corporation | Perfluorocarbons for use as standards in gas partial pressure measurements |
WO1992008130A1 (en) * | 1990-10-26 | 1992-05-14 | Diametrics Medical, Inc. | Temperature insensitive calibration system |
US5231030A (en) * | 1990-10-26 | 1993-07-27 | Diametrics Medical, Inc. | Temperature insensitive calibration system |
US5223433A (en) * | 1991-12-13 | 1993-06-29 | Diametrics Medical Inc. | Temperature stabilized fluid calibration system |
US5595687A (en) * | 1992-10-30 | 1997-01-21 | Thomas Jefferson University | Emulsion stability |
US5571396A (en) * | 1993-07-12 | 1996-11-05 | Dade International Inc. | Fluid analysis system and sensing electrode, electrode assembly, and sensing module components |
US5578194A (en) * | 1995-03-10 | 1996-11-26 | Nova Biomedical Corporation | Calibration of electrodes |
US5633169A (en) * | 1995-10-27 | 1997-05-27 | Nova Biomedical Corporation | Measurement of carbon dioxide in blood |
US6350417B1 (en) * | 1998-11-05 | 2002-02-26 | Sharper Image Corporation | Electrode self-cleaning mechanism for electro-kinetic air transporter-conditioner devices |
CN1215834C (en) * | 2000-07-20 | 2005-08-24 | 佩尔夫托拉科研生产公众股份公司 | Emulsion of perfluororganic compounds for medical purposes, method for producing said emulsion and methods for curing and preventing diseases with the aid of the emulsion |
US8925366B2 (en) | 2012-09-25 | 2015-01-06 | Nova Biomedical Corporation | Gas equilibrium coil for providing, in real-time, a gas calibrating solution |
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Publication number | Priority date | Publication date | Assignee | Title |
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US3629142A (en) * | 1969-12-08 | 1971-12-21 | Edward P Marbach | Reference standard blood serum for the calibration of automatic blood serum analyzing apparatus |
US3681255A (en) * | 1970-09-03 | 1972-08-01 | Gen Electric | Process for the preparation of liquid calibration fluids |
GB1343870A (en) * | 1971-05-19 | 1974-01-16 | Green Cross Corp | Emulsions and the preparation thereof |
US3823091A (en) * | 1971-05-19 | 1974-07-09 | Green Cross Corp | Stable emulsion of fluorocarbon particles |
US3778381A (en) * | 1972-04-24 | 1973-12-11 | Allied Chem | Fluorocarbon microemulsions |
US3911138B1 (en) * | 1973-02-26 | 1996-10-29 | Childrens Hosp Medical Center | Artificial blood and method for supporting oxygen transport in animals |
US3973413A (en) * | 1973-05-01 | 1976-08-10 | George Humphrey Tichenor | Portable hand knitting device |
JPS5331209B2 (en) * | 1973-10-05 | 1978-09-01 | ||
US3993581A (en) * | 1973-10-05 | 1976-11-23 | The Green Cross Corporation | Process for preparing stable oxygen transferable emulsion |
FR2249657B1 (en) * | 1973-11-07 | 1977-04-15 | Ugine Kuhlmann | |
US4116336A (en) * | 1975-05-30 | 1978-09-26 | Radiometer A/S | Package containing a reference liquid for blood gas equipment |
US4163734A (en) * | 1975-05-30 | 1979-08-07 | Radiometer A/S | Reference liquid for blood gas equipment |
US4001142A (en) * | 1975-07-25 | 1977-01-04 | Warner-Lambert Company | Blood gas control |
US4151108A (en) * | 1976-01-27 | 1979-04-24 | Radiometer A/S | Reference liquid for blood gas equipment |
GB1517024A (en) * | 1976-06-14 | 1978-07-05 | Green Cross Corp | Emulsions for transporting oxygen and processes for producing them |
US4040785A (en) * | 1976-10-18 | 1977-08-09 | Technicon Instruments Corporation | Lysable blood preservative composition |
DE2708337C2 (en) * | 1977-02-25 | 1986-04-03 | Radiometer A/S, Kopenhagen/Koebenhavn | Pack containing a synthetic reference liquid for quality control and / or calibration of blood gas measuring devices |
GB1555626A (en) * | 1977-02-28 | 1979-11-14 | Radiometer As | Package containing a reference liquid for blood gas equipment |
US4199471A (en) * | 1978-11-16 | 1980-04-22 | Louderback Allan Lee | Freeze-stable liquid blood control standard |
US4289648A (en) * | 1979-03-20 | 1981-09-15 | Ortho Diagnostics, Inc. | Blood gas controls composition, method and apparatus |
US4299728A (en) * | 1980-07-21 | 1981-11-10 | Instrumentation Laboratory Inc. | Blood gas control |
-
1981
- 1981-03-09 US US06/241,600 patent/US4369127A/en not_active Expired - Lifetime
- 1981-07-09 GB GB8121222A patent/GB2080525B/en not_active Expired
- 1981-07-16 AU AU73055/81A patent/AU551459B2/en not_active Ceased
- 1981-07-17 DE DE3129033A patent/DE3129033C2/en not_active Expired - Fee Related
- 1981-07-20 DK DK323181A patent/DK164674C/en not_active IP Right Cessation
- 1981-07-20 CA CA000382066A patent/CA1172945A/en not_active Expired
- 1981-07-21 NL NL8103453A patent/NL8103453A/en not_active Application Discontinuation
- 1981-07-21 FR FR8114201A patent/FR2487073A1/en active Granted
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FR2487073A1 (en) | 1982-01-22 |
GB2080525A (en) | 1982-02-03 |
DK164674B (en) | 1992-07-27 |
GB2080525B (en) | 1984-03-14 |
DK164674C (en) | 1992-12-14 |
DE3129033A1 (en) | 1982-04-15 |
AU7305581A (en) | 1982-01-28 |
DK323181A (en) | 1982-01-22 |
AU551459B2 (en) | 1986-05-01 |
NL8103453A (en) | 1982-02-16 |
US4369127A (en) | 1983-01-18 |
DE3129033C2 (en) | 1994-11-03 |
FR2487073B1 (en) | 1984-03-23 |
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