Calibration solutions useful for analysis of biological fluids and methods employing same

• US 5,505,828 A
• Filed: 02/02/1995
• Issued: 04/09/1996
• Est. Priority Date: 08/28/1992
• Status: Expired due to Fees

• Current Assignee: Segars California Partners, LP
• Original Assignee: VIA Medical Corporation (Medtronic Plc)
• Inventors: Curry, Kenneth M., Wong, David K.
• Primary Examiner(s): Bell, Bruce F.
• Application Number:
  US08/379,555
• Time in Patent Office: 432 Days
• Field of Search: 204/153.12, 204/403, 204/409, 204/412, 204/416, 204/419, 204/153.1, 128/632, 128/635, 128/760, 604/4
• US Class Current: 205/777.5
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: G01N 2496/70 Blood gas control solutios containing dissolved oxygen, bicarbonate and the like
• CPC Class Codes: G01N 2496/80 Multi-analyte reference solutions containing cholesterol, glucose and the like
• CPC Class Codes: G01N 33/4925 measuring blood gas content, e.g. O2, CO2 , HCO3
• CPC Class Codes: G01N 33/84 involving inorganic compounds or pH
• CPC Class Codes: G01N 33/96 involving blood or serum control standard

Abstract

Novel calibration solutions are provided which are useful, for example, with sensor assemblies used for analysis of CO₂, and optionally, for concurrent analysis of O₂, especially in combination infusion fluid delivery/blood chemistry analysis systems which include a sensor assembly with each of the assembly electrodes mounted in an electrode cavity in the assembly. The analysis system used in the practice of the present invention typically includes provision for delivering infusion fluid and measuring blood chemistry during reinfusion of the physiological fluid at approximately the same flow rates. The invention calibration solutions are useful for calibrating an array of sensors capable of simultaneously measuring a number of blood chemistry parameters, including the partial pressures (tensions) of carbon dioxide and oxygen, pH (hydrogen ion), sodium, potassium, ionized calcium, ionized magnesium, chloride, glucose, lactate and hematocrit, in body fluids. More particularly, this invention relates to the use of an infusible intravenous solution to facilitate calibration on a regular basis for every individual sensor in a sensor assembly, which is in constant fluid communication with the body regardless of whether the sensors are ex vivo or in vivo.

Claims

1. A method for the calibration of a sensor employed for the detection of CO₂ partial pressure (pCO₂), and optionally, O₂ partial pressure (pO₂), in physiological fluid, said method comprising

contacting a sensor assembly having:

a fluid passageway and a sensor for pCO₂, and optionally a sensor for pO₂, exposed to said fluid passageway, and

means to pass physiological fluid or calibrant or both over said sensor,

with an infusion medium/calibrant comprising;

non-buffered physiological sodium chloride-containing saline, and

an amount of a carbon dioxide source effective to provide a stable pCO₂ in the range of about 1 up to 100 mm Hg, and optionally a stable pO₂ in the range of about 0 up to 200 mm Hg, and thereafter calibrating said sensor.

2. A method according to claim 1 wherein said method further comprises the concurrent calibration of pO₂ and pCO₂.

3. A method according to claim 2 wherein said method further comprises the calibration of one or more additional species selected from Na⁺, K⁺, Ca⁺⁺, Mg⁺⁺, Cl^-, hydrogen ions, lactose or glucose, or combinations of any two or more thereof, in addition to pO₂ and pCO₂.

4. A method according to claim 3 wherein said calibration is carried out employing a multi-sensor assembly comprising a plurality of sensors which are responsive to one or more additional species selected from Na⁺, K⁺, Ca⁺⁺, Mg⁺⁺, Cl^-, hydrogen ions, lactose or glucose, or combinations of any two or more thereof, in addition to O₂ and CO₂.

5. A method according to claim 1 wherein said method further comprises the calibration of one or more additional species selected from the group consisting of Na⁺, K⁺, Ca⁺⁺, Mg⁺⁺, Cl^-, pH, lactate and glucose, in addition to pCO₂.

6. A method according to claim 5 wherein said calibration is carried out employing a multi-sensor assembly comprising a plurality of sensors which are responsive to one or more additional species selected from Na⁺, K⁺, Ca⁺⁺, Mg⁺⁺, Cl^-, hydrogen ions, lactose or glucose, or combinations of any two or more thereof, in addition to CO₂.

7. A method according to claim 1 wherein said infusion medium/calibrant is selected from:

non-buffered physiological sodium chloride-containing saline, further containing an amount of a carbon dioxide source effective to provide a stable CO₂ partial pressure in the range of about 1 up to 100 mm Hg, and optionally a stable O₂ partial pressure in the range of about 0 up to 200 mm Hg, optionally containing one or more additional electrolytes,

non-buffered 0.9% sodium chloride containing an amount of a carbon dioxide source effective to provide a stable CO₂ partial pressure in the range of about 1 up to 100 mm Hg, and optionally a stable O₂ partial pressure in the range of about 0 up to 200 mm Hg, optionally containing one or more additional electrolytes,

non-buffered Isolyte™

brand infusible injection solution containing an amount of a carbon dioxide source effective to provide a stable CO₂ partial pressure in the range of about 1 up to 100 mm Hg, and optionally a stable O₂ partial pressure in the range of about 0 up to 200 mm Hg,

non-buffered PlasmaLyte™

brand infusible injection solution containing an amount of a carbon dioxide source effective to provide a stable CO₂ partial pressure in the range of about 1 up to 100 mm Hg, and optionally a stable O₂ partial pressure in the range of about 0 up to 200 mm Hg,

non-buffered Ringer'"'"'s injection containing an amount of a carbon dioxide source effective to provide a stable CO₂ partial pressure in the range of about 1 up to 100 mm Hg, and optionally a stable O₂ partial pressure in the range of about 0 up to 200 mm Hg,

non-buffered Ringer'"'"'s Acetate containing an amount of a carbon dioxide source effective to provide a stable CO₂ partial pressure in the range of about 1 up to 100 mm Hg, and optionally a stable O₂ partial pressure in the range of about 0 up to 200 mm Hg, or

non-buffered Ringer'"'"'s Lactate containing an amount of a carbon dioxide source effective to provide a stable CO₂ partial pressure in the range of about 1 up to 100 mm Hg, and optionally a stable O₂ partial pressure in the range of about 0 up to 200 mm Hg.

8. A method according to claim 7 wherein said infusion medium/calibrant further comprises in the range of about 10 up to 10,000 mg/L of dextrose.

9. A method according to claim 7 wherein said infusion medium/calibrant further comprises in the range of about 10 up to 50,000 IU/L sodium heparin.

10. A method according to claim 7 wherein said infusion medium/calibrant further comprises one or more non-buffering pH adjusting reagents.

11. A method according to claim 1 wherein said method further comprises passing a volume of calibrant through the fluid passageway of said sensor assembly sufficient to provide contact of fresh calibrant with at least one of said sensors when calibrating.

12. A method according to claim 1 wherein said method further comprises determining the time required for transport of fluid from the source container to the sensor, and correcting the calibration of said system to reflect the diffusion loss of gases to which the tubing employed for delivery of infusible fluid is permeable.

13. A method according to claim 1 wherein said method further comprises compensating for changes in the pCO₂ in the calibrant by monitoring any changes in the pH and/or temperature of the calibrant and calculating the resulting pCO₂ based on the pH of the calibrant.

14. A method for the assay of CO₂ partial pressure (pCO₂), and optionally O₂ partial pressure (pO₂), in physiological fluid, said method comprising

contacting an assembly having:

a fluid passageway and a sensor for pCO₂, and optionally a sensor for pO₂, exposed to said fluid passageway, and

means to pass physiological fluid or calibrant or both over said sensor,

with an infusible calibrant comprising;

non-buffered physiological sodium chloride-containing saline, and

an amount of a carbon dioxide source effective to provide a stable pCO₂ in the range of about 1 up to 100 mm Hg, and optionally a stable pO₂ in the range of about 0 up to 200 mm Hg; and

calibrating said pCO₂ sensor; and

thereafter

contacting said assembly with said physiological fluid and measuring the pCO₂ in said physiological fluid.

15. In a method for the assay of pCO₂, and optionally, pO₂, in physiological fluid employing a sensor assembly, the improvement comprising using an infusible calibrant comprising:

non-buffered physiological sodium chloride-containing saline, and

an amount of a carbon dioxide source effective to provide a stable pCO₂ in the range of about 1 up to 100 mm Hg, and optionally a stable pO₂ in the range of about 0 up to 200 mm Hg.

16. In a combination infusion delivery system and chemical analysis system having a sensor which determines CO₂ partial pressure (pCO₂), and optionally, a sensor which determines O₂ partial pressure (pO₂), in physiological fluid, wherein physiological saline is employed as the infusion medium, the improvement comprising introducing an amount of a carbon dioxide source into said physiological saline effective to provide a stable pCO₂ and optionally a stable pO₂ to calibrate said CO₂ and optionally said O₂ sensor.