Glucose sensor calibration

• US 10,433,778 B2
• Filed: 02/03/2015
• Issued: 10/08/2019
• Est. Priority Date: 02/04/2014
• Status: Active Grant

• Current Assignee: Baxter Healthcare SA (Baxter International Inc.), Baxter International Inc.
• Original Assignee: Baxter International Inc.
• Inventors: Crane, Barry Colin, Barwell, Nicholas Paul, Paterson, William, Perkins, Robert
• Primary Examiner(s): Matthews, Christine H
• Assistant Examiner(s): Lannu, Joshua Daryl D
• Application Number:
  US15/115,967
• Publication Number:
  US 20170202489A1
• Time in Patent Office: 1,708 Days
• CPC Class Codes: A61B 2560/0233 Optical standards
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes

Abstract

A process for calibrating a glucose sensor under sterile conditions includes providing separate, sterile, glucose-containing calibration fluids, each having a different glucose concentration, and in turn providing these fluids to a sensing zone containing a sensing probe of a glucose sensor. Each solution is typically, in turn, propelled into the sensing zone, thus flushing out used fluid already present in the sensing zone. The process provides rapid calibration of a glucose sensor in a sterile fashion and is therefore appropriate for point-of-use calibration.

Claims

1. A process for calibrating a glucose sensor in a sterile environment, the glucose sensor comprising a sensing probe for detecting glucose, the process comprising:

(i) providing a calibration unit comprising (a) at least a first and a second sterile calibration fluid, each calibration fluid having a different concentration of glucose, (b) a sensing zone, a sensing region of the sensing probe of the glucose sensor being located within the sensing zone, wherein the sensing region of the sensing probe is surrounded by a membrane, and (c) a waste chamber for collecting used calibration fluid;

(ii) providing the first calibration fluid to the sensing zone such that the fluid is in contact with the sensing region, and determining a sensor output;

(iii) flushing the first calibration fluid to the waste chamber;

(iv) providing the second calibration fluid to the sensing zone such that the fluid is in contact with the sensing region, and determining the sensor output; and

(v) using the sensor output readings to calibrate the glucose sensor;

wherein the calibration process is carried out under sterile conditions, and wherein said glucose sensor is an invasive fiber optic glucose sensor containing a fluorescent glucose indicator system, the sensor probe being adapted to detect glucose in vivo.

2. A process according to claim 1, wherein steps (iii) and (iv) comprise a single step of providing the second calibration fluid to the sensing zone, the flow of second calibration fluid into the sensing zone forcing the first calibration fluid to be flushed into the waste chamber.

3. A process according to claim 1, wherein a third sterile calibration fluid is provided, having a different glucose concentration from both the first and second calibration fluids.

4. A process according to claim 3, wherein the process additionally comprises (iiia) flushing the second calibration fluid to the waste chamber;

and (iva) providing the third calibration fluid to the sensing zone such that the fluid is in contact with the sensing region, and determining the sensor output; and

wherein step (v) comprises using all three sensor output readings to calibrate the glucose sensor.

5. A process according to claim 3, wherein the third calibration fluid is a preliminary calibration fluid having zero glucose content and is present in the sensing zone of the calibration unit, and wherein the process comprises (ia) determining the sensor output whilst the preliminary calibration fluid is in the sensing zone;

said step (ia) being carried out prior to step (ii) of providing the first calibration fluid to the sensing zone.

6. A process according to claim 1, which further comprises placing the sensing region of the probe in a sample and determining a glucose content of the sample.

24. A process according to claim 16, further comprising calibrating the glucose sensor according to claim 1.

7. A glucose sensor kit comprising a sensing probe for detecting glucose and a calibration unit, wherein the calibration unit comprises:

a sensing zone having at least one inlet and at least one outlet, a sensing region of the sensing probe being located in the sensing zone, wherein the sensing region of the sensing probe is surrounded by a membrane;

a first calibration chamber containing a first sterile calibration fluid, the first calibration chamber being connected to, or adapted for connection to, an inlet to the sensing zone;

a second calibration chamber containing a second sterile calibration fluid having a glucose concentration different from that of the first calibration fluid, the second calibration chamber being connected to, or adapted for connection to, an inlet to the sensing zone;

at least one fluid propulsion means for propelling calibration fluid from the calibration chambers to the sensing zone;

a waste chamber configured to collect used calibration fluid which is flushed out of the sensing zone;

the glucose sensor kit configured to carry out calibration of a sensor under sterile conditions, and

wherein the sensing probe is part of an invasive fiber optic glucose sensor containing a fluorescent glucose indicator system, and the sensor probe is adapted to detect glucose in vivo.

8. A glucose sensor kit according to claim 7, comprising a controller configured to calibrate the sensor using sensor output readings from the calibration fluids.

9. A glucose sensor kit according to claim 7, wherein the fluid propulsion means are configured to propel calibration fluid into the sensing zone and simultaneously to flush fluid present in the sensing zone into the waste chamber.

10. A glucose sensor kit according to claim 7, further comprising a third calibration chamber containing a third sterile calibration fluid having a glucose concentration different from that of the first and second calibration fluids, the third calibration chamber being connected to, or adapted for connection to, an inlet to the sensing zone.

11. A glucose sensor kit according to claim 7, wherein the sensing zone contains a preliminary sterile calibration fluid, wherein the preliminary calibration fluid has zero glucose content and the first and second calibration fluids have a non-zero glucose content.

12. A calibration unit for calibrating an invasive fiber optic glucose sensor, said sensor containing a fluorescent glucose indicator system and a sensor probe being adapted to detect glucose in vivo, wherein said calibration unit comprises:

a sensing zone having at least one inlet and at least one outlet, the sensing zone configured to house a sensing region of a sensing probe of the glucose sensor, wherein the sensing region of the sensing probe is surrounded by a membrane;

a first calibration chamber containing a first sterile calibration fluid, the first calibration chamber being connected to, or adapted for connection to, the at least one inlet to the sensing zone;

a second calibration chamber containing a second sterile calibration fluid having a glucose concentration different from that of the first calibration fluid, the second calibration chamber being connected to, or adapted for connection to, the at least one inlet to the sensing zone;

at least one fluid propulsion means for propelling calibration fluid from the calibration chambers to the sensing zone; and

a waste chamber configured to collect used calibration fluid which is flushed out of the sensing zone;

the calibration unit being configured to carry out calibration of the sensor under sterile conditions.

13. A calibration unit according to claim 12, further comprising a controller configured to calibrate the sensor using sensor output readings from the calibration fluids.

14. A calibration unit according to claim 12, further comprising a third calibration chamber containing a third sterile calibration fluid having a glucose concentration different from that of the first and second calibration fluids, the third calibration chamber being connected to, or adapted for connection to, the at least one inlet to the sensing zone.

15. A calibration unit according to claim 12, wherein the sensing zone contains a preliminary sterile calibration fluid, wherein the preliminary calibration fluid has zero glucose content and the first and second calibration fluids have a non-zero glucose content.

16. A process for the preparation of a calibration unit for calibrating a glucose sensor, comprising the steps:

(i) providing glucose in solid form in a first mixing chamber, and water or an aqueous solution in a second mixing chamber;

(ii) sterilizing the first and second mixing chambers by use of heat or irradiation;

(iii) mixing contents of the first and second chambers to provide a first, sterile glucose-containing calibration fluid;

(iv) providing at least a portion of the first calibration fluid to a first calibration chamber, whilst maintaining sterility of the fluid;

(v) providing at least one further sterile calibration fluid, each further fluid having a glucose concentration different from one another and from the first calibration fluid, the further calibration fluid(s) being provided in one or more further calibration chambers;

(vi) connecting the first and one or more further calibration chambers to a calibration unit such that the calibration chambers are connected to, or adapted for connection to, an inlet to a sensing zone of the calibration unit; and

(vii) sterilizing the calibration unit using a surface sterilant, said sterilizing step using the surface sterilant being carried out either before or after step (vi), to provide said sterile calibration unit containing said first calibration fluid as a part of at least two sterile calibration fluids.

17. A process according to claim 16, wherein step (iv) comprises sealing the first calibration chamber in order to maintain sterility of the first fluid.

18. A process according to claim 16, wherein step (v) comprises repeating steps (i) to (iv) to provide a second sterile calibration fluid as a part of the at least two sterile calibration fluids in a second calibration chamber as a part of the at least one or more further calibration chambers, a glucose concentration of the second calibration fluid being different from that of the first calibration fluid.

19. A process according to any one of claims claim 16, wherein step (v) comprises providing a sterile calibration fluid having zero glucose concentration as part of the at least one further sterile calibration fluid.

20. A process according to claim 16, wherein the first mixing chamber or the second mixing chamber forms the first calibration chamber.

21. A process according to any one of claims claim 16 wherein a portion of the calibration fluid is provided in the first calibration chamber and the remaining fluid is provided within either the first or the second mixing chamber, and wherein the process further comprises determining a glucose concentration of the remaining fluid.

22. A process according to claim 16, further comprising providing a sensor probe for detecting glucose, wherein a sensing region of the sensor probe is housed within the sensing zone of the calibration unit.

23. A process according to claim 22, wherein the process further comprises providing calibration fluid having zero glucose concentration to the sensing zone.