Method and Device for Determining the Glucose Concentration in Tissue Liquid

• US 20080153118A1
• Filed: 11/07/2007
• Published: 06/26/2008
• Est. Priority Date: 05/07/2005
• Status: Active Grant

• Current Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Original Assignee: Roche Diagnostics Operations Incorporated (Roche Holding AG)
• Inventors: Ferrari, Stefano, Quarder, Ortrud, Stephan, Peter
• Granted Patent: US 8,114,623 B2
• Time in Patent Office: Days
• US Class Current: 435/14
• CPC Class Codes: A61B 5/14528 invasively
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence

Abstract

The invention relates to a method and a device for determining the glucose concentration in tissue fluid whereby test values for glucose and for an endogenous reference substance are detected in a sample liquid obtained by microdialysis, microperfusion or ultrafiltration, and the glucose value is corrected in accordance with the test value for the reference substance. The recovery rate for glucose is determined from a non-linear relationship with the recovery rate for the ionic reference substance, and the test value for glucose is corrected therewith. In addition, the concentration of lactate and/or pyruvate is used as a further reference substance in the sample liquid to make further corrections.

Claims

1. A method for determining the glucose concentration in a tissue fluid comprising the steps of:

measuring an uncorrected glucose concentration in the tissue fluid;

measuring a concentration of at least one reference substance and glucose in a sample liquid;

determining a corrected glucose concentration in the tissue fluid based upon the measured concentration of the at least one reference substance and glucose in the sample liquid.

2. The method as set forth in claim 1 wherein the at least one reference substance includes lactate or pyruvate.

3. The method as set forth in claim 1 wherein the at least one reference substance includes lactate and pyruvate.

4. The method as set forth in claim 3 further including the step of determining a concentration ratio of lactate to pyruvate in the sample liquid in order to correct the test value for glucose.

5. The method as set forth in claim 4 further including the step of utilizing a linear correction factor to determine the corrected glucose concentration in the tissue fluid if the concentration ratio of lactate to pyruvate generally falls within the range between about 10:

1 to about 20;

1.

6. The method as set forth in claim 4 further including the step of utilizing a constant to determine the corrected glucose concentration in the tissue fluid if the concentration ration of lactate to pyruvate is generally about 20:

1.

7. The method as set forth in claim 1 wherein the uncorrected glucose concentration is measured by a technique selected form the group consisting of microdialysis, microperfusion or ultrafiltration.

12. The method as set forth in claim 7 wherein the reference substance is an ion of sodium.

13. The method as set forth in claim 7 wherein the reference substance is lactate.

14. The method as set forth in claim 7 wherein the reference substance is pyruvate.

15. The method as set forth in claim 7 wherein the measuring steps are conducted ex vivo.

16. The method as set forth in claim 7 further including the steps of:

inserting a probe into the tissue; and

obtaining the sample liquid using the probe.

17. The method as set forth in claim 16 wherein the probe obtains the sample liquid using negative pressure.

18. The method as set forth in claim 7 further including the step of signaling a malfunction when a measured test value falls outside a predetermined range.

8. A method of determining a glucose concentration in a tissue fluid comprising the steps of:

measuring an uncorrected concentration of glucose in the tissue fluid;

measuring a concentration of glucose in a sample liquid;

measuring at least one reference substance in the sample liquid;

determining a recovery rate for glucose (R_GLU) determined from a recovery rate for the reference substance (R_REF); and

determining a corrected concentration of glucose from the recovery rate for glucose.

9. The method as set forth in claim 8 wherein the recovery rate for glucose is determined according to the equation 1-R_REF=(1-R_GLU)^k and k is a predetermined value.

10. The method as set forth in claim 9 further including the step of determining a value for k based upon a ratio of the resistances for the transfer of glucose and the reference substance between the tissue fluid and the sample liquid.

11. The method as set forth in claim 10 further including the step of calculating the recovery rate for the reference substance based upon the ratio of a tested value of the reference substance in the sample liquid and the constant concentration value in the tissue fluid.

19. A device for determining the glucose concentration in a tissue fluid including:

a sensor unit configured to measure a plurality of concentration values for glucose and a reference substance in a sample liquid; and

an evaluation unit configured to correct the concentration value for the glucose according to the concentration value for the reference substance;

wherein the reference substance consists of at least one of lactate and pyruvate.

20. The device as set forth in claim 19 wherein the evaluation unit calculates the concentration ratio of lactate to pyruvate in the sample liquid.

21. The device as set forth in claim 20 wherein the evaluation unit carries out a linear correction of the glucose content when the concentration of lactate to pyruvate falls within a prescribed range.

22. The device as set forth in claim 21 wherein the evaluation unit corrects the glucose content based upon a constant when the concentration of lactate to pyruvate exceeds the prescribed range.

23. The device as set forth in claim 19 wherein the evaluation unit determines the recovery rate of glucose (R_GLU) from a non-linear relationship with the recovery rate for an ionic reference substance (RREF) and calculates the corrected glucose concentration.

24. The device as set forth in claim 19 further including a signal capable of indicating a malfunction when a measured value for the test substance falls outside a predetermined range.