Condensate glucose analyzer

• US 7,914,460 B2
• Filed: 08/15/2006
• Issued: 03/29/2011
• Est. Priority Date: 08/15/2006
• Status: Active Grant

• Current Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida)
• Original Assignee: University of Florida Research Foundation, Incorporated (State University System of Florida), Xhale, Inc.
• Inventors: Booth, Matthew M., Youngblood, Ronald E., Horn, John Frederick Jr., Melker, Richard J., Batich, Christopher D., Stewart, Jon D., Dennis, Donn M., Bjoraker, David G.
• Primary Examiner(s): Mallari; Patricia C
• Application Number:
  US11/504,335
• Publication Number:
  US 20080045825A1
• Time in Patent Office: 1,687 Days
• Field of Search: 600/365, 600/532, 600/543
• US Class Current: 600/532
• CPC Class Codes: A61B 5/083 Measuring rate of metabolism by using breath test, e.g. measuring rate of oxygen consumption
• CPC Class Codes: A61B 5/1486 using enzyme electrodes, e.g. with immobilised oxidase
• CPC Class Codes: A61B 5/413 Monitoring transplanted tissue or organ, e.g. for possible rejection reactions after a transplant
• CPC Class Codes: Y10T 436/144444 Glucose

Abstract

The present invention provides systems and methods for analyzing glucose present in exhaled breath condensate (EBC). In certain embodiments of the invention, electrochemical- or coulometric-based sensing technologies are used to analyze EBC for the presence and/or concentration of glucose.

Claims

1. A non-invasive, portable glucose monitoring device comprising:

a) at least one collection reservoir for collecting at least one exhaled breath sample, wherein said collection reservoir comprises a sensor and a signaling means, said sensor, said signaling means or both either comprising or being in operative communication with at least one processor; and

b) a means for extracting condensates from the exhaled breath sample, wherein said sensor is equipped to identify glucose and at least one solute in the extracted condensate, and where the concentration of said at least one solute, the concentration of which is both tightly regulated in blood and which concentration is substantially identical in airway lining fluid to that in blood, is used by said processor as a ratio with the concentration of that same solute in blood to determine a dilution factor to be utilized in correlating the concentration of glucose in blood with the glucose identified in the extracted condensate by multiplying said dilution factor with the concentration of glucose in said condensate.

2. The device of claim 1, wherein the collection reservoir is comprised within at least one breathing tube.

3. The device of claim 2, wherein the at least one breathing tube is disposable.

4. The device of claim 2, comprising a plurality of breathing tubes that are provided in a collapsed state.

5. The device of claim 1, wherein the sensor comprises a hydrophilic hydrogel comprising at least one glucose-binding molecule.

6. The device of claim 5, wherein the glucose-binding molecule is selected from the group consisting of:

antibodies, enzymes, oligonucleotides, peptides, or proteins.

7. The device of claim 6, wherein the glucose-binding molecule is selected from the group consisting of glucose-oxidase, glucose dehydrogenase, and glucose hexokinase.

8. The device of claim 5, further comprising a pressure transducer near the hydrogel.

9. The device of claim 1, wherein the means for extracting condensates comprises a Peltier device, which surrounds the collection reservoir or is otherwise in sufficient contact to achieve control over the temperature of said collection reservoir.

10. The device of claim 1, wherein the sensor is equipped to identify chloride or other electrolytes, and wherein the sensor comprises one sensor for identifying glucose and chloride, or other electrolytes, or a first sensor for identifying glucose and a second sensor for identifying chloride or other electrolytes.

11. The device of claim 1, wherein the sensor further comprises a calibration sensor.

12. The device according to claim 1 which detects the glucose concentration in a subject at risk of hyperglycemia, hypoglycemia or fluctuations between hyperglycemia and hypoglycemia.

13. The device according to claim 12 which detects blood glucose levels at frequent intervals or constantly over a period of time.

14. The non-invasive, portable glucose monitoring device according to claim 1 wherein said airway lining fluid is comprised predominantly from alveolar lining fluid, fluid from capillary endothelial cells, and combinations thereof and wherein said solute is chloride.

15. A glucose monitoring device comprising:

(a) at least one collection reservoir for collecting at least one exhaled breath sample,

(b) at least one sensor, coupled to at least one signaling means, said sensor or said signaling means or both comprising or being in operative communication with at least one processor; and

(c) a means for extracting condensate from said at least one exhaled breath sample;

wherein said condensate is contacted with said at least one sensor;

wherein said at least one sensor is adapted to measure the concentration of glucose in said condensate and to measure the concentration of at least one solute other than glucose in said condensate such that the concentration of said at least one solute, the concentration of which is both tightly regulated in blood and which concentration is substantially identical in airway lining fluid to that in blood, is used by said processor as a ratio with the concentration of that same at least one solute in blood to determine a dilution factor which is utilized by said processor to multiply said dilution factor with the concentration of glucose measured in said condensate by said sensor, to thereby provide the concentration of glucose in blood wherein said means for extracting condensate from said at least one exhaled breath sample extracts condensate by cooling said at least one exhaled breath sample to a temperature below body temperature wherein said temperature below body temperature is a temperature selected from the group consisting of between 10 to 15 degrees Centigrade below body temperature.

16. A glucose monitoring device comprising:

(a) at least one collection reservoir for collecting at least one exhaled breath sample,

(b) at least one sensor, coupled to at least one signaling means, said sensor or said signaling means or both comprising or being in operative communication with at least one processor; and

(c) a means for extracting condensate from said at least one exhaled breath sample;

wherein said condensate is contacted with said at least one sensor;

wherein said at least one sensor is adapted to measure the concentration of glucose in said condensate and to measure the concentration of at least one solute other than glucose in said condensate such that the concentration of said at least one solute, the concentration of which is both tightly regulated in blood and which concentration is substantially identical in airway lining fluid to that in blood, is used by said processor as a ratio with the concentration of that same at least one solute in blood to determine a dilution factor which is utilized by said processor to multiply said dilution factor with the concentration of glucose measured in said condensate by said sensor, to thereby provide the concentration of glucose in blood, wherein said means for extracting condensate from said at least one exhaled breath sample extracts condensate by cooling said at least one exhaled breath sample to a temperature below body temperature wherein said temperature below body temperature is a temperature selected from the group consisting of 20.6 degrees centigrade, −

2.8 degrees centigrade, and −

17.8 degrees centigrade.

17. The glucose monitoring device according to claim 16 wherein said airway lining fluid is comprised predominantly from alveolar lining fluid, fluid from capillary endothelial cells, and combinations thereof and wherein said solute is chloride.

18. A glucose monitoring device comprising:

(a) at least one collection reservoir for extracting and collecting condensate from at least one exhaled breath sample

(b) at least one sensor, coupled to at least one signaling means, said sensor or said signaling means or both comprising or being in operative communication with at least one processor;

wherein said condensate is contacted with said at least one sensor;

wherein said at least one sensor is adapted to measure the concentration of glucose in said condensate and to measure the concentration of at least one solute other than glucose in said condensate such that the concentration of said at least one solute, the concentration of which is both tightly regulated in blood and which concentration is substantially identical in airway lining fluid to that in blood, is used by said processor as a ratio with the concentration of that same at least one solute in blood to determine a dilution factor which is utilized by said processor to multiply said dilution factor with the concentration of glucose measured in said condensate by said sensor, to thereby provide the concentration of glucose in blood.

19. The non-invasive portable glucose monitoring device of claim 18, wherein said at least one sensor comprises a first sensor for identifying glucose and a second sensor for identifying said at least one solute.

20. The device according to claim 19 which detects the glucose concentration in a subject at risk of hyperglycemia, hypoglycemia or fluctuations between hyperglycemia and hypoglycemia.

21. The device according to claim 20 which detects blood glucose levels at frequent intervals or constantly over a period of time.

22. A glucose monitoring device comprising:

(a) at least one collection reservoir for collecting at least one exhaled breath sample,

(b) at least one sensor, coupled to at least one signaling means, said sensor or said signaling means or both comprising or being in operative communication with at least one processor; and

(c) a means for extracting condensate from said at least one exhaled breath sample;

wherein said condensate is contacted with said at least one sensor;

wherein said at least one sensor is adapted to measure the concentration of glucose in said condensate and to measure the concentration of at least one solute other than glucose in said condensate such that the concentration of said at least one solute, the concentration of which is both tightly regulated in blood and which concentration is substantially identical in airway lining fluid to that in blood, is used by said processor as a ratio with the concentration of that same at least one solute in blood to determine a dilution factor which is utilized by said processor to multiply said dilution factor with the concentration of glucose measured in said condensate by said sensor, to thereby provide the concentration of glucose in blood.

23. The device of claim 22 wherein said means for extracting condensate from said at least one exhaled breath sample extracts condensate by cooling said at least one exhaled breath sample to a temperature below body temperature.

24. The device according to claim 22 which detects the glucose concentration in a subject at risk of hyperglycemia, hypoglycemia fluctuations between hyperglycemia and hypoglycemia.

25. The device according to claim 24 which detects blood glucose levels at frequent intervals or constantly over a period of time.

26. The device of claim 23, wherein said means for extracting condensate comprises a Peltier device.

27. The device of claim 22 wherein said at least one exhaled breath sample is an end-tidal exhaled breath sample.

28. The device of claim 22, wherein said at least one sensor comprises a first sensor for identifying glucose and a second sensor for identifying said at least one solute.

29. The device of claim 22 wherein said solute is an electrolyte the concentration of which is measured in said condensate, wherein said electrolyte is selected from the group consisting of chloride, sodium, potassium and combinations thereof.

30. The device of claim 29 wherein the electrolyte, the concentration of which that is measured in said condensate, is chloride.

31. A non-invasive, portable glucose monitoring device comprising at least one processor and at least one collection reservoir for extracting and collecting condensate from at least one exhaled breath sample, wherein said collection reservoir comprises a sensor and a signaling means, wherein said sensor is equipped to identify glucose and at least one solute in the extracted condensate, and where the concentration of said at least one solute, the concentration of which is both tightly regulated in blood and which concentration is substantially identical in airway lining fluid to that in blood, is used by said processor as a ratio with the concentration of that same solute in blood to determine a dilution factor to be utilized in correlating the concentration of glucose in blood with the glucose identified in the extracted condensate by multiplying said dilution factor with the concentration of glucose in said condensate.

32. The non-invasive portable glucose monitoring device of claim 31, wherein said at least one sensor comprises a first sensor for identifying glucose and a second sensor for identifying said at least one solute.

33. A glucose monitoring device comprising:

(a) at least one collection reservoir for collecting at least one exhaled breath sample,

(b) at least one sensor, coupled to at least one signaling means, said sensor or said signaling means or both comprising or being in operative communication with at least one processor; and

(c) a means for extracting condensate from said at least one exhaled breath sample;

wherein said condensate is contacted with said at least one sensor;

wherein said at least one sensor is adapted to measure the concentration of glucose in said condensate and to measure the concentration of at least one solute other than glucose in said condensate such that the concentration of said at least one solute, the concentration of which is both tightly regulated in blood and which concentration is substantially identical in airway lining fluid to that in blood, is used by said processor as a ratio with the concentration of that same at least one solute in blood to determine a dilution factor which is utilized by said processor to multiply said dilution factor with the concentration of glucose measured in said condensate by said sensor, to thereby provide the concentration of glucose in blood wherein said means for extracting condensate from said at least one exhaled breath sample extracts condensate by cooling said at least one exhaled breath sample to a temperature below body temperature.