Blood Analyte Determinations

Abstract

The present invention comprises methods and apparatuses that can provide measurement of glucose and other analytes with a variety of sensors without many of the performance-degrading problems of conventional approaches. As apparatus according to the present invention comprises a blood access system, adapted to remove blood from a body and infuse at least a portion of the removed blood back into the body. Such an apparatus also comprises an analyte sensor, mounted with the blood access system such that the analyte sensor measures the analyte in the blood that has been removed from the body by the blood access system. A method according to the present invention comprises removing blood from a body, using an analyte sensor to measure an analyte in the removed blood, and infusing at least a portion of the removed blood back into the body. The use of a non-contact sensor with a closed system creates a system will minimal infection risk.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a scatter plot of 542 paired glucose measurements from “Experience with continuous glucose monitoring system a medical intensive care unit”, by Goldberg at al, Diabetes Technology and Therapeutics, Volume 6, Number 3, 2004.

FIG. 2 is an illustration of error grid analysis of glucose readings.

FIG. 3 is a schematic illustration of an example embodiment of the present invention comprising a blood access system using a blood flow loop.

FIG. 4 is a schematic illustration of a blood loop system with a peristaltic pump.

FIG. 5 is a schematic illustration of a blood access system implemented based upon a pull-push mechanism with a second circuit provided to prevent fluid overload.

FIG. 6 is a schematic illustration of a blood access system based upon a pull-push mechanism with a second circuit provided to prevent fluid overload.

FIG. 7 is a schematic illustration of a blood access system based upon a pull-push mechanism.

FIG. 8 is a schematic illustration of a blood access system implemented based upon a pull-push mechanism with a second circuit provided to prevent fluid overload.

FIG. 9 is a schematic illustration of an example embodiment that allows a blood sample for measurement to be isolated at a point near the patient and then transported to the instrument for measurement.

FIG. 10 is an illustration of the control of the blood volume and the integration of the total amount of glucose measured.

FIG. 11 is a schematic illustration of an example embodiment that allows a blood sample for measurement to be isolated at a point near the patient and then transported to the instrument for measurement through the use of leading and the following air gaps.

FIG. 12 is a schematic illustration of an example embodiment of the present invention.

FIG. 13 is a schematic illustration of an example embodiment of the present invention.

FIG. 14 is a schematic illustration of an example embodiment of the present invention.

FIG. 15 is a schematic illustration of an example embodiment of the present invention.

FIG. 16 is a plot showing the relationship between pressure, tubing diameter and blood fraction.

FIG. 17 is a plot showing the relationship between pressure, tubing diameter and blood fraction.

FIG. 18 is a schematic illustration of an example embodiment of the present invention.

FIG. 19 is a schematic illustration of an example embodiment of the present invention.

FIG. 20 is a schematic illustration of an example embodiment of the present invention.

FIG. 21 is a schematic illustration of the operation of an example embodiment of the present invention.

FIG. 22 is a schematic illustration of the operation of an example embodiment of the present invention.

FIG. 23 is a schematic illustration of an example embodiment of the present invention.

FIG. 24 is a schematic illustration of an example embodiment of the present invention.

Claims

1. An apparatus for measuring an analyte in blood taken from a patient, comprising: a. An analyte measurement system;b. A fluidics system, adapted to remove blood from a body, transport a portion of the removed blood to the analyte measurement system for measurement, infuse a portion of the blood measured by the analyte measurement system back into the patient, flow a maintenance substance to the analyte measurement system without infusing a substantial amount of the maintenance substance into the patient, and flow at least a portion of the maintenance substance from the analyte measurement system to a waste channel.

2. An apparatus as in claim 1, wherein the maintenance substance is a fluid that cleans the analyte measurement system.

3. An apparatus as in claim 1, wherein the maintenance substance is a fluid that provides a calibration measurement using the analyte measurement system.

4. An apparatus as in claim 1, wherein the analyte is glucose, and the analyte measurement device is a glucose measurement device.

5. An apparatus as in claim 4, wherein the glucose measurement device comprises one or more of; electrochemical sensor, microfluidic sensor, micropost sensor, fluorescent measurement device, and an enzyme-based sensor, a spectroscopic measurement sensor.

6. An apparatus for measuring an analyte in blood, comprising: a. A blood removal element, adapted to communicate blood with the circulatory system of a patient;b. A first fluid transport apparatus, in fluid communication with the blood removal element;c. A second fluid transport apparatus, in fluid communication with the blood removal element and the first fluid transport apparatus;d. An analyte sensor, in fluid communication with the first fluid transport apparatus;e. A fluid management system, in fluid communication with the first and second fluid transport apparatuses and adapted to control fluid flow in the first and second fluid transport apparatuses.

7. An apparatus as in claim 6, wherein the fluid management system comprises: a. a first pump, connected between the first fluid transport apparatus and the second fluid transport apparatus;b. a fluid networks in fluid communication with at least one of the first fluid transport apparatus or the second fluid transport apparatus;c. a second pump in fluid communication with the fluid network;d. a waste channel in fluid communication with the fluid network;e. a maintenance fluid reservoir in fluid communication with the fluid network.

8. An apparatus as in claim 6, further comprising a pressure sensor operatively connected with at least one of the first fluid transport apparatus or the second fluid transport apparatus.

9. An apparatus as in claim 6, wherein the fluid management system comprises: a. a first pump;b. a second pump connected between the first fluid transport apparatus and the first pump;c. wherein the first pump is in fluid communication with the first fluid transport apparatus or second fluid transport apparatus;d. a fluid reservoir in fluid communication with at least one of (i) the first fluid transport apparatus, (ii) the second fluid transport apparatus, and (iii) a path between the first and second pumps.

10. An apparatus as in claim 6, wherein the fluid management system comprises a first pump connected with the first and second fluid transport apparatuses and a fluid reservoir in fluid communication with either the first or second fluid transport apparatus such that the pump can cause fluid to flow in the first and second fluid transport apparatuses independently.

11. A method of determining an analyte property of blood using an apparatus as in claim 9, comprising: a. Drawing fluid from the first fluid transport apparatus such that blood flows from the blood removal element into the first fluid transport apparatus and to the analyte sensor.b. Determining the analyte property of the blood using the analyte sensor;c. Transporting blood from the first fluid transport apparatus to the second fluid transport apparatus;d. Infusing blood from the second fluid transport apparatus to the blood removal element.

12. A method of determining an analyte property of blood as in claim 11 further comprising: a. Using a sensor to indicate the arrival of blood at a predetermined location in the first fluid transport apparatus;b. Determining the volume of the combination of the blood removal element and the first fluid transport apparatus from the circulatory system of the patient to the sensor from the operating parameters of the first and second pump and the sensor indication of the arrival of blood, and using the determined volume in subsequent control of the pumps.

13. An apparatus for measuring an analyte in blood, comprising: a. a blood removal element, adapted to communicate blood with the circulatory system of a patient;b. a first fluid transport apparatus, in fluid communication with the brood removal element;c. a second fluid transport apparatus, in fluid communication with the blood removal element and the first fluid transport apparatus;d. an analyte sensor, in bidirectional fluid communication with at least one of the first fluid transport apparatus and second fluid transport apparatus;e. a first fluid pump, mounted with the first fluid transport apparatus such that the first fluid pump can draw fluid into and push fluid out of the first fluid transport apparatus;f. a second fluid pump, in fluid communication with the second fluid transport apparatus;g. a maintenance fluid reservoir, in fluid communication with the first fluid pump and adapted to supply a maintenance fluid to the first fluid pump;h. a waste system, in fluid communication with the second fluid pump.

14. An apparatus as in claim 13, further comprising an air embolus detector operatively connected with at least one of the first fluid transport apparatus and the second fluid transport apparatus.

15. An apparatus as in claim 13, further comprising a pressure sensor operatively connected with at least one of the first fluid transport apparatus and the second fluid transport apparatus.

16. An apparatus as in claim 13, further comprising a fluid reservoir in fluid communication with the sensor and with the pump.

17. An apparatus as in claim 13, further comprising a blood leak detector operatively connected with at least one of the first fluid transport apparatus and the second fluid transport apparatus.

18. A method of determining an analyte property of blood using an apparatus as in claim 13 where the analyte sensor is in fluid communication with the first fluid transport apparatus, comprising: a. Operating the first fluid pump to draw blood from the blood removal element into the first fluid transport apparatus and to the analyte sensor;b. Determining the analyte property of the blood using the analyte sensor;c. Operating the first pump to draw maintenance fluid from the maintenance fluid reservoir and push a sufficient volume of maintenance fluid into the first fluid transport apparatus that an operative volume of the blood in the first fluid transport apparatus is infused into the patient using the blood removal element;d. Operating the first pump to draw maintenance fluid from the maintenance fluid reservoir and push maintenance fluid into the first fluid transport apparatus, and operating the second pump to draw fluid from the first fluid transport apparatus and through the second fluid transport apparatus to the waste system, where the flow rates of the first and second pumps are such that an insubstantial volume of maintenance fluid is infused into the patient through the blood removal element.

19. A method as in claim 18, wherein step b) is performed at least in part white blood is flowing through the analyte sensor.

20. A method as in claim 18, wherein in step d) the first and second pumps are operated such that variable flow is attained in the first fluid transport apparatus, the second fluid transport apparatus, or both.

21. An apparatus as in claim 13, further comprising a fluid network, and a flow control device between the sensor and the fluid network, and wherein the pump is in fluid communication through a flow control device with the fluid network, and wherein the maintenance fluid reservoir is in fluid communication through a flow control device with the fluid network.

22. An apparatus as in claim 13, wherein the second pump is in fluid communication with the second fluid transport apparatus through a flow control device, and in fluid communication with the waste system; and further comprising a passive reservoir in fluid communication with the pump in the first fluid transport apparatus; and further comprising a fluid communication path from the fluid reservoir to the second pump.

23. A method as in claim 18, further comprising, during step a), operating the second pump to prevent fluid pressure in the first fluid transport apparatus from exceeding a predetermined pressure.

24. A method as in claim 29, further comprising, during step a), operating the first pump to prevent fluid pressure in the second fluid transport apparatus from exceeding a predetermined pressure.

25. A method of determining an analyte property of blood using an apparatus as in claim 21, comprising: a. Operating the first fluid pump to draw a sufficient volume of blood from the blood removal element into the first fluid transport apparatus;b. Operating the first fluid pump to transport the blood in the first fluid transport apparatus to the analyte sensor while operating the second fluid pump to supply maintenance fluid from the maintenance fluid reservoir through the second fluid transport apparatus to the first fluid transport apparatus;c. Determining the analyte property of the blood using the analyte sensor;d. Operating the first and second fluid pumps such that an operative volume of the blood withdrawn in step a) is infused into the patient using the blood removal element;e. Operating the first and second fluid pumps to push maintenance fluid through the first and second fluid transport apparatuses, where the flow rates of the first and second pumps are such that an insubstantial volume of maintenance fluid is infused into the patient through the blood removal element.

26. An apparatus as in claim 9, further comprising: a. a waste channel in fluid communication with at least one of (i) the first fluid transport apparatus, (ii) the second fluid transport apparatus, and (iii) a path between the first and second pumps;b. a maintenance fluid reservoir in fluid communication with at least one of (i) the first fluid transport apparatus, (ii) the second fluid transport apparatus, and (iii) a path between the first and second pumps.

27. An apparatus as in claim 6, wherein the fluid management system comprises a. a first pump connected between the first fluid transport apparatus and the second fluid transport apparatus;b. a second pump in fluid communication with the first fluid transport apparatus or the second fluid transport apparatus;c. a fluid reservoir in fluid communication with at least one of (i) the first fluid transport apparatus, (ii) the second fluid transport apparatus, and (iii) the second pump.

28. A method of determining an analyte property of blood using an apparatus as in claim 27, comprising: a. Drawing fluid from the first fluid transport apparatus such that blood flows from the blood removal element into the first fluid transport apparatus and to the analyte sensors;b. Determining the analyte property of the blood using the analyte sensor;c. Transporting blood from the first fluid transport apparatus to the second fluid transport apparatus;d. Infusing blood from the second fluid transport apparatus to the blood removal element.

29. A method of determining an analyte property of blood using an apparatus as in claim 13 where the analyte sensor is in fluid communication with the second fluid transport apparatus, comprising: a. Operating the second fluid pump to draw blood from the blood removal element into the second fluid transport apparatus and to the analyte sensor;b. Determining the analyte property of the blood using the analyte sensor;c. Operating the second pump to push an operative volume of the blood in the second fluid transport apparatus into the patient using the blood removal element;d. Operating the first pump to draw maintenance fluid from the maintenance fluid reservoir and push maintenance fluid into the first fluid transport apparatus, and operating the second pump to draw fluid from the first fluid transport apparatus and through the second fluid transport apparatus to the waste system, where the flow rates of the first and second pumps are such that an insubstantial volume of maintenance fluid is infused into the patient through the blood removal element.

30. A method as in claim 29, wherein step b) is performed at least in part while blood is flowing through the analyte sensor.

31. A method as in claim 18, wherein in step d) the first and second pumps are operated such that at some time during step d) flow is reversed through the first fluid transport apparatus the second fluid transport apparatus, or both.

32. A method as in claim 25, wherein, during step b), less than a substantial volume of blood is withdrawn from the patient.

33. A method as in claim 25, wherein, during step c), at least some maintenance fluid is infused into the patient.

34. An method for measuring an analyte in blood taken from a patient, comprising: a. removing a sample of blood from the patient;b. transporting the sample of blood in a sterile manner to an analyte measurement system;c. measuring the analyte parameter in the transported sample using the analyte measurement system;d. transporting at least a portion of the measured blood to the patient in a sterile manner and infusing the portion into the patient;e. transporting a maintenance substance to the analyte measurement system without infusing a substantial amount of the maintenance substance into the patient;f. transporting at least a portion of the maintenance substance from the analyte measurement system to a waste channel.

35. A blood access system comprising: a. A junction in fluid communication with a catheter;b. An analyte sensor having a first side in fluid communication with a first side of the junction;c. A first pinch valve having a first side in fluid communication with a second side of the first pinch valve;d. A second pinch valve having a first side in fluid communication with a second side of the first pinch valve;e. A waste channel in fluid communication with a second side of the second pinch valve;f. A first pump in fluid communication with the second side of the first pinch valve;g. A third pinch valve having a first side in fluid communication with the second side of the first pinch valve;h. a maintenance fluid container connection in fluid communication with a second side of the third pinch valve; andi. a second pump having a first side in fluid communication with the first side of the first pinch valve and having a second side in fluid communication with a second side of the junction.

36. A blood access system comprising: a. A junction in fluid communication with a catheter;b. An analyte sensor having a first side in fluid communication with a first side of the junction;c. A first pinch valve having a first side in fluid communication with a second side of the analyte sensor;d. A second pinch valve having a first side in fluid communication with a second side of the first pinch valve;e. A waste channel in fluid communication with a second side of the second pinch valve;f. A first pump having a first side in fluid communication with the second side of the first pinch valve;g. A tubing reservoir in fluid communication with e second side of the first pump;h. A third pinch valve having a first side in fluid communication with the second side of the first pinch valve;i. A maintenance fluid container connection in fluid communication with a second side of the third pinch valve;j. A second pump having a first side in fluid communication with the first side of the first pinch valve and having a second side in fluid communication with a second side of the junction.

37. A blood access system comprising: a. A junction in fluid communication with a catheter;b. An analyte sensor having a first side in fluid communication with a first side of the junction;c. An air detector mounted intermediate the first side of the junction in fluid communication with the first side of the analyte sensor;d. A pressure measurement device in fluid communication with a second side of the analyte sensor;e. A firs pump having a first side in fluid communication with a second side of the analyte sensor;f. A maintenance fluid container connection in fluid communication with e second side of the first pump;g. A second pump having a first side in fluid communication with a second side of the junction;h. A blood leak detector mounted intermediate the first side of the second pump in fluid communication with the second side of the junction; andi. A waste channel in fluid communication with a second side of the second pump.

38. A blood access system as in claim 37, where the first pump having a first side in fluid communication with a second side of the analyte sensor further comprises a blood access port located intermediate the first pump and the analyte sensor.

39. A blood access system as in claim 37, wherein the first pump having a first side in fluid communication with a second side of the analyte sensor further comprises a tubing reservoir located intermediate the first pump and the analyte sensor.

40. A blood access system comprising: a. A junction in fluid communication with a catheter;b. An analyte sensor having a first side in fluid communication with a first side of the junction;c. An air detector mounted intermediate the first side of the junction in fluid communication with the first side of the analyte sensor;d. A pressure measurement device in fluid communication with a second side of the analyte sensor;e. a first pinch valve having a first side in fluid communication with a second side of the analyte sensor;f. a second pinch valve having a first side in fluid communication with e second side of the first pinch valve;g. a maintenance fluid container connection in fluid communication with a second side of the first pinch valve;h. a first pump in fluid communication with the second side of the first pinch valve;i. a third pinch valve having a first side in fluid communication with the second side of the first pinch valve;j. a waste channel having a first side in fluid communication with a second side of the third pinch valve;k. a second pump having a first side in fluid communication with a second side of the waster channel and having a second side in fluid communication with a second side of the junction; andl. a blood leak detector mounted intermediate the second side of the second pump in fluid communication with the second side of the junction.

41. A blood access system, comprising: a. A junction in fluid communication with a catheter;b. An analyte sensor having a first side in fluid communication with a first side of the junction;c. An air detector mounted intermediate the first side of the junction in fluid communication with the first side of the analyte sensor;d. A pressure measurement device in fluid communication with a second side of the analyte sensor;e. A first pump having a first side in fluid communication with the second side of the analyte sensor;f. A passive reservoir having a first side in fluid communication with a second side of the first pump;g. A first pinch valve having a first side in fluid communication with a second side of the passive reservoir;h. A maintenance fluid container connection in fluid communication with a second side of the first pinch valvei. A second pinch valve having a first side in fluid communication with the second side of the passive fluid reservoir;j. A second pump having a first side in fluid communication with a second side of the second pinch valve;k. A waste channel in fluid communication with a second side of the second pump;l. A blood teak detector mounted intermediate the second side of the second pump in fluid communication with the waste channel; andm. A third pinch valve having a first side in fluid communication with the second side of the second pinch valve and having a second side in fluid communication with a second side of the junction;