On-Line Measuring System of Body Substances

• US 20110213230A1
• Filed: 07/02/2009
• Published: 09/01/2011
• Est. Priority Date: 07/02/2008
• Status: Active Grant

• Current Assignee: Maquet Critical Care AB (Getinge AB)
• Original Assignee: Maquet Critical Care AB (Getinge AB)
• Inventors: Carlsson, Anders, Lindgren, Stefan, Jobst, Gerhard, Karlsson, Anton, Falkén, Henrik
• Granted Patent: US 9,101,304 B2
• Time in Patent Office: Days
• US Class Current: 600/365
• CPC Class Codes: A61B 5/14525 using microdialysis
• 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 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/14865 invasive, e.g. introduced into the body by a catheter or needle or using implanted sensors
• CPC Class Codes: A61B 5/1495 Calibrating or testing of in-vivo probes
• CPC Class Codes: A61B 5/412 Detecting or monitoring sepsis

Abstract

A measuring system (100) for continuously measuring body fluid constituents, said measuring system (100) comprising a microdialysis catheter or probe (110) comprising a microdialysis membrane (116) to be placed in a blood stream or in tissue fluid. The measuring system further comprises a flow through sensor (200) for continuously measuring the concentration of substances present in the fluid that has passed the microdialysis membrane (116). The measuring system (100) further comprises a waste container (126).

Claims

1-22. -22. (canceled)

23. A measuring system for measuring the concentration of substances or analytes in a body fluid or in a body tissue, comprising:

a microdialysis probe comprising a microdialysis membrane, both being adapted to be placed in blood or in tissue,

a flow through sensor for analysing a fluid having passed said microdialysis probe,

a pump for pumping said fluid to and through said microdialysis probe and further to and through said sensor, and

tubing connecting said pump to said microdialysis probe and said microdialysis probe to said sensor,

said pump effecting a flow rate in said system in the interval 0.2-15 microliters per minute, wherein the sensor comprises a flow channel having a flow resistance or pressure drop adapted to the characteristics of the microdialysis membrane so as to eliminate, or at least substantially reduce, ultra filtering in the microdialysis membrane.

24. A measuring system according claim 23, wherein the cross-sectional area of the flow channel is adapted to one or more characteristics of the microdialysis membrane, said characteristics comprising at least one of the microdialysis membrane area and the liquid permeability of the microdialysis membrane;

preferably, the microdialysis membrane area is between 20 to 200 mm², and preferably, the liquid permeability of the microdialysis membrane is between 1 to 3×

10<sup>−

4</sup> cm/bar×

s.

25. A measuring system according to claim 23, wherein said the flow channel has a flow resistance or pressure drop less than about 100 Pa at a flow rate of about 0.5 microliters per minute.

26. A measuring system according to claim 23, wherein the flow channel has a flow resistance or pressure drop less than about 1.6 kPa at a flow rate of about 10 microliters per minute.

27. A measuring system according to claim according to claim 23, wherein the microdialysis probe comprises a multilumen tube and a microdialysis membrane, said tube exhibiting at least two longitudinally arranged inner bores, said bores extending from a proximal end of the tube to the distal end of the tube, where at least two channels are provided, one from each of said at least two bores to the outside of said tube, said bores blocked for passage of liquid distally of the respective channels, a tubular membrane arranged circumferentially around the tube such as to cover the at least two channels, said membrane is sealingly fastened to the tube thereby forming a space between the tube and the membrane.

28. A measuring system according to claim 23, wherein said flow channel has a flow channel width in the interval of 250-1000 micrometer and a flow channel height in the interval of 10 micrometer to 1 millimeter, more preferably 25-100 micrometer, and most preferably the dimension of the flow channel width is about 550 micrometer, and the dimension of the flow channel height is about 75 micrometer.

29. A measuring system according to claim 23, wherein said sensor includes at least one measuring electrode with multiple membrane layers wherein said layers comprise:

an oxidase membrane layer comprising immobilized oxidase enzyme capable of reacting the analyte with oxygen in a hydrogen peroxide generating reaction; and

a diffusion limiting membrane adapted to provide a higher diffusion resistance for the analyte than for oxygen and to provide lower flow of analyte to the oxidase membrane layer than the conversion rate of the oxidase enzyme.

30. A measuring system according to claim 29, wherein the diffusion limiting membrane has a thickness of about 10 micrometer.

31. A measuring system according to claim 29, wherein the diffusion limiting membrane is made from a hydrogel, preferably the hydrogel is poly-HEMA.

32. A measuring system according to claim 23, wherein said sensor further comprises a catalase membrane with a sufficient extension and catalase activity to substantially decompose all the hydrogen peroxide reaching the membrane.

33. A measuring system according to claim 32, wherein said catalase membrane has a thickness in the interval of 5 to 10 micrometer.

34. A measuring system according to claim 29, wherein the oxidase membrane layer has an area adapted so that the output signal of said measuring electrode is sufficiently high relative a potential noise level or noise signal for the lowest analyte concentration in the linear measurement range of the measuring electrode.

35. A measuring system according to claim 29, wherein said oxidase membrane layer has an essentially circular area with a diameter from about 250 to about 1000 micrometer, preferably about 450 micrometer.

36. A measuring system according to claim 29, wherein the oxidase is glucose oxidase and/or lactate oxidase.

37. A measuring system according to claim 23, comprising several consecutively arranged measuring electrodes, wherein each measuring electrode comprises multiple membrane layers wherein said layers comprise:

an oxidase membrane layer comprising immobilized oxidase enzyme capable of reacting the analyte with oxygen in a hydrogen peroxide generating reaction; and

a diffusion limiting membrane adapted to provide a higher diffusion resistance for the analyte than for oxygen and to provide lower flow of analyte to the oxidase membrane layer than the conversion rate of the oxidase enzyme.

38. A measuring system according to claim 23, wherein the microdialysis membrane has the size selective layer located on its outside facing body fluid.

39. A measuring system according to claim 23, wherein a waste container is connected to an outflow end of said flow channel for collecting fluid flowing out from said flow channel, said waste container comprising an absorbent, said absorbent advantageously being anti bacterial.

40. A measuring system according to claim 39, wherein said waste container advantageously further comprises a pressure relief valve, said pressure relief valve advantageously being impermeable to bacteria.

41. A measuring system according to claim 39, wherein said waste container comprises means adapted for connection to a receptacle for collecting fluid in said receptacle for further analysis of said fluid.

42. A measuring system according to claim 25 that is essentially free from ultrafiltration when operated with a flow rate of about 0.5 microliters/minute when continuously measuring and monitoring physiologically and clinically relevant levels of glucose and/or lactate with a sensor having a sensor flow resistance or pressure drop of less than about 100 Pa, wherein the microdialysis membrane has an extension of about 30 mm active length and a liquid (hydraulic) permeability of about 2×

10<sup>−

4</sup> cm/bar×

s; and

the sensor flow channel has a flow channel with width of about 550 micrometer.

43. A measuring system according to claim 26 that is essentially free from ultrafiltration when operated with a flow rate of about 10 microliters/minute when continuously measuring and monitoring physiologically and clinically relevant levels of glucose and/or lactate with a sensor having a sensor flow resistance or pressure drop of less than about 1.6 kPa, wherein the microdialysis membrane has an extension of about 40 mm active length and a liquid (hydraulic) permeability of about 2×

10<sup>−

4</sup> cm/bar×

s; and

the sensor flow channel has a flow channel with width of about 550 micrometer.

44. A measuring system according to claim 42, wherein the flow channel length is about 7.5 mm.

45. A measuring system according to claim 43, wherein the flow channel length is about 7.5 mm.