Microdialysis probes and methods of use

• US 20030009100A1
• Filed: 06/21/2002
• Published: 01/09/2003
• Est. Priority Date: 06/22/2001
• Status: Active Grant

• Current Assignee: University of Florida (State University System of Florida)
• Original Assignee: University of Florida (State University System of Florida)
• Inventors: Mueller, Markus, Derendorf, Hartmut
• Granted Patent: US 6,904,309 B2
• Time in Patent Office: Days
• US Class Current: 600/424
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 2010/008 Interstitial fluid
• CPC Class Codes: A61B 2090/3925 ultrasonic
• CPC Class Codes: A61B 5/145 Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissuemeasuring of blood pressure or blood flow A61B5/02; non-radiation detecting or locating of foreign bodies in blood A61B5/06
• CPC Class Codes: A61B 5/14528 invasively
• CPC Class Codes: A61B 5/411 Detecting or monitoring allergy or intolerance reactions to an allergenic agent or substance
• CPC Class Codes: A61B 6/12 Arrangements for detecting or locating foreign bodies
• CPC Class Codes: A61B 8/0833 involving detecting or locating foreign bodies or organic structures

Abstract

The subject invention pertains to novel microdialysis probes having highly advantageous structural features, particularly for clinical applications. A microdialysis probe of the subject invention can be introduced into a biological tissue using insertion means such that the insertion means can the be completely dissociated from the biological tissue and the microdialysis probe. The microdialysis probes of the subject invention can further include guiding means composed of imageable material that may be used to guide the microdialysis probes to a target tissue using the appropriate sensing equipment. A further aspect of the subject invention relates to methods of using novel microdialysis probes to assess the presence or absence of a substance within biological tissue. The subject invention further relates to methods of using novel microdialysis probes to deliver a substance within biological tissue.

Claims

1. A microdialysis probe comprising:

a membrane portion;

an outer tube, wherein said outer tube has a proximal end, a distal end, an inner surface, and an outer surface, wherein said membrane portion is disposed on said distal end of said outer tube;

an inner tube, wherein said inner tube has a proximal end, a distal end, an inner surface, and an outer surface, and wherein said inner tube is arranged within said outer tube;

and a guiding means located on said probe in a known spatial relationship with said membrane portion.

2. The microdialysis probe of claim 1, wherein said guiding means comprises an imageable material.

3. The microdialysis probe of claim 1, wherein said guiding means comprises an imageable material having an image signature that is discernable from that of biological tissue.

4. The microdialysis probe of claim 1, wherein said guiding means comprises an echogenic material.

5. The microdialysis probe of claim 1, wherein said guiding means comprises an echogenic material having an acoustic impedance different from that of the surrounding medium into which said guiding means is introduced.

6. The microdialysis probe of claim 1, wherein said guiding means comprises an imageable material selected from the group consisting of aluminum, plastic, sand, and metal particles.

7. The microdialysis probe of claim 1, wherein said guiding means comprises an imageable material that is radio-opaque.

8. The microdialysis probe of claim 1, wherein said guiding means comprises an imageable material that can be imaged with magnetic resonance imaging or magnetic resonance spectroscopy.

9. The microdialysis probe of claim 1, wherein said guiding means comprises an imageable material that can be imaged with single photon emission tomography or positron emission tomography.

10. The microdialysis probe of claim 1, wherein said guiding means comprises an imageable material that is formulated as a coating on said microdialysis probe.

11. The microdialysis probe of claim 1, wherein said guiding means occupies a known position on or within said probe, such that imaging said guiding means provides information as to the location of the membrane portion when said probe is inserted into a medium.

12. The microdialysis probe of claim 11, wherein said guiding means also provides information as to the spatial orientation of said membrane portion when said membrane portion is inserted into a medium and when said guiding means is imaged.

13. The microdialysis probe of claim 1, wherein said guiding means provides information as to at least one geometric parameter of said membrane portion when said guiding means is imaged.

14. The microdialysis probe of claim 1, wherein said membrane portion is defined by boundaries, and wherein said guiding means occupies an area on said microdialysis probe such that said guiding means delineates one or more of said boundaries when said guiding means is imaged.

15. The microdialysis probe of claim 14, wherein said guiding means is coextensive with one or more of said boundaries.

16. The microdialysis probe of claim 1, wherein said membrane portion has a length and a width, and wherein said guiding means is coextensive with said length of said membrane portion, or said width of said membrane portion, or both said length and said width of said membrane portion.

17. The microdialysis probe of claim 1, wherein said guiding means has a cross-sectional shape selected from the group consisting of circular, square, rectangular, triangular, and irregular.

18. The microdialysis probe of claim 1, wherein said guiding means comprises two or more structures on said probe.

19. The microdialysis probe of claim 1, wherein said inner tube is composed of an imageable material.

20. The microdialysis probe of claim 1, wherein said membrane portion has a length, and wherein said guiding means comprises at least one projection that extends longitudinally along at least part of the length of said membrane portion.

21. The microdialysis probe of claim 20, wherein said projection is a shaft or wire.

22. The microdialysis probe of claim 20, wherein said projection has a proximal end and a distal end, and wherein said proximal end of said projection is attached to said distal end of said inner tube.

23. The microdialysis probe of claim 20, wherein said inner tube is composed of an imageable material and said projection is integral with said distal end of said inner tube.

24. The microdialysis probe of claim 1, wherein said inner tube and said guiding means are composed of an imageable material.

25. The microdialysis probe of claim 24, wherein said inner tube and said guiding means are composed of the same imageable material.

26. The microdialysis probe of claim 1, wherein said outer tube is substantially circular in cross-section.

27. The microdialysis probe of claim 1, wherein said inner tube is semi-circular in cross-section.

28. The microdialysis probe of claim 1, wherein said guiding means is attached to said distal end of said outer tube.

29. The microdialysis probe of claim 1, wherein said guiding means is attached to said inner surface of said outer tube.

30. The microdialysis probe of claim 1, wherein said membrane portion is attached to said inner surface of said outer tube, and wherein said guiding means is attached to said membrane portion adjacent to where said membrane portion is attached to said inner surface of said outer tube.

31. The microdialysis probe of claim 1, wherein said guiding means is attached to said distal end of said outer tube, and wherein said guiding means surrounds said membrane portion.

32. The microdialysis probe of claim 1, wherein said guiding means comprises one or more ring members that encircle said membrane portion.

33. The microdialysis probe of claim 1, wherein said guiding means comprises one or more ring members that encircle said distal end of said outer tube.

34. The microdialysis probe of claim 1, wherein said membrane portion has a closed distal end and a proximal end having an opening, wherein said proximal end of said membrane portion is attached to said distal end of said outer tube, wherein said guiding means comprises a first ring member and a second ring member, and wherein said first ring member is located on or adjacent to said proximal end of said membrane portion and wherein said second ring member is located on or adjacent to said distal end of said membrane portion.

35. The microdialysis probe of claim 34, wherein said first ring member is located on said inner surface of said distal end of said outer tube.

36. The microdialysis probe of claim 34, wherein said membrane portion has an outer surface and an inner surface, and wherein said first ring member is located on said inner surface of said proximal end of said membrane portion.

37. The microdialysis probe of claim 36, wherein said second ring member is located on said inner surface of said distal end of said membrane portion.

38. The microdialysis probe of claim 1, wherein said outer tube has a longitudinal axis, wherein said inner tube has a longitudinal axis, and wherein said longitudinal axis of said outer tube is parallel to said longitudinal axis of said inner tube.

39. The microdialysis probe of claim 1, wherein said guiding means is flexible.

40. The microdialysis probe of claim 1, wherein said guiding means is rigid.

41. The microdialysis probe of claim 1, wherein said guiding means is shaped as a coil, and wherein said guiding means encircles said membrane portion.

42. The microdialysis probe of claim 1, wherein said inner tube and said outer tube are concentric.

43. The microdialysis probe of claim 1, wherein said inner tube and said outer tube are not concentric.

44. The microdialysis probe of claim 1, wherein said inner tube is longer than said outer tube.

45. The microdialysis probe of claim 1, wherein said inner tube is shorter than said outer tube.

46. The microdialysis probe of claim 1, wherein said outer tube is flexible.

47. The microdialysis probe of claim 1, wherein said outer tube is compressible.

48. The microdialysis probe of claim 1, wherein said outer tube is plastic.

49. The microdialysis probe of claim 1, wherein said outer tube is composed of a material selected from the group consisting of urethane, ethylene, silicone, polyethylene, polyurethane, polyvinyl chloride, polypropylene, polyester, and polytetrafluorothylene.

50. The microdialysis probe of claim 1, wherein said outer tube has a cross-sectional shape selected from the group consisting of circle, oval, triangle, and square.

51. The microdialysis probe of claim 1, wherein said outer tube has an inner diameter within the range of about 300 micrometers to about 1000 micrometers.

52. The microdialysis probe of claim 1, wherein said inner tube has an inner diameter within the range of about 25 micrometers and 700 micrometers.

53. A microdialysis probe comprising:

a membrane portion;

an outer tube, wherein said outer tube has a proximal end, a distal end, an inner surface, and an outer surface, wherein said distal end of said outer tube is closed, and wherein said outer surface of said outer tube defines an aperture exposing said membrane portion;

an inner tube, wherein said inner tube has a proximal end, a distal end, an inner surface, and an outer surface, and wherein said inner tube is arranged within said outer tube;

and a guiding means located on said probe in a known spatial relationship with said membrane portion.

54. A microdialysis probe comprising:

a membrane portion;

an outer tube, wherein said outer tube has a proximal end and a distal end, and wherein said membrane portion is disposed on said distal end of said outer tube; and

an inner tube, wherein said inner tube is arranged within said outer tube, and wherein said inner tube comprises an imageable material.

55. The microdialysis probe of claim 54, wherein said imageable material has an image signature that is discernable from that of surrounding medium into which said membrane portion is introduced.

56. The microdialysis probe of claim 54, wherein said imageable material is an echogenic material.

57. The microdialysis probe of claim 54, wherein said imageable material is selected from the group consisting of aluminum, plastic, sand, and metal particles.

58. The microdialysis probe of claim 54, wherein said imageable material is radio-opaque.

59. The microdialysis probe of claim 54, wherein said imageable material can be imaged with magnetic resonance imaging or magnetic resonance microscopy.

60. The microdialysis probe of claim 54, wherein said imageable material can be imaged with single photon emission tomography or positron emission tomography.

61. A microdialysis system comprising:

a microdialysis probe comprising

a membrane portion,

an outer tube, wherein said outer tube has a proximal end and a distal end, wherein said membrane portion is disposed on said distal end of said outer tube, and

an inner tube arranged within said outer tube, wherein said inner tube has an inner diameter and an outer diameter; and

means for inserting said microdialysis probe into tissue, wherein said insertion means has a lumen with an inner diameter, and wherein said microdialysis probe has an outer diameter smaller than said inner diameter of said lumen of said insertion means such that said microdialysis probe can be inserted completely into said lumen of said insertion means.

62. The microdialysis system of claim 61, wherein said microdialysis probe further comprises a guiding means located on said probe in a known spatial relationship with said membrane portion.

63. The microdialysis system of claim 62, wherein said guiding means is at least partially composed of an imageable material.

64. The microdialysis system of claim 61, wherein said inner tube has a proximal end and a distal end, and wherein said microdialysis system further comprises inlet tubing and outlet tubing, wherein said inlet tubing is attached to said proximal end of said outer tube and said outlet tubing is attached to said proximal end of said inner tube, or wherein said outlet tubing is attached to said proximal end of said outer tube and said inlet tubing is attached to said proximal end of said inner tube.

65. The microdialysis system of claim 64, further comprising a liquid pump in operable communication with said inlet tubing.

66. The microdialysis system of claim 61, wherein said outer tube has an inner diameter within the range of about 300 micrometers to about 1000 micrometers.

67. The microdialysis system of claim 61, wherein said inner tube has an inner diameter within the range of about 25 micrometers and 700 micrometers.

69. The microdialysis system of claim 68, wherein said microdialysis probe further comprises a guiding means located on said probe in a known spatial relationship with said membrane portion.

70. The microdialysis system of claim 69, wherein said guiding means is at least partially composed of an imageable material.

68. A microdialysis system comprising:

a microdialysis probe comprising

a membrane portion,

a compressible outer tube, wherein said compressible outer tube has a compressed state and an uncompressed state, wherein said outer tube has a proximal end and a distal end, wherein said membrane portion is disposed on said distal end of said outer tube, and

an inner tube, wherein said inner tube is arranged within said outer tube; and

means for inserting said microdialysis probe into tissue, wherein said insertion means has a lumen with an inner diameter, and wherein said outer tube has an outer diameter that is larger than said inner diameter of said lumen of said insertion means when said outer tube is in said uncompressed state, and wherein said outer diameter of said outer tube is smaller than said inner diameter of said lumen of said insertion means when said outer tube is in said compressed state.

71. A method for introducing a microdialysis probe into a medium comprising:

providing a microdialysis probe, insertion means, and puncture means, wherein the insertion means has a proximal end, a distal end, and a lumen having an inner diameter, and wherein the puncture means has a proximal end and a distal end;

inserting the puncture means into the lumen of the insertion means such that the distal end of the puncture means extends outside of the distal end of the insertion means;

inserting the puncture means and the insertion means into the medium;

withdrawing the puncture means from the lumen of the insertion means, leaving the insertion means within the medium;

inserting the microdialysis probe into the lumen of the insertion means; and

withdrawing the insertion means from the medium and completely over and off of the microdialysis probe, thereby leaving the microdialysis probe within the medium.

72. The method according to claim 71, wherein the medium is biological tissue.

73. The method according to claim 71, wherein the medium is an internal organ.

74. The method according to claim 71, wherein the microdialysis probe comprises a membrane portion and a guiding means, wherein the guiding mean is located on the microdialysis probe in a known spatial relationship with the membrane portion.

75. The method according to claim 74, wherein the guiding means comprises an imageable material.

76. The method according to claim 75, further comprising imaging the guiding means within the medium.

77. The method according to claim 76, further comprising guiding the membrane portion to a target area within the medium while imaging the guiding means.

78. The method according to claim 77, wherein the medium is biological tissue and the target area is a tissue layer.

79. The method according to claim 71, further comprising attaching inlet tubing and outlet tubing to the microdialysis probe.

80. The method according to claim 71, wherein the microdialysis probe has an outer diameter smaller than the inner diameter of the lumen of the insertion means.

81. The method according to claim 71, wherein the microdialysis probe comprises a compressible outer tube, an inner tube contained within the compressible outer tube, and a membrane portion disposed on the compressible outer tube, wherein the compressible outer tube has a compressed state and an uncompressed state, wherein the compressible outer tube has an outer diameter that is larger than the inner diameter of the lumen of the insertion means when the compressible outer tube is in an uncompressed state, and wherein the outer diameter of the compressible outer tube is smaller than the inner diameter of the lumen when the outer tube is in a compressed state.

82. The method according to claim 81, further comprising compressing the microdialysis probe before the microdialysis probe is inserted into the lumen of the insertion means.

83. The method according to claim 71, wherein the insertion means is an insertion cannula.

84. The method according to claim 71, wherein the piercing means is a needle.