Method and apparatus for enhancing the integrity of an implantable sensor device

• US 20050049641A1
• Filed: 08/26/2004
• Published: 03/03/2005
• Est. Priority Date: 09/27/2002
• Status: Active Grant

• Current Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Original Assignee: Medtronic Minimed Incorporated (Medtronic Plc)
• Inventors: Shah, Rajiv, Miller, Michael E., Gottlieb, Rebecca, Reghabi, Bahar, Zhang, Yanan
• Granted Patent: US 7,552,522 B2
• Time in Patent Office: Days
• US Class Current: 607/2
• CPC Class Codes: A61B 2562/02 Details of sensors specially adapted for in-vivo measurements
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• 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 5/686 Permanently implanted devices, e.g. pacemakers, other stimulators, biochips A61B5/6861 takes precedence
• CPC Class Codes: G01N 33/5438 Electrodes
• CPC Class Codes: Y10T 29/49002 Electrical device making
• CPC Class Codes: Y10T 29/49007 Indicating transducer
• CPC Class Codes: Y10T 29/49128 Assembling formed circuit to base
• CPC Class Codes: Y10T 29/49155 Manufacturing circuit on or in base

Abstract

A method and apparatus for enhancing the integrity of an implantable sensor. Voids formed between an outer tubing and a sensor substrate or spacing element may be back-filled with a curable, implantable material, minimizing the extent to which unwanted fluids diffuse within the sensor. An enzyme or protein matrix pellet below the sensor window may be pre-treated with a reducing agent to enhance its bond stability, and to reduce undesired swelling that may cause the sensor window to detach or leak. The bonding between the enzyme pellet and a hydrogel layer may be reinforced by application of an intervening bonding layer of a protein material, such as human serum albumin (HSA). The size of the window may be minimized by minimizing the size of an underlying electrode, providing reduced flux and lengthening sensor. A coating may be deposited on the surface of the sensor leads, providing stiffening and lubrication.

Claims

1-16. -16. (Cancelled).

17. A method of making an implantable sensing apparatus comprising:

surrounding a sensor module with an outer tubing, said sensor module having internal elements;

forming a window opening in said outer tubing; and

through said window opening, back-filling one or more voids between said outer tubing and said internal elements.

18. The method of claim 17, wherein said back-filling comprises:

applying a flowable back-fill material through said window opening to fill said one or more voids; and

curing said back-fill material until said back-fill material is non-flowable.

19. The method of claim 18, wherein said back-fill material is applied in liquid form, using a syringe.

20. The method of claim 18, wherein said back-fill material is applied in liquid form, using a pipette.

21. The method of claim 17, wherein said back-filling comprises inserting one or more pre-molded structures into said one or more voids.

22. The method of claim 17, wherein said internal elements comprise a substrate having an electrode.

23. The method of claim 22, wherein said internal elements further comprise one or more beads formed adjacent to at least one end of said substrate.

24. The method of claim 22, wherein said internal elements further comprise a spacing element disposed adjacent to said substrate.

25. The method of claim 17, further comprising coating the outer tubing with a lubricious coating.

26. The method of claim 25, wherein the lubricious coating is siloxane.

27. The method of claim 17, further comprising disposing an inner tubing within an interior of the outer tubing.

28. The method of claim 27, wherein the inner tubing is made from an elastomeric material.

29. The method of claim 27, wherein the inner tubing is made from a metal.

30-37. -37. (Cancelled).

38. A method of making an implantable sensing apparatus comprising:

surrounding a substrate with an outer tubing;

forming a window in said outer tubing above said electrode;

treating an enzyme with a reducing agent to inhibit excessive swelling; and

inserting said enzyme into said window.

39. The method of claim 38, wherein treating said enzyme comprises washing said enzyme in a solution of said reducing agent.

40. The method of claim 39, wherein washing is performed under agitation.

41. The method of claim 38, wherein said reducing agent comprises Ascorbate.

42. The method of claim 38, wherein treating said enzyme comprises reducing a Schiff base bond in said enzyme to permit cross-linking.

43. The method of claim 38, further comprising coating the outer tubing with a lubricious coating.

44. The method of claim 43, wherein the lubricious coating is siloxane.

45. The method of claim 38, further comprising disposing an inner tubing within an interior of the outer tubing.

46. The method of claim 45, wherein the inner tubing is made from an elastomeric material.

47. The method of claim 45, wherein the inner tubing is made from a metal.

48. The method of claim 38, wherein the enzyme comprises a protein matrix.

49-59. -59. (Cancelled).

60. A method of making an implantable sensing apparatus comprising:

surrounding a substrate with an outer tubing, said substrate having an electrode;

forming a window in said outer tubing above said electrode;

inserting an enzyme into said window;

applying a bonding layer over said enzyme; and

applying a layer of hydrogel to fill said window, wherein said bonding layer bonds said hydrogel to said enzyme.

61. The method of claim 60, wherein said bonding layer is a protein.

62. The method of claim 60, wherein said bonding layer is human serum albumin (HSA).

63. The method of claim 60, wherein said bonding layer is a polypeptide.

64. The method of claim 60, wherein said bonding layer is an adhesive.

65. The method of claim 60, further comprising applying a cross-linking agent to said bonding layer to facilitate cross-linking with said enzyme and said layer of hydrogel.

66. The method of claim 65, wherein said cross-linking agent is gluteraldehyde.

67. The method of claim 60, wherein said bonding layer is applied with a volumetric dispenser.

68. The method of claim 67, wherein said volumetric dispenser is a syringe.

69. The method of claim 67, wherein said volumetric dispenser is a dropper.

70. The method of claim 67, wherein said volumetric dispenser is a pipette.

71. The method of claim 67, further comprising coating the outer tubing with a lubricious coating.

72. The method of claim 71, wherein the lubricious coating is siloxane.

73. The method of claim 60, further comprising disposing an inner tubing within an interior of the outer tubing.

74. The method of claim 73, wherein the inner tubing is made from an elastomeric material.

75. The method of claim 73, wherein the inner tubing is made from a metal.

76. The method of claim 60, wherein the enzyme comprises a protein matrix.

77-83. -83. (Cancelled).

84. A method of making an implantable sensing apparatus comprising:

placing a spacing element adjacent to a substrate having an electrode;

surrounding said spacing element and said substrate with an outer tubing;

forming a window in said outer tubing above said electrode;

applying a curable, implantable material through said window to backfill a void defined by said outer tubing and one or more of said spacing element and said substrate;

treating an enzyme with a reducing agent;

inserting said enzyme into said window;

applying a bonding layer of protein material over said enzyme; and

applying a layer of hydrogel to fill said window, wherein said layer of protein material bonds said hydrogel to said enzyme pellet.

85. The method of claim 84, further comprising coating the outer tubing with a lubricious coating.

86. The method of claim 85, wherein the lubricious coating is siloxane.

87. The method of claim 85, further comprising disposing an inner tubing within an interior of the outer tubing.

88. The method of claim 87, wherein the inner tubing is made from an elastomeric material.

89. The method of claim 87, wherein the inner tubing is made from a metal.

90. The method of claim 84, wherein the enzyme comprises a protein matrix.