IMPLANTABLE BIOSENSOR AND METHODS OF USE THEREOF

• US 20160270703A1
• Filed: 05/27/2016
• Published: 09/22/2016
• Est. Priority Date: 12/18/2003
• Status: Active Grant

• Current Assignee: Metronom Health Inc.
• Original Assignee: Metronom Health Inc.
• Inventors: Botvinick, Elliot, Bremer, Troy M.
• Granted Patent: US 11,160,474 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/1459 invasive, e.g. introduced into the body by a catheter A61B5/1464 takes precedence
• CPC Class Codes: A61B 5/1473 invasive, e.g. introduced into the body by a catheter A61B5/1482 takes precedence
• 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

Abstract

Provided herein is a stabilized oxygen transport matrix that includes a reversible oxygen binding protein, such as hemoglobin, immobilized throughout the stabilized oxygen transport matrix. The stabilized oxygen transport matrix is used to transport oxygen and can be used as an oxygen transport region and a reaction region of an analyte sensor, such as an implantable glucose sensor. The reversible binding protein can also function as an oxygen probe within the analyte sensor.

Claims

1-55. -55. (canceled)

56. A stabilized oxygen transport matrix comprising:

a reversible oxygen binding protein that is immobilized throughout the stabilized oxygen transport matrix; and

a membrane that encapsulates at least a portion of the stabilized oxygen transport matrix;

wherein the stabilized oxygen transport matrix is capable of transporting oxygen from a region surrounding a first surface of the stabilized oxygen transport matrix having a relatively high oxygen concentration to a region surrounding a second surface of the stabilized oxygen transport matrix having a lower or no oxygen concentration; and

wherein both the first and second surfaces are permeable to oxygen.

57. The stabilized oxygen transport matrix of claim 56, wherein the reversible oxygen binding protein is an engineered hemeprotein or a heme derivative.

58. The stabilized oxygen transport matrix of claim 56, wherein the reversible oxygen binding protein is hemoglobin.

59. The stabilized oxygen transport matrix of claim 56, further comprising a polymer selected from the group consisting of polyglycolic acid, polylactic acid, poly (lactic-co-glycolic acid), poly(caprolactone), poly(dioxanone), polytetrafluoroethylene, expanded polytetrafluoroethylene, polypropylene and polyvinyl alcohol, wherein the reversible oxygen binding protein is present at about 10% by mass or higher within the polymer.

60. The stabilized oxygen transport matrix of claim 56, further comprising a carrier protein.

61. The stabilized oxygen transport matrix of claim 60, wherein the carrier protein is serum albumin, gelatin or a combination thereof.

62. The stabilized oxygen transport matrix of claim 56, wherein the reversible oxygen binding agent is immobilized throughout the stabilized oxygen transport matrix.

63. A sensor, comprising:

a) an oxygen transport region comprising;

(i) a stabilized oxygen transport matrix;

(ii) an oxygen permeable first surface in communication with an external environment; and

(iii) an oxygen permeable second surface that is impermeable to a target analyte;

b) a target analyte reaction region in communication with the oxygen transport region at the oxygen permeable second surface, wherein the target analyte reaction region comprises a target analyte oxidase enzyme and a target analyte-permeable surface; and

c) a sensing region comprising at least one detector probe in communication with the target analyte reaction region.

64. The sensor of claim 63, wherein the target analyte is selected from the group consisting of glucose, galactose, lactose, peroxide, cholesterol, amino acids, alcohol, lactic acid and mixtures thereof.

65. The sensor of claim 63, wherein the target analyte is glucose and the sensor is a glucose sensor.

66. The sensor of claim 63, further comprising a first reversible oxygen binding protein immobilized in the stabilized oxygen transport matrix.

67. The sensor of claim 66, wherein the first reversible oxygen binding protein is an engineered hemeprotein or a heme derivative.

68. The sensor of claim 67, wherein the first reversible oxygen binding protein is hemoglobin.

69. The sensor of claim 63, wherein at least one of the oxygen transport region, the target analyte reaction region, and the sensing region comprise a stabilized matrix.

70. The sensor of claim 63, wherein the at least one detector probe is at least one substantially non-oxygen consuming detector probe.

71. The sensor of claim 70, wherein the sensing region further comprises an oxygen probe.

72. The sensor of claim 71, wherein the oxygen probe comprises a second reversible oxygen binding protein.

73. The sensor of claim 63, wherein the at least one detector probe comprises a spectrometer.

74. The sensor of claim 63, wherein the at least one detector probe is capable of emitting and/or receiving light.

75. The sensor of claim 74, wherein the at least one detector probe is capable of emitting and receiving light at an oxygen sensitive engineered hemeprotein, or heme derivative absorption wavelength.