Implantable device

• US 20050136092A1
• Filed: 11/30/2004
• Published: 06/23/2005
• Est. Priority Date: 01/12/2000
• Status: Active Grant

• Current Assignee: Beta Cell Technologies Pty., Ltd.
• Original Assignee: Beta-O2 Technologies Ltd.
• Inventors: Rotem, Avi, Bloch, Konstantin, Vardi, Pnina, Evron, Yoav
• Granted Patent: US 8,012,500 B2
• Time in Patent Office: Days
• US Class Current: 424/423
• CPC Class Codes: A61F 2/022 Artificial gland structures using bioreactors hemodialysis A61M1/16; hemofiltration A61M1/34; other extracorporeal blood treatment A61M1/36
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 13/12 of the kidneys
• CPC Class Codes: A61P 15/00 Drugs for genital or sexual disorders for disorders of sex hormones A61P5/24; Contraceptives
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 25/16 Anti-Parkinson drugs
• CPC Class Codes: A61P 25/28 for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 5/14 of the thyroid hormones, e.g. T3, T4
• CPC Class Codes: A61P 5/38 of the suprarenal hormones
• CPC Class Codes: A61P 5/48 of the pancreatic hormones

Abstract

Apparatus is provided including a chamber, which is adapted to be implanted in a body of an individual, the chamber including functional cells and chlorophyll-containing elements comprising chlorophyll of an obligate photoautotroph.

Claims

1. Apparatus comprising a chamber, which is adapted to be implanted in a body of an individual, the chamber comprising:

functional cells; and

chlorophyll-containing elements comprising chlorophyll of an obligate photoautotroph.

2. The apparatus according to claim 1, wherein the functional cells comprise a single cell type.

3. The apparatus according to claim 1, wherein the functional cells comprise a plurality of cell types.

4. The apparatus according to claim 1, wherein the chlorophyll-containing elements comprise chlorophyll of a unicellular obligate photoautotroph.

5. The apparatus according to claim 1, wherein the chlorophyll-containing elements comprise chlorophyll of a multicellular obligate photoautotroph.

6. The apparatus according to claim 1, wherein the chlorophyll-containing elements are positioned in a vicinity of the functional cells in a manner that facilitates providing of oxygen by the chlorophyll-containing elements to the functional cells.

7. The apparatus according to claim 1, wherein the chlorophyll-containing elements are positioned in a vicinity of the functional cells in a manner that facilitates consumption by the chlorophyll-containing elements of carbon dioxide produced by the functional cells.

8. The apparatus according to claim 1, wherein the functional cells are mixed with the chlorophyll-containing elements.

9. The apparatus according to claim 1, wherein the functional cells are not immunoisolated from the chlorophyll-containing elements.

10. The apparatus according to claim 1, wherein the chamber comprises a liquid medium, in which the functional cells are dispersed.

11. The apparatus according to claim 1, wherein the chamber comprises a matrix, in which the functional cells are dispersed.

12. The apparatus according to claim 1, wherein the chamber comprises a substrate, to which the functional cells are attached.

13. The apparatus according to claim 1, wherein the chamber comprises one or more walls, adapted to immunoisolate the functional cells from constituents of the body.

14. The apparatus according to claim 1, wherein the chamber is adapted to be implanted subcutaneously in the body.

15. The apparatus according to claim 1, wherein the chamber is adapted to be implanted in peritoneum of the body.

16. The apparatus according to claim 1, wherein the chamber comprises a gel matrix, in which the functional cells and the chlorophyll-containing elements are embedded.

17. The apparatus according to claim 1, wherein the chlorophyll-containing elements comprise chlorophyll of a genetically-engineered obligate photoautotroph.

18. The apparatus according to claim 1, wherein the chamber is prism-shaped.

19. The apparatus according to claim 1, wherein the chamber comprises an oxygen reservoir.

20. The apparatus according to claim 1, comprising a rechargeable battery.

21. The apparatus according to claim 1, wherein the chamber is coated with a vascular growth factor.

22. The apparatus according to claim 1, wherein the obligate photoautotroph includes bacteria of the genus Thiobacilli.

23. The apparatus according to claim 1, wherein the obligate photoautotroph includes bacteria of the genus Chlorobium.

24. The apparatus according to claim 1, wherein the obligate photoautotroph includes cyanobacteria.

25. The apparatus according to claim 24, wherein the cyanobacteria include cyanobacteria of the genus Synechococcus.

26. The apparatus according to claim 1, wherein at least a portion of the chlorophyll-containing elements include intact cells of the obligate photoautotroph.

27. The apparatus according to claim 26, wherein the chamber comprises between 10,000 and 600,000 pancreatic islets.

28. The apparatus according to claim 26, wherein the chamber comprises fewer than 10,000 pancreatic islets.

29. The apparatus according to claim 1, wherein the chamber comprises a membrane, configured to separate the functional cells from the chlorophyll-containing elements.

30. The apparatus according to claim 29, wherein the membrane is configured to permit passage of a gas therethrough.

31. The apparatus according to claim 1, comprising a light source, configured to provide light to the chlorophyll-containing elements.

32. The apparatus according to claim 31, comprising a control unit, adapted to drive the light source to provide the light in a series of pulses.

33. The apparatus according to claim 31, comprising a control unit, adapted to drive the light source to provide the light intermittently during alternating “

on” and

“

off”

periods.

34. The apparatus according to claim 31, comprising a control unit, adapted to control a level of oxygen provided by the chlorophyll-containing elements, by controlling a level of the light provided by the light source.

35. The apparatus according to claim 31, wherein the light source is physically coupled to the chamber.

36. The apparatus according to claim 31, wherein the light source is configured to be implanted in the body in a vicinity of the chamber.

37. The apparatus according to claim 31, wherein the light source is configured to be placed external to the body in a vicinity of the chamber.

38. The apparatus according to claim 1, wherein the functional cells are capable of releasing a substance, and wherein the chamber comprises one or more walls that are permeable to the substance and are substantially not permeable to the functional cells, such that the substance is released to the body.

39. The apparatus according to claim 38, wherein the functional cells are selected from the list consisting of:

pancreatic islet cells, hepatocytes, thyroid cells, parathyroid cells, neural cells, ovarian cells, adrenal cells, renal cortex cells, vascular endothelial cells, thymic cells, ovarian cells, testicular cells, genetically engineered cells, cloned cells, and stem cells.

40. The apparatus according to claim 38, wherein the functional cells comprise pancreatic beta cells.

41. The apparatus according to claim 40, wherein the chamber comprises between 10 million and 600 million of the beta cells.

42. The apparatus according to claim 40, wherein the chamber comprises fewer than 10 million of the beta cells.

43. The apparatus according to claim 40, wherein the chamber comprises pancreatic islets containing the beta cells.

44. The apparatus according to claim 43, wherein the chamber comprises between 10,000 and 600,000 of the islets.

45. The apparatus according to claim 43, wherein the chamber comprises fewer than 10,000 of the islets.

46. The apparatus according to claim 1, wherein the functional cells are capable of performing at least one of the actions selected from the list consisting of:

absorbing a substance from the body, and degrading a substance from the body.

47. The apparatus according to claim 46, wherein the functional cells comprise hepatic cells.

48. The apparatus according to claim 1, comprising an oxygen sensor for determining an oxygen concentration in a vicinity of the functional cells.

49. The apparatus according to claim 48, comprising a control unit configured to activate the chlorophyll-containing elements when the oxygen concentration in the vicinity of the functional cells is below a first threshold, and to inactivate the chlorophyll-containing elements when the oxygen concentration in the vicinity of the functional cells is above a second threshold.

50. The apparatus according to claim 49, comprising a light source, wherein the control unit is adapted to control a level of oxygen provided by the chlorophyll-containing elements by controlling a level of light generated by the light source.

51. The apparatus according to claim 49, wherein the first threshold is between 30 and 50 mmHg, and the second threshold is between 80 and 100 mmHg.

52. The apparatus according to claim 1, comprising a control unit adapted to determine an indication of a level in the body of a substance to which the functional cells are sensitive.

53. The apparatus according to claim 52, wherein the control unit is adapted to determine the indication by monitoring a property selected from the list consisting of:

a property of the functional cells, and a property of the chlorophyll-containing elements.

54. The apparatus according to claim 53, wherein the property of the functional cells includes an electrical property of the functional cells, and wherein the control unit is adapted to monitor the electrical property of the functional cells.

55. The apparatus according to claim 53, wherein the property of the functional cells includes an optical property of the functional cells, and wherein the control unit is adapted to monitor the optical property of the functional cells.

56. The apparatus according to claim 52, wherein the substance includes glucose, and wherein the control unit is adapted to determine the indication of the level of the glucose.

57. The apparatus according to claim 52, wherein the functional cells comprise pancreatic beta cells.

58. Apparatus for use with functional cells, the apparatus comprising a chamber, which is adapted to be implanted in a body of an individual, and to hold the functional cells, the chamber comprising chlorophyll-containing elements containing chlorophyll of an obligate photoautotroph.

59. The apparatus according to claim 58, wherein the functional cells include autologous functional cells of the individual, and wherein the chamber is adapted to hold the autologous functional cells.

60. Apparatus comprising:

a chamber, which is adapted to be implanted in a body of an individual, the chamber comprising functional cells and chlorophyll-containing elements;

a light source, configured to provide light to the chlorophyll-containing elements; and

a control unit, adapted to drive the light source to provide the light in a series of pulses.

61. The apparatus according to claim 60, wherein the chlorophyll-containing elements comprise chlorophyll of algae cells.

62. The apparatus according to claim 60, wherein the chlorophyll-containing elements comprise chlorophyll of an obligate photoautotroph.

63. The apparatus according to claim 60, wherein the control unit is adapted to configure each of the pulses to have a duration of between 50 and 1000 nanoseconds.

64. The apparatus according to claim 60, wherein the control unit is adapted to configure each of the pulses to have a duration of between 1 and 5000 microseconds.

65. The apparatus according to claim 60, wherein the control unit is adapted to drive the light source to withhold applying light between successive pulses for a period having a duration of between 5000 and 10,000 nanoseconds.

66. The apparatus according to claim 60, wherein the control unit is adapted to configure each of the pulses to have a duration of between 700 and 900 nanoseconds, and to drive the light source to withhold applying light between successive pulses for a period having a duration of between 4000 and 6000 nanoseconds.

67. The apparatus according to claim 60, wherein the light source comprises one or more LEDs.

68. The apparatus according to claim 60, wherein the light source is physically coupled to the chamber.

69. The apparatus according to claim 60, wherein the light source is configured to be implanted in the body in a vicinity of the chamber.

70. The apparatus according to claim 60, wherein the light source is configured to be placed external to the body in a vicinity of the chamber.

71. The apparatus according to claim 60, wherein the chlorophyll-containing elements are positioned in a vicinity of the functional cells in a manner that facilitates consumption by the chlorophyll-containing elements of carbon dioxide produced by the functional cells.

72. The apparatus according to claim 60, wherein the functional cells are mixed with the chlorophyll-containing elements.

73. The apparatus according to claim 60, wherein the chamber comprises a matrix, in which the functional cells are dispersed.

74. The apparatus according to claim 60, wherein the chamber comprises a gel matrix, in which the functional cells and the chlorophyll-containing elements are embedded.

75. The apparatus according to claim 60, wherein the chamber is coated with a vascular growth factor.

76. The apparatus according to claim 60, wherein at least a portion of the chlorophyll-containing elements include intact photosynthetic cells.

77. The apparatus according to claim 60, wherein at least a portion of the chlorophyll-containing elements include isolated chloroplasts.

78. The apparatus according to claim 60, wherein the light source is configured to provide light having a wavelength of between 400 and 800 nm.

79. The apparatus according to claim 78, wherein the light source is configured to provide light having a wavelength of between 630 and 670 nm.

80. The apparatus according to claim 60, wherein the control unit is adapted to provide the light during less than 90% of a time period having a duration of at least 24 hours.

81. The apparatus according to claim 80, wherein the control unit is adapted to provide the light during less than 50% of the time period.

82. The apparatus according to claim 81, wherein the control unit is adapted to provide the light during less than 10% of the time period.

83. The apparatus according to claim 60, wherein the control unit is adapted to drive the light source to provide the light intermittently during alternating “

on” and

“

off”

periods.

84. The apparatus according to claim 83, wherein each of the “

on”

periods has a duration of between 0.5 minutes and 5 minutes.

85. The apparatus according to claim 83, wherein each of the “

on”

periods has a duration of between 5 minutes and 5 hours.

86. The apparatus according to claim 83, wherein each of the “

off”

periods has a duration of between 0.5 minutes and 5 minutes.

87. The apparatus according to claim 83, wherein each of the “

off”

periods has a duration of between 5 minutes and 5 hours.

88. The apparatus according to claim 83, wherein each of the “

on”

periods has a duration equal to between 10% and 1000% of a duration of each of the “

off”

periods.

89. The apparatus according to claim 88, wherein each of the “

on”

periods has a duration equal to between 50% and 200% of a duration of each of the “

off”

periods.

90. The apparatus according to claim 60, wherein the chamber comprises an oxygen reservoir.

91. The apparatus according to claim 90, wherein the control unit is adapted to set at least one parameter of the pulses responsively to at least one oxygen storage property of the oxygen reservoir.

92. The apparatus according to claim 60, wherein the control unit is adapted to set at least one parameter of the pulses responsively to at least one sensed parameter selected from the list consisting of:

a sensed parameter of the functional cells, and a sensed parameter of the chlorophyll-containing elements.

93. The apparatus according to claim 92, comprising an oxygen sensor for determining an oxygen concentration in the chamber, wherein the at least one sensed parameter includes the oxygen concentration, and wherein the control unit is adapted to set the at least one parameter of the pulses responsively to the oxygen concentration.

94. The apparatus according to claim 60, wherein the chlorophyll-containing elements are positioned in a vicinity of the functional cells in a manner that facilitates providing of oxygen by the chlorophyll-containing elements to the functional cells.

95. The apparatus according to claim 94, wherein the control unit is adapted to control a level of the oxygen provided by the chlorophyll-containing elements, by setting at least one parameter of the pulses.

96. The apparatus according to claim 60, wherein the functional cells are capable of releasing a substance, and wherein the chamber comprises one or more walls that are permeable to the substance and are substantially not permeable to the functional cells, such that the substance is released to the body.

97. The apparatus according to claim 96, wherein the functional cells are selected from the list consisting of:

pancreatic islet cells, hepatocytes, thyroid cells, parathyroid cells, neural cells, ovarian cells, adrenal cells, renal cortex cells, vascular endothelial cells, thymic cells, ovarian cells, testicular cells, genetically engineered cells, cloned cells, and stem cells.

98. The apparatus according to claim 96, wherein the functional cells comprise pancreatic beta cells.

99. The apparatus according to claim 60, wherein the functional cells are capable of performing at least one of the actions selected from the list consisting of:

absorbing a substance from the body, and degrading a substance from the body.

100. The apparatus according to claim 99, wherein the functional cells comprise hepatic cells.

101. The apparatus according to claim 60, wherein the control unit is adapted to determine an indication of a level in the body of a substance to which the functional cells are sensitive.

102. The apparatus according to claim 101, wherein the control unit is adapted to determine the indication by monitoring a property selected from the list consisting of:

a property of the functional cells and a property of the chlorophyll-containing elements.

103. The apparatus according to claim 101, wherein the substance includes glucose, and wherein the control unit is adapted to determine the indication of the level of the glucose.

104. The apparatus according to claim 101, wherein the functional cells comprise pancreatic beta cells.

105. Apparatus for use with functional cells, the apparatus comprising:

a chamber, which is adapted to be implanted in a body of an individual, and to hold the functional cells, the chamber comprising chlorophyll-containing elements;

a light source, configured to provide light to the chlorophyll-containing elements; and

a control unit, adapted to drive the light source to provide the light in a series of pulses.

106. Apparatus comprising a chamber, which is adapted to be implanted in a body of an individual, the chamber comprising:

functional cells;

chlorophyll-containing elements; and

an oxygen reservoir.

107. The apparatus according to claim 106, wherein at least a portion of the chlorophyll-containing elements include intact photosynthetic cells.

108. The apparatus according to claim 106, wherein at least a portion of the chlorophyll-containing elements include isolated chloroplasts.

109. The apparatus according to claim 106, wherein the chlorophyll-containing elements comprise chlorophyll of algae cells.

110. The apparatus according to claim 106, wherein the chlorophyll-containing elements comprise chlorophyll of an obligate photoautotroph.

111. The apparatus according to claim 106, wherein at least one of the functional cells and the chlorophyll-containing elements is contained in the oxygen reservoir.

112. The apparatus according to claim 106, wherein the chamber is coated with a vascular growth factor.

113. The apparatus according to claim 106, wherein the oxygen reservoir comprises a perfluorocarbon compound.

114. The apparatus according to claim 106, wherein the oxygen reservoir comprises hemoglobin.

115. The apparatus according to claim 106, wherein the oxygen reservoir comprises silicone.

116. The apparatus according to claim 106, wherein the oxygen reservoir comprises a water-based material.

117. The apparatus according to claim 116, wherein the water-based material comprises a hydrogel.

118. The apparatus according to claim 117, wherein the hydrogel is selected from the list consisting of:

alginate and agarose.

119. The apparatus according to claim 106, wherein the oxygen reservoir comprises a gel matrix.

120. The apparatus according to claim 119, wherein the functional cells and the chlorophyll-containing elements are embedded in the gel matrix.

121. The apparatus according to claim 106, comprising:

a light source, configured to provide light to the chlorophyll-containing elements; and

a control unit, adapted to drive the light source to provide the light in a series of pulses.

122. The apparatus according to claim 121, wherein the control unit is adapted to set at least one parameter of the pulses responsively to at least one oxygen storage property of the oxygen reservoir.

123. Apparatus for use with functional cells, the apparatus comprising a chamber, which is adapted to be implanted in a body of an individual, and to hold the functional cells, the chamber comprising:

chlorophyll-containing elements; and

an oxygen reservoir.

124. Apparatus comprising:

a chamber, which is adapted to be implanted subcutaneously in a body of an individual, the chamber comprising functional cells; and

an oxygen generator, adapted to be placed outside the body in a vicinity of the skin, and to convey oxygen through the skin to the functional cells.

125. The apparatus according to claim 124, wherein the oxygen generator is adapted to be placed directly against the skin.

126. The apparatus according to claim 124, comprising a treatment unit, adapted to treat the skin in a manner that enhances oxygen diffusion therethrough.

127. The apparatus according to claim 124, wherein the oxygen generator is adapted to utilize electrolysis to generate oxygen.

128. The apparatus according to claim 124, wherein the chamber is coated with a vascular growth factor.

129. The apparatus according to claim 124, wherein the oxygen generator is adapted to be placed within between 1 mm and 15 mm of the skin.

130. The apparatus according to claim 129, wherein the oxygen generator is adapted to be placed within 10 mm of the skin.

131. The apparatus according to claim 124, comprising a control unit, adapted to activate and inactive the oxygen generator.

132. The apparatus according to claim 131, wherein the control unit is configured to activate the oxygen generator when an oxygen concentration in a vicinity of the functional cells is below a first threshold, and to inactivate the oxygen generator when the oxygen concentration in the vicinity of the functional cells is above a second threshold.

133. The apparatus according to claim 124, wherein the functional cells are capable of releasing a substance, and wherein the chamber comprises one or more walls that are permeable to the substance and are substantially not permeable to the functional cells, such that the substance is released to the body.

134. The apparatus according to claim 133, wherein the functional cells are selected from the list consisting of:

pancreatic islet cells, hepatocytes, thyroid cells, parathyroid cells, neural cells, ovarian cells, adrenal cells, renal cortex cells, vascular endothelial cells, thymic cells, ovarian cells, testicular cells, genetically engineered cells, cloned cells, and stem cells.

135. The apparatus according to claim 133, wherein the functional cells comprise pancreatic beta cells.

136. The apparatus according to claim 124, wherein the functional cells are capable of performing at least one of the actions selected from the list consisting of:

absorbing a substance from the body, and degrading a substance from the body.

137. The apparatus according to claim 136, wherein the functional cells comprise hepatic cells.

138. The apparatus according to claim 124, comprising a control unit adapted to determine an indication of a level in the body of a substance to which the functional cells are sensitive.

139. The apparatus according to claim 138, wherein the control unit is adapted to determine the indication by monitoring a property of the functional cells.

140. The apparatus according to claim 138, wherein the substance includes glucose, and wherein the control unit is adapted to determine the indication of the level of the glucose.

141. The apparatus according to claim 138, wherein the functional cells comprise pancreatic beta cells.

142. Apparatus for use with functional cells, the apparatus comprising:

a chamber, which is adapted to be implanted subcutaneously in a body of an individual, and to hold the functional cells; and

an oxygen generator, adapted to be placed outside the body in a vicinity of the skin, and to convey oxygen through the skin to the functional cells.

143. Apparatus comprising a chamber, which is adapted to be implanted in a body of an individual, the chamber comprising:

functional cells;

chlorophyll-containing elements; and

a gas-permeable, liquid-impermeable membrane, configured to separate the chlorophyll-containing elements from at least one of;

(a) the functional cells, and (b) a fluid of the body.

144. The apparatus according to claim 143, wherein the membrane is configured to separate the chlorophyll-containing elements from the functional cells.

145. The apparatus according to claim 143, wherein the membrane is configured to separate the chlorophyll-containing elements from the fluid of the body.

146. The apparatus according to claim 143, wherein the membrane is configured to separate the chlorophyll-containing elements from the functional cells and the fluid of the body.

147. The apparatus according to claim 143, wherein the chlorophyll-containing elements comprise chlorophyll of algae cells.

148. The apparatus according to claim 143, wherein the chamber comprises an oxygen reservoir.

149. The apparatus according to claim 143, wherein the functional cells are capable of releasing a substance, and wherein the chamber comprises one or more walls that are permeable to the substance and are substantially not permeable to the functional cells, such that the substance is released to the body.

150. The apparatus according to claim 143, wherein the functional cells are capable of performing at least one of the actions selected from the list consisting of:

absorbing a substance from the body, and degrading a substance from the body.

151. The apparatus according to claim 143, comprising a light source, configured to provide light to the chlorophyll-containing elements.

152. The apparatus according to claim 151, comprising a control unit, adapted to drive the light source to provide the light in a series of pulses.

153. The apparatus according to claim 151, comprising a control unit, adapted to drive the light source to provide the light intermittently during alternating “

on” and

“

off”

periods.

154. A method comprising implanting, in a body of an individual, a chamber holding functional cells and chlorophyll-containing elements that include chlorophyll of an obligate photoautotroph.

155. A method comprising loading, into a chamber adapted to be implanted in a body of an individual, functional cells and chlorophyll-containing elements that include chlorophyll of an obligate photoautotroph.

156. A method comprising:

implanting, in a body of an individual, a chamber holding functional cells and chlorophyll-containing elements; and

providing light, in a series of pulses, to the chlorophyll-containing elements.

157. A method comprising implanting, in a body of an individual, a chamber including an oxygen reservoir and holding functional cells and chlorophyll-containing elements.

158. A method comprising:

subcutaneously implanting, in a body of an individual, a chamber holding functional cells;

generating oxygen outside the body; and

conveying the oxygen through the skin to the functional cells.

159. A method comprising:

placing functional cells and chlorophyll-containing elements in a chamber;

separating, using a gas-permeable, liquid-impermeable membrane, the chlorophyll-containing elements from at least one of;

(a) the functional cells and (b) fluid of a body of an individual; and

implanting the chamber in the body of the individual.

160. The method according to claim 159, wherein separating comprises separating the chlorophyll-containing elements from both the functional cells and the fluid of the body.