INJECTABLE AND IMPLANTABLE CELLULAR-SCALE ELECTRONIC DEVICES

• US 20160066789A1
• Filed: 02/11/2014
• Published: 03/10/2016
• Est. Priority Date: 02/13/2013
• Status: Active Grant

• Current Assignee: Board of Trustees of The University of Illinois, Washington University In St Louis
• Original Assignee: Board of Trustees of The University of Illinois, Daniel Brenner, John Rogers, Washington University In Stlouis
• Inventors: ROGERS, John A., BRUCHAS, Michael Raymond, GEREAU, Robert, MCCALL, Jordan Gary, BRENNER, Daniel, KIM, Tae-il, SHIN, Gunchul, JEONG, Jaewoong
• Granted Patent: US 10,617,300 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61B 2017/00004 (bio)absorbable, (bio)resorbable or resorptive
• CPC Class Codes: A61B 2562/0285 Nanoscale sensors
• CPC Class Codes: A61B 2562/06 Arrangements of multiple sensors of different types
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• CPC Class Codes: A61B 5/0031 Implanted circuitry
• CPC Class Codes: A61B 5/685 Microneedles
• CPC Class Codes: A61B 5/686 Permanently implanted devices, e.g. pacemakers, other stimulators, biochips A61B5/6861 takes precedence
• CPC Class Codes: A61M 2037/0007 having means for enhancing the permeation of substances through the epidermis, e.g. using suction or depression, electric or magnetic fields, sound waves or chemical agents
• CPC Class Codes: A61M 2037/0053 Methods for producing microneedles
• CPC Class Codes: A61M 2037/0061 Methods for using microneedles
• CPC Class Codes: A61M 2205/04 implanted
• CPC Class Codes: A61M 2205/05 combined with other kinds of therapy
• CPC Class Codes: A61M 2205/054 with electrotherapy
• CPC Class Codes: A61N 1/05 for implantation or insertion into the body, e.g. heart electrode A61N1/06 takes precedence
• CPC Class Codes: A61N 2005/0612 using probes penetrating tissue; interstitial probes
• CPC Class Codes: A61N 5/062 Photodynamic therapy, i.e. excitation of an agent

Abstract

Provided are implantable or surface mounted biomedical devices and related methods for interfacing with a target tissue. The devices have a substrate and device component supported by the substrate. The components of the device are specially configured and packaged to be ultra-thin and mechanically compliant. In particular, device thicknesses are less than 1 mm and have lateral dimensions between about 1 μm and 10 mm, depending on the application. Delivery substrates may be incorporated to assist with device implantation and handling. The devices can be shaped to provide injection in a minimally invasive manner, thereby avoiding unnecessary tissue damage and providing a platform for long-term implantation for interfacing with biological tissue.

Claims

1. An implantable or surface mounted biomedical device for interfacing with a target tissue, said device comprising:

a substrate; and

a device component comprising;

one or more inorganic semiconductor components;

one or more metallic components;

or one or more inorganic semiconductor components and one or more metallic components;

wherein said device component is supported by said substrate and said device component has a thickness that is less than or equal to 100 μ

m;

wherein said substrate and device component in combination have a lateral dimension and a thickness;

said lateral dimension selected from a range that is greater than or equal to 1 μ

m and less than or equal to 10 mm; and

said thickness selected from a range that is greater than or equal to 100 nm and less than or equal to 1 mm.

2. The device of claim 1, wherein said device component comprises one or more electronic devices, optical devices, optoelectronic devices, microfluidic devices or arrays thereof.

3. The device of claim 1, wherein said device component comprises one or more optical, mechanical, electrophysiological, acoustic, chemical, magnetic or thermal actuators;

or one or more optical, mechanical, electrophysiological, acoustic, chemical, magnetic or thermal sensors;

or any combinations of these.

4. The device of claim 1, wherein said device component comprises one or more photodiode, light emitting diode, laser, electrode, piezoelectric element, antenna, nanoelectromechanical (NEMS) device, microelectromechanical (MEMS) device, acoustic source, micro- or nano-heater, integrated electronic circuit, energy source, chemical source, biological source, wireless receiver, wireless transmitter or any combinations of these.

5. The device of claim 1, wherein said device component has a thickness selected from the range of 500 nm to 50 μ

m.

6. The device of claim 1, wherein said device component comprises a flexible or stretchable electronic device, optical device or optoelectronic device.

7. The device of claim 1, wherein said device component or portion thereof is individually addressed to a cell or group of cells of said target tissue.

8. The device of claim 1, wherein said device component has an active area exposed to said target tissue less than or equal to 1×

10⁶ μ

m².

10. The device of claim 1, wherein said device component comprises one or more optical sources each independently having an emitting area less than or equal to 1×

10⁵ μ

m².

11. The device of claim 1, wherein said device component comprises one or more optical sources each independently having an emitting area selected from the range of 1×

10³ μ

m² to 1×

10⁵ μ

m².

12. The device of claim 11, wherein said optical source provides a radiant output characterized by a plurality of different wavelength maxima.

13. The device of claim 11, wherein said optical source provides a radiant output characterized by a surface power density of 0.1 mW mm² to 10 mW mm².

14. The device of claim 11, wherein said optical source provides a radiant output providing a change in the temperature of said target tissue equal to or less than 1°

C.

15. The device of claim 1, wherein said device component comprises one or more photodetectors each independently having an active light receiving area less than or equal to 1×

10⁶ μ

m².

17. The device of claim 1, wherein said device component comprises one or more electrodes each independently having an active electrode area less than or equal to 1×

10⁶ μ

m².

19. The device of claim 1, wherein said device component and said substrate form a functional layer comprising a functional electronic device that interfaces with said target tissue.

20. The device of claim 19, comprising a plurality of functional layers arranged in a stacked configuration.

21. The device of claim 20, wherein said plurality of functional layers number from a range that is greater than or equal to 2 and less than or equal to 10, wherein said plurality of functional layers together have a total thickness that is selected from a range that is greater than or equal to 500 nm and less than or equal to 100 μ

m.

22. The device of claim 20, wherein said stacked configuration has a shape that corresponds to a micro-needle.

23. The device of claim 20, wherein said plurality of functional layers comprises at least two different functional layers to provide a multifunctional implantable or surface mounted biomedical device.

24. The device of claim 23, wherein said multifunctional device electrically, optically and thermally interfaces with said target tissue.

25. The device of claim 24, wherein said plurality of functional layers in said stacked configuration comprises:

a microelectrode;

an optical detector;

an optical source; and

a temperature sensor.

26. The device of claim 24, wherein said multifunctional electrical, optical and thermal interfacing is simultaneous.

27. The device of claim 20, wherein said plurality of functional layers interface with an interfacing region within a biological tissue, said interfacing region having an interfacing surface area selected from a range that is greater than or equal to 10 μ

m² and less than or equal to 100 mm².

28. The device of claim 27, wherein at least one functional electronic device selectively interfaces with an individual biological cell or biological component thereof within the interfacing region.

29. The device of claim 1, wherein said one or more inorganic semiconductor components or said one or more metallic conductor components independently comprise one or more thin film structures.

31. The device of claim 1, wherein said one or more inorganic semiconductor components or said one or more metallic conductor components each independently have a thickness less than or equal to 100 nm.

32. The device of claim 1, comprising said one or more inorganic semiconductor components.

33. The device of claim 32, wherein each of said one or more inorganic semiconductor components independently comprise a nanomembrane structure.

35. The device of claim 1, wherein at least one of said inorganic semiconductor components or said one or more metallic conductor components is a flexible or a stretchable structure.

36. The device of claim 35, wherein said flexible or stretchable structure is an interconnect that connects island structures.

37. The device of claim 1, wherein at least one of said inorganic semiconductor components or said one or more metallic conductor components is a nanoribbon, a nanomembrane, a nanowire, a transistor channel, a diode, a p-n junction, a photodiode, a light emitting diode, a laser or a combination of these.

38. The device of claim 1, wherein at least one of said inorganic semiconductor components or said one or more metallic conductor components has a Young'"'"'s modulus selected from the range of 0.5 MPa to 10 GPa.

39. The device of claim 1, wherein at least one of said inorganic semiconductor components or said one or more metallic conductor components has a net bending stiffness less than or equal to 1×

10⁸ GPa μ

m⁴.

40. The device of claim 1, wherein said substrate comprises a material selected from the group consisting of MgO, silk, collagen, gelatin, PLGA, polyvinylalcohol (PVA), PLA, SiO₂, polyanhydrides(polyesters), polyhdroxyalkanates (PHAs), polydimethylsiloxane (PDMS) and polyphosphates.

41. The device of claim 1, wherein said substrate and device component in combination have a longitudinal length selected from a range that is greater than or equal to 1 mm and less than or equal to 10 cm.

42. The device of claim 19, wherein said functional electronic device corresponds to a size of a biological component within the target tissue.

43. The device of claim 42, wherein said size of said biological component is an average diameter selected from a range that is greater than or equal to 1 and less than or equal to 100 μ

m.

44. The device of claim 19, wherein said functional layer comprises an array of independently addressable functional electronic devices for independently interfacing with individual biological cells within said target tissue.

45. The device of claim 1, further comprising an encapsulating material at least partially encapsulating one or more of said inorganic semiconductor components or one or more of said metallic conductor components.

46. The device of claim 1, further comprising a barrier layer that covers one or more of said inorganic semiconductor components or one or more of said metallic conductor components.

47. The device of claim 1, wherein said substrate has a first end that is tapered for insertion into said target tissue.

48. The device of claim 47, further comprising a delivery substrate that supports said substrate.

49. The device of claim 48, further comprising an adhesive layer between said delivery substrate and said substrate.

50. The device of claim 49, wherein said adhesive layer dissolves or is bioresorbed and said delivery substrate is removed after implantation.

51. The device of claim 49, wherein said adhesive layer comprises a silk material.

52. The device of claim 48, wherein said delivery substrate has a mechanical property that is substantially higher than a corresponding mechanical property of said device component and said substrate, said mechanical property selected to support and protect said device component and said substrate during handling and implantation.

53. The device of claim 52, wherein said mechanical property is effective Young'"'"'s modulus or net bending stiffness.

54. The device of claim 48, wherein said delivery substrate has a first end that tapers to a tip.

55. The device of claim 54, wherein said device is shaped into a micro-needle geometry and said device is injectable into target tissue.

56. The device of claim 1, having a cross-sectional surface area selected from a range that is less than or equal to 1 mm².

57. The device of claim 1, wherein said device component is partially or completely embedded within said substrate.

58. The device of claim 1, wherein said target tissue is soft tissue of a living animal.

59. The device of claim 58, wherein said target tissue is selected from the group consisting of brain, heart, kidney, liver, pancreas, bladder, lung, eye, blood vessel, and skin.

60. The device of claim 59, wherein said soft tissue is brain and said interfacing is at a penetration depth selected from a range that is greater than or equal to 1 mm and less than or equal to 10 cm from a soft tissue surface.

61. The device of claim 1, further comprising a wireless transmitter and a wireless receiver operably connected to said device for wirelessly receiving data and transmitting instructions to said device implanted in said target tissue.

62. The device of claim 1, wherein said substrate has a substrate first end, said device further comprising a probe connected to said substrate first end.

63. The device of claim 62, wherein said probe is a positioning probe to indicate device position within said target tissue.

64. The device of claim 63, wherein said probe is confined to a probe confinement area on said substrate first end that is less than or equal to 1000 μ

m².

65. The device of claim 1, wherein said device component comprises a microfluidic device.

66. The device of claim 65, wherein said microfluidic device provides one-way or two-way fluid communication with said target tissue.

67. The device of claim 65, wherein said microfluidic device comprises a fluid reservoir positioned proximate to a heat expandable material.

68. The device of claim 67, wherein said heat expandable material is positioned in thermal communication with a heater.

94. The device of claim 1, wherein said substrate has a distal end comprising a minimum lateral dimension selected from a range that is less than 1 μ

m.

95. The device of claim 1, wherein said substrate has a distal end that is a taper geometry.

9. (canceled)

16. (canceled)

18. (canceled)

30. (canceled)

34. (canceled)

69. An injectable and implantable biomedical device for interfacing with a target tissue, said device comprising:

a substrate;

a device component comprising;

one or more inorganic semiconductor components;

one or more metallic components;

or one or more inorganic semiconductor components and one or more metallic components;

wherein said device component is supported by said substrate and said device component has a thickness that is less than or equal to 100 μ

m;

a delivery substrate having a first end that is tapered for insertion into the target tissue, wherein said delivery substrate supports said substrate and device component; and

wherein said device has a lateral dimension and a thickness;

said lateral dimension selected from a range that is greater than or equal to 1 μ

m and less than or equal to 10 mm; and

said thickness selected from a range that is greater than or equal to 1 μ

m and less than or equal to 1 mm.

70. The device of claim 69, wherein said delivery substrate has a thickness selected from a range that is greater than or equal to 1 μ

m and less than or equal to 100 and said substrate and said device component in combination have a thickness that is less than 10 μ

m.

71. The device of claim 69, wherein said device component and said substrate form a functional layer comprising a functional electronic device that interfaces with said target tissue.

72. The device of claim 71, comprising a plurality of functional layers arranged in a stacked configuration with said delivery substrate.

73. The device of claim 69, wherein said stacked configuration has a shape that corresponds to a micro-needle.

74. The device of claim 69, further comprising an adhesive layer that adheres said delivery substrate and said substrate, wherein in response to a stimulus said adhesive layer dissolves or is bioresorbed and said delivery substrate is removed from the substrate.

75. The device of claim 74, wherein said adhesive layer comprises a silk material and said stimulus is a solvent that dissolves said silk material.

76. The device of claim 69, wherein said delivery substrate has a bendability, elasticity, or flexibility that is substantially higher than the substrate that supports the device component.

77. The device of claim 69, wherein an insertion cross-sectional area of said device is less than or equal to 4 mm².

78. The device of claim 77, wherein after implantation removal of the base substrate, an implanted cross sectional area is less than or equal to 1 mm².

79. The device of claim 69, having a ratio of cross-sectional insertion area to cross-sectional implantation area that is selected from a range that is less than or equal to 10 and greater than or equal to 2.

89. A method of implanting the injectable and implantable biomedical device of claim 69, the method comprising the steps of:

positioning said device adjacent to a soft tissue surface in which said target tissue is located;

inserting said device into said soft tissue and adjacent to or within said target tissue;

releasing said substrate and said device component from said delivery substrate; and

removing said delivery substrate from said soft tissue;

thereby implanting said substrate and said device component in said soft tissue.

90. The method of claim 89, wherein said inserting and removing steps are confined to a cross-sectional disturbance area in said soft tissue that is less than or equal to 5 mm².

91. The method of claim 89, wherein said soft tissue is brain, and said interfacing is along a dorsal-ventral plane within an interior region of said brain.

93. The method of claim 89, further comprising a step of interfacing said implanted substrate and said device component with said target tissue, wherein said interfacing is wirelessly controlled and monitored.

80. A method of making an injectable and implantable biomedical device, the method comprising the steps of:

providing a functional device layer comprising a functional electronic device, said functional device layer having;

a thickness that is less than or equal to 20 μ

m and a lateral dimension selected from a range that is greater than or equal to 1 μ

m and less than or equal to 10 mm; and

one or more inorganic semiconductor components;

one or more metallic components;

or one or more inorganic semiconductor components and one or more metallic components;

providing a delivery substrate;

stacking the functional device layer and the delivery substrate; and

bonding the functional device layer to the delivery substrate.

81-88. -88. (canceled)

92. (canceled)

96-99. -99. (canceled)

100. A method of treating a biological tissue comprising the steps of:

a. transforming one or more cells of said biological tissue with a nucleic acid encoding one or more light responsive proteins, thereby generating at least one transformed cell that is light responsive;

b. providing an implantable or surface mounted biomedical device in optical communication with said at least one transformed cell of said biological tissue;

wherein said implantable or surface mounted biomedical device comprises;

i. a substrate;

ii. a device component comprising;

one or more inorganic semiconductor components;

one or more metallic components;

or one or more inorganic semiconductor components and one or more metallic components;

wherein said device component is supported by said substrate and said device component has a thickness that is less than or equal to 100 μ

m;

wherein said substrate and device component in combination have a lateral dimension and a thickness;

said lateral dimension selected from a range that is greater than or equal to 1 μ

m and less than or equal to 10 mm; and

said thickness selected from a range that is greater than or equal to 100 nm and less than or equal to 1 mm;

c. exposing said at least one transformed cell to an optical stimulus from said implantable or surface mounted biomedical device;

thereby treating said biological tissue.

101. The method of claim 100, wherein exposing said at least one transformed cell to said optical stimulus from said implantable or surface mounted biomedical device increases or decreases expression of said one or more light-responsive proteins.

102. The method of claim 100, wherein said implantable or surface mounted device or one or more components thereof individually addresses one or more transformed cells of said biological tissue.

103. The method of claim 100, wherein said at least one transformed cell of the biological tissue expresses photoactivatable proteins, receptors or channels.

104. The method of claim 100, wherein said exposing step is carried out in vivo.

105. The method of claim 100, further comprising a step of implanting said implantable biomedical device into said biological tissue, thereby providing said implantable biomedical device in said optical communication with said at least one transformed cell of said biological tissue.

106. The method of claim 100, further comprising a step of providing said implantable or surface mounted biomedical device in conformal contact with said biological tissue, thereby providing said implantable or surface mounted biomedical device in said optical communication with said at least one transformed cell of said biological tissue.

107. The method of claim 100, wherein said transformed cell is a mammalian neuron or glial cell.

108-122. -122. (canceled)

123. A method of treating a biological tissue, said method comprising the steps of:

a. providing an implantable or surface mounted biomedical device comprising;

i. a substrate;

ii. a device component comprising;

one or more inorganic semiconductor components;

one or more metallic components;

or one or more inorganic semiconductor components and one or more metallic components;

wherein said device component is supported by said substrate and said device component has a thickness that is less than or equal to 100 μ

m;

wherein said substrate and device component in combination have a lateral dimension and a thickness;

said lateral dimension selected from a range that is greater than or equal to 1 μ

m and less than or equal to 10 mm; and

said thickness selected from a range that is greater than or equal to 100 nm and less than or equal to 1 mm;

b. contacting said biological tissue with said implantable or surface mounted biomedical device;

wherein said device provides one or more therapeutic agents to said biological tissue; and

c. optically activating said therapeutic agent in contact with said biological tissue;

thereby treating said biological tissue.

124. The method of claim 123, wherein said one or more therapeutic agents comprises a phototherapeutic agent.

125-128. -128. (canceled)