Injectable and implantable cellular-scale electronic devices

• US 10,617,300 B2
• Filed: 02/11/2014
• Issued: 04/14/2020
• 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
• Inventors: Rogers, John A., Bruchas, Michael Raymond, Gereau, Robert, McCall, Jordan Gary, Brenner, Daniel, Kim, Tae-il, Shin, Gunchul, Jeong, Jaewoong
• Primary Examiner(s): Shah, Nilay J
• Application Number:
  US14/766,926
• Publication Number:
  US 20160066789A1
• Time in Patent Office: 2,254 Days
• CPC Class Codes: A61B 2017/00004 (bio)absorbable, (bio)resorbable, resorptive for implantable prostheses A61F2210/0004
• 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 m 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 biomedical device for interfacing with a target tissue, said device comprising:

a substrate; and

a device component comprising;

one or more inorganic semiconductor components comprising one or more light emitting diodes and a wireless power system utilizing radiofrequency power scavenging;

wherein said device component is supported by said substrate;

wherein said one or more light emitting diodes comprise microscale inorganic light emitting diodes (μ

-ILEDs);

wherein steady state operation of said one or more light emitting diodes provides a change in a temperature of said target tissue equal to or less than 1°

C.;

wherein the target tissue is a brain tissue;

wherein said substrate and said device component in combination have a lateral dimension and a thickness selected to allow for implantation and illumination of a brain with a minimal adverse biological effect to said brain tissue, and

wherein said substrate and said device component in combination have a thickness of not greater than 100 μ

m.

2. The device of claim 1, wherein said device component further 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 further 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 further comprises one or more photodiode, 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 a 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.

9. The device of claim 1, wherein said one or more light emitting diodes each independently has an emitting area less than or equal to 1×

10⁵ μ

m².

10. The device of claim 1, wherein said one or more light emitting diodes each independently has an emitting area selected from a range of 1×

10³ μ

m² to 1×

10⁵ μ

m² and wherein said one or more light emitting diodes provides a radiant output characterized by a surface power density of 0.1 mW mm<sup>−

2</sup> to 10 mW mm<sup>−

2</sup>.

11. The device of claim 10, wherein said one or more light emitting diodes provides the radiant output characterized by a plurality of different wavelength maxima.

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

10⁶ μ

m².

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

10⁶ μ

m².

14. 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.

15. The device of claim 14, comprising at least one additional functional layer, the functional layer and the at least one additional functional layer together comprising a plurality of functional layers arranged in a stacked configuration.

16. The device of claim 15, 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.

17. The device of claim 15, wherein said stacked configuration has a shape that corresponds to a micro-needle.

18. The device of claim 15, wherein said plurality of functional layers comprises at least two different functional layers to provide a multifunctional implantable or surface mounted biomedical device.

19. The device of claim 18, wherein said multifunctional device electrically, optically and thermally interfaces with said target tissue.

20. The device of claim 19, wherein said plurality of functional layers in said stacked configuration comprises:

said one or more light emitting diodes and said wireless power system.

21. The device of claim 19, wherein said multifunctional device electrical, optical and thermal interfacing is simultaneous.

22. The device of claim 15, 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.

23. The device of claim 22, wherein at least one functional electronic device selectively interfaces with an individual biological cell or biological component thereof within the interfacing region.

24. The device of claim 14, wherein said functional electronic device corresponds to a size of a biological component within the target tissue.

25. The device of claim 24, wherein said size of said biological component is an average diameter selected from a range that is greater than or equal to 1 μ

m and less than or equal to 100 μ

m.

26. The device of claim 14, wherein said functional layer comprises an array of independently addressable functional electronic devices for independently interfacing with individual biological cells within said target tissue.

27. The device of claim 1, wherein said one or more inorganic semiconductor components comprise one or more thin film structures.

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

29. The device of claim 1, wherein each of said one or more inorganic semiconductor components independently comprise a nanomembrane structure.

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

31. The device of claim 30, wherein said flexible or stretchable structure is an interconnect that connects island structures.

32. The device of claim 1, wherein at least one of said one or more inorganic semiconductor 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.

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

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

10⁸ GPa μ

m⁴.

35. 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.

36. The device of claim 1, wherein said substrate and said 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.

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

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

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

40. The device of claim 39, further comprising a delivery substrate that supports said substrate.

41. The device of claim 40, further comprising an adhesive layer between said delivery substrate and said substrate.

42. The device of claim 41, wherein said adhesive layer dissolves or is bioresorbed and said delivery substrate is removed after implantation.

43. The device of claim 41, wherein said adhesive layer comprises a silk material.

44. The device of claim 40, 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.

45. The device of claim 44, wherein said mechanical property is effective Young'"'"'s modulus or net bending stiffness.

46. The device of claim 40, wherein said delivery substrate has a first end that tapers to a tip.

47. The device of claim 46, wherein said device is shaped into a micro-needle geometry and said device is injectable into said target tissue.

48. The device of claim 1, having any cross-sectional surface area of the device less than or equal to 1 mm².

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

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

51. The device of claim 1, wherein 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 brain surface.

52. 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.

53. 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.

54. The device of claim 53, wherein said probe is a positioning probe to indicate device position within said target tissue.

55. The device of claim 54, 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.

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

57. The device of claim 56, wherein said microfluidic device provides one-way or two-way fluid communication with said target tissue.

58. The device of claim 56, wherein said microfluidic device comprises a fluid reservoir positioned proximate to a heat expandable material.

59. The device of claim 58, wherein said heat expandable material is positioned in thermal communication with a heater.

60. 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.

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

62. The device of claim 1 wherein said microscale inorganic light emitting diodes comprise a plurality of microscale inorganic light emitting diodes.

63. The device of claim 62 wherein said plurality of microscale inorganic light emitting diodes include microscale inorganic light emitting diodes having different wavelength maxima.

64. The device of claim 1 wherein said wireless power system is configured to power said one or more light emitting diodes.

65. The device of claim 1 wherein said wireless power system is configured to control said one or more light emitting diodes.

66. The device of claim 1, wherein said wireless power system is configured for receiving a wireless power transmission.

67. The device of claim 1, wherein said wireless power system is a wireless power harvester.

68. The device of claim 67 wherein a radio frequency power that reaches a biological tissue is less than or equal to 3 mW/cm².

69. The device of claim 1, wherein said wireless power system comprises one or more antenna.

70. The device of claim 69, wherein said one or more antenna are radio frequency antenna.

71. The device of claim 69, wherein said one or more antenna are flexible antenna.

72. The device of claim 1 wherein said wireless power system further comprises one or more impedance matching inductor, rectifier, voltage multiplexer, amplifier, Schottky diode or any combination of these.

73. The device of claim 1, wherein said lateral dimensions are selected from a range that is greater than or equal to 1 μ

m and less than or equal to 10 mm; and

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

74. 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 comprising one or more light emitting diodes and a wireless power system utilizing radiofrequency power scavenging;

wherein said device component is supported by said substrate; and

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

wherein steady state operation of said one or more light emitting diodes provides a change in a temperature of said target tissue equal to or less than 1°

C.

wherein said one or more light emitting diodes comprise microscale inorganic light emitting diodes (μ

-ILEDs);

wherein the target tissue is a brain tissue; and

wherein said device has a lateral dimension and a thickness selected to allow for implantation and illumination of a brain with a minimal adverse biological effect to said brain tissue

wherein said device has a thickness of not greater than 100 μ

m.

75. The device of claim 74, 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 μ

m, and said substrate and said device component in combination have a thickness that is less than 10 μ

m.

76. The device of claim 74, wherein said device component and said substrate form a functional layer comprising a functional electronic device that interfaces with said target tissue.

77. The device of claim 76, comprising at least one additional functional layer, the functional layer and the at least one additional functional layer together comprising a plurality of functional layers arranged in a stacked configuration with said delivery substrate.

78. The device of claim 74, 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.

79. The device of claim 78, wherein said adhesive layer comprises a silk material and said stimulus is a solvent that dissolves said silk material.

80. The device of claim 74, wherein said delivery substrate has a bendability, elasticity, or flexibility that is substantially lower than the substrate that supports the device component.

81. The device of claim 74, wherein an insertion cross-sectional area of said device is less than or equal to 4 mm².

82. The device of claim 81, wherein after implantation removal of the delivery substrate, an implanted cross sectional area is less than or equal to 1 mm².

83. The device of claim 74, 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.

84. The device of claim 74, wherein 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

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

m and less than or equal to 1 mm.