High-Speed, High-Resolution Electrophysiology In-Vivo Using Conformal Electronics

• US 20120157804A1
• Filed: 12/15/2010
• Published: 06/21/2012
• Est. Priority Date: 12/16/2009
• Status: Active Grant

• Current Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Original Assignee: Trustees Of The University Of Pennsylvania (University of Pennsylvania)
• Inventors: ROGERS, John A., KIM, Dae Hyeong, LITT, Brian, VIVENTI, Jonathan, MOSS, Joshua D., CALLANS, David J.
• Granted Patent: US 10,918,298 B2
• Time in Patent Office: Days
• US Class Current: 600/345
• CPC Class Codes: A61B 2562/02 Details of sensors specially adapted for in-vivo measurements
• CPC Class Codes: A61B 2562/066 in a matrix array
• CPC Class Codes: A61B 2562/12 Manufacturing methods specially adapted for producing sensors for in-vivo measurements
• CPC Class Codes: A61B 2562/164 the sensor is mounted in or on a conformable substrate or carrier
• CPC Class Codes: A61B 5/076 Permanent implantations telemetry using implanted circuitry A61B5/0031; implanted stimulators for therapy A61N1/3605, A61N1/362, A61N1/372
• CPC Class Codes: A61B 5/287 Holders for multiple electrodes, e.g. electrode catheters for electrophysiological study [EPS]
• CPC Class Codes: A61B 5/6867 specially adapted to be attached or implanted in a specific body part A61B5/6847 takes precedence
• CPC Class Codes: A61N 1/0472 Structure-related aspects
• 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 1/0587 Epicardial electrode systems; Endocardial electrodes piercing the pericardium
• CPC Class Codes: A61N 1/36002 Cancer treatment, e.g. tumour
• CPC Class Codes: A61N 2005/0652 Arrays of diodes
• CPC Class Codes: A61N 5/0622 Optical stimulation for exciting neural tissue
• CPC Class Codes: H01L 21/6835 using temporarily an auxiliary support
• CPC Class Codes: H01L 2221/6835 used as a support during build up manufacturing of active devices
• CPC Class Codes: H01L 2221/68386 Separation by peeling
• CPC Class Codes: H01L 2224/24137 the bodies being arranged next to each other, e.g. on a common substrate
• CPC Class Codes: H01L 2224/793 by means of pressure
• CPC Class Codes: H01L 2224/86203 Thermo-compression bonding
• CPC Class Codes: H01L 2224/8685 using a polymer adhesive, e.g. an adhesive based on silicone, epoxy, polyimide, polyester
• CPC Class Codes: H01L 23/3121 : a substrate forming part of the encapsulation
• CPC Class Codes: H01L 23/3192 : Multilayer coating
• CPC Class Codes: H01L 24/24 : of an individual high density interconnect connector
• CPC Class Codes: H01L 24/50 : Tape automated bonding [TAB] connectors, i.e. film carriers; Manufacturing methods related thereto thin flexible metallic tape with or without a film carrier H01L23/49572, flexible insulating substrates H01L23/4985, H01L23/5387
• CPC Class Codes: H01L 24/82 : by forming build-up interconnects at chip-level, e.g. for high density interconnects [HDI] interconnection structure between a plurality of semiconductor chips H01L23/5389
• CPC Class Codes: H01L 24/86 : using tape automated bonding [TAB]
• CPC Class Codes: H01L 27/1218 : with a particular composition or structure of the substrate
• CPC Class Codes: H01L 29/78603 : characterised by the insulating substrate or support H01L29/78657 takes precedence
• CPC Class Codes: H01L 29/7869 : having a semiconductor body comprising an oxide semiconductor material, e.g. zinc oxide, copper aluminium oxide, cadmium stannate
• CPC Class Codes: H01L 2924/00 : Indexing scheme for arrangements or methods for connecting or disconnecting semiconductor or solid-state bodies as covered by H01L24/00
• CPC Class Codes: H01L 2924/12036 : PN diode
• CPC Class Codes: H01L 2924/12041 : LED
• CPC Class Codes: H01L 2924/12043 : Photo diode
• CPC Class Codes: H01L 2924/12044 : OLED
• CPC Class Codes: H01L 2924/14 : Integrated circuits
• CPC Class Codes: H01L 2924/15788 : Glasses, e.g. amorphous oxides, nitrides or fluorides
• CPC Class Codes: H01L 2924/19041 : being a capacitor
• CPC Class Codes: H01L 2924/3011 : Impedance
• CPC Class Codes: H01L 2924/3025 : Electromagnetic shielding
• CPC Class Codes: H05K 1/0283 : Stretchable printed circuits
• CPC Class Codes: H05K 1/147 : at least one of the printed circuits being bent or folded, e.g. by using a flexible printed circuit H05K1/148 takes precedence
• CPC Class Codes: H05K 2201/09263 : Meander
• CPC Class Codes: H05K 3/323 : by applying an anisotropic conductive adhesive layer over an array of pads

Abstract

Provided herein are biomedical devices and methods of making and using biomedical devices for sensing and actuation applications. For example, flexible and/or stretchable biomedical devices are provided including electronic devices useful for establishing in situ conformal contact with a tissue in a biological environment. The invention includes implantable electronic devices and devices administered to the surfaces(s) of a target tissue, for example, for obtaining electrophysiology data from a tissue such as cardiac, brain tissue or skin.

Claims

1. A device for interfacing with a tissue in a biological environment, the device comprising:

a flexible or stretchable substrate;

a flexible or stretchable electronic circuit comprising one or more inorganic semiconductor circuit elements supported by the flexible or stretchable substrate; and

a barrier layer encapsulating at least a portion of the flexible or stretchable electronic circuit;

wherein the barrier layer and the flexible or stretchable substrate limit a net leakage current from the flexible or stretchable electronic circuit to an amount which does not adversely affect the tissue; and

wherein the flexible or stretchable substrate, the flexible or stretchable electronic circuit and the barrier layer provide a net bending stiffness of the device low enough that the device establishes conformal contact with the tissue in the biological environment.

8. The device of claim 1, wherein the biological environment is an in-vivo biological environment.

9. The device of claim 1, wherein the biological environment comprises a conductive ionic solution.

10. The device of claim 1, wherein the device is for sensing or actuating the tissue in the biological environment.

11. The device of claim 1, wherein the tissue in the biological environment comprises heart tissue, brain tissue, skin, muscle tissue, nervous system tissue, vascular tissue, epithelial tissue, retina tissue, ear drum, tumor tissue, digestive system structures or any combination of these.

12. The device of claim 1, wherein the device establishes conformal contact with the tissue in situ when the device is placed in physical contact with the tissue in the biological environment, and wherein the conformal contact with the tissue in the biological environment is maintained as the tissue moves or when the device moves.

13. The device of claim 1, wherein the device is in electrical contact with the tissue in the biological environment, wherein the electrical contact with the tissue in the biological environment is maintained as the tissue moves or when the device moves.

14. The device of claim 1, wherein the substrate, the electronic circuit and the barrier layer provide a net bending stiffness of the device less than or equal to 1×

10⁸ GPa μ

m⁴.

15. The device of claim 1, wherein the substrate, the electronic circuit and the barrier layer provide a net flexural rigidity of the device less than or equal to 1×

10<sup>−

4</sup> Nm.

16. The device of claim 1, wherein the substrate is a flexible substrate and the electronic circuit is a flexible electronic circuit.

17. The device of claim 1, wherein the substrate is a stretchable substrate and the electronic circuit is a stretchable electronic circuit.

18. The device of claim 1, wherein the device has a neutral mechanical plane and at least a portion of the inorganic semiconductor circuit elements are positioned proximate to the neutral mechanical plane.

19. The device of claim 18, wherein a thickness of the barrier layer and a thickness of the flexible or stretchable substrate are selected so as to position at least a portion of the inorganic semiconductor circuit elements proximate to the neutral mechanical plane.

20. The device of claim 1, wherein the barrier layer has a thickness over at least a portion of the electronic circuit selected over the range of 0.25 μ

m to 1000 μ

m.

21. The device of claim 1, wherein the barrier layer has an average thickness over of the electronic circuit less than or equal to 1000 μ

m.

22. The device of claim 1, wherein the barrier layer has an average modulus selected over the range of 0.5 KPa to 10 GPa.

23. The device of claim 1, wherein the barrier layer has an average thickness and the flexible or stretchable substrate has an average thickness, wherein the ratio of the average thickness of the barrier layer to the average thickness of the flexible or stretchable substrate is selected over the range of 0.1 to 10.

24. The device of claim 1, wherein the barrier layer has an average thickness and the flexible or stretchable substrate has an average thickness, wherein the ratio of the average thickness of the barrier layer to the average thickness of the flexible or stretchable substrate is selected over the range of 0.5 to 2.

25. The device of claim 1, wherein the barrier layer comprises a material selected from the group consisting of:

a polymer, an inorganic polymer, an organic polymer, an elastomer, a biopolymer, a ceramic, and any combination of these.

26. The device of claim 1, wherein the barrier layer comprises an elastomer.

27. The device of claim 1, wherein the barrier layer comprises PDMS, polyimide, SU-8, parylene, parylene C, silicon carbide (SiC), or Si₃N₄.

28. The device of claim 1, wherein the barrier layer is a biocompatible material or a bioinert material.

29. The device of claim 1, wherein the barrier layer is a microstructured or nanostructured layer having one or more nanostructured or microstructured openings, channels, optically transmissive regions, optically opaque regions or selectively permeable regions that are permeable to one or more target molecules.

30. The device of claim 1, wherein the flexible or stretchable substrate has an average thickness selected over the range of 0.25 μ

m to 1000 μ

m.

31. The device of claim 1, wherein the flexible or stretchable substrate is a flexible thin film having an average thickness less than or equal to 100 μ

m.

32. The device of claim 1, wherein the flexible or stretchable substrate has a substantially uniform thickness over the electronic circuit.

33. The device of claim 1, wherein the flexible or stretchable substrate has a thickness that varies selectively along one or more lateral dimension over the electronic circuit.

34. The device of claim 1, wherein the flexible or stretchable substrate is a flexible or stretchable mesh structure.

35. The device of claim 1, wherein the flexible or stretchable substrate has an average modulus selected over the range of 0.5 KPa to 10 GPa.

36. The device of claim 1, wherein the flexible or stretchable substrate comprises material selected from the group consisting of:

a polymer, an inorganic polymer, an organic polymer, a plastic, an elastomer, a biopolymer, a thermoset, rubber, fabric, paper and any combination of these.

37. The device of claim 1, wherein the flexible or stretchable substrate comprises PDMS, parylene or polyimide.

38. The device of claim 1, wherein the flexible or stretchable substrate is a biocompatible material or a bioinert material.

39. The device of claim 1, wherein the flexible or stretchable electronic circuit comprises one or more flexible or stretchable inorganic semiconductor structures.

40. The device of claim 39, wherein each of the flexible or stretchable inorganic semiconductor structures comprise a single crystalline inorganic semiconductor or a doped single crystalline inorganic semiconductor.

41. The device of claim 39, wherein each of the flexible or stretchable inorganic semiconductor structures has an average thickness less than or equal to 100 microns.

42. The device of claim 39, wherein each of the flexible or stretchable inorganic semiconductor structures has an average thickness selected over the range of 250 nanometers to 100 microns.

43. The device of claim 39, wherein each of the flexible or stretchable inorganic semiconductor structures has a net flexural rigidity less than or equal to 1×

10⁴ Nm.

44. The device of claim 39, wherein each of the flexible or stretchable inorganic semiconductor structures has a net bending stiffness less than or equal to 1×

10⁸ GPa μ

m⁴

45. The device of claim 39, wherein each of the flexible or stretchable inorganic semiconductor structures is independently a flexible or stretchable semiconductor nanoribbon, semiconductor membrane, semiconductor nanowire or any combination of these.

46. The device of claim 39, wherein the flexible or stretchable electronic circuit further comprises one or more flexible or stretchable dielectric structures, wherein at least a portion of the flexible or stretchable inorganic semiconductor structures is in physical contact with one or more of the dielectric structures.

47. The device of claim 46, wherein each of the flexible or stretchable dielectric structures has a thickness equal to or less than 100 microns.

48. The device of claim 39, wherein the flexible or stretchable electronic circuit further comprises one or more flexible or stretchable electrodes, wherein at least a portion of the flexible or stretchable inorganic semiconductor structures is in electrical contact with one or more of the electrodes.

49. The device of claim 48, wherein each of the flexible or stretchable electrodes has a thickness equal to or less than 500 microns.

50. The device of claim 1, wherein the flexible or stretchable electronic circuit comprises a plurality of electronically interconnected island and bridge structures.

51. The device of claim 50, wherein the island structures comprise the one or more semiconductor circuit elements.

52. The device of claim 50, wherein the bridge structures comprise one or more flexible or stretchable electrical interconnections.

53. The device of claim 52, wherein at least a portion of the flexible or stretchable electrical interconnections have a serpentine geometry.

54. The device of claim 1, wherein the flexible or stretchable electronic circuit is selected from the group consisting of:

a flexible or stretchable transistor, a flexible or stretchable diode, a flexible or stretchable amplifier, a flexible or stretchable multiplexer, a flexible or stretchable light emitting diode, a flexible or stretchable laser, a flexible or stretchable photodiode, a flexible or stretchable integrated circuit and any combination of these.

55. The device of claim 1, wherein the flexible or stretchable electronic circuit further comprises a plurality of sensing or actuating elements spatially arranged over the flexible or stretchable substrate, wherein each sensing or actuating element is in electrical communication with at least one of the plurality of flexible semiconductor circuit elements.

56. The device of claim 55, wherein at least one of the plurality of sensing or actuating elements is in electrical communication or optical communication with the tissue when the device is in conformal contact with the tissue in the biological environment.

57. The device of claim 55, wherein the actuating elements comprise circuit elements selected from the group consisting of:

electrode elements, electromagnetic radiation emitting elements, heating elements and any combination of these.

58. The device of claim 55, wherein at least a portion of the sensing or actuating elements is encapsulated by the barrier layer.

2. A device for interfacing with a tissue in a biological environment, the device comprising:

a flexible or stretchable substrate;

a flexible or stretchable electronic circuit comprising one or more inorganic semiconductor circuit elements supported by the flexible or stretchable substrate; and

a barrier layer encapsulating at least a portion of the flexible or stretchable electronic circuit;

wherein the barrier layer is patterned so as to selectively modulate physical contact, thermal contact, optical communication or electrical communication between the flexible or stretchable electronic circuit and the tissue in the biological environment; and

wherein the flexible or stretchable substrate, the flexible or stretchable electronic circuit and the barrier layer provide a net bending stiffness of the device low enough that the device establishes conformal contact with the tissue in the biological environment.

3. A device for interfacing with a tissue in a biological environment, the device comprising:

a flexible or stretchable substrate;

a flexible or stretchable electronic circuit comprising one or more inorganic semiconductor circuit elements supported by the flexible or stretchable substrate; and

a barrier layer encapsulating at least a portion of the flexible or stretchable electronic circuit;

wherein the barrier layer and the flexible or stretchable substrate limits heat transfer from the flexible or stretchable electronic circuit to the tissue in the biological environment to an amount that does not adversely affect the tissue in the biological environment; and

wherein the flexible or stretchable substrate, the flexible or stretchable electronic circuit and the barrier layer provide a net bending stiffness of the device low enough that the device establishes conformal contact with the tissue in the biological environment.

4. A device for interfacing with a tissue in a biological environment, the device comprising:

a flexible or stretchable substrate;

a flexible or stretchable electronic circuit comprising one or more inorganic semiconductor circuit elements supported by the flexible or stretchable substrate; and

a barrier layer encapsulating at least a portion of the flexible or stretchable electronic circuit;

wherein the barrier layer is patterned so as to provide one or more permeable regions that are selectively permeable to one or more target molecules to allow transport of the target molecules from the biological environment to the flexible or stretchable electronic circuit or from the flexible or stretchable electronic circuit to the biological environment; and

wherein the flexible or stretchable substrate, the flexible or stretchable electronic circuit and the barrier layer provide a net bending stiffness of the device low enough that the device establishes conformal contact with the tissue in the biological environment.

5. A device for interfacing with a tissue in a biological environment, the device comprising:

a flexible or stretchable substrate;

a flexible or stretchable electronic circuit comprising one or more inorganic semiconductor circuit elements supported by the flexible or stretchable substrate; and

a barrier layer encapsulating at least a portion of the flexible or stretchable electronic circuit;

wherein the barrier layer is patterned so as to provide one or more impermeable regions that are impermeable to one or more target molecules to prevent transport of the target molecules from the biological environment to the flexible or stretchable electronic circuit or from the flexible or stretchable electronic circuit to the biological environment; and

wherein the flexible or stretchable substrate, the flexible or stretchable electronic circuit and the barrier layer provide a net bending stiffness of the device low enough that the device establishes conformal contact with the tissue in the biological environment.

6. A device for interfacing with a tissue in a biological environment, the device comprising:

a flexible or stretchable substrate;

a flexible or stretchable electronic circuit comprising one or more inorganic semiconductor circuit elements supported by the flexible or stretchable substrate; and

a barrier layer encapsulating at least a portion of the flexible or stretchable electronic circuit;

wherein the barrier layer is patterned to provide one or more transparent regions, wherein the transparent regions transmit to or from the flexible or stretchable electronic circuit ultraviolet, visible or near-infrared electromagnetic radiation having a preselected wavelength distribution or wherein the barrier layer is patterned to provide one or more opaque regions that substantially prevent transmission to or from the flexible or stretchable electronic circuit of electromagnetic radiation having a preselected distribution of wavelengths in the ultraviolet, visible or near-infrared regions of the electromagnetic spectrum; and

wherein the flexible or stretchable substrate, the flexible or stretchable electronic device and the barrier layer provide a net bending stiffness of the device low enough that the device establishes conformal contact with the tissue in the biological environment.

7. A device for interfacing with a tissue in a biological environment, the device comprising:

a flexible or stretchable substrate;

a flexible or stretchable electronic circuit supported by the flexible or stretchable substrate, wherein the flexible or stretchable electronic circuit comprises a plurality of sensors, actuators or both sensors and actuators provided in an array and one or more inorganic semiconductor circuit elements;

a controller in communication with the flexible or stretchable electronic circuit, the controller configured to receive input signals from the flexible or stretchable electronic circuit and provide output signals to the flexible or stretchable electronic circuit, wherein the controller receives and analyzes input signals corresponding to one or more measurements from said sensors and generates output signals that control or provide one or more sensing or actuation parameter to the flexible or stretchable electronic circuit; and

a barrier layer encapsulating at least a portion of the flexible or stretchable electronic circuit;

wherein the flexible or stretchable substrate, the flexible or stretchable electronic circuit and the barrier layer provide a net bending stiffness of the device low enough that the device establishes conformal contact with the tissue in the biological environment.

59. An device for collecting electrophysiology data from a tissue in a biological environment, the device comprising:

a flexible or stretchable substrate;

a flexible or stretchable electrode array comprising one or more inorganic semiconductor circuit elements and a plurality of electrode elements positioned in electrical communication with at least a portion of the semiconductor circuit elements, wherein the one or more inorganic semiconductor circuit elements include multiplex circuitry and amplification circuitry, and wherein the electrode array is supported by the flexible or stretchable substrate;

a barrier layer encapsulating at least a portion of the flexible or stretchable electrode array to limit a net leakage current from flexible or stretchable electrode array to the tissue to an amount that does not adversely affect the tissue;

wherein the flexible or stretchable substrate, the flexible or stretchable electrode array and the barrier layer provide a net bending stiffness of the device low enough that the device establishes conformal contact with the tissue in the biological environment, thereby, positioning at least one of the plurality of electrode elements in electrical communication with the tissue in the biological environment.

60. A method of collecting electrophysiology data from a tissue in a biological environment, the method comprising the steps of:

providing a conformable electronic device comprising;

a flexible or stretchable substrate;

a flexible or stretchable electrode array comprising one or more inorganic semiconductor circuit elements and a plurality of electrode elements positioned in electrical communication with at least a portion of the semiconductor circuit elements, wherein the one or more inorganic semiconductor circuit elements include multiplex circuitry and amplification circuitry, and wherein the electrode array is supported by the flexible or stretchable substrate;

a barrier layer encapsulating at least a portion of the flexible or stretchable electrode array to limit a net leakage current from flexible or stretchable electrode array to the tissue to an amount that does not adversely affect the tissue;

wherein the flexible or stretchable substrate, the flexible or stretchable electronic device and the barrier layer provide a net bending stiffness of the device low enough that the device establishes conformal contact with the tissue in the biological environment;

contacting the tissue with the conformable electronic device, thereby establishing the conformal contact such that at least a portion of the plurality of electrode elements is provided in electrical communication with the tissue in the biological environment; and

measuring voltages associated with the tissue in the biological environment on at least a portion of the plurality of electrode elements.

61. The method of claim 60, wherein the voltages associated with the tissue have a spatial arrangement corresponding to a spatial arrangement of the electrode elements.

62. A device for interfacing with a tissue in a biological environment, the device comprising:

a flexible or stretchable substrate;

a stretchable or flexible array of light emitting diodes comprising a plurality of light emitting diodes in electrical communication with a plurality of stretchable or flexible electrical interconnects, the stretchable or flexible array of light emitting diodes supported by the flexible or stretchable substrate;

a barrier layer encapsulating at least a portion of the stretchable or flexible array of light emitting diodes to limit a net leakage current from the stretchable or flexible array of light emitting diodes to the tissue to an amount that does not adversely affect the tissue;

wherein the flexible or stretchable substrate, stretchable or flexible array of light emitting diodes and the barrier layer provide a net bending stiffness of the device low enough that the device establishes conformal contact with the tissue in the biological environment.

63. The device of claim 62 comprising an implantable or skin-mounted array of light emitting diodes.

64. A method of interfacing an array of light emitting diodes with a tissue of a subject, the method comprising the steps of:

providing a conformable device for interfacing with a tissue in a biological environment, the device comprising;

a flexible or stretchable substrate;

a stretchable or flexible array of light emitting diodes comprising a plurality of light emitting diodes in electrical communication with a plurality of stretchable or flexible electrical interconnects, the stretchable or flexible array of light emitting diodes supported by the flexible or stretchable substrate;

a barrier layer encapsulating at least a portion of the stretchable or flexible array of light emitting diodes to limit a net leakage current from the stretchable or flexible array of light emitting diodes to the tissue to an amount that does not adversely affect the tissue;

wherein the flexible or stretchable substrate, stretchable or flexible array of light emitting diodes and the barrier layer provide a net bending stiffness of the device low enough that the device establishes conformal contact with the tissue in the biological environment; and

contacting the conformable device with the tissue of the subject, thereby establishing the conformal contact with the tissue in the biological environment.

65. A method of sensing or actuating a tissue in a biological environment;

the method comprising;

providing a subject having the tissue in the biological environment;

providing a conformable device, the device comprising

a flexible or stretchable substrate;

a flexible or stretchable electronic circuit supported by the flexible or stretchable substrate, wherein the flexible or stretchable electronic circuit comprises an plurality of sensors, actuators or both sensors and actuators provided in an array, wherein said sensors or actuators comprise one or more inorganic semiconductor circuit elements; and

a barrier layer encapsulating at least a portion of the flexible or stretchable electronic circuit;

wherein the barrier layer and the flexible or stretchable substrate limit a net leakage current from the flexible or stretchable electronic circuit to an amount which does not adversely affect the tissue or said barrier layer is patterned so as to selectively modulate physical contact, thermal contact, optical communication or electrical communication between said flexible or stretchable electronic circuit and said tissue in said biological environment;

wherein the flexible or stretchable substrate, the flexible or stretchable electronic circuit and the barrier layer provide a net bending stiffness of the device low enough that the conformable device establishes conformal contact with the tissue in the biological environment;

contacting the tissue with the conformable device, thereby establishing the conformal contact such that at least a portion of the plurality of sensors, actuators or both sensors and actuators of the array is provided in physical contact, electrical communication, optical communication, fluid communication or thermal communication with the tissue in the biological environment; and

sensing or actuating the tissue in contact with the conformable device.

66. The method of claim 65, wherein the biological environment is an in-vivo biological environment.

67. The method of claim 65, wherein the tissue in the biological environment comprises heart tissue, brain tissue, muscle tissue, skin, nervous system tissue, vascular tissue, epithelial tissue, retina tissue, ear drum, tumor tissue, a digestive system structure or any combination of these.

68. The method of claim 65, wherein the step of contacting the tissue with the conformable device establishes conformal contact between one or more contact surfaces of the conformable device and an area of the tissue selected from the range of from 10 mm² to 10,000 mm².

69. The method of claim 65, further comprising the step of moving the conformable device along a surface of the tissue in the biological environment.

70. The method of claim 65, wherein the step of sensing or actuating the tissue in contact with the conformable device comprises:

generating one or more voltages at a plurality of different regions on a surface of the tissue;

sensing one or more voltages at a plurality of different regions on a surface of the tissue;

or

sensing one or more voltages at a plurality of different regions on a surface of the tissue and generating one or more voltages at a plurality of different regions on the surface of the tissue.

71. The method of claim 70 wherein the voltages are selected from the range of −

100 V to 100 V.

72. The method of claim 65, wherein the step of sensing or actuating the tissue in contact with the conformable device comprises:

generating one or more currents at a plurality of different regions on a surface of the tissue;

sensing one or more currents at a plurality of different regions on a surface of the tissue;

or

sensing one or more currents at a plurality of different regions on a surface of the tissue and generating one or more currents at a plurality of different regions on the surface of the tissue.

73. The method of claim 65, wherein the step of sensing or actuating the tissue in contact with the conformable device comprises:

sensing electromagnetic radiation at a surface of the tissue;

generating electromagnetic radiation at a surface of the tissue;

or

sensing electromagnetic radiation at a surface of the tissue and generating electromagnetic radiation at the surface of the tissue.

74. The method of claim 65, wherein the step of sensing or actuating the tissue in contact with the conformable device comprises ablating at least a portion of said tissue.

75. The method of claim 65, wherein the step of sensing or actuating the tissue in contact with the conformable device comprises:

transporting a target molecule from a surface of the tissue to the flexible or stretchable electronic circuit;

transporting a target molecule from the flexible or stretchable electronic circuit to a surface of the tissue;

or

transporting a target molecule from a surface of the tissue to the flexible or stretchable electronic circuit and transporting a target molecule from the flexible or stretchable electronic circuit to a surface of the tissue.

76. The method of claim 75, wherein the target molecule is selected from the group consisting of polypeptides, polynucleotides, carbohydrates, proteins, steroids, glycopeptides, lipids, metabolites and drugs

77. The method of claim 65, wherein the step of sensing or actuating the tissue in contact with the conformable device comprises:

sensing or changing a temperature of a region of the tissue;

sensing or changing a pressure of a region of the tissue;

sensing or changing a position of the tissue;

sensing or generating an electrical field at a region of the tissue;

or

sensing or generating a magnetic field at a region of the tissue.

78. The method of claim 65, further comprising administering to the subject a therapeutic agent, wherein the therapeutic agent localizes at the tissue, wherein the step of sensing or actuating the tissue in contact with the conformable device comprises activating the therapeutic agent at the tissue.

79. The method of claim 65, wherein the step of sensing or actuating the tissue in contact with the conformable device comprises measuring an electrophysiological signal from the tissue, measuring an intensity of electromagnetic radiation from the tissue, measuring a change in the concentration of a target molecule at the target tissue, measuring an acceleration of the tissue, measuring a movement of the tissue, or measuring a temperature of the tissue.

80. The method of claim 65, wherein the tissue is heart tissue, and wherein the step of sensing or actuating the tissue in contact with the conformable device comprises simultaneously applying multiple pacing stimuli to the heart tissue.

81. The method of claim 80, wherein the tissue is epicardium tissue.

82. The method of claim 65, wherein said step of contacting the tissue with the conformable device is carried out via a surgical technique.

83. The method of claim 65, wherein said step of contacting the tissue with the conformable device is carried out using a catheter.

84. The method of claim 83, wherein the conformable device is collapsed, rolled or wrapped on itself and inserted into the catheter, and wherein the catheter is subsequently positioned at the tissue and the conformable device is released from the catheter, thereby delivering the conformable device to a surface of the tissue.

85. The method of claim 84, wherein the conformable device changes conformation upon release from the catheter so as to establish conformal contact with said tissue.

86. The method of claim 65, comprising a diagnostic or therapeutic procedure.

87. The method of claim 86, wherein the diagnostic or therapeutic procedure is selected from the group consisting of anatomic mapping, physiologic mapping, resynchronization therapy, measuring cardiac contractility, measuring myocardial wall displacement, measuring myocardial wall stress, measuring myocardial movement, measuring ischemic changes, cardiac mapping, cardiac resynchronization therapy and cardiac ablation therapy.

88. The method of claim 65, wherein said flexible or stretchable electronic circuit comprises a plurality of sensors for determination or discrimination of tissue properties and one or more actuators comprising an ablation source for ablating one or more regions of the tissue.

89. The method of claim 88, wherein said sensors for determination or discrimination of tissue properties distinguish one or more components of said tissue selected from the group consisting of a lesion, epicardial muscle, myocardial tissue, epicardial fat, a coronary artery, and a nerve.

90. The method of claim 89, wherein said ablation source selectively ablates said lesion component of said tissue.