Tissue sensor and uses thereof

• US 20060105357A1
• Filed: 02/04/2005
• Published: 05/18/2006
• Est. Priority Date: 02/18/1998
• Status: Abandoned Application

• Current Assignee: Myomics, Inc.
• Original Assignee: Myomics, Inc.
• Inventors: Vandenburgh, Herman H., Crawford, Gregory Philip, Valentini, Robert Francis, Barbata, Victoria Margit, Benesch, Frank
• Application Number:
  US11/051,736
• Publication Number:
  US 20060105357A1
• Time in Patent Office: Days
• US Class Current: 435/6
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/0819 Microarrays; Biochips
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: B01L 3/5088 confining liquids at a location by surface tension, e.g. virtual wells on plates, wires B01L3/50857 takes precedence
• CPC Class Codes: G01N 33/5088 of vertebrates
• CPC Class Codes: G01N 33/6887 from muscle, cartilage or connective tissue

Abstract

Described are assemblies for screening a compound for bioactivity, the assemblies comprising a tissue and a sensor. A change in a biological parameter is measured by the sensor, such that a change in a parameter occurring when the tissue is contacted with a candidate compound is detected by the sensor. Assemblies provided herein include single sensor/tissue assemblies and arrays of such assemblies, including plates comprising tissues in combination with one or more sensors. Also provided are methods of screening a compound using tissue/sensor tissue assemblies as described.

Claims

1. A composition comprising a container comprising at least one viable tissue in combination with a sensor, wherein said tissue was formed in vitro.

2. The composition of claim 1 wherein said tissue is independent of said sensor.

3. The composition of claim 1, wherein said tissue is not independent from said sensor.

4. The composition of claim 1, wherein said tissue comprises muscle cells.

5. The composition of claim 3, wherein said muscle cells are selected from the group consisting of:

smooth, skeletal or cardiac muscle cells.

6. The composition of claim 1, wherein said tissue is organized.

7. The composition of claim 1, wherein said sensor measures an optical, physical, chemical, genetic or electrical property of said tissue.

8. The composition of claim 1, wherein said sensor measures at least one of muscle contraction, muscle relaxation, muscle hypertrophy and muscle length.

9. The composition of claim 1, further comprising a device to provide a readout for a change in a property of said tissue.

10. A plate comprising at least one tissue in combination with a sensor, wherein said tissue was formed in vitro.

11. The plate of claim 10, wherein said sensor is independent from said tissue.

12. The plate of claim 10, wherein said tissue is not independent from said sensor.

13. The plate of claim 10 wherein said plate comprises at least two microposts.

14. The plate of claim 13 wherein said microposts are attached to said plate.

15. The plate of claim 13 wherein said microposts are supported by an extracellular matrix material.

16. The plate of claim 15 wherein said extracellular matrix material comprises collagen.

17. The plate of claim 10 wherein said tissue is in contact with two or more microposts.

18. The plate of claim 13 that comprises an array of microposts.

19. The plate of claim 18 wherein said array comprises one or more lattice unit cells defined by the arrangement of said microposts.

20. The plate of claim 10 which comprises a plurality of wells that comprise said tissue.

21. The plate of claim 20 wherein a well of said plurality of wells comprises at least two microposts.

22. The plate of claim 21 wherein a well of said plurality of wells comprises an array of microposts.

23. The plate of claim 22 wherein a said array comprises one or more lattice unit cells defined by the arrangement of said microposts.

24. The plate of claim 13 wherein said tissue is in contact with at least two of said microposts.

25. The plate of claim 24 wherein said tissue is in contact with and located between at least two of said microposts.

26. The plate of claim 22 wherein a said tissue is in contact with and located between a plurality of pairs of the microposts in said array.

27. The plate of claim 23 wherein a said tissue is in contact with and located between each micropost defining a lattice unit cell.

28. The plate of claim 10, wherein said tissue comprises muscle cells.

29. The plate of claim 10, wherein said muscle cells are selected from the group consisting of:

smooth, skeletal or cardiac muscle cells.

30. The plate of claim 10, wherein said tissue is organized.

31. The plate of claim 10 which comprises one or more essentially linear grooves.

32. The plate of claim 31 wherein said one or more essentially linear grooves are located in one or more wells on said plate.

33. The plate of claim 31 wherein said grooves are arranged substantially parallel to each other.

34. The plate of claim 31 wherein said tissue is arranged in said one or more grooves.

35. The plate of claim 31 wherein one or more of said grooves comprise at least two microposts.

36. The plate of claim 35 wherein said tissue is in contact with and located between at least two of said microposts.

37. The plate of claim 13, wherein said sensor measures a change in the distance between said microposts.

38. The plate of claim 10, wherein said sensor measures at least one of muscle contraction, muscle relaxation, muscle hypertrophy, and muscle length.

39. The plate of claim 10, further comprising a device to provide a readout for a change in a property of said tissue.

40. An array comprising at least one tissue in combination with a sensor, wherein said tissue was formed in vitro.

41. The array of claim 40, wherein said sensor is independent from said tissue.

42. The array of claim 40, wherein said tissue is not independent from said sensor.

43. The array of claim 40, wherein said tissue comprises muscle cells.

44. The array of claim 40, wherein said muscle cells are selected from the group consisting of:

smooth, skeletal or cardiac cells.

45. The array of claim 40, wherein said tissue is organized.

46. The array of claim 40, wherein said sensor is optical, physical, electrical or chemical.

47. The array of claim 40, wherein said sensor measures at least one of muscle contraction, muscle relaxation, muscle hypertrophy, and muscle length.

48. The array of claim 40 comprising a plurality of microposts.

49. The array of claim 48 wherein said tissue is in contact with and located between at least two of said microposts.

50. The array of claim 40, further comprising a device to provide a readout for a change in a property of said tissue.

51. An apparatus comprising at least a tissue formed in vitro, in combination with:

a) a sensor; and

b) a device that provides a readout for a change in a property of the tissue.

52. A method of screening a compound for bioactivity, comprising contacting a candidate bioactive compound with a tissue, wherein said tissue is in combination with a sensor, and measuring in said tissue a biological parameter that is associated with bioactivity, wherein a change in the biological parameter that occurs as a result of said contacting step is indicative of bioactivity of said candidate compound.

67. The method of claim 52 or 53, wherein said biological parameter is selected from the group consisting of:

muscle contraction, muscle relaxation, muscle hypertrophy, muscle length, gene expression, mRNA expression, protein expression, enzymatic activity.

68. The method of any one of claims 52-54, wherein said method is performed in real-time.

53. A method of screening a library of compounds for bioactivity, comprising contacting a candidate bioactive compound from said library with a tissue, wherein said tissue is in combination with a sensor, and measuring in a tissue a biological parameter that is associated with bioactivity, wherein a change in the biological parameter that occurs as a result of said contacting step is indicative of bioactivity of said candidate compound.

54. A method of identifying a compound that increases or decreases muscle contraction or muscle relaxation comprising contacting a candidate compound with a tissue, wherein said tissue is in combination with a sensor, and measuring in said tissue, muscle contraction, wherein an increase or decrease in muscle contraction that occurs as a result of said contacting step is indicative of said compound modulating muscle contraction.

55. A method of monitoring the effect of an agent on a tissue, the method comprising the steps of:

a) providing a plurality of tissues formed in vitro, wherein at least one of said tissues is in combination with a sensor;

b) contacting said plurality of tissues with an agent;

c) obtaining a measurement from said sensor; and

d) detecting a nucleic acid sequence in a said tissue, wherein an effect of said agent on said tissues is determined.

56. The method of claim 55 wherein the step of detecting a nucleic acid sequence in a said tissue comprises isolating nucleic acid from a tissue of said plurality.

57. The method of claim 55 wherein the step of detecting a nucleic acid sequence in a said tissue comprises amplification of a nucleic acid sequence from a tissue of said plurality.

58. The method of claim 55 wherein the step of detecting a nucleic acid sequence in a said tissue comprises hybridization of nucleic acid prepared from said tissue to an array.

59. The method of claim 55 wherein the step of detecting a nucleic acid sequence in a said tissue comprises obtaining a genetic expression profile for said tissue.

60. The method of claim 55 wherein said contacting step is repeated at least once.

61. The method of claim 55 wherein steps (c) and (d) are repeated at least once.

62. The method of claim 61 wherein said steps of detecting detect a change in the genetic expression profile for said tissues.

63. The method of claim 55 wherein said tissue is prepared from cells from an individual having a condition affecting said tissue.

64. The method of claim 55 wherein said tissue comprises a genetically modified cell.

65. A method of inducing muscle contraction or muscle relaxation in a tissue in combination with a sensor, wherein said tissue is contacted with a compound, a mechanical force or an electrical force.

66. A method of measuring permeability of a compound that increases or decreases at least one of muscle contraction, muscle relaxation, muscle hypertrophy, muscle mass and muscle length, comprising introducing said compound into a sensor, wherein said sensor is in combination with a tissue, and wherein said permeability is measured by determining a change in at least one of muscle contraction, muscle hypertrophy, muscle mass and muscle length of said tissue.

69. A device for measuring a parameter of a tissue, the device comprising:

a) a hollow tube;

b) a distal end of elastic material extending from said hollow tube;

c) a tissue adhered to an exterior surface of said distal end.

70. The device of claim 69 wherein said distal end is approximately spherical.

71. The device of claim 69 wherein said tube communicates with a pressure transducer.

72. The device of claim 71 wherein a change in pressure inside said tube is detected by said pressure transducer.

73. The device of claim 69 wherein said tissue is grown on said exterior surface of said distal end.

74. The device of claim 69 wherein said tissue comprises muscle tissue.

75. The device of claim 74 wherein said muscle tissue comprises cardiac muscle, smooth muscle or striated muscle.

76. The device of claim 74 wherein contraction of said muscle tissue results in a detectable change in pressure inside said tube.

77. The device of claim 69 wherein said elastic material comprises a silicon membrane.

78. A method of determining the bioactivity of a compound, the method comprising contacting a device of claim 69 with said compound and detecting a change in pressure inside said tube.

79. The method of claim 78 wherein said tissue comprises muscle.

80. An array of devices of claim 69.

81. A device comprising:

a) a hollow tube; and

b) an elastic membrane covering a distal end of said tube, said membrane in contact with a tissue.

82. The device of claim 81 wherein said tube communicates with a pressure transducer.

83. The device of claim 81 wherein said membrane comprises a silicon membrane.

84. The device of claim 81 wherein said tissue is formed on said membrane.

85. The device of claim 81 wherein said tissue is not formed on said membrane.

86. The device of claim 81 wherein said tissue comprises muscle tissue.

87. The device of claim 86 wherein said muscle tissue comprises cardiac muscle, smooth muscle or striated muscle.

88. The device of claim 86 wherein contraction of said muscle tissue results in a detectable change in pressure inside said tube.

89. A method of determining the bioactivity of a compound, the method comprising contacting a device of claim 86 with said compound and detecting a change in pressure inside said tube.

90. The method of claim 89 wherein said tissue comprises muscle.

91. An array of devices of claim 81.