SYSTEMS AND METHODS FOR BIODOSIMETRY WITH BIOCHIP USING GENE EXPRESSION SIGNATURES

• US 20080176755A1
• Filed: 08/24/2007
• Published: 07/24/2008
• Est. Priority Date: 08/25/2006
• Status: Abandoned Application

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Wong, Chee Wei, Amundson, Sally A., Attinger, Daniel
• Application Number:
  US11/844,906
• Publication Number:
  US 20080176755A1
• Time in Patent Office: Days
• US Class Current: 506/7
• CPC Class Codes: B01L 2200/10 Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
• CPC Class Codes: B01L 2300/0636 Integrated biosensor, microarrays
• CPC Class Codes: B01L 2300/1827 using resistive heater
• CPC Class Codes: B01L 3/5027 by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip B01L3/5023 takes precedence; micromixers B01F33/30; microreactors for synthesis B01J19/0093; microcapillary devices in general B81B1/00
• CPC Class Codes: B01L 3/502723 characterised by venting arrangements
• CPC Class Codes: B01L 3/502738 characterised by integrated valves microvalves F16K99/0001
• CPC Class Codes: C40B 30/10 by measuring physical properties, e.g. mass
• CPC Class Codes: C40B 60/12 for screening libraries
• CPC Class Codes: G01T 1/02 Dosimeters G01T1/15 takes precedence

Abstract

Exposure to ionizing radiation can produce a well-defined dose dependent signature in terms of changes in gene expression. In approaches and devices described herein, such a signature can be used to generate and use a self-contained radiation biodosimeter device, based on, for example, a blood finger stick. Various aspects of the invention are directed to biodosimetry with a fully integrated biochip using gene expression signatures.

Claims

4-1. The device of claim 1 wherein the microfluidic chip is adapted to contain at least one biological sample from at least one organism.

5-2. The device of claim 1 wherein the imaging element is a charge-coupled device sensor.

6-3. The device of claim 1 further comprising a memory for storing the image.

27. A method of determining radiation exposure of an organism comprising:

(a) applying a light source to the microfluidic chip;

(b) capturing an image of the microfluidic chip using an imaging element and a microlens wherein the microlens is coupled to the microfluidic chip; and

(c) analyzing the image to determine radiation exposure of the organism.

28. The method of claim 27 wherein the microfluidic chip includes a micropump.

29. The method of claim 28 wherein said micropump is electrochemically operated.

30. The method of claim 28 wherein said micropump is pneumatically operated.

31. The method of claim 28 wherein said micropump is thermopneumatically operated.

32. The method of claim 27 wherein the microfluidic chip includes a valve.

33. The method of claim 27 wherein the microfluidic chip includes a mixer.

34. The method of claim 27 wherein the microfluidic chip is includes a heater.

35. The method of claim 34 wherein the heater is a diode.

36. The method of claim 27 wherein the microfluidic chip includes at least one DNA microarray sensor.

37. The method of claim 27 wherein the microfluidic chip is comprised of an optically transparent material.

38. The method of claim 27 wherein the microfluidic chip includes a blood sample collection device.

39. The method of claim 27 wherein the microfluidic chip includes an RNA extraction device.

40. The method of claim 27 wherein the microfluidic chip includes at least one thermally-activated paraffin based microvalve.

41. The method of claim 27 wherein the microfluidic chip includes a power source.

42. The method of claim 27, further comprising performing a polymerase chain reaction assay using the microfluidic chip.

43. The method of claim 27 further comprising performing a DNA hybridization assay using the microfluidic chip.

44. The method of claim 27 further comprising performing a DNA detection assay using the microfluidic chip.

45. The method of claim 27 further comprising adding a reagent to the biological sample in the microfluidic chip.

46. The method of claim 27 further comprising coupling a lens to the microfluidic chip.

47. The method of claim 27 further comprising coupling an imaging element to the microfluidic chip.

48. The method of claim 47 wherein the imaging element is a charge-coupled device sensor.

49. The method of claim 27 wherein a processor is used to analyze the image.

50. The method of claim 49 further comprising storing the image in a memory.

51. The method of claim 27 wherein the analyzing the image comprises counting the number of cells shown in the image.

52. The method of claim 27 wherein the analyzing the image comprises counting the number of damaged cells shown in the image.

53. The method of claim 51 wherein the number of cells shown in the image is compared to a predetermined threshold to determine whether the organism has been exposed to a predetermined level of radiation.

54. The method of claim 53 further comprising normalizing the predetermined threshold based on an analysis of a plurality of biological samples.

55. The method of claim 27 further comprising flushing the biological sample from the microfluidic chip.

56. The method of claim 27, wherein the capturing of the image of the microfluidic chip includes transmitting the image through an aperture between the microlens and the imaging element.

57. The method of claim 56, wherein the aperture is less than 5 mm in diameter.

58. The method of claim 27, wherein the imaging element is a charge coupled device sensor.

59. The method of claim 27, wherein the imaging element is a CMOS sensor.

60. The method of claim 27, further comprising separating a control amount from the biological sample, exposing the control amount to a predetermined radiation level, extracting a predetermined element from the control amount;

capturing an image of the control amount;

analyzing the image of the control amount to determine radiation exposure; and

comparing the control amount to the biological sample.

61. The method of claim 27, further comprising normalizing any data derived therefrom through self normalization.

62. A system for determining radiation exposure of an organism comprising:

(a) illumination means for illuminating the microfluidic chip;

(b) image capturing means for capturing an image of the microfluidic chip;

(c) imaging means coupled to the microfluidic chip;

(c) analyzing means for analyzing the image to determine radiation exposure of the organism.

63. The system of claim 62 wherein the microfluidic chip includes a pumping means.

64. The system of claim 63 wherein said pumping means is electrochemically operated.

65. The system of claim 64 wherein said pumping means is thermopneumatically operated.

66. The system of claim 62 wherein the microfluidic chip includes a flow regulating means.

67. The system of claim 66 wherein the flow regulating means is a valve.

68. The system of claim 62 wherein the microfluidic chip includes a mixing means.

69. The system of claim 62 wherein the microfluidic chip includes a heating means.

70. The system of claim 69 wherein the heating means is a diode.

71. The system of claim 62 wherein the microfluidic chip includes at least one sensor means.

72. The system of claim 71 wherein the at least one sensor means is a DNA microarray sensor.

73. The system of claim 62 wherein the microfluidic chip is comprised of an optically transparent material.

74. The system of claim 62 wherein the microfluidic chip includes a blood sample collection means.

75. The system of claim 62 wherein the microfluidic chip includes an RNA extraction means.

76. The system of claim 66 wherein the flow regulating means is at least one thermally-activated paraffin based microvalve.

77. The system of claim 62 wherein the microfluidic chip includes a power providing means.

78. The system of claim 62 wherein the microfluidic chip includes a means for performing a polymerase chain reaction assay.

79. The system of claim 62 wherein the microfluidic chip includes a means for performing a DNA hybridization assay.

80. The system of claim 62 wherein the microfluidic chip includes a means for performing a DNA detection assay.

81. The system of claim 62 further comprising a means for adding to the biological sample in the microfluidic chip.

82. The system of claim 62 wherein the imaging means is a lens.

83. The system of claim 62 further comprising a flushing means for flushing the biological sample from the microfluidic chip.

84. The system of claim 62 wherein the imaging means is a charge-coupled device sensor.

85. The system of claim 62 wherein the analyzing means is a processor.

86. The system of claim 85 further comprising a storage means and a memory means, wherein the storing means stores the image in the memory means.

87. The system of claim 85 wherein the processor counts the number of cells shown in the image.

88. The system of claim 85 wherein the processor counts the number of damaged cells shown in the image.

89. The system of claim 88 wherein the number of damaged cells shown in the image is compared to a predetermined threshold to determine whether the organism has been exposed to a predetermined level of radiation.

90. The system of claim 89 wherein the processor normalizes the predetermined threshold based on an analysis of a plurality of biological samples.