Method and apparatus for chemical imaging in a microfluidic circuit

• US 7,394,542 B2
• Filed: 08/18/2004
• Issued: 07/01/2008
• Est. Priority Date: 08/18/2004
• Status: Active Grant

• Current Assignee: Chemimage Corporation
• Original Assignee: Chemimage Corporation
• Inventors: Tuschel, David, Voigt, Thomas
• Primary Examiner(s): EVANS, FANNIE L
• Application Number:
  US10/920,320
• Publication Number:
  US 20060039001A1
• Time in Patent Office: 1,413 Days
• Field of Search: 356/301, 356/317, 356/318, 356/417
• US Class Current: 356/417
• 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: G01J 3/0227 using notch filters
• CPC Class Codes: G01J 3/4406 Fluorescence spectrometry
• CPC Class Codes: G01N 2021/0325 Cells for testing reactions, e.g. containing reagents
• CPC Class Codes: G01N 2021/0346 Capillary cells; Microcells
• CPC Class Codes: G01N 2021/651 Cuvettes therefore
• CPC Class Codes: G01N 21/03 Cuvette constructions
• CPC Class Codes: G01N 21/05 Flow-through cuvettes G01N21/09 takes precedence; handling fluid samples G01N1/10
• CPC Class Codes: G01N 21/31 Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry G01N21/72 takes precedence
• CPC Class Codes: G01N 21/3577 for analysing liquids, e.g. polluted water
• CPC Class Codes: G01N 21/64 Fluorescence; Phosphorescence
• CPC Class Codes: G01N 21/65 Raman scattering

Abstract

The disclosure generally relates to a system for detecting a change in an attribute of a substance. The system may include a photon source for producing a first of a plurality of photons which interact with the substance while an attribute of the substance changes to produce a second plurality of photons. The system may also include a filter for receiving the collected photons and providing filtered photons; a photon detector for receiving the filtered photons and obtaining therefrom a spectrum of the substance; and a processor for detecting an aspect of the filtered photons wherein the aspect of the filtered photons is the function of the attribute of the substance.

Claims

1. A system for determining a change in an attribute of a substance, while the substance moves along at least one axis of a channel of a microfluidic circuit, the system comprising:

a photon source for providing a first plurality of photons which interact with the substance while an attribute of the substance changes to thereby produce a second plurality of photons;

an optical lens for collecting said second plurality of photons;

a filter for receiving the collected photons and providing therefrom filtered photons;

a photon detector for receiving the filtered photons and obtaining therefrom a spectrum of the substance; and

a processor for determining an aspect of the filtered photons wherein the aspect of the filtered photons is a function of the attribute of the substance and a position of the substance along said at least one axis, to thereby determine a change in the attribute of the substance.

2. The system of claim 1 wherein the attribute is selected from the group consisting of a physical property, a chemical property, an electrical property, a magnetic property, an optical property, and a biological property.

3. The system of claim 2 wherein the substance is a single molecule or a group of molecules.

4. The system of claim 1 wherein the attribute is a physical structure.

5. The system of claim 1 wherein the attribute is a physical orientation.

6. The system of claim 1 wherein the attribute is a chemical structure.

7. The system of claim 1 wherein the attribute is a chemical composition.

8. The system of claim 1 wherein the attribute is a chemical state.

9. The system of claim 1 wherein the attribute is an index of refraction.

10. The system of claim 1 wherein the substance is selected from the group consisting of a cell, an element, a compound, a molecule, a reactant, a solvent, a solute, a fluid, and a biological substance.

11. The system of claim 1 wherein said photon source is selected from the group consisting of a laser and a light emitting diode.

12. The system of claim 11 wherein the first plurality of photons have a wavelength in the infrared wavelength range.

13. The system of claim 11 wherein the first plurality of photons have a wavelength in the near infrared wavelength range.

14. The system of claim 11 wherein the first plurality of photons have a wavelength in the visible wavelength range.

15. The system of claim 11 wherein the first plurality of photons have a wavelength in the ultraviolet wavelength range.

16. The system of claim 11 wherein the first plurality of photons have a wavelength in the x-ray wavelength range.

17. The system of claim 1 wherein said photon source is selected from the group consisting of electro-generated luminescence and chemi-luminescence.

18. The system of claim 1 wherein said filter is selected from the group consisting of a notch filter, a bandpass filter, a spectral filter, a tunable filter, a liquid crystal tunable filter, an acousto-optical tunable filter, and Evans split element filter, a Lyot filter, a Solc filter, and a photonic crystal filter.

19. The system of claim 1 wherein said photon detector is selected from the group consisting of a charge-coupled device, a complementary metal oxide semiconductor, a charge injection device, an intensified charge injection device, an electron multiplying charge-coupled device, a photo diode, a silicon photo diode, a silicon avalanche diode, a camera, and a focal plane array.

20. The system of claim 1 wherein the aspect of the received photons is selected from the group consisting of a wavelength, a frequency, a phase, a polarization, and an intensity.

21. The system of claim 1 wherein the interaction of the first plurality of photons with the substance is selected from the group consisting of scattering, emission, reflection, and refraction.

22. The system of claim 1 wherein the spectrum is selected from the group consisting of a Raman spectrum, a luminescence spectrum, a near infrared spectrum, an infrared spectrum, and an ultraviolet spectrum, and an x ray spectrum.

23. The system of claim 1 wherein said processor comprises software programmed to determine the aspect of the received photons.

24. The system of claim 1 wherein said processor comprises firmware programmed to determine the aspect of the received photons.

25. A method for determining a change in an attribute of a substance while the substance moves along at least one axis of a channel of a microfluidic circuit, the method comprising the steps of:

illuminating the substance with a first plurality of photons which interact with the substance while an attribute of the substance changes to thereby produce a second plurality of photons;

collecting said second plurality of photons;

receiving the collected photons and providing therefrom filtered photons;

detecting the filtered photons and obtaining therefrom a spectrum of the substance;

determining an aspect of the filtered photons wherein the aspect of the filtered photons is a function of the attribute of the substancc and a position of the substance along said at least one axis, to thereby determine a change in the attribute of the substance; and

reporting said change in the attribute of the substance.

26. The method of claim 25 wherein the attribute is selected from the group consisting of a physical property, a chemical property, an electrical property, a magnetic property, an optical property, and a biological property.

27. The method of claim 25 wherein the substance is a single molecule or a group of molecules.

28. The method of claim 25 wherein the attribute is a physical structure.

29. The method of claim 25 wherein the attribute is a physical orientation.

30. The method of claim 25 wherein the attribute is a chemical structure.

31. The method of claim 25 wherein the attribute is a chemical composition.

32. The method of claim 25 wherein the attribute is a chemical state.

33. The method of claim 25 wherein the attribute is an index of refraction.

34. The method of claim 25 wherein the substance is selected from the group consisting of a cell, an element, a compound, a molecule, a reactant, a solvent, a solute, a fluid, and a biological substance.

35. The method of claim 25 wherein the first plurality of photons have a wavelength in the infrared wavelength range.

36. The method of claim 25 wherein the first plurality of photons have a wavelength in the near infrared wavelength range.

37. The method of claim 25 wherein the first plurality of photons have a wavelength in the visible wavelength range.

38. The method of claim 25 wherein the first plurality of photons have a wavelength in the ultraviolet wavelength range.

39. The method of claim 25 wherein the first plurality of photons have a wavelength in the x-ray wavelength range.

40. The method of claim 25 wherein the aspect of the received photons is selected from the group consisting of a wavelength, a frequency, a phase, a polarization, and an intensity.

41. The method of claim 25 wherein the interaction of the first plurality of photons with the substance is selected from the group consisting of scattering, emission, reflection, and refraction.

42. The method of claim 25 wherein the spectrum is selected from the group consisting of a Raman spectrum, a luminescence spectrum, a near infrared spectrum, an infrared spectrum, and an ultraviolet spectrum, and an x ray spectrum.

43. The method of claim 25 wherein, the step of illuminating the substance comprises passing the first plurality of photons through a fluid flow channel of a microfluidic circuit.

44. A system for determining a change in an attribute of a substance, the system comprising:

a photon source;

a microfluidic circuit;

an optical lens;

a filter;

a photon detector; and

a processor, wherein the substance passes through at least a portion of said microfluidic circuit while the attribute of the substance changes, and wherein said photon detector receives photons from the substance wherein an aspect of the received photons is a function of the attribute of the substance, and wherein said processor determines the aspect of the received photons to thereby determine a change in the attribute of the substance.

45. The system of claim 44 wherein the attribute is selected from the group consisting of a physical property, a chemical property, an electrical property, a magnetic property, an optical property, and a biological property.

46. The system of claim 45 wherein the substance is a single molecule or a group of molecules.

47. The system of claim 44 wherein the attribute is a physical structure.

48. The system of claim 44 wherein the attribute is a physical orientation.

49. The system of claim 44 wherein the attribute is a chemical structure.

50. The system of claim 44 wherein the attribute is a chemical composition.

51. The system of claim 44 wherein the attribute is a chemical state.

52. The system of claim 44 wherein the attribute is an index of refraction.

53. The system of claim 44 wherein the substance is selected from the group consisting of a cell, an element, a compound, a molecule, a reactant, a solvent, a solute, a fluid, and a biological substance.

54. The system of claim 44 wherein said photon source is selected from the group consisting of a laser and a light emitting diode.

55. The system of claim 54 wherein the photons emitted from said photon source have a wavelength in the infrared wavelength range.

56. The system of claim 54 wherein the photons emitted from said photon source have a wavelength in the near infrared wavelength range.

57. The system of claim 54 wherein the photons emitted from said photon source have a wavelength in the visible wavelength range.

58. The system of claim 54 wherein the photons emitted from said photon source have a wavelength in the ultraviolet wavelength range.

59. The system of claim 54 wherein the photons emitted from said photon source have a wavelength in the x-ray wavelength range.

60. The system of claim 44 wherein said photon source is selected from the group consisting of electro-generated luminescence and chemi-luminescence.

61. The system of claim 44 wherein said microfluidic circuit includes at least one channel through which a fluid flows and said photon source transmits photons through said channel.

62. The system of claim 44 wherein said filter is selected from the group consisting of a notch filter, a bandpass filter, a spectral filter, a tunable filter, a liquid crystal tunable filter, an acousto-optical tunable filter, and Evans split element filter, a Lyot filter, a Solc filter, and a photonic crystal filter.

63. The system of claim 44 wherein said photon detector is selected from the group consisting of a charge-coupled device, a complementary metal oxide semiconductor, a charge injection device, an intensified charge injection device, an electron multiplying charge-coupled device, a photo diode, a silicon photo diode, a silicon avalanche diode, a camera, and a focal plane array.

64. The system of claim 44 wherein the aspect of the received photons is selected from the group consisting of a wavelength, a frequency, a phase, a polarization, and an intensity.

65. The system of claim 44 wherein the received photons are selected from the group consisting of photons that are scattered by the substance, emitted by the substance, reflected by the substance, and refracted by the substance.

66. The system of claim 44 wherein the received photons have a wavelength in the infrared wavelength range.

67. The system of claim 44 wherein the received photons have a wavelength in the near infrared wavelength range.

68. The system of claim 44 wherein the received photons have a wavelength in the visible wavelength range.

69. The system of claim 44 wherein the received photons have a wavelength in the ultraviolet wavelength range.

70. The system of claim 44 wherein said processor comprises software programmed to determine the aspect of the received photons.

71. The system of claim 44 wherein said processor comprises firmware programmed to determine the aspect of the received photons.

72. A system for determining a change in an attribute of a substance, the system comprising:

a photon source for providing a first plurality of photons which interact with the substance to thereby produce a second plurality of photons;

a microfluidic circuit through at least a portion of which the substance passes while the attribute of the substance changes;

an optical lens for collecting said second plurality of photons;

a filter for receiving the collected photons and providing therefrom filtered photons;

a photon detector for receiving the filtered photons and obtaining therefrom a spectrum of the substance; and

a processor for determining an aspect of the filtered photons wherein the aspect of the filtered photons is a function of the attribute of the substance, to thereby determine a change in the attribute of the substance.

73. The system of claim 72 wherein the attribute is selected from the group consisting of a physical property, a chemical property, an electrical property, a magnetic property, an optical property, and a biological property.

74. The system of claim 73 wherein the substance is a single molecule or a group of molecules.

75. The system of claim 72 wherein the attribute is a physical structure.

76. The system of claim 72 wherein the attribute is a physical orientation.

77. The system of claim 72 wherein the attribute is a chemical structure.

78. The system of claim 72 wherein the attribute is a chemical composition.

79. The system of claim 72 wherein the attribute is a chemical state.

80. The system of claim 72 wherein the attribute is an index of refraction.

81. The system of claim 72 wherein the substance is selected from the group consisting of a cell, an element, a compound, a molecule, a reactant, a solvent, a solute, a fluid, and a biological substance.

82. The system of claim 72 wherein said photon source is selected from the group consisting of a laser and a light emitting diode.

83. The system of claim 82 wherein the first plurality of photons have a wavelength in the infrared wavelength range.

84. The system of claim 82 wherein the first plurality of photons have a wavelength in the near infrared wavelength range.

85. The system of claim 82 wherein the first plurality of photons have a wavelength in the visible wavelength range.

86. The system of claim 82 wherein the first plurality of photons have a wavelength in the ultraviolet wavelength range.

87. The system of claim 82 wherein the first plurality of photons have a wavelength in the x-ray wavelength range.

88. The system of claim 72 wherein said photon source is selected from the group consisting of electro-generated luminescence and chemi-luminescence.

89. The system of claim 72 wherein said microfluidic circuit includes at least one channel through which a fluid flows and said photon source transmits said first plurality of photons through said channel.

90. The system of claim 72 wherein said filter is selected from the group consisting of a notch filter, a bandpass filter, a spectral filter, a tunable filter, a liquid crystal tunable filter, an acousto-optical tunable filter, and Evans split element filter, a Lyot filter, a Solc filter, and a photonic crystal filter.

91. The system of claim 72 wherein said photon detector is selected from the group consisting of a charge-coupled device, a complementary metal oxide semiconductor, a charge injection device, an intensified charge injection device, an electron multiplying charge-coupled device, a photo diode, a silicon photo diode, a silicon avalanche diode, a camera, and a focal plane array.

92. The system of claim 72 wherein the aspect of the received photons is selected from the group consisting of a wavelength, a frequency, a phase, a polarization, and an intensity.

93. The system of claim 72 wherein the interaction of the first plurality of photons with the substancc is selected from the group consisting of scattering, emission, reflection, and refraction.

94. The system of claim 72 wherein the spectrum is selected from the group consisting of a Raman spectrum, a luminescence spectrum, a near infrared spectrum, an infrared spectrum, and an ultraviolet spectrum, and an x ray spectrum.

95. The system of claim 72 wherein said processor comprises software programmed to determine the aspect of the received photons.

96. The system of claim 72 wherein said processor comprises firmware programmed to determine the aspect of the received photons.

97. A method for determining a change in an attribute of a substance, the method comprising the steps of:

providing a microfluidic circuit through at least a portion of which the substance passes while the attribute of the substance changes;

illuminating the substance with a first plurality of photons which interact with the substance to thereby produce a second plurality of photons;

collecting said second plurality of photons;

receiving the collected photons and providing therefrom filtered photons;

detecting the filtered photons and obtaining therefrom a spectrum of the substance;

determining an aspect of the filtered photons wherein the aspect of the filtered photons is a function of the attribute of the substance, to thereby determine a change in the attribute of the substance; and

reporting said change in the attribute of the substance.

98. The method of claim aim 97 wherein the attribute is selected from the group consisting of a physical property, a chemical property, an electrical property, a magnetic property, an optical property, and a biological property.

99. The method of claim aim 97 wherein the substance is a single molecule or a group of molecules.

100. The method of claim aim 97 wherein the attribute is a physical structure.

101. The method of claim aim 97 wherein the attribute is a physical orientation.

102. The method of claim aim 97 wherein the attribute is a chemical structure.

103. The method of claim aim 97 wherein the attribute is a chemical composition.

104. The method of claim aim 97 wherein the attribute is a chemical state.

105. The method of claim aim 97 wherein the attribute is an index of refraction.

106. The method of claim aim 97 wherein the substance is selected from the group consisting of a cell, an clement, a compound, a molecule, a reactant, a solvent, a solute, a fluid, and a biological substancc.

107. The method of claim aim 97 wherein the first plurality of photons have a wavelength in the infrared wavelength range.

108. The method of claim aim 97 wherein the first plurality of photons have a wavelength in the near infrared wavelength range.

109. The method of claim aim 97 wherein the first plurality of photons have a wavelength in the visible wavelength range.

110. The method of claim aim 97 wherein the first plurality of photons have a wavelength in the ultraviolet wavelength range.

111. The method of claim aim 97 wherein the first plurality of photons have a wavelength in the x-ray wavelength range.

112. The method of claim aim 97 wherein the aspect of the received photons is selected from the group consisting of a wavelength, a frequency, a phase, a polarization, and an intensity.

113. The method of claim aim 97 wherein the interaction of the first plurality of photons with the substance is selected from the group consisting of scattering, emission, reflection, and refraction.

114. The method of claim aim 97 wherein the spectrum is selected from the group consisting of a Raman spectrum, a luminescence spectrum, a near infrared spectrum, an infrared spectrum, and an ultraviolet spectrum, and an x ray spectrum.

115. The method of claim aim 97 wherein the step of illuminating the substance comprises passing the first plurality of photons through a fluid flow channel of the microfluidic circuit.