Diffraction grating-based encoded micro-particles for multiplexed experiments

• US 7,349,158 B2
• Filed: 09/12/2003
• Issued: 03/25/2008
• Est. Priority Date: 09/12/2002
• Status: Expired due to Fees

• Current Assignee: Illumina Incorporated
• Original Assignee: CyVera Corporation (Illumina Incorporated)
• Inventors: Putnam, Martin A., Moon, John A.
• Primary Examiner(s): LAVARIAS, ARNEL C
• Application Number:
  US10/661,031
• Publication Number:
  US 20040125424A1
• Time in Patent Office: 1,656 Days
• Field of Search: 359/2, 359/566, 359/569, 359/558, 359/571, 359/572, 356/72, 356/73.1, 385/12, 385/128, 385/37, 250/559.04, 250/559.11, 250/559.4, 250/227.14, 250/227.29, 250/566, 250/568, 235/473, 435/4, 435/6, 435/228.7, 436/518, 436/524, 436/525, 436/526, 436/527, 436/528, 436/531
• US Class Current: 359/569
• CPC Class Codes: B01J 2219/00459 Beads
• CPC Class Codes: B01J 2219/00463 Directed sorting
• CPC Class Codes: B01J 2219/0047 Pins
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00547 Bar codes
• CPC Class Codes: B01J 2219/00576 fluorophore
• CPC Class Codes: B01J 2219/00702 Processes involving means for analysing and characterising the products
• CPC Class Codes: B01L 2200/0636 Focussing flows, e.g. to laminate flows
• CPC Class Codes: B01L 2200/0668 Trapping microscopic beads
• CPC Class Codes: B01L 2300/0654 Lenses; Optical fibres
• CPC Class Codes: B01L 2400/0409 centrifugal forces
• CPC Class Codes: B01L 2400/0457 passive flow or gravitation
• CPC Class Codes: B01L 2400/0487 fluid pressure, pneumatics
• CPC Class Codes: B01L 3/502761 specially adapted for handling suspended solids or molecules independently from the bulk fluid flow, e.g. for trapping or sorting beads, for physically stretching molecules investigating characteristics of particles G01N15/00
• CPC Class Codes: B01L 3/5085 for multiple samples, e.g. microtitration plates
• CPC Class Codes: G03H 1/0272 Substrate bearing the hologram
• CPC Class Codes: G03H 2210/53 Coded object not directly interpretable, e.g. encrypted object, barcode
• CPC Class Codes: G03H 2230/10 Microhologram not registered to the substrate
• CPC Class Codes: G03H 2270/20 Shape
• CPC Class Codes: G03H 2270/24 Having particular size, e.g. microscopic

Abstract

Microparticles 8 includes an optical substrate 10 having at least one diffraction grating 12 disposed therein. The grating 12 having a plurality of colocated pitches Λ which represent a unique identification digital code that is detected when illuminated by incident light 24. The incident light 24 may be directed transversely from the side of the substrate 10 with a narrow band (single wavelength) or multiple wavelength source, in which case the code is represented by a spatial distribution of light or a wavelength spectrum, respectively. The code may be digital binary or may be other numerical bases. The micro-particles 8 can provide a large number of unique codes, e.g., greater than 67 million codes, and can withstand harsh environments. The micro-particles 8 are functionalized by coating them with a material/substance of interest, which are then used to perform multiplexed experiments involving chemical processes, e.g., DNA testing and combinatorial chemistry.

Claims

1. An optical identification element having a chemical attached thereto, comprising:

a substrate;

at least a portion of said substrate being made of a substantially single material and having at least one diffraction grating embedded therein, said grating having a resultant refractive index variation within the substantially single material at a grating location; and

said grating providing an output optical signal indicative of a code when illuminated by an incident light signal propagating from outside the substrate, said output optical signal being a result of passive, non-resonant scattering from said grating when illuminated by said incident light signal; and

the chemical being attached to at least a portion of said substrate.

2. The apparatus of claim 1 wherein said refractive index variation comprises at least one refractive index pitch superimposed at said grating location.

3. The apparatus of claim 1 wherein said refractive index variation comprises a plurality of refractive index pitches superimposed at said grating location.

4. The apparatus of claim 1 wherein said substrate is made of a material selected from the group:

glass, silica, plastic, rubber, and polymer.

5. The apparatus of claim 1 wherein said code comprises a plurality of digital bits.

6. The apparatus of claim 1 wherein said code comprises at least a predetermined number of bits, said number being:

3, 5, 7, 9, 10, 12, 14, 16, 18, 20, 24, 28, 30, 40, 50, or 100.

7. The apparatus of claim 1 wherein said code comprises a plurality of bits, each bit having a plurality of states.

8. The apparatus of claim 1 wherein said code comprises a plurality of bits, each bit having a corresponding spatial location and each bit in said code having a value related to the intensity of said output optical signal at the spatial location of each bit.

9. The apparatus of claim 8 wherein the value of each bit corresponds to the magnitude of refractive index variation of a corresponding refractive index pitch in said grating.

10. The apparatus of claim 1 wherein said code comprises a plurality of digital bits, each bit having a corresponding spatial location and each bit in said code having a binary value related to the intensity of said output optical signal at the spatial location of each bit.

11. The apparatus of claim 10 wherein the value of each bit corresponds to the presence or absence of a corresponding refractive index pitch in said grating.

12. The apparatus of claim 1 wherein said incident beam comprises a single wavelength.

13. The apparatus of claim 1 wherein said incident light comprises a plurality of wavelengths or a single wavelength scanned over a predetermined wavelength range.

14. The apparatus of claim 13 wherein said code comprises a plurality of bits, and each bit in said code having a value related to the intensity of said output optical signal at a wavelength corresponding to each bit.

15. The apparatus of claim 14 wherein the value of each bit corresponds to the magnitude of refractive index variation of a corresponding refractive index pitch in said grating.

16. The apparatus of claim 13 wherein said code comprises a plurality of digital bits, and each bit in said code having a binary value related to the intensity of said output optical signal at the wavelength corresponding to each bit.

17. The apparatus of claim 16 wherein the value of each bit corresponds to the presence or absence of a corresponding refractive index pitch in said grating.

18. The apparatus of claim 1 wherein said substrate has a length that is less than about 500 microns.

19. The apparatus of claim 1 wherein said substrate has a diameter that is less than about 125 microns.

20. The apparatus of claim 1 wherein said substrate has a reflective coating disposed thereon.

21. The apparatus of claim 1 wherein said substrate has a coating disposed on at least a portion of said substrate, at least a portion of said coating being made of a material that allows sufficient amount of said incident light signal to pass through said material to allow detection of said code.

22. The apparatus of claim 1 wherein said substrate has a coating material disposed on at least a portion of said substrate, said coating comprising a polymer.

23. The apparatus of claim 1 wherein said substrate has a magnetic or electric charge polarization.

24. The apparatus of claim 1 wherein said substrate has geometry having holes therein or protruding sections therein.

25. The apparatus of claim 1 wherein at least a portion of said substrate has an end cross sectional geometry selected from the group:

circular, square, rectangular, elliptical, clam-shell, D-shaped, and polygon.

26. The apparatus of claim 1 wherein at least a portion of said substrate has a side view geometry selected from the group:

circular, square, rectangular, elliptical, clam-shell, D-shaped, and polygon.

27. The apparatus of claim 1 wherein at least a portion of said substrate has a 3-D shape selected from the group:

a cylinder, a sphere, a cube, and a pyramid.

28. The apparatus of claim 1 wherein said substrate has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said substrate has a plurality of grating regions.

29. The apparatus of claim 1 wherein said substrate has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said grating region has a refractive index that is greater than that of said non-grating region.

30. The apparatus of claim 1 wherein said substrate has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said grating region has a refractive index that is not greater than that of said non-grating region.

31. The apparatus of claim 1 wherein said incident light is incident on said substrate along a longitudinal grating axis of said grating.

32. The apparatus of claim 1 wherein said incident light is incident on said substrate at an angle to a longitudinal grating axis of said grating.

33. The apparatus of claim 1 wherein said incident light comprises laser light.

34. The apparatus of claim 1 wherein said grating is a thin grating or a blazed grating.

35. The apparatus of claim 1 wherein said substrate comprises a plurality of said gratings.

36. The apparatus of claim 1 wherein said substrate comprises a plurality of said gratings each at different locations within said substrate.

37. The apparatus of claim 1 wherein said substrate comprises a particle or bead.

38. The apparatus of claim 1 wherein said chemical comprises at least one gene, oligonucleotide, protein, antibody, peptide, amino acid, DNA cDNA, RNA, nucleic acid oligomer, polymer, or biological cell, or portion thereof.

39. An encoded particle having a chemical attached thereto, comprising:

a particle;

at least a portion of said particle being made of a substantially single material and having at least one diffraction grating embedded therein, said grating having a resultant refractive index variation within the substantially single material at a grating location; and

said grating providing an output optical signal indicative of a code when illuminated by an incident light signal propagating from outside the substrate, said output optical signal being a result of passive, non-resonant scattering from said grating when illuminated by said incident light signal; and

the chemical being attached to at least a portion of said particle.

40. The apparatus of claim 39 wherein said refractive index variation comprises at least one refractive index pitch superimposed at said grating location.

41. The apparatus of claim 39 wherein said refractive index variation comprises a plurality of refractive index pitches superimposed at said grating location.

42. The apparatus of claim 39 wherein said particle is made of a material selected from the group:

glass, silica, plastic, rubber, and polymer.

43. The apparatus of claim 39 wherein said code comprises a plurality of digital bits.

44. The apparatus of claim 39 wherein said code comprises at least a predetermined number of bits, said number being:

3, 5, 7, 9, 10, 12, 14, 16, 18, 20, 24, 28, 30, 40, 50, or 100.

45. The apparatus of claim 39 wherein said code comprises a plurality of bits, each bit having a plurality of states.

46. The apparatus of claim 39 wherein said code comprises a plurality of bits, each bit having a corresponding spatial location in said output optical signal and each bit in said code having a value related to the intensity of said output optical signal at the spatial location of each bit.

47. The apparatus of claim 46 wherein the value of each bit corresponds to the magnitude of refractive index variation of a corresponding refractive index pitch in said grating.

48. The apparatus of claim 39 wherein said code comprises a plurality of digital bits, each bit having a corresponding spatial location in said output optical signal and each bit in said code having a binary value related to the intensity of said output optical signal at the spatial location of each bit.

49. The apparatus of claim 48 wherein the value of each bit corresponds to the presence or absence of a corresponding refractive index pitch in said grating.

50. The apparatus of claim 39 wherein said incident light comprises a single wavelength.

51. The apparatus of claim 39 wherein said incident light comprises a plurality of wavelengths or a single wavelength scanned over a predetermined wavelength range.

52. The apparatus of claim 51 wherein said code comprises a plurality of bits, and each bit in said code having a value related to the intensity of said output optical signal at a wavelength corresponding to each bit.

53. The apparatus of claim 52 wherein the value of each bit corresponds to the magnitude of refractive index variation of a corresponding refractive index pitch in said grating.

54. The apparatus of claim 51 wherein said code comprises a plurality of digital bits, and each bit in said code having a binary value related to the intensity of said output optical signal at the wavelength corresponding to each bit.

55. The apparatus of claim 54 wherein the value of each bit corresponds to the presence or absence of a corresponding refractive index pitch in said grating.

56. The apparatus of claim 39 wherein said particle has a length that is less than about 1000 microns.

57. The apparatus of claim 39 wherein said particle has a diameter that is less than about 1000 microns.

58. The apparatus of claim 39 wherein said particle has a reflective coating disposed thereon.

59. The apparatus of claim 39 wherein said particle has a coating disposed on at least a portion of said particle, at least a portion of said coating being made of a material that allows sufficient amount of said incident light signal to pass through said material to allow detection of said code.

60. The apparatus of claim 39 wherein said particle has a coating material disposed on at least a portion of said particle, said coating comprising a polymer.

61. The apparatus of claim 39 wherein said particle has a magnetic or electric charge polarization.

62. The apparatus of claim 39 wherein said particle has geometry having holes therein or protruding sections therein.

63. The apparatus of claim 39 wherein at least a portion of said particle has an end cross sectional geometry selected from the group:

circular, square, rectangular, elliptical, clam-shell, D-shaped, and polygon.

64. The apparatus of claim 39 wherein at least a portion of said particle has a side view geometry selected from the group:

circular, square, rectangular, elliptical, clam-shell, D-shaped, and polygon.

65. The apparatus of claim 39 wherein at least a portion of said particle has a 3-D shape selected from the group:

a cylinder, a sphere, a cube, and a pyramid.

66. The apparatus of claim 39 wherein said particle has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said particle has a plurality of grating regions.

67. The apparatus of claim 39 wherein said particle has a grating region where said grating is located and a non-gracing region where said grating is not located;

and wherein said grating region has a refractive index that is greater than that of said non-grating region.

68. The apparatus of claim 39 wherein said particle has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said grating region has a refractive index that is not greater than that of said non-grating region.

69. The apparatus of claim 39 wherein said incident light is incident on said particle along a longitudinal grating axis of said grating.

70. The apparatus of claim 39 wherein said incident light is incident on said particle at an angle to a longitudinal grating axis of said grating.

71. The apparatus of claim 39 wherein said incident light comprises laser light.

72. The apparatus of claim 39 wherein said grating is a thin grating or a blazed grating.

73. The apparatus of claim 39 wherein said particle comprises a plurality of said gratings.

74. The apparatus of claim 39 wherein said particle comprises a plurality of said gratings each at different locations within said particle.

75. The apparatus of claim 39 wherein said chemical comprises at least one gene, oligonucleotide, protein, antibody, peptide, amino acid, DNA, cDNA, RNA, nucleic acid oligomer, polymer, or biological cell, or portion thereof.

76. A method of reading an encoded optical identification element having a chemical attached thereto, comprising:

obtaining a substrate, at least a portion of which being made of a substantially single material and having at least one diffraction grating embedded therein, said grating having a resultant refractive index variation within the substantially single material at a grating location;

attaching the chemical to at least a portion of said substrate;

illuminating said substrate with incident light, said substrate providing an output optical signal indicative of a code, said output optical signal being a result of passive, non-resonant scattering from said grating when illuminated by said incident light; and

reading said output light signal and detecting said code therefrom.

77. The method of claim 76 wherein said refractive index variation comprises at least one refractive index pitch superimposed at said grating location.

78. The method of claim 76 wherein said refractive index variation comprises a plurality of refractive index pitches superimposed at said grating location.

79. The method of claim 76 wherein said substrate is made of a material selected from the group:

glass, silica, plastic, rubber, and polymer.

80. The method of claim 76 wherein said code comprises a plurality of digital bits.

81. The method of claim 76 wherein said code comprises at least a predetermined number of bits, said number being:

3, 5, 7, 9, 10, 12, 14, 16, 18, 20, 24, 28, 30, 40, 50, or 100.

82. The method of claim 76 wherein said code comprises a plurality of digital bits, each bit having a corresponding spatial location in said output optical signal and each bit in said code having a binary value related to the intensity of said output optical signal at the spatial location of each bit.

83. The method of claim 82 wherein the value of each bit corresponds to the presence or absence of a corresponding refractive index pitch in said grating.

84. The method of claim 76 wherein said incident light comprises a single wavelength.

85. The method of claim 76 wherein said substrate has a coating disposed on at least a portion of said substrate, at least a portion of said coating being made of a material that allows sufficient amount of said incident light signal to pass through said material to allow detection of said code.

86. The method of claim 76 wherein at least a portion of said substrate has a 3-D shape selected from the group:

a cylinder, a sphere, a cube, and a pyramid.

87. The method of claim 76 wherein said substrate has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said substrate has a plurality of grating regions.

88. The method of claim 76 wherein said substrate has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said gracing region has a refractive index that is greater than that of said non-grating region.

89. The method of claim 76 wherein said substrate has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said grating region has a refractive index that is not greater than that of said non-grating region.

90. The method of claim 76 wherein said incident light is incident on said substrate along a longitudinal grating axis of said grating.

91. The method of claim 76 wherein said incident light is incident on said substrate at an angle to a longitudinal grating axis of said grating.

92. The method of claim 76 wherein said grating comprises a thin grating.

93. The method of claim 76 wherein said substrate comprises a plurality of said gratings.

94. The method of claim 76 wherein said substrate comprises a particle or bead.

95. The method of claim 76 wherein said chemical comprises at least one gene, oligonucleotide, protein, antibody, peptide, amino acid, NDA, cDNA, RNA, nucleic acid oligomer, polymer, or biological cell, or portion thereof.

96. A method of reading an encoded particle having a chemical attached thereto, comprising:

obtaining a particle, at least a portion of which being made of a substantially single material and having at least one diffraction grating embedded therein, said grating having a resultant refractive index variation within the substantially single material at a grating location;

attaching the chemical to at least a portion of said particle;

illuminating said particle with incident light, said particle providing an output optical signal indicative of a code, said output signal being a result of passive, non-resonant scattering from said grating when illuminated by said incident light; and

reading said output light signal and detecting said code therefrom.

97. The method of claim 96 wherein said refractive index variation comprises at least one refractive index pitch superimposed at said grating location.

98. The method of claim 96 wherein said refractive index variation comprises a plurality of refractive index pitches superimposed at said grating location.

99. The method of claim 96 wherein said particle is made of a material selected from the group:

glass, silica plastic, rubber, and polymer.

100. The method of claim 96 wherein said code comprises a plurality of digital bits.

101. The method of claim 96 wherein said code comprises at least a predetermined number of bits, said number being:

3, 5, 7, 9, 10, 12, 14, 16, 18, 20, 24, 28,30, 40, 50, or 100.

102. The method of claim 96 wherein said code comprises a plurality of digital bits, each bit having a corresponding spatial location in said optical output signal and each bit in said code having a binary value related to the intensity of said output optical signal at the spatial location of each bit.

103. The method of claim 102 wherein the value of each bit corresponds to the presence or absence of a corresponding refractive index pitch in said grating.

104. The method of claim 96 wherein said incident light comprises a single wavelength.

105. The method of claim 96 wherein said substrate has a coating disposed on at least a portion of said substrate, at least a portion of said coating being made of a material that allows sufficient amount of said incident light signal to pass through said material to allow detection of said code.

106. The method of claim 96 wherein at least a portion of said substrate has a 3-D shape selected from the group:

a cylinder, a sphere, a cube, and a pyramid.

107. The method of claim 96 wherein said substrate has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said substrate has a plurality of grating regions.

108. The method of claim 96 wherein said substrate has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said grating region has a refractive index that is greater than that of said non-grating region.

109. The method of claim 96 wherein said substrate has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said grating region has a refractive index that is not greater than that of said non-grating region.

110. The method of claim 96 wherein said incident light is incident on said substrate along a longitudinal grating axis of said grating.

111. The method of claim 96 wherein said incident light is incident on said substrate at an angle to a longitudinal grating axis of said grating.

112. The method of claim 96 wherein said grating comprises a thin grating or a blazed grating.

113. The method of claim 96 wherein said substrate comprises a plurality of said gratings.

114. The method of claim 96 wherein said substrate comprises a particle or bead.

115. The method of claim 96 wherein said chemical comprises at least one gene, oligonucleotide, protein, antibody, peptide, amino acid DNA, cDNA, RNA, nucleic acid oligomer, polymer, or biological cell, or portion thereof.

116. A method of performing a multiplexed particle assay, comprising:

obtaining a plurality of particles each being made of a substantially single material and having at least one diffraction grating embedded therein, said grating having a resultant refractive index variation within the substantially single material at a grating location;

attaching at least one probe to at least one of said particles, thereby providing functionalized particles;

placing said functionalized particles in contact with at least one analyte, said analyte having a corresponding label disposed thereon;

illuminating said particles with a first and second incident light, said particle providing a first output optical signal responsive to said first incident light indicative of a code and a second output optical signal responsive to said second incident light indicative of said label, said first output optical signal being a result of passive, non-resonant scattering from said grating when illuminated by said incident light;

reading said first output optical signal and detecting said code therefrom; and

reading said second output optical signal and detecting said label therefrom.

117. The method of claim 116 wherein said refractive index variation comprises at least one refractive index pitch superimposed at said grating location.

118. The method of claim 116 wherein said refractive index variation comprises a plurality of refractive index pitches superimposed at said grating location.

119. The method of claim 116 wherein said particle is made of a material selected from the group:

glass, silica, plastic, rubber, and polymer.

120. The method of claim 116 wherein said code comprises a plurality of digital bits.

121. The method of claim 116 wherein said code comprises at least a predetermined number of bits, said number being:

3, 5, 7, 9, 10, 12, 14, 16, 18, 20, 24, 28, 30, 40, 50, or 100.

122. The method of claim 116 wherein said code comprises a plurality of digital bits, each bit having a corresponding spatial location in said first output optical signal and each bit in said code having a binary value related to the intensity of said first output optical signal at the spatial location of each bit.

123. The method of claim 122 wherein the value of each bit corresponds to the presence or absence of a corresponding refractive index pitch in said grating.

124. The method of claim 116 wherein said incident light comprises a single wavelength.

125. The method of claim 116 wherein said substrate has a coating disposed on at least a portion of said substrate, at least a portion of said coating being made of a material that allows sufficient amount of said incident light signal to pass through said material to allow detection of said code.

126. The method of claim 116 wherein at least a portion of said substrate has a 3-D shape selected from the group:

a cylinder, a sphere, a cube, and a pyramid.

127. The method of claim 116 wherein said substrate has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said substrate has a plurality of grating regions.

128. The method of claim 116 wherein said substrate has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said grating region has a refractive index that is greater than that of said non-grating region.

129. The method of claim 116 wherein said substrate has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said grating region has a refractive index that is not greater than that of said non-grating region.

130. The method of claim 116 wherein said incident light is incident on said substrate along a longitudinal grating axis of said grating.

131. The method of claim 116 wherein said incident light is incident on said substrate at an angle to a longitudinal grating axis of said grating.

132. The method of claim 116 wherein said grating comprises a thin grating or a blazed grating.

133. The method of claim 116 wherein said substrate comprises a plurality of said gratings.

134. The method of claim 116 wherein said chemical comprises at least one gene, oligonucleotide, protein, antibody, peptide, amino acid, DNA, cDNA, RNA, nucleic acid oligomer, polymer, or biological cell, or portion thereof.

135. The method of claim 116, wherein said first and second incident light signals are the same signal.

136. The method of claim 116, wherein said second output optical signal is a result of fluorescences emissions.