Method of reading encoded particles

• US 7,923,260 B2
• Filed: 10/06/2006
• Issued: 04/12/2011
• Est. Priority Date: 08/20/2002
• Status: Expired due to Fees

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: Putnam, Martin A., Moon, John A.
• Primary Examiner(s): Siefke; Sam P
• Assistant Examiner(s): Kilpatrick; Bryan T
• Application Number:
  US11/544,309
• Publication Number:
  US 20080085565A1
• Time in Patent Office: 1,649 Days
• Field of Search: 436/164, 436/94
• US Class Current: 436/164
• CPC Class Codes: G01N 21/6428 Measuring fluorescence of fluorescent products of reactions or of fluorochrome labelled reactive substances, e.g. measuring quenching effects, using measuring "optrodes" in vivo A61B5/00; immunoassay G01N33/53
• CPC Class Codes: G01N 21/645 Specially adapted constructive features of fluorimeters
• CPC Class Codes: Y10T 436/143333 Saccharide [e.g., DNA, etc.]

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. A method, comprising:

providing a particle having a grating disposed therein, the grating comprising a superposition of different predetermined regular periodic variations of an index of refraction disposed along a grating axis and indicative of a code;

directing an illuminating light beam at the particle other than along the grating axis and other than fully transverse to the grating axis;

reading the code by at least one of i) sensing light that is reflected by the grating and ii) sensing light transmitted through the grating;

determining which of the periodic variations are present; and

constructing a string of bits with each bit in the string predetermined to correspond to a particular one of the periodic variations, the bits being set so as to indicate whether the particular one of the periodic variations is present in the light reflected by the grating or the light transmitted through the grating.

2. A method as in claim 1, wherein the periodic variations are read using one wavelength for the illuminating light beam and observing the light reflected by the grating at a plurality of predetermined angles, or using many wavelengths and one angle, or using many wavelengths and many angles.

3. A method as in claim 1, wherein the reading includes both sensing light reflected by the grating and sensing light transmitted through the grating.

4. A method as in claim 1, wherein the particle has a particle substrate formed of a transparent dielectric material with the index of refraction at each point in the dielectric material, and the superposition of different regular periodic variations in the index of refraction is disposed along a length of the particle substrate.

5. A method as in claim 1, wherein the superposition is provided so as to correspond to a predetermined code for identifying the particle.

6. A method according to claim 4, wherein said particle substrate has an elongated shape and wherein said superposition of different regular periodic variations in the index of refraction occurs along a length of said particle substrate.

7. A method according to claim 6, wherein the code is readable based on the grating altering the transmitted light beam, wherein the light is transmitted through the particle substrate in a direction transverse to an elongated dimension of the particle substrate.

8. A method according to claim 1, wherein the superposition includes a combination of one or more individual sinusoidal spatial periods or pitches of refractive index variation along the particle.

9. A method according to claim 1, wherein at least a portion of said particle is made of a substantially single material and has at least one diffraction grating embedded therein.

10. A method according to claim 9, wherein said diffraction grating has a resultant refractive index variation within the single material at a grating location, said resultant refractive index variation comprising a plurality of refractive index pitches superimposed at said grating location.

11. A method according to claim 1, wherein the particle responds to the illuminating light beam, for providing a grating output optical signal that is a result of passive, non-resonant scattering from said grating when illuminated by said illuminating light beam.

12. A method according to claim 4, wherein said particle substrate is made of a material selected from the group:

glass, silica, plastic, rubber, and polymer.

13. A method according to claim 5, wherein said predetermined code comprises a plurality of digital bits.

14. A method according to claim 5, wherein said predetermined code comprises at least 3 predetermined bits.

15. A method according to claim 5, wherein said predetermined code comprises at least 16 predetermined bits.

16. A method according to claim 5, wherein said predetermined code comprises a plurality of bits, each bit having a plurality of states.

17. A method according to claim 5, wherein said predetermined code comprises a plurality of bits, each bit having a corresponding spatial location and each bit in said predetermined code having a value related to an intensity of a grating output optical signal at the spatial location of each bit.

18. A method according to claim 17, wherein the value of each bit corresponds to a magnitude of refractive index variation of a corresponding refractive index pitch in said grating.

19. A method according to claim 4, wherein said particle substrate has a coating disposed on at least a portion of said particle substrate, at least a portion of said coating being made of a material that allows sufficient amount of the illuminating light beam to pass through said material to allow detection of said code.

20. A method according to claim 4, wherein at least a portion of said particle substrate has a 3-D shape selected from a group:

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

21. A method according to claim 4, wherein said particle substrate has a grating region where said grating is located and a non-grating region where said grating is not located;

and wherein said particle substrate has a plurality of grating regions.

22. A method according to claim 1, wherein said grating is a thin grating or a blazed grating.

23. A method according to claim 4, wherein said particle substrate comprises a plurality of said gratings.

24. A method according to claim 4, wherein said particle substrate comprises a plurality of said gratings each at different locations within said particle substrate.

25. A method according to claim 11, wherein said light signal comprises laser light.

26. A method according to claim 4, wherein said substrate is photosensitive at least at said grating location.

27. A method according to claim 1, wherein said illuminating light beam comprises a substantially single wavelength.

28. A method according to claim 1, wherein said illuminating light beam comprises a plurality of wavelengths.

29. A method according to claim 4, wherein said illuminating light beam is incident on said particle substrate along a longitudinal grating axis of said grating.

30. A method according to claim 4, wherein said illuminating light beam is incident on said particle substrate at an angle to a longitudinal grating axis of said grating.

31. A method according to claim 4, wherein a chemical is attached to at least a portion of the particle substrate.

32. A method according to claim 31, 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.