Fourier scattering methods for encoding microbeads and methods and apparatus for reading the same

• US 8,081,792 B2
• Filed: 11/16/2005
• Issued: 12/20/2011
• Est. Priority Date: 08/20/2003
• Status: Active Grant

• Current Assignee: Illumina Incorporated
• Original Assignee: Illumina Incorporated
• Inventors: Moon, John A., Putnam, Martin A.
• Primary Examiner(s): CHEN, WENPENG
• Application Number:
  US11/281,907
• Publication Number:
  US 20060119913A1
• Time in Patent Office: 2,225 Days
• Field of Search: 382/100, 235/380, 356/601
• US Class Current: 382/100
• CPC Class Codes: B01J 2219/00459 Beads
• CPC Class Codes: B01J 2219/005 Beads
• CPC Class Codes: B01J 2219/00704 integrated with the reactor apparatus
• CPC Class Codes: B82Y 20/00 Nanooptics, e.g. quantum optics or photonic crystals
• CPC Class Codes: G01N 15/1468 with spatial resolution of the texture or inner structure of the particle
• CPC Class Codes: G02B 1/005 made of photonic crystals or photonic band gap materials photonic band-gap structures or photonic lattices in integrated optics G02B6/1225; photonic band-gap structures or photonic lattices in optical fibres G02B6/02295
• CPC Class Codes: G06E 3/005 using electro-optical or opto-electronic means
• CPC Class Codes: G06K 7/10722 Photodetector array or CCD scanning
• CPC Class Codes: G06K 7/10821 further details of bar or optical code scanning devices

Abstract

A method, optical arrangement, and apparatus for reading a microbead having a code. The method includes reflecting an incident light from the microbead to provide an output light. The output light is projected on a Fourier plane. The method also includes reading the code from the Fourier plane.

Claims

1. A method for reading microbeads having different respective codes, comprising:

providing a plurality of microbeads in a random manner onto a support substrate, the microbeads being oriented in a predetermined manner on the support substrate, wherein each of the microbeads has an individually identifiable code that can be projected on and read from a Fourier plane;

illuminating the microbeads with an incident light, the codes providing corresponding output light signals indicative of the respective codes, wherein the corresponding output light signal from each of the microbeads is projected individually on the Fourier plane, wherein only one microbead is illuminated at a time by the incident light to read the respective code; and

reading the respective codes from the Fourier plane.

2. A method according to claim 1, wherein the output light signals are projected on the Fourier plane by scattering the incident light off or through the microbeads.

3. A method according to claim 1, wherein the respective codes are read from the Fourier plane using a charge coupled device (CCD).

4. A method according to claim 1, wherein a transform lens is arranged between the microbead and the Fourier plane at a distance of about one focal length f from the Fourier plane and at a distance of about one focal length f from a corresponding one microbead being read, the transform lens focusing the output light signals onto the Fourier plane.

5. A method according to claim 1, wherein the reading the respective codes includes using a Fourier plane transform processor to perform Fourier plane analysis to determine the respective codes.

6. A method according to claim 1, wherein each of the microbeads includes periodic layers of material with different reflectivity that reflect the incident light to provide the output light signal.

7. A method according to claim 1, wherein each of the microbeads includes one of:

periodic layers of material having a different phase, including index of refraction differences;

periodic spatial modulations having a different phase or amplitude; and

a periodic binary phase change used to code information in the Fourier plane.

8. A method according to claim 1, wherein the microbeads are microscopic in size.

9. A method according to claim 1, wherein each of the microbeads includes an optical substrate having a refractive index of an inner region less than or equal to a refractive index of an outer region.

10. A method according to claim 1, wherein each of the microbeads includes one of:

a single photoactive inner and/or outer region;

a series of longitudinal holes;

different fluorescence regions; and

concentric rings of material in the preform.

11. A method according to claim 1, wherein each of the microbeads includes photonic crystal microparticles having encoded information, the microparticles including a pattern of holes where the pattern of the holes causes interferences between the incident and scattered light to form spatial and spectral patterns in a far field that are unique to the pattern of holes.

12. A method according to claim 1, wherein each of the output light signals projected on the Fourier plane includes readout beams having a spatial coherence Lc large enough to resolve adjacent frequency components used to identify the corresponding microbead.

13. A method according to claim 12, further comprising identifying the microbeads by looking at the presence or absence of predetermined Fourier spatial frequencies.

14. A method according to claim 1, wherein the reading the respective codes includes using a computer program running in a processor, a controller, or a reading module of an optical system.

15. A method according to claim 1, wherein the output light signals on the Fourier plane form corresponding bar codes or digital images, the respective codes on the microbeads being unintelligible as the corresponding bar code or the corresponding digital image.

16. A method according to claim 1, wherein the microbeads have chemical probes immobilized thereto, each of the chemical probes being associated with a corresponding one of the respective codes.

17. A method according to claim 16 further comprising detecting a label on at least one microbead that is indicative of a binding event between the chemical probe that is immobilized to the at least one microbead and a target analyte.

18. A method according to claim 8, wherein the microbead has a length of about 1,000 microns or smaller.

19. A method according to claim 8, wherein the microbeads have an elongated shape that extends along a central longitudinal axis and wherein a cross-section of the microbeads taken transverse to the longitudinal axis has an outer diameter of about 1,000 microns or smaller.

20. A method according to claim 1, wherein the microbeads are randomly distributed along a surface of the support substrate when the respective codes are being read.

21. A method according to claim 1, wherein a transform lens is arranged between each of the microbeads and the Fourier plane when the microbead is read, the transform lens providing different light beams that are imaged on the Fourier plane at different predetermined locations with respect to each other according to a predetermined coding system, the different locations being side-by-side.

22. A method according to claim 21, wherein images formed at the different predetermined locations have different levels of light that are analyzed to determine the code.

23. A method according to claim 1 wherein the support substrate comprises grooves configured to align the microbeads.

24. An optical system for reading microbeads having different respective codes, the optical system comprising:

a support substrate configured to receive a plurality of microbeads in a random manner, the microbeads being oriented in a predetermined manner on the support substrate, wherein each of the microbeads has an individually identifiable code that can be projected on and read from a Fourier plane;

an input light source configured to direct an incident light onto the codes of the microbeads to provide an output light signal from each of the microbeads that is projected individually on the Fourier plane, the output light signals being indicative of the respective codes, wherein only one microbead is illuminated at a time by the incident light to read the respective code; and

a detector that is configured to detect the corresponding output light signal from each of the microbeads from the Fourier plane.

25. An optical system according to claim 24, wherein the output light signals are projected on the Fourier plane by scattering the incident light off or through the microbeads.

26. An optical system according to claim 24, wherein detector includes a charge coupled device (CCD).

27. An optical system according to claim 24, further comprising a transform lens that is arranged between the microbeads and the Fourier plane at a distance of about one focal length f from the Fourier plane and at a distance of about one focal length f from a corresponding one microbead being read, the transform lens focusing the output light signals onto the Fourier plane.

28. An optical system according to claim 24, further comprising a Fourier plane transform processor that performs Fourier plane analysis to determine the respective codes.

29. An optical system according to claim 24, wherein the output light signals projected on the Fourier plane include readout beams having a spatial coherence Lc large enough to resolve adjacent frequency components used to identify the corresponding microbead.

30. An optical system according to claim 29, wherein the respective codes are read by looking at the presence or absence of predetermined Fourier spatial frequencies.

31. An optical system according to claim 29, wherein the output light signals on the Fourier plane form corresponding bar codes or digital images, the respective codes on the microbeads being unintelligible as the corresponding bar code or the corresponding digital image.

32. An optical system according to claim 24, wherein the microbeads have chemical probes immobilized thereto, each of the chemical probes being associated with a corresponding one of the respective codes, the optical system further comprising a label detector, the label detector configured to detect optical activity that is indicative of binding events between the chemical probes and target analytes.

33. An optical system according to claim 24 wherein the support substrate comprises grooves configured to align the microbeads.

34. An optical system according to claim 24, wherein the microbeads are microscopic in size, the support substrate being configured to hold the microscopic microbeads so that the microbeads are substantially co-planar when being read.

35. An optical system according to claim 34, wherein the microbeads have a length of about 1,000 microns or smaller.

36. A method for reading a code from an encoded microbead, the method comprising:

providing an encoded microbead, the microbead having a chemical probe immobilized thereto, wherein the microbead has an individually identifiable code that is correlated to the chemical probe immobilized thereto, the code configured to be projected on and read from the Fourier plane;

illuminating the microbead with an incident light thereby providing an output light signal, the output light signal being projected onto a Fourier plane;

performing Fourier plane analysis of the output light signal projected onto the Fourier plane to determine a code therefrom;

identifying the chemical probe using the code; and

determining whether the chemical probe has selectively bound to a target analyte after the microbead is exposed to the target analyte.

37. A method according to claim 36 wherein the providing operation includes providing a plurality of said microbeads in a random manner onto a support substrate, the microbeads being oriented in a predetermined manner on the support substrate.

38. A method according to claim 37 wherein the support substrate comprises grooves configured to align the microbeads in the predetermined manner.

39. A method according to claim 36 wherein the providing operation includes providing a plurality of said microbeads, wherein the microbeads have lengths of about 1,000 microns or smaller.

40. An apparatus for reading encoded microbeads, each microbead providing output light signals projected individually onto a Fourier plane when illuminated by an incident light, the apparatus comprising:

a support substrate configured to receive a plurality of microbeads in a random manner, the microbeads being oriented in a predetermined manner on the support substrate, wherein each of the microbeads has an individually identifiable code that can be projected on and read from the Fourier plane;

a reading device positioned to detect the corresponding output light signal of each microbead from the Fourier plane, wherein the reading device is configured to read the corresponding output light signal of each microbead one at a time; and

a processor configured to perform Fourier plane analysis of the output light signals projected onto the Fourier plane to determine different respective codes of the encoded microbeads.